Crossover Study Research Articles

The effect of ischemic preconditioning on repeated sprint cycling performance: a randomized crossover study.

Ischemic preconditioning (IPC) has been suggested to improve exercise performance by 1-8%. Prior research concerning its impact on short-duration exercises, such as sprints, has been limited and yielded conflicting results. The aim of this study, which included a non-occlusion-based placebo control, was to determine whether IPC improves repeated sprint performance in a manner that accounted for psychophysiological effects. Twenty-two healthy males participated in this study, which employed a randomized crossover design. Following the 10-min baseline period, participants received intervention under four different conditions: 1) no-intervention control (CON); 2) non-occlusion-based placebo control (SHAM); 3) remote IPC (RIPC); and 4) local IPC (LIPC). Participants then performed a standardized repeated sprint cycling (5×10s maximal cycling sprint, separated by a 40-s rest in each set). Repeated sprint performance, as indexed by average power output, peak power output, and total work, the improvement was observed in the RIPC and LIPC during the initial phase (set 1-3) when compared with CON (P<0.05). SHAM condition also showed an increase in peak power output in the set 1 (CON 9.97±1.05 vs. SHAM 10.30±1.13 w/kg, P<0.05), which may represent a psychophysiological component in the IPC-induced improvement. Higher lactate concertation was found in the SHAM and LIPC groups, than in the CON group, 5 minutes after the exercise (CON 15.72±0.68 vs. SHAM 16.82±0.41 vs. LIPC 17.19±0.39 mmol/L, P<0.0001 for both, respectively). In conclusion, LIPC enhanced repeated sprint cycling performance during the initial phase, beyond what could be accounted for entirely by a psychophysiological effect. The improvement associated with RIPC, however, did not surpass the effect of a placebo intervention.

Acute Effects of Cadence-Controlled Walking on Cognition and Vascular Function in Physically Inactive Older Adults: A Randomized Crossover Study.

Cadence-controlled walking may be a desirable approach for older adults to self-monitor exercise intensity and achieve physical activity guidelines. We examined the acute effects of cadence-controlled walking on cognition and vascular function in physically inactive older adults. In a randomized crossover design, 26 participants (65% females, 67.8 ± 11.3years) underwent 30-min acute exercise (walking at 100steps/min) and control (sitting) conditions. We measured cognition, central blood pressure (BP), and arterial stiffness before, and immediately, after each condition. We observed significant Time × Condition interactions in the Flanker Inhibitory Control and Attention (Flanker) test and Dimensional Change Card Sort (DCCS) test scores, and in central systolic BP, central pulse pressure, and carotid to femoral pulse wave velocity (p < .05). The Flanker and DCCS scores significantly increased after walking (d = 0.4 and 0.5, respectively), but not after sitting. Central systolic BP, central pulse pressure, and carotid to femoral pulse wave velocity significantly increased after sitting but remained unchanged after acute walking (d = 0.4-0.2), with p-values < .05. After walking, significant correlations were observed between DCCS and diastolic BP and central pulse pressure change scores and change scores in central pulse wave velocity,Flanker, and DCCS (rs = -0.45 to -0.52). These findings suggest that a single bout of cadence-controlled walking elicited an immediate improvement in cognition and might have mitigated increases in arterial stiffness and central BP observed in the seated control condition. Further research is needed to examine the association between cognition and vascular function following acute exercise compared to control conditions. Our findings may have practical implications for developing daily physical activity recommendations for improving the cognitive health for successful aging.

Single intravenous and oral dose pharmacokinetics of the antiseizure medication brivaracetam in healthy cats.

The number of available antiseizure medications with demonstrated efficacy in cats is limited. As such, there is a need to evaluate the pharmacokinetics of newer medications so that proper dosing regimens can be made. Brivaracetam (BRV) is a more potent analogue of levetiracetam, and is Food and Drug Administration approved for use in people. The goal of this study was to describe the pharmacokinetics of intravenous and oral doses of BRV in healthy cats. A cross-over study involving eight healthy cats, that were administered 10 mg of BRV intravenously as a bolus and orally in the fasted state. Blood samples were collected over 24 h. Analysis was performed using liquid chromatography-mass spectrometry. Data were subjected to non-compartmental analysis. Median (min-max) of maximal concentration, time to maximal concentration, area under the curve, elimination half-life and oral absolute bioavailability were 902 (682-1036) ng/mL, 0.6 (0.5-2.0) h, 6.4 (5.2-7.2) h, 8145 (6669-9351) ng × h/mL and 100% (85-110) respectively. BRV appeared to be well tolerated by all cats. A single dose of BRV is well tolerated both orally and intravenously. Maximal concentrations are produced rapidly and within the human reference interval considered to be therapeutic.

