Intranasal sufentanil given in the emergency department triage zone for severe acute traumatic pain: a randomized double-blind controlled trial.

The goal of our study was to determine if an intranasal (IN) dose of sufentanil delivered in the ED triage zone would improve the management of severely painful patients. We performed a randomized, double blind and placebo-controlled trial on adult patients suffering from an acute severe pain (≥ 6/10) consecutive to an isolated limb injury. We compared 2 analgesic strategies: the usual pain treatment with IV-only multimodal analgesics (IVMA) including IV opioids if needed (control group) and another strategy (active group) based on a single dose of IN sufentanil (0.4 µg/kg) given at triage and followed by IV multimodal analgesia. Our primary outcome was the proportion of patients reaching pain-relief (≤ 3/10) 30 min after IN injection at triage. Secondary outcomes were rates of adverse events, frequency of clinical interventions required by these events, and satisfaction of patients. A total of 144 adult participants completed the study, 72 in each group. Compared with usual IV-only pain management, the analgesic strategy initiated in triage zone with a dose of IN sufentanil increased the proportion of patients reaching pain relief in 30 min: 72.2% versus 51.4%, in our trial (p = 0.01 and number needed to treat of 5). There was no serious adverse event (AE) in both groups. Patients who received IN sufentanil experienced more frequently minor opiate side effects. Proportion of respiratory AEs was higher in the active group (12.5% of bradypnea < 10 cycles per minute versus 1.4%) but these events were of mild severity, as only 2 participants (one in each group) received temporary low dose oxygen therapy, and none required naloxone. Lengths of stay in the ED were similar in both groups, as well as satisfaction of patients (above 9/10) and pain scores at discharge (< 2/10). We found that a single dose of IN sufentanil delivered in the ED triage zone significantly increases the proportion of severely painful patients reaching painrelief in 30 min, compared to usual analgesia with IV-only multimodal analgesia.

Adverse Events With Ketamine Versus Ketofol for Procedural Sedation on Adults: A Double-blind, Randomized Controlled Trial.

OBJECTIVES: The goal of our study was to compare the frequency and severity of recovery reactions between ketamine and ketamine-propofol 1:1 admixture ("ketofol"). METHODS: We performed a multicentric, randomized, double-blind trial in which adult patients received emergency procedural sedations with ketamine or ketofol. Our primary outcome was the proportion of unpleasant recovery reactions. Other outcomes were frequency of interventions required by these recovery reactions, rates of respiratory or hemodynamic events, emesis, and satisfaction of patients as well as providers. RESULTS: A total of 152 patients completed the study, 76 in each arm. Compared with ketamine, ketofol determined a 22% reduction in recovery reactions incidence (p < 0.01) and less clinical and pharmacologic interventions required by these reactions. There was no serious adverse event in both groups. Rates in hemodynamic or respiratory events as well as satisfaction scores were similar. Significantly fewer patients experienced emesis with ketofol, with a threefold reduction in incidence compared with ketamine. CONCLUSION: We found a significant reduction in recovery reactions and emesis frequencies among adult patients receiving emergency procedural sedations with ketofol, compared with ketamine.

Clinical effect of molecular methods in sarcoma diagnosis (GENSARC): a prospective, multicentre, observational study.

