The purposes of this study were: (1) to evaluate feasibility and acceptability of MRI augmented cardiopulmonary exercise testing (MR-CPET) in healthy adults and (2) to test whether peak values obtained at conventional and MR-CPET correlate and to demonstrate variation in peak oxygen consumption (VO2) relates to both peak cardiac output (CO) and peak oxygen extraction (ΔcO2). Seventeen healthy adults underwent CPET and MR-CPET using an MR compatible ergometer and CPET system customised for MR use. Continuous aortic flow measurement used a validated UNFOLD-SENSE spiral phase contrast magnetic resonance (PCMR) sequence.Fifteen of 17 volunteers completed exercise; exclusions were due to claustrophobia and inability to effectively master exercise technique. Measures of acceptability were lower but still satisfactory for MR-CPET.There were strong correlations between conventional and MR-CPET for peak VO2 (r = 0.94, p < 0.001); VCO2 (r = 0.87, p < 0.001) and VE (r = 0.88, p < 0.001).Multiple linear regression analysis demonstrated peak CO and ΔcO2 were independent predictors of peak VO2 measured during MR-CPET (β = 0.73 and 0.38 p < 0.0001) and conventional CPET (β = 0.78, 0.28 p < 0.0001).MR-CPET is feasible, acceptable and demonstrates physiology not apparent with conventional CPET. MR-CPET allows differentiation of the contributions of CO and ΔcO2 to variation in peak VO2. We believe that this will be useful in understanding the origin of reduced exercise capacity in cardiac disease.
BackgroundIn addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). The aim of this single-blind, randomised, controlled phase II trial is to compare auto-adjusting CPAP (APAP) with standard care to standard care alone in individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life.Methods/DesignEligibility criteria include: ability to provide informed consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of < 90% for < 30% of the night (i.e. not meeting current criteria for overnight oxygen therapy). Key exclusion criteria are: overnight respiratory support; respiratory or decompensated cardiac failure; chronic transfusion; or contraindications to APAP therapy or magnetic resonance imaging (MRI).Sixty individuals with HbSS (30 children and 30 adults) will be randomised to standard care + APAP or standard care alone for six months. Minimisation factors are: age group (8–11, 12–15, 16–22 and > 23 years); silent infarction on MRI; minimum overnight oxygen saturation > 90% or < 90%; and hydroxyurea use.For APAP individuals, the intervention is administered at home. Adherence and effectiveness are recorded using software documenting hours of use each night and overnight oximetry. Participant support in terms of appropriate facemask and facilitating adherence are provided by an unblinded sleep physiologist.The primary outcome is change in the cancellation subtest from the Wechsler scales. Secondary outcomes include general cognitive functioning, quantitative brain MRI, blood and urine chemistry, quality of life and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI heart, echocardiography, and 6-min walk. These outcomes will be assessed at baseline and after six months of treatment by assessors blind to treatment assignment.DiscussionAltering oxygen saturation in HbSS may lead to bone marrow suppression. This risk will be reduced by monitoring full blood counts at baseline, two weeks, three months and six months, providing treatment as appropriate and reporting as safety events.Trial registrationISRCTN46012373. Registered on 10 July 2015.Protocol Version: 6.0 Date: 24th December 2015Sponsor: University Hospital Southampton. Sponsor’s protocol code: RHMCHIOT53
MR-augmented cardiopulmonary exercise testing is feasible in both healthy children and children with cardiac disease. Using this novel technique, we have demonstrated abnormal exercise patterns in oxygen uptake, cardiac output, and arteriovenous oxygen content difference.
SUMMARYLittle evidence is available on the pharmacokinetics of antituberculous medication in premature infants. We report rifampicin (RMP) pharmacokinetics in an extremely premature, low-birthweight female infant born to a mother with known miliary tuberculosis. Intravenous RMP, isoniazid (INH), ciprofloxacin and amikacin were used, as the enteral route was not possible. Area under the curve calculations revealed low average RMP concentrations at doses of 5-10 mg/kg. We review the literature with regard to the dosing regimen and therapeutic drug levels of RMP and INH in premature infants and discuss issues of management. Evidence from this case suggests 10 mg/kg/day is the minimum dose required.
BACKGROUND
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