Maelenn Gouillou

Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study

Background Glucocorticoids are the cornerstone treatment of polymyalgia rheumatica (PMR) but induce adverse events. Objectives To evaluate the efficacy and safety of first-line tocilizumab in PMR. Methods In a prospective open-label study (ClinicalTrials.gov: NCT01713842), 20 glucocorticoid-free patients fulfilling Chuangs PMR criteria, with symptom onset within the last 12u2005months and a PMR activity score (PMR-AS) >10, each received three tocilizumab infusions at 4-week intervals, without glucocorticoids, followed by oral prednisone from weeks 12 to 24 (0.15u2005mg/kg if PMR-AS ≤10 and 0.30u2005mg/kg otherwise). The primary end point was the proportion of patients with PMR-AS≤10 at week 12. Results Baseline median PMR-AS was 36.6 (IQR 30.4–43.8). At week 12, all patients had PMR-AS≤10 and received the low prednisone dosage. Median PMR-AS at weeks 12 and 24 was 4.5 (3.2–6.8) and 0.95 (IQR 0.4–2), respectively (p<0.001 vs baseline for both time points). No patient required rescue treatment. Positron emission tomography-CT showed significant improvements. The most common adverse events were transient neutropenia (n=3) and leucopenia (n=5); in one patient, the second tocilizumab infusion was omitted due to leucopenia. Conclusions Tocilizumab monotherapy is effective in recent-onset PMR. Randomised controlled trials are warranted. Trial registration number NCT01713842.

Value of 18 F-FDG PET/CT for therapeutic assessment of patients with polymyalgia rheumatica receiving tocilizumab as first-line treatment

PurposeTo evaluate the use of 18F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR).MethodsPatients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman’s rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR.ResultsOf 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4xa0mg/l and ESR from 49 to 6.5xa0mm; all pu2009<u20090.05) as did the median SUVmax (from 5.8 to 5.2; pu2009<u20090.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; pu2009<u20090.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ∆SUVmax and the other parameters including ∆PMR-AS, ∆CRP and ∆ESR in the patient-based and region-based analysis.ConclusionFDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity.

Risk of recurrent venous thromboembolism on progestin-only contraception: a cohort study.

Choice of contraception after venous thromboembolism (VTE) is challenging because hormonal contraception may increase the risk of recurrent VTE. Estrogen contraception is usually contraindicated in women with a personal history of VTE (category 4, unacceptable health risk according to the World

Does midazolam enhance pain control in prehospital management of traumatic severe pain

PURPOSEnMidazolam comedication with morphine is a routine practice in pre and postoperative patients but has not been evaluated in prehospital setting. We aimed to evaluate the comedication effect of midazolam in the prehospital traumatic adults.nnnMETHODSnA prehospital prospective randomized double-blind placebo-controlled trial of intravenous morphine 0.10 mg/kg and midazolam 0.04 mg/kg vs morphine 0.10 mg/kg and placebo. Pain assessment was done using a validated numeric rating scale (NRS). The primary end point was to achieve an efficient analgesic effect (NRS≤3) 20 minutes after the baseline. The secondary end points were treatment safety, total morphine dose required until obtaining NRS≤3, and efficient analgesic effect 30 minutes after the baseline.nnnFINDINGSnNinety-one patients were randomized into midazolam (n=41) and placebo (n=50) groups. No significant difference in proportion of patients with a pain score≤3 was observed between midazolam (43.6%) and placebo (45.7%) after 20 minutes (P=.849). Secondary end points were similar in regard with proportion of patients with a pain score≤3 at T30, the side effects and adverse events except for drowsiness in midazolam vs placebo, 43.6% vs 6.5% (P<.001). No significant difference in total morphine dose was observed, that is, midazolam (14.09 mg±6.64) vs placebo (15.53 mg±6.27) (P=.315).nnnCONCLUSIONSnAccording to our study, midazolam does not enhance pain control as an adjunctive to morphine regimen in the management of trauma-induced pain in prehospital setting. However, such midazolam use seems to be associated with an increase in drowsiness.

