Prospective Randomized Crossover Trial Research Articles

3D printed versus milled stabilization splints for the management of bruxism and temporomandibular disorders: study protocol for a randomized prospective single-blinded crossover trial

BackgroundNowadays, stabilization splints for the management of bruxism and temporomandibular disorders (TMD) can be produced utilizing a digital workflow comprising a digital impression of the teeth, digital splint design, and computer-aided manufacturing of the splints. The latter is usually a milling process, however, more recently 3D printing gained popularity due to its better cost and time efficiency. It remains unknown whether 3D printed stabilization splints are inferior to milled splints regarding clinical outcomes.MethodsThis clinical trial assesses the non-inferiority of 3D printed occlusal splints compared to milled occlusal splints in a monocentric prospective randomized single-blinded crossover trial with two cohorts. One cohort includes 20 participants with bruxism, the other 20 participants with pain-related TMD, i.e., myalgia, myofascial pain, or arthralgia of the jaw muscles/the temporomandibular joint(s) diagnosed according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Michigan-type stabilization splints are fabricated in a digital workflow by milling or 3D printing using CE-marked materials within their intended purpose. The participants wear a milled and a 3D printed splint in a randomized order for 3 months each, with follow-up visits after 2 weeks and 3 months. Investigated outcome parameters are oral health-related quality of life (OHRQoL) evaluated by the Oral Health Impact Profile (OHIP-G14), participant satisfaction as rated on a visual analog scale, therapeutic efficacy, and technical result of the splints. In this context, therapeutic efficacy means antagonist wear and—in the TMD group—reduction of pain/disability assessed by the Graded Chronic Pain Scale (GCPS v2.0) and clinical assessment following the DC/TMD standard, while technical outcome measures splint fit, wear and fracture rate.DiscussionThe trial will provide important information on the clinical outcome of 3D printed stabilization splints in comparison to milled splints and will, therefore, enable an evidence-based decision in favor of or against a manufacturing process. This, in turn, will guarantee for a maximum of the patient’s OHRQoL during splint therapy, therapeutic efficacy, and longevity of the splints.Trial registrationGerman Clinical Trials Register (DRKS) DRKS00033904. Registered on March 15, 2024.

Comparing two mucin secretagogues for the treatment of dry eye disease: a prospective randomized crossover trial

This study aimed to compare the clinical efficacy and investigate patients’ preferences for two mucin secretagogues in the treatment of dry eye disease (DED). Thirty patients with DED were randomly treated with either 3% diquafosol or 2% rebamipide ophthalmic solution for 4 weeks, followed by an additional 4-week treatment using the other eye drop after a 2-week washout period. Objective and subjective assessments, including the corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer 1 test, tear osmolarity, tear matrix metalloproteinase-9 (MMP-9), lipid layer thickness (LLT) and ocular surface disease index (OSDI), were performed at baseline, 4 weeks, 6 weeks, and 10 weeks. Patient preferences were assessed based on four categories (comfort, efficacy, convenience, willingness to continue) using a questionnaire and the overall subjective satisfaction score for each drug was obtained at the end of the trial. In total, 28 eyes from 28 patients were included in the analysis. Both diquafosol and rebamipide significantly improved the OSDI (p = 0.033 and 0.034, respectively), TBUT (p < 0.001 and 0.026, respectively), and corneal (p < 0.001 and 0.001, respectively) and conjunctival (p = 0.017 and 0.042, respectively) staining after 4 weeks of treatment. An increase in Schirmer test scores was observed only after rebamipide treatment (p = 0.007). No significant changes were detected in tear osmolarity, MMP-9, and LLT following both treatments. The patients’ preference was slightly greater for diquafosol (46.4%) than rebamipide (36.7%), presumably due to rebamipide's bitter taste. The self-efficacy of both drugs and overall satisfaction scores were comparable. These findings indicate that two mucin secretagogues showed comparable effects in ameliorating symptoms and improving signs (TBUT, corneal and conjunctival staining) in patients with DED.

Comparative Effectiveness of Personal Sound Amplification Products Versus Hearing Aids for Unilateral Hearing Loss: A Prospective Randomized Crossover Trial.

This study compared hearing outcomes with use of personal sound amplification products (PSAPs) and hearing aids (HAs) in patients with moderate to moderately severe unilateral hearing loss. Thirty-nine participants were prospectively enrolled, and randomly assigned to use either one HA (basic or premium type) or one PSAP (basic or high-end type) for the first 8 weeks and then the other device for the following 8 weeks. Participants underwent a battery of examinations at three visits, including sound-field audiometry, word recognition score (WRS), speech perception in quiet and in noise, real-ear measurement, and self-report questionnaires. Functional gain was significantly higher with HAs across all frequencies (P < 0.001). While both PSAPs and HAs improved WRS from the unaided condition, HAs were superior to PSAPs. The speech recognition threshold in quiet conditions and signal-to-noise ratio in noisy conditions were significantly lower in the HA-aided condition than in the PSAP-aided condition, and in the PSAP-aided condition than in the unaided condition. Subjective satisfaction also favored HAs than PSAPs in questionnaires, Abbreviated Profile of Hearing Aid Benefit, International Outcome Inventory for Hearing Aids, and Host Institutional Questionnaire. While PSAPs provide some benefit for moderate to moderately severe unilateral hearing loss, HAs are more effective. This underscores the potential role of PSAPs as an accessible, affordable first-line intervention in hearing rehabilitation, particularly for individuals facing challenges in accessing conventional HAs.