BACKGROUND: Advances in molecular genetics of sarcoma have enabled the identification of type-specific aberrations. We aimed to assess the clinical effect of systematic implementation of molecular assays to improve sarcoma misdiagnosis. METHODS: In this multicentre, observational study, we recruited patients from 32 centres of the French Sarcoma Group/Reference Network in Pathology of Sarcomas. Eligibility criteria included: biopsy or surgical resection; suspicion of: dermatofibrosarcoma protuberans (cohort 1), dedifferentiated liposarcoma (cohort 2), Ewing's sarcoma family of tumours (cohort 3), synovial sarcoma (cohort 4), alveolar rhabdomyosarcoma (cohort 5), and myxoid or round cell liposarcoma (cohort 6); review by one sarcoma-expert pathologist; availability of frozen material (except for cohort 1 of patients with dermatofibrosarcoma protuberans because anti-CD34 immunohistochemistry is performed on paraffin-embedded tissue); and patient information. For each case, the pathologist made one primary diagnosis followed by up to two differential diagnoses, based on histological characteristics only. Each diagnosis was classified as certain, probable, or possible. For each case to determine the molecular classification, we did fluorescence in-situ hybridisation on paraffin-embedded samples. We also did comparative genomic hybridisation and quantitative PCR (cohort 2) or reverse transcriptase PCR (cohorts 3-6) on frozen and paraffin-embedded samples. We made a final diagnosis based on the molecular results. The clinical effect of diagnosis correction was assessed by a board of experts. FINDING: Between June 22, 2009, and Oct 30, 2012, 395 patients were enrolled in the study, of which 384 were eligible for inclusion. The diagnosis was eventually modified by molecular genetics for 53 patients: eight (16%) of 50 patients with dermatofibrosarcoma (cohort 1), seven (23%) of 30 patients with dedifferentiated liposarcoma (cohort 2), 13 (12%) of 112 with Ewing's sarcoma family of tumours (cohort 3), 16 (16%) of 97 patients with synovial sarcoma (cohort 4), seven (15%) of 46 patients with alveolar rhabdomyosarcoma (cohort 5), and two (4%) of 49 patients with myxoid or round cell liposarcoma (cohort 6), with an effect on primary management or prognosis assessment in 45 cases. INTERPRETATION: Molecular genetic testing should be mandatory for diagnostic accuracy of sarcoma and appropriate clinical management, even when histological diagnosis is made by pathologist experts in this field. FUNDING: French National Cancer Institute and Nice University Hospital.

[Comparative cost analysis of molecular biology methods in the diagnosis of sarcomas]. / Analyse comparative des coûts de techniques de biologie moléculaire dans le diagnostic de sarcomes.

Sarcomas represent a complex and heterogeneous group of rare malignant tumors and their correct diagnosis is often difficult. Recent molecular biological techniques have been of great diagnostic use and there is a need to assess the cost of these procedures in routine clinical practice. Using prospective and observational data from eight molecular biology laboratories in France, we used "microcosting" method to assess the cost of molecular biological techniques in the diagnosis of five types of sarcoma. The mean cost of fluorescence in situ hybridization (FISH) was 318 € (273-393) per sample; mean reverse transcription polymerase chain reaction (RT-PCR) cost ranged from 300 € (229-481) per formalin-fixed, paraffin-embedded specimen to 258 € (213-339) per frozen specimen; mean quantitative polymerase chain reaction (Q-PCR) cost was 184 € (112-229) and mean CGH-array cost was 332 € (329-335). The cost of these recently implemented techniques varied according to the type of sarcoma; the method of tissue collection and local organizational factors including the level of local expertise and investment. The cost of molecular diagnostic techniques needs to be balanced against their respective performance.

An abnormal ProC Global test result is associated with an increased risk of venous thromboembolism independent of test sensitivity for protein C pathway abnormalities.

The ProC Global assay is a clotting assay primarily developed to globally evaluate the functionality of the protein C (PC) pathway. It was shown to lack both sensitivity and specificity for PC pathway abnormalities, i.e. factor V Leiden mutation, PC and PS deficiency. The hypothesis that an abnormal test result could be associated with venous thromboembolism (VTE) was evaluated in a case-control study. The proportion of reduced response was significantly higher in cases than in controls [n = 71/139 (51.1%) vs. n = 28/147 (19.0%); p < 0.0001] and the same applied after exclusion of those subjects with any PC pathway abnormality [n = 53/119 (44.5%) vs. n = 25/143 (17.5%); p < 0.0001]. An abnormal ProC Global assay result was significantly associated with thrombosis both in the whole population (odds ratio [OR]=4.44, 95% confidence interval [CI]=2.61-7.53) and in those subjects without any PC pathway abnormality (OR = 3.70, 95%CI = 2.16-6.66). The ProC Global assay result was significantly lower in cases with idiopathic VTE than in those with secondary VTE (p < 0.0001). No significant difference was observed when cases were classified according to the presence or absence of recurrent episodes. Moreover, a reduced response was found to be associated with VTE both in subjects with normal or elevated factor VIII (FVIII) level. In vitro, FVIII was found to play a critical role in the ProC Global assay result as suggested by the significant trend toward decreasing response with increasing FVIII levels. In conclusion, our results suggest that an abnormal ProC Global assay result is associated with an increased risk of VTE independently of its sensitivity for PC pathway abnormalities.