Automatic versus manual oxygen administration in the emergency department

Oxygen is commonly administered in hospitals, with poor adherence to treatment recommendations. We conducted a multicentre randomised controlled study in patients admitted to the emergency department requiring O2 ≥3u2005L·min−1. Patients were randomised to automated closed-loop or manual O2 titration during 3u2005h. Patients were stratified according to arterial carbon dioxide tension (PaCO2) (hypoxaemic PaCO2≤45u2005mmHg; or hypercapnic PaCO2>45–≤55u2005mmHg) and study centre. Arterial oxygen saturation measured by pulse oximetry (SpO2) goals were 92–96% for hypoxaemic, or 88–92% for hypercapnic patients. Primary outcome was % time within SpO2 target. Secondary endpoints were hypoxaemia and hyperoxia prevalence, O2 weaning, O2 duration and hospital length of stay. 187 patients were randomised (93 automated, 94 manual) and baseline characteristics were similar between the groups. Time within the SpO2 target was higher under automated titration (81±21% versus 51±30%, p<0.001). Time with hypoxaemia (3±9% versus 5±12%, p=0.04) and hyperoxia under O2 (4±9% versus 22±30%, p<0.001) were lower with automated titration. O2 could be weaned at the end of the study in 14.1% versus 4.3% patients in the automated and manual titration group, respectively (p<0.001). O2 duration during the hospital stay was significantly reduced (5.6±5.4 versus 7.1±6.3u2005days, p=0.002). Automated O2 titration in the emergency department improved oxygenation parameters and adherence to guidelines, with potential clinical benefits. Automated oxygen titration is superior to manual administration in terms of time within oxygenation targets http://ow.ly/pgWC30c2sLv

Actigraphy is not a reliable method for measuring sleep patterns in neonates

Polysomnography is the gold standard for studying sleep, but it is complex to use, and this can be problematic in clinically unstable preterm infants. We evaluated the reliability of actigraphy and polysomnography in detecting sleep–wake patterns in newborn infants.

A new SPECT/CT reconstruction algorithm: reliability and accuracy in clinical routine for non-oncologic bone diseases

BackgroundxSPECT Bone® (xB) is a new reconstruction algorithm developed by Siemens® in bone hybrid imaging (SPECT/CT). A CT-based tissue segmentation is incorporated into SPECT reconstruction to provide SPECT images with bone anatomy appearance. The objectives of this study were to assess xB/CT reconstruction diagnostic reliability and accuracy in comparison with Flash 3D® (F3D)/CT in clinical routine. Two hundred thirteen consecutive patients referred to the Brest Nuclear Medicine Department for non-oncological bone diseases were evaluated retrospectively. Two hundred seven SPECT/CT were included. All SPECT/CT were independently interpreted by two nuclear medicine physicians (a junior and a senior expert) with xB/CT then with F3D/CT three months later. Inter-observer agreement (IOA) and diagnostic confidence were determined using McNemar test, and unweighted Kappa coefficient. The study objectives were then re-assessed for validation through > 18 months of clinical and paraclinical follow-up.ResultsNo statistically significant differences between IOA xB and IOA F3D were found (p = 0.532). Agreement for xB after categorical classification of the diagnoses was high (κxB = 0.89 [95% CI 0.84 –0.93]) but without statistically significant difference F3D (κ F3D = 0.90 [95% CI 0.86 – 0.94]). Thirty-one (14.9%) inter-reconstruction diagnostic discrepancies were observed of which 21 (10.1%) were classified as major. The follow-up confirmed the diagnosis of F3D in 10 cases, xB in 6 cases and was non-contributory in 5 cases.ConclusionsxB reconstruction algorithm was found reliable, providing high interobserver agreement and similar diagnostic confidence to F3D reconstruction in clinical routine.