Effect of metoprolol in hypertrophic obstructive cardiomyopathy patients after alcohol septal ablation

BackgroundThe use of beta-blockers in hypertrophic obstructive cardiomyopathy (HOCM) patients after alcohol septal ablation (ASA) lacks data support. We aimed to evaluate the effect of metoprolol on exercise capacity, hemodynamic and laboratory parameters, and quality of life in HOCM patients after ASA. MethodsThis was a prospective randomized single-center open-label crossover trial in 21 HOCM patients after ASA. Patients received metoprolol and no beta-blocker for two periods of three months. The endpoints were: peak oxygen uptake (pVO2), maximal left ventricular outflow tract (LVOT) pressure gradient at peak exercise, a ratio of mitral peak velocity of the early filling (E) to early diastolic mitral annular velocity (e′) (E/e′) at rest, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) plasmatic concentration. ResultsNo significant association was found between the treatment and any of the endpoints in the assessed patients: 1) pVO2 (19.5 ± 5.3 ml/kg/min vs. 19.4 ± 4.1 ml/kg/min, p = 0.90), 2) exercise-induced pressure gradient in LVOT 32 ± 37 mmHg vs. 32 ± 30 mmHg, p = 0.84, 3) E/e′ ratio at rest (11 ± 4 vs. 10 ± 4, p = 0.23), 4) KCCQ overall summary score (78 ± 11 vs. 77 te ± 15, p = 0.56), 5) NT-proBNP (215 pg/ml [121–333] vs. 153 pg/ml [102–228], p = 0.19). ConclusionsIn HOCM patients after successful ASA, metoprolol treatment did not improve exercise capacity, hemodynamic and laboratory parameters, or quality of life.

Impact of Personal Protective Equipment on Cardiopulmonary Resuscitation and Rescuer Safety

Background. High-quality cardiopulmonary resuscitation (CPR) is a key element in the rescue of cardiac arrest patients but is difficult to achieve in circumstances involving aerosol transmission, such as the COVID-19 pandemic. Methods. This prospective randomized crossover trial included 30 experienced health care providers to evaluate the impact of personal protective equipment (PPE) on CPR quality and rescuer safety. Participants were asked to perform continuous CPR for 5 minutes on a manikin with three types of PPE: level D-PPE, level C-PPE, and PAPR. The primary outcome was effective chest compression per minute. Secondary outcomes were the fit factor by PortaCount, vital signs and fatigue scores before and after CPR, and perceptions related to wearing PPE. Repeated-measures ANOVA was used, and a two-tailed test value of 0.05 was considered statistically significant. Results. The rates of effective chest compressions for 5 minutes with level D-PPE, level C-PPE, and PAPRs were 82.0 ± 0.2%, 78.4 ± 0.2%, and 78.0 ± 0.2%, respectively ( p = 0.584 ). The fit-factor test values of level C-PPE and PAPRs were 182.9 ± 39.9 vs. 198.9 ± 9.2 ( p &lt; 0.001 ). The differences in vital signs before and after CPR were not significantly different among the groups. In addition, the fatigue and total perception scores of wearing PPE were significantly higher for level C-PPE than PAPRs: 3.8 ± 1.6 vs. 3.0 ± 1.6 ( p &lt; 0.001 ) and 27.9 ± 5.4 vs. 26.0 ± 5.3 ( p &lt; 0.001 ), respectively. Conclusion. PAPRs are recommended when performing CPR in situations where aerosol transmission is suspected. When PAPRs are in short supply, individual fit-tested N95 masks are an alternative. This trial is registered with NCT04802109.