H-coil repetitive transcranial magnetic stimulation does not improve executive function in patients with chronic peripheral neuropathic pain: a randomized sham-controlled crossover study

H-coil repetitive transcranial magnetic stimulation does not improve executive function in patients with chronic peripheral neuropathic pain: a randomized sham-controlled crossover study

Retraction. Pharmacokinetic Profile of Caffeine and Its Two Main Metabolites in Dried Blood Spots After Five Different Oral Caffeine Administration Forms—A Randomized Crossover Study

Retraction. Pharmacokinetic Profile of Caffeine and Its Two Main Metabolites in Dried Blood Spots After Five Different Oral Caffeine Administration Forms—A Randomized Crossover Study

Performance and safety of the PRICO closed-loop oxygen saturation targeting system in neonates: pragmatic multicentre cross-over study (TarOx Study).

This study aims to evaluate the performance of the fabian-Predictive-Intelligent-Control-of-Oxygenation (PRICO) system for automated control of the fraction of inspired oxygen (FiO2). Multicentre randomised cross-over study. Five neonatal intensive care units experienced with automated control of FiO2 and the fabian ventilator. 39 infants: median gestational age of 27 weeks (IQR: 26-30), postnatal age 7 days (IQR: 2-17), weight 1120 g (IQR: 915-1588), FiO2 0.32 (IQR: 0.22-0.43) receiving both non-invasive (27) and invasive (12) respiratory support. Randomised sequential 24-hour periods of automated and manual FiO2 control. Proportion (%) of time in normoxaemia (90%-95% with FiO2>0.21 and 90%-100% when FiO2=0.21) was the primary endpoint. Secondary endpoints were severe hypoxaemia (<80%) and severe hyperoxaemia (>98% with FiO2>0.21) and prevalence of episodes ≥60 s at these two SpO2 extremes. During automated control, subjects spent more time in normoxaemia (74%±22% vs 51%±22%, p<0.001) with less time above and below (<90% (9%±8% vs 12%±11%, p<0.001) and >95% with FiO2>0.21 (16%±19% vs 35%±24%) p<0.001). They spent less time in severe hyperoxaemia (1% (0%-3.5%) vs 5% (1%-10%), p<0.001) but exposure to severe hypoxaemia was low in both arms and not different. The differences in prolonged episodes of SpO2 were consistent with the times at extremes. This study demonstrates the ability of the PRICO automated oxygen control algorithm to improve the maintenance of SpO2 in normoxaemia and to avoid hyperoxaemia without increasing hypoxaemia.

Bioequivalence and Food Effect Assessment of Eltrombopag Olamine Tablets in Healthy Chinese Subjects: An Open, Randomized, Single-Dose, and Two-Period Crossover Study.

Eltrombopag, a nonpeptide thrombopoietin receptor agonist, is primarily used for treating immune thrombocytopenic purpura. The aim of this study was to investigate the pharmacokinetic profile and food-drug interaction of test and reference eltrombopag olamine tablets among healthy Chinese volunteers. An open, randomized, single-dose, 2-period crossover design was employed, involving fasting and fed conditions with a 10-day washout period. Ninety-six healthy volunteers received a single oral dose of 25mg of the 2 eltrombopag formulations, with 48 participants in each group: fasting volunteers and those consuming a high-fat, low-calcium meal. Plasma eltrombopag concentrations were analyzed using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were derived from the concentration-time profiles. The geometric mean ratios, with 90% confidence intervals, for the maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable concentration, and area under the concentration-time curve from time 0 to infinity fell within the bioequivalence acceptance criteria (80%-125%) under both fasting and fed conditions, indicating bioequivalence between the test and reference formulations. Administration of eltrombopag with a high-fat, low-calcium diet reduced the net systemic exposure by approximately 40%. Adverse events were recorded, and no serious adverse events were observed in either fasting or fed conditions. In conclusion, eltrombopag is well tolerated and exhibits a favorable safety profile in the Chinese population. The achievement of bioequivalence under fasting and fed conditions supports the demonstration of biosimilarity between the test and reference formulations.

