Assessment of major salivary gland size in primary Sjögren's syndrome: Comparison between clinical examination and ultrasonography.

OBJECTIVE: Parotidomegaly is a criterion of the EULAR Primary Sjögren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment. METHODS: Outpatients with primary Sjögren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement. RESULTS: Thirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76-1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42-0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found. CONCLUSION: Clinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination.

Multi-modal pain assessment: are near-infrared spectroscopy, skin conductance, salivary cortisol, physiologic parameters, and Neonatal Facial Coding System interrelated during venepuncture in healthy, term neonates?

BACKGROUND: Improving pain and stress assessments in neonates remains important in preventing the short- and long-term consequences. We aimed to identify the relationships between different pain assessment parameters by simultaneously measuring changes in cortical, autonomic, hormonal, physiological, and behavioral evoked responses to venepuncture in healthy, full-term neonates. METHODS: This observational, prospective study (ancillary to the ACTISUCROSE trial) included 113 healthy, 3-day old, full-term neonates who underwent venepuncture for systematic neonatal screening, from July to October 2013, in a tertiary-level maternity ward of a university hospital. During venepuncture, we simultaneously measured the cortical single-channel near-infrared spectroscopy (NIRS) signals, foot skin conductance, salivary cortisol, physiological responses, and behavioral (Neonatal Facial Coding System [NFCS]) evoked responses. RESULTS: Regarding the NIRS analysis, the highest correlation was between the NFCS at venepuncture and the change in NIRS integrated values of total hemoglobin (r=0.41, P<0.001) or oxygenated hemoglobin (r=0.27, P<0.001). The NFCS at venepuncture was moderately positively correlated with changes in salivary cortisol (r=0.42, P<0.001) and skin conductance (r=0.29, P<0.001). Salivary cortisol and skin conductance changes were not correlated; the latter parameters were not correlated with heart rate, respiratory rate, or SpO2. CONCLUSION: During venepuncture, NFCS was mildly or moderately correlated with salivary cortisol, skin conductance, and cortical NIRS changes.

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

BACKGROUND: xSPECT 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. RESULTS: No 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 (κ xB = 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. CONCLUSIONS: xB reconstruction algorithm was found reliable, providing high interobserver agreement and similar diagnostic confidence to F3D reconstruction in clinical routine.

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

Objective: The 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. Methods: We 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. Results: In 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. Conclusion: Alternatives 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.

Ultrasonography and magnetic resonance imaging changes in patients with polymyalgia rheumatica treated by tocilizumab.

BACKGROUND: This study assessed inflammatory changes using ultrasound (US) and magnetic resonance imaging (MRI) in patients taking tocilizumab for polymyalgia rheumatica (PMR). METHODS: Eighteen patients were included in the prospective open-label TENOR study and received three tocilizumab infusions, without corticosteroids. B-mode and power Doppler US and MRI (T1 and T2-short time inversion recuperation weighted sequences) of the hips and shoulders were performed at weeks 0, 2, and 12. Subacromial, trochanteric, and iliopsoas bursitis and intraarticular glenohumeral and coxofemoral effusions/synovitis were scored from 0 to 3. Changes over time and US-MRI correlations were evaluated. RESULTS: At baseline, the proportions of shoulders and hips with bursitis were 93 and 100% by MRI and 61 and 13% by US; and the corresponding proportions for intraarticular effusions/synovitis were 100 and 100% by MRI and 57 and 53% by US. Imaging findings did not improve during the first two treatment weeks. From baseline to week 12, bursitis improved significantly at all four joints by MRI (P = 0.005) and US (P = 0.029) and intraarticular effusions/synovitis by US only (P = 0.001). The proportion of abnormalities that improved by week 12 was 42% by MRI and 37% by US. MRI detected bursitis in a larger proportion of hips (73% versus 13%) and US in a larger proportion of shoulders (57% versus 28%), whereas no difference was found for intraarticular effusions/synovitis. At baseline, agreement between US and MRI findings was poor. CONCLUSIONS: US and MRI showed significant improvements in inflammatory lesions during tocilizumab treatment of PMR.

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 5 years 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 36.5 months. 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.

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 ≥3 L·min-1 Patients were randomised to automated closed-loop or manual O2 titration during 3 h. Patients were stratified according to arterial carbon dioxide tension (PaCO2 ) (hypoxaemic PaCO2 ≤45 mmHg; or hypercapnic PaCO2 >45-≤55 mmHg) 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±6.3 days, p=0.002).Automated O2 titration in the emergency department improved oxygenation parameters and adherence to guidelines, with potential clinical benefits.

Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab.

BACKGROUND: Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity. OBJECTIVE: We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck. PATIENTS AND METHODS: Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7 years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%). RESULTS: Sixty-nine patients received at least 7 cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade ≥ 3 dermatitis; grade ≥ 2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade ≥ 3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56 days (47-75) compared to 51 days (47-65) in patients who did not require toxicity-related radiation interruptions (p < 0.05). After a median follow-up of 17.5 months (1.3-107.6) for all patients, median overall survival was 17.9 months (95% CI: 12.7-23.2), and loco-regional control (LRC) was 9.2 months (95% CI: 3.9-14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade ≥ 2 were independent prognostic factors for LRC (p = 0.023 and p = 0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p = 0.048 and 0.052, respectively). CONCLUSIONS: Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.

Current incidence of venous thromboembolism and comparison with 1998: a community-based study in Western France.

In 1998 we estimated the incidence of venous thromboembolism (VTE) to be 1.8/1,000 per year. The aim of this study was to compare current VTE incidence to that observed in 1998. We prospectively recorded all cases of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) of the lower limbs diagnosed between March 1, 2013 and February 28, 2014 in hospitals and in the community, using the same method and geographic area than in 1998. The 2013 incidence rates of VTE were computed and compared with those of 1998 using age- and sex-specific standardised incidence ratios (SIRs). In 2013, we recorded 576 VTE cases (279 isolated DVT and 297 PE ± DVT). Among 367,911 inhabitants, the overall incidence of VTE was 1.57/1,000 (95 % CI 1.44-1.69). The overall VTE incidence was significantly lower in 2013 as compared with 1998: SIR 0.72 (95 % CI 0.67-0.79) as well as the incidence of isolated DVT: SIR 0.53 (95 % CI 0.47-0.60); conversely, the overall incidence of PE was unchanged: SIR 1.10 (95 % CI, 0.98-1.23) despite an increase in the incidence of isolated PE: SIR 1.29 (95 % CI, 1.10-1.52). In 1998, 4.4 % of PE cases were diagnosed using CTPA as compared with 73.7 % in 2013 (p < 0.001). In conclusion, between 1998 and 2013, the incidence of symptomatic DVT decreased. Conversely, we found no similar reduction in the incidence of symptomatic PE; whether this is due to changes in diagnostic tests and algorithms in the management of suspected PE requires further investigations.

Major changes in the number and indications of liver biopsy for chronic liver diseases over one decade in France.

AIMS: French clinical practice guidelines on the use of liver biopsy (LB) published in 2002 focused on ultrasound guidance (USG) and ambulatory LB. The aims of this study were as follows: (i) to evaluate the number and indications for LB for chronic liver diseases and (ii) to evaluate LB modalities according to French clinical practice guidelines. Data recorded included the number and indications for LB, procedures, use of USG, and complications. RESULTS: A total of 131 centers participated: 8741 LB were performed versus 12 000 in 1997; ambulatory LB was performed in 48.6% of cases (vs. 27% in 1997; P<0.001). USG during LB was used in 89.7% of the centers, among which 42 (31.8%) used real-time USG (vs. 56 and 22%, respectively, in 1997; P<0.01). The main indications for LB were chronic hepatitis C in 24.6% of cases (vs. 54.1% in 1997; P<0.001), and viral B or B-delta in 15.0% (vs. 5.8%; P<0.001). Severe complications were less frequent at centers with systematical USG during LB than at those without such guidance (P<0.01). CONCLUSION: In this large nationwide study, major trends were as follows: (i) a marked decrease in LB number, related to a decrease in LB for chronic viral hepatitis C; (ii) increased use of USG; and (iii) an increase in the number of ambulatory LB. Severe complications decreased significantly at centers in which USG was systematically applied.

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 Chuang's PMR criteria, with symptom onset within the last 12 months 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 (0.15 mg/kg if PMR-AS ≤10 and 0.30 mg/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.

Serum levels of 25(OH)D are not associated with venous thromboembolism in the elderly population. A case-control study.