Prospective randomised crossover trial comparing mixed and post-dilution haemodiafiltration: COMPare HDF study

Prospective randomised crossover trial comparing mixed and post-dilution haemodiafiltration: COMPare HDF study

Melatonin versus Sleep Deprivation for Sleep Induction in Nap Electroencephalography: Protocol for a Prospective Randomized Crossover Trial in Children and Young Adults with Epilepsy

Electroencephalography (EEG) continues to be a pivotal investigation in children with epilepsy, providing diagnostic evidence and supporting syndromic classification. In the pediatric population, electroencephalographic recordings are frequently performed during sleep, since this procedure reduces the number of artifacts and activates epileptiform abnormalities. To date, no shared guidelines are available for sleep induction in EEG. Among the interventions used in the clinical setting, melatonin and sleep deprivation represent the most used methods. The main purpose of this study is to test the non-inferiority of 3-5 mg melatonin versus sleep deprivation in achieving sleep in nap electroencephalography in children and young adult patients with epilepsy. To test non-inferiority, a randomized crossover trial is proposed where 30 patients will be randomized to receive 3-5 mg melatonin or sleep deprivation. Each enrolled subject will perform EEG recordings during sleep in the early afternoon for a total of 60 EEGs. In the melatonin group, the study drug will be administered a single oral dose 30 min prior to the EEG recording. In the sleep deprivation group, parents will be required to subject the child to sleep deprivation the night before registration. Urinary and salivary concentrations of melatonin and of its main metabolite 6-hydroxymelatonin will be determined by using a validated LC-MS method. The present protocol aims to offer a standardized protocol for sleep induction to be applied to EEG recordings in those of pediatric age. In addition, melatonin metabolism and elimination will be characterized and its potential interference in interictal abnormalities will be assessed.

Air Sense Autoset for Her and Him

Introduction: Several studies have shown that Obstructive Sleep Apnoea (OSA) results in gender specific or gender typical symptoms. The algorithms of automated CPAP devices (APAP) up to now focus on the therapy of typical male OSA symptoms. The “Air Sense 10 Autoset for Her” device was developed to provide a therapy with the focus on the treatment of typical female OSA symptoms. In this study the efficiency of the “Air Sense 10 Autoset for Her” Algorithm (AfH) in treatment of female as well as of male OSA symptoms was investigated in comparison to the standard APAP mode (ASstd). Methods: In 40 women and 40 men a prospective randomized intraindividual cross-over trial was done where each OSA patient was half night treated with AfH algorithm and half night with ASstd algorithm. The flattening degree of each breath was calculated by deviding the relative inspiratory tidal volume by the relation of inspiration to expiration time (OC = Obstructive Coefficient© SOMNOmedics, Randersacker, Germany) in order to have analyzed all breaths of a whole night time recording because better treatment of inspiratory flattening is a major target of the AfH algorithm. The OC values under AfH/ASstd therapy were compared for each sleep stage separately for women and for men. Results: In women the AfH algorithm provided better flattening treatment during N2 sleep (p&lt;0.01, 104.115 breaths) and REM sleep (p&lt;0.01, 32.348 breaths) while the ASstd algorithm was superior during N3 sleep (p&lt;0.01, 57.286 breaths). No difference between the algorithms was observed during N1 sleep (15.803 breaths). In men the AfH algorithm was superior to the ASstd algorithm during each sleep stage (N1, N2, N3, REM, p&lt;0.01, 211.440 breaths). When looking only at the number of breaths treated, independent from the sleep stage, in women AfH was superior to ASstd in 43.8% of the breaths, ASstd superior to AfH in 32.8% of the breaths and no algorithm preference was observed in 23.5% of the breaths. In men 52.7% of the breaths were better treated by AfH, 29.2% by ASstd, and in 18.1% no algorithm preference was observed. Discussion: The AfH algorithm that has been especially developed for OSA treatment in women is only during N2- and REM-sleep more efficient in flattening treatment than the ASstd algorithm. The faster and more sensitive reaction to detected flow limitations did not provide better treatment in all sleep stages in women, but in the OSA treatment of men instead. The treatment of respiratory events was completely independent from this result and was similar effective in women as in men with no difference between the two APAP algorithms.

Physiological and psychological effectiveness of facial massage in women: A randomized crossover trial

Objective: This study aimed to examine the effectiveness of facial massage, as a nursing technique, in alleviating stress in healthy women using physiological and psychological indicators. Methods: A crossover design was employed; participants were 22 healthy females between the ages of 20 and 22. Participants were assigned to Sequence 1, wherein they received a 3-minute facial massage in Period I and 3-minute rest in Period II, or Sequence 2, which employed the reverse order. Participants' blood pressure (BP), pulse rate, salivary alpha-amylase (sAA), Profile of Mood States (POMS), "Relaxation level," "Comfort level," and "Wakefulness level," as measured by the Visual Analog Scale (VAS), were assessed before and after the facial massage or resting intervention. Results: Between the two groups, changes in systolic BP increased in the facial massage group, but there was no difference in pulse and sAA. While there was no difference between the two groups in the POMS, VAS scores revealed an increase in the "Relaxation level" and "Comfort level" in the facial massage group. Facial massage participants reported feeling "refreshed," whereas the control group reported feeling "sleepy." Conclusions: The 3-minute facial massage increased relaxation with respect to psychological measures; however, BP change could not explain stress reduction. (This study was enrolled in the UMIN as an intervention study and as a prospective randomized crossover trial. The trial registration number is UMIN000033939.)

A prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma.

163 Background: Appendiceal adenocarcinoma is both a rare and heterogenous tumor, with marked contrast in the natural history of low-grade and high-grade tumors (5-year OS 68% for low-grade vs. 7% for high-grade). While low-grade appendiceal adenocarcinoma is primarily treated with surgical resection sometimes followed by hyperthermic intraperitoneal chemotherapy (HIPEC), many inoperable candidates are treated with systemic chemotherapy although there is no prospective data supporting this practice. The purpose of our study was to objectively evaluate the effectiveness of systemic chemotherapy in low-grade mucinous appendiceal adenocarcinoma. Methods: A randomized crossover trial of surgically unresectable low-grade (well differentiated) mucinous appendiceal adenocarcinoma was performed with patients randomized to either 6 months observation followed by 6 months of chemotherapy (physician’s choice), or initial chemotherapy followed by observation. In this way each patient would serve as their own control. Enrollment of 30 patients was planned to have complete 6- and 12-month tumor measurements for 24 patients, providing 80% power at 0.05 significance level to detect a 5.0% difference in change in tumor size as measured by peritoneal RECIST in observation vs. treatment periods. Results: The trial closed early due to slow accrual. A total of 24 patients were enrolled. The majority of patients were treated with either 5FU or capecitabine (n = 15, 63%), bevacizumab was added for 3 (13%), and 3 were treated with doublet chemotherapy (FOLFOX/FOLFIRI). 15 patients who completed both treatment and observation periods were available for the primary analysis, the mean difference in tumor size was -4.5% (95% CI: -12.6, 3.7), indicating a slight trend towards faster growth on treatment than observation. This difference was not statistically or clinically significant (8.4% growth on treatment vs. 4.0% observation, p=0.26). Of the 18 patients who received any chemotherapy during the study period, zero achieved an objective response, 14 (77.8%) had stable disease during the entire year of follow up, and 4 (12.2%) had progression on study. Patient reported quality of life metrics identified that fatigue (p=0.02), peripheral neuropathy (p=0.014), and financial difficulty (p=0.0013) were all significantly worse while on treatment. There was not a significant difference in rate of bowel obstruction between the treatment first vs. observation first arms (12.5%, (n=3) vs 8.3%, (n=2)). Conclusions: These data from a prospective, randomized crossover trial indicate that patients with low-grade mucinous appendiceal adenocarcinoma do not derive benefit from 5FU based chemotherapy but do incur toxicity. These data further highlight the unique biology of low-grade appendiceal cancer and demonstrates the need to identify novel systemic therapies for this patient population. Clinical trial information: NCT01946854 .

Alfentanil Pretreatment for Electroconvulsive Therapy-Associated Hemodynamic Lability: A Prospective Randomized Crossover Trial.

Electroconvulsive therapy (ECT) is frequently associated with significant hemodynamic changes that increase myocardial oxygen demand including significant hypertension poststimulus. This raises concern about the cumulative effect of repetitive stress from ECT. Historically, various agents have been used to blunt this response and reduce hemodynamic fluctuations in these patients with varying degrees of efficacy. We hypothesized that bolus alfentanil administration timed with the ECT stimulus may reduce near-term hypertension and heart rate (HR) increases in patients undergoing ECT. A randomized, double-blind, placebo-controlled AB/BA crossover trial of 87 patients 18 years or older with mood disorders was carried out. Patients received a standardized anesthetic regimen including induction with methohexital and succinylcholine and were randomized to receive either 20 μg/kg ideal bodyweight of alfentanil or placebo 60 seconds before the ECT stimulus for the first treatment and then crossed over to the other group for the second treatment. The primary outcome was the within-individual difference in preinduction systolic blood pressure and the first systolic blood pressure after the ECT stimulus. Eighty-seven patients completed the protocol. The primary outcome of increase in systolic blood pressure pre-ECT to post-ECT was 16.9 mm Hg less in the alfentanil group than the placebo group (95% confidence interval, -26.0 to -7.8; P < 0.001). The maximum HR was 6.5 beats per minute lower (95% confidence interval, -12.1 to -0.9; P = 0.024) when patients received alfentanil compared with placebo. Premedication with alfentanil reduces poststimulus hypertension and increased HR in patients receiving ECT and therefore, may reduce morbidity related to this in susceptible patients.

A randomized clinical trial to compare ketamine-butorphanol-azaperone-medetomidine and detomidine-etorphine-acepromazine for anesthesia of captive Przewalski horses (Equus przewalskii).