The effect of high-definition transcranial direct current stimulation on pain in somatic symptom disorder with predominant pain: A randomized single-blind sham-controlled crossover study

The effect of high-definition transcranial direct current stimulation on pain in somatic symptom disorder with predominant pain: A randomized single-blind sham-controlled crossover study

The MeViDa Study: Bioequivalence Study of FDC of Dapagliflozin, Vildagliptin SR and Metformin SR in Healthy Indian Volunteers: A Randomized, Open-Label, Crossover Study

The MeViDa Study: Bioequivalence Study of FDC of Dapagliflozin, Vildagliptin SR and Metformin SR in Healthy Indian Volunteers: A Randomized, Open-Label, Crossover Study

Pharmacodynamic Comparison of Two Aspirin Formulations in the Caribbean: The ARC Study.

This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer® low-dose enteric-coated aspirin 81mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore® low-dose phospholipid-aspirin liquid-filled 81mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU). Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer® LD EC-ASA daily for 14days, with a washout period of 28days, followed by Vazalore® LD PL-ASA daily for 14days, again followed by ARU testing. Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer® LD EC-ASA vs. Vazalore® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer® LD EC-ASA ARU value (p value 0.788) or Vazalore® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events. There were no significant differences in aspirin resistance between Bayer® LD EC-ASA and Vazalore® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings. ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024.

Double dosing ulipristal acetate emergency contraception for individuals with obesity: a randomised crossover trial

ObjectiveTo determine whether increasing the dose of ulipristal acetate (UPA)-containing emergency contraception (EC) improves pharmacodynamic outcomes in individuals with obesity.Study designWe enrolled healthy, regularly-cycling, confirmed ovulatory, reproductive-age individuals with body...

The impact of hindsight bias on the diagnosis of perioperative events by anesthesia providers: A multicenter randomized crossover study

Study objectiveHindsight bias is the tendency to overestimate the predictability of an event after it has already occurred. We aimed to evaluate whether hindsight bias influences the retrospective interpretation of clinical scenarios in the field of anesthesiology, which relies on clinicians making rapid decisions in the setting of perioperative adverse events. DesignTwo clinical scenarios were developed (intraoperative hypotension and intraoperative hypoxia) with 3 potential diagnoses for each. Participants completed a crossover study reviewing one case without being informed of the supposed ultimate diagnosis (i.e., no ‘anchor’ diagnosis), referred to as their foresight case, and the other as a hindsight case wherein they were informed in the leading sentence of the scenario that 1 of the 3 conditions provided was the ultimate diagnosis (i.e., the diagnosis the participant might ‘anchor’ to if given this information at the start). Participants were randomly assigned to (1) which scenario (hypotension or hypoxia) was presented as the initial foresight case and (2) which of the 3 potential diagnoses for the second case (the hindsight case, which defaulted to whichever case the participant was not assigned for the first case) was presented as the ultimate diagnosis in the leading sentence in a 2 (scenario order) x 3 (hindsight case anchor) between-subjects factorial design (6 possible randomization assignments). SettingTwo academic medical centers. ParticipantsFaculty, fellow, and resident anesthesiologists and certified nurse anesthetists (CRNAs). InterventionsNone. MeasurementsAfter reading each clinical scenario, participants were asked to rate the probability (%) of each of three potential diagnoses to have caused the hypotension or hypoxia. Compositional data analysis (CoDA) was used to compare whether diagnosis probabilities differ between the hindsight and the foresight case. Main results113 participants completed the study. 59 participants (52%) were resident anesthesiologists. Participants randomized to the hypotension scenario as a hindsight case were 2.82 times more likely to assign higher probability to the pulmonary embolus diagnosis if provided as an anchor (95% CI, 1.35–5.90; P = 0.006) and twice as likely to assign higher probability to the myocardial infarction diagnosis if provided as an anchor (95% CI, 1.12–3.58; P = 0.020). Participants randomized to the hypoxia scenario as a hindsight case were 1.78 times more likely to assign higher probability to the mainstem bronchus intubation diagnosis if provided in the anchor statement (95% CI, 1.00–3.14; P = 0.048) and 3.72 times more likely to assign higher probability to the pulmonary edema diagnosis if provided as an anchor (95% CI, 1.88–7.35; P < 0.001). ConclusionsHindsight bias influences the clinical diagnosis probabilities assigned by anesthesia providers. Clinicians should be educated on hindsight bias in perioperative medicine and be cognizant of the effect of hindsight bias when interpreting clinical outcomes.