The prevalence of both vitamin D deficiency and venous thromboembolism (VTE) is important in the elderly. Previous studies have provided evidence for a possible association between vitamin D status and the risk of VTE. Thus, we aimed to investigate the association between vitamin D levels and VTE in the population aged 75 and over included in the EDITH case-control study. The association between vitamin D status and VTE was analysed. We also analysed the monthly and seasonal variations of VTE and vitamin D. Between May 2000 and December 2009, 340 elderly patients (mean age 81.5 years, 32% men) with unprovoked VTE and their controls were included. The univariate and multivariate analysis found no significant association between serum levels of vitamin D and the risk of unprovoked VTE. In the unadjusted analysis, a higher BMI was statistically associated with an increased risk of VTE (OR 1.09; 95% CI 1.05-1.13) whereas a better walking capacity and living at home were associated with a decreased rate of VTE: OR 0.57; 95% CI 0.36-0.90 and 0.40; 95% CI 0.25-0.66, respectively. Although not significant, more VTE events occurred during winter (p=0.09). No seasonal variations of vitamin D levels were found (p=0.11). In conclusion, in contrast with previous reports our findings suggest that vitamin D is not associated with VTE in the elderly population.

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

AIM: 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. METHODS: A prospective, monocentric study was conducted that measured the sleep patterns of 48 infants: 24 late preterm neonates born at 34-36 weeks of gestational age and 24 term neonates. We used both polysomnography and the Actiwatch Mini during a three-hour period and then compared the results from the two methods. RESULTS: The baseline measurements for the preterm and terms groups were as follows: gestational age (34.5 weeks and 39.2 weeks), birthweight (2368 g and 3393 g) and age (6.4 days and 0.72 days). With the Actiwatch Mini, sensitivity for the late preterm and full-term infants was 78% and 87% for the leg actigraph and 78% and 93% for the arm actigraph. For specificity, the respective figures were 42% and 31% for the leg and 34% and 20% for the arm. CONCLUSION: Actigraphy using the Actiwatch Mini was not a reliable method for measuring sleep patterns in healthy late preterm and term neonates a few days after birth.

Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects.

Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV(+)) treatment-naive individuals (n = 17), HIV(+) individuals on combination antiretroviral therapy with viral loads below detection (n = 11), and HIV-seronegative (HIV(-)) individuals (n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, monocytes from HIV(+) persons had significantly increased surface expression of Glut1 compared with those from HIV(-) controls. Nonclassical (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocyte subpopulations showed higher Glut1 expression than did classical (CD14(++)CD16(-)) monocytes. Intermediate monocytes from treatment-naive HIV(+) individuals also showed increased uptake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV(-) controls. Our results show that HIV infection is associated with increased glucose metabolism in monocytes and that Glut1 expression by proinflammatory monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.

MRI investigation of radiating pain in the lower limbs: value of an additional sequence dedicated to the lumbosacral plexus and pelvic girdle.

OBJECTIVE: In some cases, sciatica-like symptoms radiating through the buttock, anterior thigh, or leg result from spinal root compression in an extraspinal location or from injury to the pelvic girdle. It has been suggested that adding a coronal STIR sequence dedicated to the lumbosacral plexus and pelvis to the routine MRI protocol can provide a good depiction of disorders of this type. MATERIALS AND METHODS: Two hundred nine patients with sciatica-like symptoms of suspected lumbar origin were included in the study. Disorders responsible for symptoms involving extraspinal compression of the lumbosacral plexus or pelvic girdle were retrospectively noted and correlated with age, sex, location of pain, referring physician, presence of discoradicular impingement liable to explain symptoms, and history of neoplasia. RESULTS: An extraspinal cause of symptoms was depicted in 12 cases (5.7%), including three cases of extraspinal compression and nine differential diagnoses in the pelvic region. Prevalence of an extraspinal cause of pain was significantly correlated with the absence of discoradicular impingement in the spine (p=0.046). A higher prevalence of extraspinal compression of the lumbosacral plexus (p=0.029) was seen in patients 60 years old or older, whereas no other feature was statistically associated with an extraspinal cause of pain. CONCLUSION: Because of its short acquisition time and subsequent low cost, the additional coronal STIR sequence should be performed in the routine MRI investigation of sciatica-like symptoms when no discoradicular impingement is seen in the spine to depict an extraspinal cause of symptoms.

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

PURPOSE: Midazolam 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. METHODS: A 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. FINDINGS: Ninety-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). CONCLUSIONS: According 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.