To compare ketamine-butorphanol-azaperone-medetomidine (KBAM) to detomidine-etorphine-acepromazine (DEA) for field anesthesia in captive Przewalski horses (Equus przewalskii). 10 adult Przewalski horses. A prospective randomized crossover trial was conducted. Each horse was immobilized once with KBAM (200 mg ketamine, 109.2 mg butorphanol, 36.4 mg azaperone, and 43.6 mg medetomidine) and once with DEA (40 mg detomidine premedication, followed 20 minutes later by 3.9 to 4.4 mg etorphine and 16 to 18 mg acepromazine). Both protocols were administered by IM remote dart injection with a washout period of 6 months between treatments. Selected cardiorespiratory variables and quality of anesthesia were recorded. Antagonists were administered IM (KBAM, 215 mg atipamezole and 50 mg naltrexone; DEA, 4 mg RX821002 and 100 mg naltrexone). All horses were anesthetized and recovered uneventfully. Inductions (DEA, 6.8 min; KBAM, 11.6 min; P = 0.04) and recoveries (DEA, 3.2 min; KBAM, 19.6 min; P < 0.01) were faster with DEA compared with KBAM. Quality scores for induction and recovery did not differ between protocols, but maintenance quality was poorer for DEA (P < 0.01). Clinical concerns during DEA immobilizations included apnea, severe hypoxemia (arterial partial pressure of oxygen < 60 mm Hg), muscle rigidity, and tremors. Horses treated with KBAM were moderately hypoxemic, but arterial partial pressures of oxygen were higher compared with DEA (P < 0.01). Captive Przewalski horses are effectively immobilized with KBAM, and this protocol results in superior muscle relaxation and less marked hypoxemia during the maintenance phase, but slower inductions and recoveries, compared with DEA.

Postprandial Responses of Energy Substrates in Dogs Fed High Fat‐ vs High Protein‐Low Carbohydrate Ketogenic Foods Relative to a High Carbohydrate Food

ObjectiveReduction of dietary carbohydrate (CHO) can increase circulating ketone availability and may aid disease management including inflammatory bowel disease, cancer, diabetes and cognitive decline. Companion animal dogs are prone to all of these maladies. Postprandial to a mixed macronutrient meal, non‐esterified fatty acids (NEFA) and beta‐hydroxybutyrate (BHB) decrease. In contrast, both glucose and blood urea nitrogen (BUN) increase. Triglycerides (TG) comprise circulating fat energy after a fat‐containing meal although medium chain TG (MCT) are preferentially catabolized to ketones. The postprandial responses of dogs to habitual feeding of high fat versus high protein low CHO foods, relative to high CHO foods, is not known. Therefore, we compared fasting (0 hr) and 2‐0 hr delta values for BHB, NEFA, TG, glucose, BUN as markers of available energy for these foods in dogs.MethodsDogs housed in pairs, with daily group exercise in outdoor grassy runs. Dogs returned to the colony healthy after the study; no invasive procedures. Blood collections under approved protocols at 0 hours (immediately before a meal) and at 2 hours postprandial. Macronutrients (P/F/C; % energy) for the 3 foods: HiCHO (25/37/38); LoCHOprot (50/44/6); LoCHOfat (28/68/4). The LoCHOfat food further contained 22% of dietary fat energy as MCT. Prospective randomized crossover trial (2 groups, n = 18). HiCHO was the wash‐in food followed by LoCHOprot or LoCHOfat in randomized order (5 wk feeding each food). Foods analyzed according to AOAC methods. Energy substrates BHB, NEFA, TG, glucose and BUN measured by Cobas or enzymatic reaction. Individual diet differences by dependent samples t‐test, linear mixed modeling for overall diet effect. Significance at α = 0.05.ResultsAnalyzed ketogenic ratios of the foods: HiCHO (0.46), LoCHOprot (1.1), and LoCHOfat (1.7). At fasting, LoCHOprot and LoCHOfat elevated circulating BHB above HiCHO food with LoCHOfat BHB higher than LoCHOprot. Between 0‐2 hours postprandial, BHB decreased for HiCHO (‐23%) and increased more for LoCHOfat (+100%) than LoCHOprot (+33%). Fasting NEFA were higher in LoCHOprot than LoCHOfat, and not different otherwise. From 0‐2 hours postprandial all foods showed decreased NEFA: HiCHO (‐43%), LoCHOprot (‐57%), LoCHOfat (‐12%). Fasting glucose was not different between groups. From 0‐2 hours postprandial LoCHOprot (‐4%) and LoCHOfat (‐8%) showed decreased glucose while HiCHO was unchanged. Fasting TG levels were different between all foods with the LoCHOprot (‐45%) and LoCHOfat (‐37%) lower than HiCHO. From 0‐2 hours postprandial all dogs showed increased TG with all values different between groups: HiCHO (+135%), LoCHOprot (+356%), LoCHOfat (+591%). Fasting BUN was higher with LoCHOprot than either HiCHO (‐27%) or LoCHOfat (‐26%). From 0‐2 hours postprandial all dogs showed increased BUN with all changes different: HiCHO (+17%), LoCHOprot (+42%), LoCHOfat (+23%).ConclusionsThe LoCHOfat food increased postprandial availability of BHB, NEFA and TG energy while decreasing glucose energy. LoCHOprot primarily enhanced available energy from protein as shown by increased amino acid catabolism to BUN, with additional contributions from BHB, NEFA and TG. The HiCHO food presented only glucose and TG as energy postprandial. Together these data show that a moderate protein, high fat, low CHO food with added MCT can selectively apportion postprandial energy toward ketone and fats while decreasing availability of glucose.