Efficacy of plantar tactile sensation and balance in patients with subacute stroke following plantar kinesio taping: a randomized, cross-over preliminary study

ABSTRACT Background Kinesio tape (KT) is known to enhance tactile sensation. In stroke rehabilitation, KT is often used alongside conventional therapy (CT) to improve balance recovery. Objective In this study, we aimed to evaluate the effectiveness of plantar KT in enhancing plantar tactile sensation (PTS) and balance ability in subacute stroke patients. Methods In this randomized crossover trial, 22 subacute stroke participants were randomly assigned to receive no taping, paretic plantar KT, or bilateral plantar KT, with a 24-h washout period between each condition. All participants underwent 30 min of CT. The primary outcome was PTS, involving tactile sensitivity in five areas on the plantar surface and the contact area with the ground of the paretic foot. The one-leg stand (OLS) time, functional reach test (FRT), and timed up-and-go test (TUG) were employed as secondary outcomes. Results Paretic plantar KT application led to significant increases in the contact area, OLS, FRT, and TUG test times. Particularly, bilateral plantar KT showed significantly greater improvement in PTS compared to paretic plantar KT. Additionally, bilateral plantar KT significantly improved OLS (p < 0.001, η2 = 0.575), FRT (p < 0.001, η2 = 781), and TUG (p < 0.001, η2 = 0.771) times compared with paretic plantar KT. Conclusions This study demonstrated that plantar KT improved PTS and balance ability in stroke rehabilitation. The findings suggest that bilateral plantar KT as an adjunct to CT may have a beneficial effect on balance recovery in patients with subacute stroke. Trial registration Clinical trial KCT0009048

Effect of a High-Fat Meal on the Pharmacokinetics of an Immediate Release Atogepant Tablet.

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, is approved for the preventive treatment of migraine. A phase 1, open-label, single-dose, 2-period crossover study evaluated the effect of a high-fat meal on the pharmacokinetics and safety of atogepant in 20 healthy adults. Administration of atogepant 60mg immediate-release (IR) tablets under fed conditions reduced the area under the plasma concentration-time curve (AUC) from 0 to time t and from 0 to time infinity by approximately 18% and reduced the maximum plasma concentration (Cmax) by 22%. The 90% confidence intervals for the geometric mean ratios of Cmax and AUC were not contained within the bioequivalence limits of 80%-125%. There was no change in the median time to maximum plasma concentration in the fed versus fasted state. The incidence of treatment-emergent adverse events (TEAEs) was similar between fed and fasted conditions. Four TEAEs were considered related to study intervention and were reported after participants received atogepant under fasted conditions (3 participants). A single-dose atogepant 60mg IR tablet was safe and tolerated under both fed and fasted states. Due to the wide effective dose range of 10-60mg/day for atogepant for the preventive treatment of migraine, the food effect on its pharmacokinetics is not considered clinically relevant.

α- or β-Adrenergic blockade does not affect transplanted islet cell responses to hypoglycemia in type 1 diabetes.

Type 1 diabetes recipients of intrahepatic islet transplantation exhibit glucose-dependent suppression of insulin and activation of glucagon secretion in response to insulin-induced hypoglycemia associated with clinical protection from hypoglycemia. Whether sympathetic activation of adrenergic receptors on transplanted islets is required for these responses in defense against hypoglycemia is not known. To evaluate the adrenergic contribution to post-transplant glucose counterregulation, we performed a randomized, double-blind crossover study of responses during a hyperinsulinemic euglycemic-hypoglycemic clamp under phentolamine (α-adrenergic blockage), propranolol (β-adrenergic blockage), or placebo infusion. Participants (5 female/4 male) were median (range) age 53 (34-63) years, diabetes duration 29 (18-56) years, post-transplant 7.0 (1.9-8.4) years, HbA1c 5.8 (4.5-6.8)%, insulin in-/dependent 5/4, all on tacrolimus-based immunosuppression. During the clamp, blood pressure was lower with phentolamine and heart rate lower with propranolol vs. placebo (P <0.05). There was no difference in suppression of endogenous insulin secretion (derived from C-peptide measurements) during the euglycemic or hypoglycemic phases, and while levels of glucagon were similar with phentolamine or propranolol vs. placebo, the increase in glucagon from eu- to hypoglycemia was greater with propranolol vs. placebo (P < 0.05). Pancreatic polypeptide was greater with phentolamine vs. placebo during the euglycemic phase (P < 0.05), and free fatty acids were lower and the glucose infusion rate higher with propranolol vs. placebo during the hypoglycemic phase (P < 0.05). These results indicate that neither physiologic α- nor β-adrenergic blockade attenuates transplanted islet responses to hypoglycemia, suggesting sympathetic re-innervation of the islet graft is not necessary for post-transplant glucose counterregulation.