Risk of recurrent venous thromboembolism in COPD patients: results from a prospective cohort study

We aimed to assess the risk of recurrent venous thromboembolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) following cessation of anticoagulation therapy. In a prospective cohort of 1468 patients with a documented episode of VTE, followed for up to 5u2005years after cessation of anticoagulation therapy, the diagnosis of COPD was confirmed in 136. The main outcome was recurrent VTE. The secondary outcome was overall mortality. Univariate and multivariate analyses were performed to identify the risk factors of recurrence. Of the 1468 patients included, recurrent VTE was observed in 306 (34 with COPD and 272 without) during a median follow-up period of 36.5u2005months. The incidence rate of recurrent VTE was 9.1% (95% CI 6.5–12.8) for COPD patients and 7.0% (95% CI 6.2–7.9) for non-COPD patients. COPD was not associated with an increased risk of VTE recurrence on univariate or multivariate analyses (hazard ratio: 1.0 (95% CI 0.7–1.4)). The risk of death, adjusted for demographic and clinical characteristics, showed no increase in COPD patients, as compared to non-COPD patients. In patients with COPD who had an acute episode of VTE, the risk of recurrent VTE was not any higher than that in non-COPD patients. Patients with venous thromboembolism and COPD do not have a higher risk of recurrence or death http://ow.ly/T9oE30cbIgC

Automation of oxygen titration in patients with acute respiratory distress at the emergency department. A multicentric international randomised controlled study

Oxygen therapy is commonly administered in critical care and emergency medicine. Its benefits are well known but potential side-effects may be underestimated. Compliance to recommendations remains dependent on staff workload. We developed FreeO2, an innovative device that automatically titrates oxygen flow delivered through nasal cannulas or masks to maintain the patients in the SpO2 target set by the clinician1.

Assessing polymyalgia rheumatica activity when C-reactive protein is unavailable or uninterpretable

ObjectivenThe PMR activity score (PMR-AS) includes the CRP value, which may be lacking or invalid owing to anti-IL-6 therapy. Our objective was to develop alternatives to PMR-AS that do not require CRP.nnnMethodsnWe used the Club Rhumatisme et Inflammation (CRI; 89 patients with PMR) and the Tolerance and Efficacy of tocilizumab iN pOlymyalgia Rheumatica (TENOR; 20 patients with recent-onset PMR naive to glucocorticoid who received three tocilizumab infusions, at weeks 0, 4 and 8, followed by prednisone from weeks 12 to 24) cohorts. In the CRI cohort, we evaluated correlations between PMR-AS items to select the best item for imputing CRP. Then we calculated the PMR-AS with (PMR-AS) and without (clin-PMR-AS) CRP and we used the linear regression between PMR-AS and clin-PMR-AS to obtain CRP-imputed (CRP-imp) PMR-AS. Finally, we evaluated agreement between clin-PMR-AS, CRP-imp PMR-AS, PMR-AS and ESR-PMR-AS in the TENOR cohort during tocilizumab therapy.nnnResultsnIn the CRI cohort, agreement between PMR-AS and clin-PMR-AS was excellent (κ = 0.90). Linear regression between PMR-AS and clin-PMR-AS [CRP-imp PMR-AS = 1.12(clin-PMR-AS)+0.26] allowed us to build the CRP-imp PMR-AS. Mean (s.d.) values were as follows: 8.40 (9.76) for PMR-AS, 7.24 (8.58) for clin-PMR-AS and 7.84 (9.61) for CRP-imp PMR-AS. CRP-imp PMR-AS agreed more closely with PMR-AS than did clin-PMR-AS. The results in the TENOR cohort confirmed that CRP-imp PMR-AS or ESR-PMR-AS could be used.nnnConclusionnAlternatives to the PMR-AS obtained without CRP can be used to monitor PMR activity in everyday practice in patients without available CRP values and in those receiving IL-6 antagonist therapy.