Randomized controlled trial comparing an open surgical technique and a Seldinger technique for cricothyrotomy performed on a simulated airway.

Emergency cricothyrotomy is a lifesaving procedure performed when intubation fails and oxygenation cannot occur. There are multiple techniques and kits to perform this procedure. However, current evidence does not provide a definitive answer as to which method is superior. Two techniques in common use are a surgical technique and a percutaneous Seldinger-based cricothyrotomy kit. The objective was to determine which of these two methods was quickest to perform and to determine which was most preferred by participants. A prospective randomized controlled crossover trial was conducted involving emergency physicians and trainees. Each participant performed both cricothyrotomy techniques in succession on an airway model, with the technique performed first being randomized for each participant. The primary outcome was time to first insufflation of the artificial lung. A survey was completed by participants asking their comfort with each technique on a 5-point scale from 1 (not at all comfortable) to 5 (very comfortable) and which technique they preferred. Twenty-one emergency physicians and nine emergency medicine trainees were recruited. The surgical technique was performed the fastest, with a mean (±SD) time of 51.6 (±16.3) s versus 66.6 (±14.9) s for the Seldinger technique, with a statistically significant difference of 15.0s (95% confidence interval=8.5 to 21.5, p<0.001). The surgical technique was rated the most comfortable to perform, with a median rating of 5 (interquartile range [IQR]=4-5) versus 4 (IQR=3-5) for the Seldinger technique. The surgical technique was most preferred by participants (80% vs 20%). The surgical technique was the fastest to perform and was rated the most comfortable to perform and the most preferred technique.

Comparison of the efficiency of endobronchial ultrasound-guided transbronchial needle aspiration using a 22G needle versus 25G needle for the diagnosis of lymph node metastasis in patients with lung cancer: a prospective randomized, crossover study.

BackgroundEndobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is generally performed for the diagnosis of hilar/mediastinal lymph node metastasis in patients with lung cancer. Recently, a 25-gauge (G) needle became available, but robust evidence of its usefulness in routine clinical practice is still lacking.MethodsA prospective randomized crossover trial was performed, in which patients with suspected hilar/mediastinal lymph node metastasis of lung cancer underwent EBUS-TBNA. The primary endpoint was the rate of yield histology specimens containing malignant cells.ResultsFrom December 2018 to February 2020, 102 patients were randomly assigned to EBUS-TBNA using a 22G needle first, followed by a 25G needle (n=50) or EBUS-TBNA using a 25G needle first, followed by a 22G needle (n=52). There was no difference in the diagnostic yield of malignancy between the histology specimens obtained by using the 22G and 25G needles (75% vs. 75%, respectively, P=0.37). The sizes of the tissue samples (16.4 vs. 4.9 mm2, respectively) and number of malignant cells in the tissue samples (626 vs. 400, respectively) were both significantly higher when using the 22G needle than when using the 25G needle.ConclusionsNo significant difference in the diagnostic yield between the 22G and 25G needles was observed for the diagnosis of lymph node metastasis of lung cancer, suggesting that needles of either gauge could be used for the biopsy. However, we would recommend use of the 22G needle, because it provided larger specimens and specimens containing larger numbers of malignant cells.Trial RegistrationUniversity hospital Medical Information Network Clinical Trial Registry (ID: UMIN000036680).

Effects of Pressure Control Device (SensAwake™) on Obstructive Sleep Apnea (OSA) Patients Who Remove the Mask for Unknown Reasons during Automatic Continuous Positive Airway Pressure (Auto-CPAP) Therapy: A Prospective Randomized Crossover Trial.

Backgroundand Objectives: Obstructive sleep apnea (OSA) patients may remove their mask unconsciously during automatic continuous positive airway pressure (Auto-CPAP) therapy and therefore cannot receive good treatment. The discomfort from the airflow of Auto-CPAP may be one reason for interrupted sleep. Sens Awake (SA) can detect the arousal and lower the pressure to prevent patients from fully awakening from sleep. Materials and Methods: To evaluate the effect of SA, we designed a prospective, randomized, crossover trial comparing Auto-CPAP with and without SA on Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Nasal Obstruction Symptom Evaluation (NOSE) Scale and recorded data from the auto-CPAP machine. Results: In the 25 patients who completed the study, the gender, age, body mass index, neck circumference, polysomnography data, and previous CPAP use were not significantly different between the two arms. The average and 90th percentile pressures were significantly lower during SA on (SA on vs. off: 6.9 ± 2.7 vs. 7.3 ± 2.6 [p = 0.032] and 8.6 ± 3.0 vs. 9.2 ± 2.9 [p = 0.002], respectively). The time used, days used, compliance, average and 90th percentile leaks, and the residual Apnea-Hypopnea Index (AHI) were not significantly changed between the SA on-and-off. Based on the subjective evaluation, PSQI, ESS, and NOSE were not significantly different between the SA on-and-off; however, based on additional analyses which were compared with baseline data, the ESS was significantly lower when the SA was on (SA on vs. baseline: 11.1 ± 6.1 vs. 13.2 ± 6.0 [p = 0.023]). Conclusions: CPAP therapy with or without two weeks of the SA had a similar effect on CPAP use, sleep quality, daytime sleepiness, and nasal obstruction. The SA may have a tendency to improve daytime sleepiness, but needs further study with a longer duration of treatment.