Randomized investigation of increased dialyzer membrane hydrophilicity on hemocompatibility and performance

BackgroundHemodialyzers should efficiently eliminate small and middle molecular uremic toxins and possess exceptional hemocompatibility to improve well-being of patients with end-stage kidney disease. However, performance and hemocompatibility get compromised during treatment due to adsorption of plasma proteins to the dialyzer membrane. Increased membrane hydrophilicity reduces protein adsorption to the membrane and was implemented in the novel FX CorAL dialyzer. The present randomized controlled trial compares performance and hemocompatibility profiles of the FX CorAL dialyzer to other commonly used dialyzers applied in hemodiafiltration treatments.MethodsThis prospective, open, controlled, multicentric, interventional, crossover study randomized stable patients on post-dilution online hemodiafiltration (HDF) to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun) each for 4 weeks. Primary outcome was β2-microglobulin removal rate (β2-m RR). Non-inferiority and superiority of FX CorAL versus comparators were tested. Secondary endpoints were RR and/or clearance of small and middle molecules, and intra- and interdialytic profiles of hemocompatibility markers, with regards to complement activation, cell activation/inflammation, platelet activation and oxidative stress. Further endpoints were patient reported outcomes (PROs) and clinical safety.Results82 patients were included and 76 analyzed as intention-to-treat (ITT) population. FX CorAL showed the highest β2-m RR (76.28%), followed by FX CorDiax (75.69%) and xevonta (74.48%). Non-inferiority to both comparators and superiority to xevonta were statistically significant. Secondary endpoints related to middle molecules corroborated these results; performance for small molecules was comparable between dialyzers. Regarding intradialytic hemocompatibility, FX CorAL showed lower complement, white blood cell, and platelet activation. There were no differences in interdialytic hemocompatibility, PROs, or clinical safety.ConclusionsThe novel FX CorAL with increased membrane hydrophilicity showed strong performance and a favorable hemocompatibility profile as compared to other commonly used dialyzers in clinical practice. Further long-term investigations should examine whether the benefits of FX CorAL will translate into improved cardiovascular and mortality endpoints.Trial registrationeMPORA III registration on 19/01/2021 at ClinicalTrials.gov (NCT04714281).

Randomized investigation of increased dialyzer membrane hydrophilicity on hemocompatibility and performance

BackgroundHemodialyzers should efficiently eliminate small and middle molecular uremic toxins and possess exceptional hemocompatibility to improve well-being of patients with end-stage kidney disease. However, performance and hemocompatibility get compromised during treatment due to adsorption of plasma proteins to the dialyzer membrane. Increased membrane hydrophilicity reduces protein adsorption to the membrane and was implemented in the novel FX CorAL dialyzer. The present randomized controlled trial compares performance and hemocompatibility profiles of the FX CorAL dialyzer to other commonly used dialyzers applied in hemodiafiltration treatments.MethodsThis prospective, open, controlled, multicentric, interventional, crossover study randomized stable patients on post-dilution online hemodiafiltration (HDF) to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun) each for 4 weeks. Primary outcome was β2-microglobulin removal rate (β2-m RR). Non-inferiority and superiority of FX CorAL versus comparators were tested. Secondary endpoints were RR and/or clearance of small and middle molecules, and intra- and interdialytic profiles of hemocompatibility markers, with regards to complement activation, cell activation/inflammation, platelet activation and oxidative stress. Further endpoints were patient reported outcomes (PROs) and clinical safety.Results82 patients were included and 76 analyzed as intention-to-treat (ITT) population. FX CorAL showed the highest β2-m RR (76.28%), followed by FX CorDiax (75.69%) and xevonta (74.48%). Non-inferiority to both comparators and superiority to xevonta were statistically significant. Secondary endpoints related to middle molecules corroborated these results; performance for small molecules was comparable between dialyzers. Regarding intradialytic hemocompatibility, FX CorAL showed lower complement, white blood cell, and platelet activation. There were no differences in interdialytic hemocompatibility, PROs, or clinical safety.ConclusionsThe novel FX CorAL with increased membrane hydrophilicity showed strong performance and a favorable hemocompatibility profile as compared to other commonly used dialyzers in clinical practice. Further long-term investigations should examine whether the benefits of FX CorAL will translate into improved cardiovascular and mortality endpoints.Trial registrationeMPORA III registration on 19/01/2021 at ClinicalTrials.gov (NCT04714281).