A Moderate‐Protein and Controlled‐Phosphorus Ketogenic Food Improves Lipid Metabolism in Dogs while Preventing Elevations in Circulating Urea and Phosphorus

Objective Ketogenic foods (KF) limit digestible carbohydrate (carb) and offer benefits to disease management including cancer, diabetes, renal failure and cognition. While companion dogs are susceptible, their metabolic response to ketogenic foods that vary in protein/fat ratio is not known. We sought to compare metabolic effects of two KF varying in protein/fat, and further compare their effects to a standard adult food (CON). The first KF (KFA) was commercially available and the second (KFB) was developed for this experiment as a moderate protein, controlled phosphorus (Pi) food to make it amenable to at-risk populations. Methods Dogs housed in pairs, with daily group exercise in outdoor grassy runs. All dogs returned to the colony healthy after the study; no invasive procedures. Fasted blood collections under approved protocols. Macronutrients (P/F/C; % energy): CON (21/32/48); KFA (52/42/5); KFB (26/68/5). Food ash, Pi (dry mass, DMB): CON (ash 4.9%, Pi 0.68%), KFA (ash 8.6%; Pi 1.2%), KFB (ash 4.9%, Pi 0.58%). Prospective randomized crossover trial (n = 16). CON the wash-in food followed by KFA then KFB in randomized order (5 wk feeding each). Foods by AOAC methods. Serum beta-hydroxybutyrate (BHB) by enzymatic reaction. Clinical measurements by Cobas. Fatty acid (FA) elongase (ELO) and desaturase (ACD) substrate/product ratios by GC-FID from serum FA. Linear mixed modeling for diet effects. Least-squared means with pooled variance presented. Significance at a = 0.05. Results Ketogenic ratios (KR) of the foods: CON (KR 0.46), KFA (KR 0.97), KFB (KR 1.63). Clinical blood values remained in normal ranges. Despite only 5% carb as energy, the KFA food was not ketogenic; KFA (KFA 101.2 ± 0.09 uM) did not elevate serum BHB above that of the CON food containing 48% starch as energy (CON 93.6 ± 0.09 uM). In contrast, the KFB food was ketogenic; increasing BHB (KFB 143.8 ± 0.09 uM) relative to both KFA and CON. Serum glucose was not different. The KFA elevated insulin and glucagon relative to CON; the KFB food not different from KFA or CON. The KFA increased blood urea and Pi above KFB and CON; KFB food was not different from CON. Liver enzymes ALP and AST were lowest when dogs were fed KFB. Both KFA and KFB decreased serum triglycerides (TG) by 30% compared to the CON food, but increased total cholesterol. The KFB decreased the product/substrate ratios of d-9 (16:1/16:0, 18:1/18:0) and d-5 ACD (20:4n6/20:3n6) but increased that of d-6 ACD (18:3n6/18:2n6, 20:3n6/18:2n6). KFB also increased apparent these ratios for ELOs elov5 (20:3n6/18:3n6) and elov6 (18:0/16:0). Conclusions: A low-carb, moderate protein, controlled Pi ketogenic food increased circulating ketone BHB 40% above that of a low-carb food that contained 80% more protein. Moderating protein and reducing Pi in the KFB prevented elevations in blood urea and Pi that occurred with KFA. Thus, high levels of protein and ash may limit a food's ketogenic potential and it's use in renal patients. The TG-lowering effect of ketogenic foods observed in humans was mirrored in this canine study; we further found that KFB altered fatty acid metabolism. These results will further enable the personalization of nutritional recommendations for ketogenic foods to benefit a broad spectrum of health states.

Comparison of Graphic Organizers Versus Online Flash Cards as Study Aids in an Elective Veterinary Cardiology Course.

The ideal study aid format for veterinary students remains unknown. Both graphic organizers (GOs) and flash cards (FCs) have shown utility for enhancing learning in specific contexts. A mixed-methods prospective randomized crossover trial was undertaken with veterinary students (n= 59) in an elective cardiology course. All students received identical content presented via weekly in-class lectures and were given study aids in either GO or FC format. One week later, students completed quizzes of content knowledge for each lesson and indicated amount of time spent studying. Crossover occurred such that groups of students alternated between receiving GOs and FCs. Quantitative and qualitative data were collected in the form of in-depth pre- and post-course surveys. Overall, there was no significant difference in quiz scores (p= .26) or time spent studying (p= .33) based on study aid type. Time spent studying for each quiz, as well as other measures of study habits, decreased significantly throughout the semester. Post-course survey responses showed overall higher student satisfaction for GOs compared to FCs (p=.022), as well as a shift in preference away from FCs throughout the semester (p= .03). Free-text survey responses revealed that individual students had strong preferences either for or against FCs in the context of their particular study habits. In an elective veterinary cardiology course, use of GO format compared to FC format study aids resulted in equivalent short-term learning outcomes and time spent studying, with each study aid format appealing to specific learning preferences of individual students.

Comparison of Instructor-Provided Versus Student-Generated Graphic Organizers in an Elective Veterinary Cardiology Course.

Graphic organizers (GOs) are visual and spatial displays that facilitate learning by making conceptual relationships between content more apparent. It remains unknown whether GOs are more effective when completed by the teacher (instructor-provided [IP]) versus the learner (student-generated [SG]). A mixed-methods prospective randomized crossover trial was undertaken with veterinary students (n = 60) in an elective cardiology course. All students received identical content presented via weekly in-class lectures and were subsequently given study aids in either IP or SG format. One week later, students completed quizzes of content knowledge for each lesson and indicated amount of time spent studying. Crossover occurred such that groups of students alternated between receiving IP and SG. Quantitative and qualitative data were collected in the form of in-depth pre- and post-course surveys. Overall, there was no significant difference in quiz scores based on study aid type (p = .06). Students spent an average of 25% less time studying per lesson when using IP GOs compared with SG GOs (p < .001). Time spent studying for each quiz, as well as time period between date of studying and date of quiz, decreased significantly throughout the semester. Overall, students strongly preferred IP to SG format (p < .001); reasons listed included confidence in accuracy and completeness of information, as well as increased study efficiency. In an elective veterinary cardiology course, use of IP compared to SG format study aids resulted in higher study efficiency and student satisfaction with equivalent short-term learning outcomes.

Neurally adjusted ventilatory assist vs. pressure support to deliver protective mechanical ventilation in patients with acute respiratory distress syndrome: a randomized crossover trial

BackgroundProtective mechanical ventilation is recommended for patients with acute respiratory distress syndrome (ARDS), but it usually requires controlled ventilation and sedation. Using neurally adjusted ventilatory assist (NAVA) or pressure support ventilation (PSV) could have additional benefits, including the use of lower sedative doses, improved patient–ventilator interaction and shortened duration of mechanical ventilation. We designed a pilot study to assess the feasibility of keeping tidal volume (VT) at protective levels with NAVA and PSV in patients with ARDS.MethodsWe conducted a prospective randomized crossover trial in five ICUs from a university hospital in Brazil and included patients with ARDS transitioning from controlled ventilation to partial ventilatory support. NAVA and PSV were applied in random order, for 15 min each, followed by 3 h in NAVA. Flow, peak airway pressure (Paw) and electrical activity of the diaphragm (EAdi) were captured from the ventilator, and a software (Matlab, Mathworks, USA), automatically detected inspiratory efforts and calculated respiratory rate (RR) and VT. Asynchrony events detection was based on waveform analysis.ResultsWe randomized 20 patients, but the protocol was interrupted for five (25%) patients for whom we were unable to maintain VT below 6.5 mL/kg in PSV due to strong inspiratory efforts and for one patient for whom we could not detect EAdi signal. For the 14 patients who completed the protocol, VT was 5.8 ± 1.1 mL/kg for NAVA and 5.6 ± 1.0 mL/kg for PSV (p = 0.455) and there were no differences in RR (24 ± 7 for NAVA and 23 ± 7 for PSV, p = 0.661). Paw was greater in NAVA (21 ± 3 cmH2O) than in PSV (19 ± 3 cmH2O, p = 0.001). Most patients were under continuous sedation during the study. NAVA reduced triggering delay compared to PSV (p = 0.020) and the median asynchrony Index was 0.7% (0–2.7) in PSV and 0% (0–2.2) in NAVA (p = 0.6835).ConclusionsIt was feasible to keep VT in protective levels with NAVA and PSV for 75% of the patients. NAVA resulted in similar VT, RR and Paw compared to PSV. Our findings suggest that partial ventilatory assistance with NAVA and PSV is feasible as a protective ventilation strategy in selected ARDS patients under continuous sedation.Trial registration ClinicalTrials.gov (NCT01519258). Registered 26 January 2012, https://clinicaltrials.gov/ct2/show/NCT01519258