Short and long-term acceptability and efficacy of extended-release cornstarch in the hepatic glycogen storage diseases: results from the Glyde study

BackgroundHypoglycaemia is the primary manifestation of all the hepatic types of glycogen storage disease (GSD). In 2008, Glycosade®, an extended-release waxy maize cornstarch, was reported as an alternative to uncooked cornstarch (UCCS) which could prolong the duration of fasting in the GSD population. To date, there has been minimal published experience in (a) young children, (b) the ketotic forms of GSD, and (c) with daytime dosing. The Glyde study was created as a prospective, global initiative to test the efficacy and tolerance of Glycosade use across a broader and more diverse population.MethodsA randomised double-blind cross-over fasting study assessing the tolerance and efficacy of Glycosade compared with cornstarch was performed across disease types and ages. Participants and clinicians chose the product deemed superior, whilst still blinded. Participants were followed for 2 years to assess long-term metabolic control, growth, and quality of life.ResultsSixty-one participants (age 2–62 years; 59% female) were enrolled, and 58 participants completed the fasting studies (28 GSD I; 30 GSD III, VI, IX). Glycosade improved duration of fasting in GSD I and duration of fasting without ketosis in the ketotic forms. Chronic Glycosade use was chosen by 69% of participants. Those treated with Glycosade for the 2-year chronic phase used fewer doses of therapy while markers of metabolic control remained stable.ConclusionThe Glyde study is the first multi-centre international trial demonstrating the efficacy and tolerance of Glycosade in a large cohort of hepatic GSD patients across a diverse international population. The ability to use fewer doses of therapy per day and avoidance of overnight therapy may improve compliance, safety, and quality of life without sacrificing metabolic control.

Assessing the Impact of Non-Exhaust Emissions on the Asthmatic Airway (IONA) Protocol for a Randomised Three-Exposure Crossover Study

Background: People living with asthma are disproportionately affected by air pollution, with increased symptoms, medication usage, hospital admissions, and the risk of death. To date, there has been a focus on exhaust emissions, but traffic-related air pollution (TRAP) can also arise from the mechanical abrasion of tyres, brakes, and road surfaces. We therefore created a study with the aim of investigating the acute impacts of non-exhaust emissions (NEEs) on the lung function and airway immune status of asthmatic adults. Methods: A randomised three-condition crossover panel design will expose adults with asthma using a 2.5 h intermittent cycling protocol in a random order at three locations in London, selected to provide the greatest contrast in the NEE components within TRAP. Lung function will be monitored using oscillometry, fractional exhaled nitric oxide, and spirometry (the primary outcome is the forced expiratory volume in one second). Biomarkers of inflammation and airborne metal exposure will be measured in the upper airway using nasal lavage. Symptom responses will be monitored using questionnaires. Sources of exhaust and non-exhaust concentrations will be established using source apportionment via the positive matrix factorisation of high-time resolution chemical measures conducted at the exposure sites. Discussion: Collectively, this study will provide us with valuable information on the health effects of NEE components within ambient PM2.5 and PM10, whilst establishing a biological mechanism to help contextualise current epidemiological observations.

Assessing the Impact of Non-Exhaust Emissions on the Asthmatic Airway (IONA) Protocol for a Randomised Three-Exposure Crossover Study

Background: People living with asthma are disproportionately affected by air pollution, with increased symptoms, medication usage, hospital admissions, and the risk of death. To date, there has been a focus on exhaust emissions, but traffic-related air pollution (TRAP) can also arise from the mechanical abrasion of tyres, brakes, and road surfaces. We therefore created a study with the aim of investigating the acute impacts of non-exhaust emissions (NEEs) on the lung function and airway immune status of asthmatic adults. Methods: A randomised three-condition crossover panel design will expose adults with asthma using a 2.5 h intermittent cycling protocol in a random order at three locations in London, selected to provide the greatest contrast in the NEE components within TRAP. Lung function will be monitored using oscillometry, fractional exhaled nitric oxide, and spirometry (the primary outcome is the forced expiratory volume in one second). Biomarkers of inflammation and airborne metal exposure will be measured in the upper airway using nasal lavage. Symptom responses will be monitored using questionnaires. Sources of exhaust and non-exhaust concentrations will be established using source apportionment via the positive matrix factorisation of high-time resolution chemical measures conducted at the exposure sites. Discussion: Collectively, this study will provide us with valuable information on the health effects of NEE components within ambient PM2.5 and PM10, whilst establishing a biological mechanism to help contextualise current epidemiological observations.