Nebulized hypertonic saline 3% for 1 versus 3 days in hospitalized bronchiolitis: a blinded non-inferiority randomized controlled trial.

BACKGROUND: The use and optimal duration of treatment with nebulized hypertonic saline (HS) in infants hospitalized for acute bronchiolitis is unclear. The objective was to compare the efficacy of 1 versus 3 days of nebulized 3% HS at 72 h of treatment. We conducted a blinded non-inferiority randomized controlled trial including infants aged less than 12 months old, hospitalized for a moderate bronchiolitis. METHODS: Nebulisations of 3% HS for 1 day were followed by either the continuation of 3% HS (HS3d group) or switched to 0.9% normal isotonic saline (HS1d group) for 2 days Randomization was performed according to a predefined list with a 1:1 ratio, obtained with a random generator number with blocks.. Main outcome was mean Wang clinical severity score (CSS) after 72 h of treatment. RESULTS: One hundred sixteen infants (HS1d n = 59 and HS3d n = 57), were included over two epidemic seasons from 2014 to 2016, but recruitement did not reach the planned sample size. The difference for the Wang CSS score in the HS3d vs HS1d group was 0.71 [IC 90% 0.1; 1.3], above the precluded value of 0.4 set in the protocol defining the non-inferiority of shorter treatment duration. Clinical remission was more rapidly obtained in the HS3d than in HS1d (2.3 ± 1.6 vs 2.9 ± 1.4 days, p = 0.04), with a non-significant tendency for less need of nutritional support and supplemental oxygen in HS3d group. Clinical worsening and treatment intolerance were similar in the 2 groups. CONCLUSIONS: Despite being underpowered, results seem not to be in favour of reducing the duration of nebulised HS treatment from 3 to 1 day in acute moderate bronchiolitis. TRIAL REGISTRATION: Clinical trials NCT02538458, October 2014.

Impact of Cone Beam Computed Tomography Dose in Pre-Surgical Implant Analysis.

OBJECTIVES: Cone-Beam Computed Tomography (CBCT) produces vital information required for the accurate and prudent placement of dental implants. Lack of standardization between CBCT machines may result in unsafe patient exposure to harmful radiation; higher doses are not necessarily associated with improved image quality. AIM: The study aimed to assess the influence of low- and high-dose milliamperage settings on CBCT images for objective and subjective implant planning. METHODS: Two dry skulls (4 hemi-maxillary segments of the maxilla and 4 hemi-maxillary segments of the mandible) were scanned under low (2 mA) and high (6.3 mA) dosage settings using a CBCT (Carestream CS 9300). Cross-sectional slices of both image qualities were evaluated by five expert clinicians, for image quality for implant planning and objective bone measurements. RESULTS: There were no significant differences in bone measurements taken on high or low dose images (p > 0.05). In qualitative image assessments, assessment and image quality for almost all observers were independent of each other. For planning posterior mandibular implant placement, increased dosage improved concordance and kappa values between low and high dose images. CONCLUSION: Reduction in milliamperage did not affect diagnostic image quality for objective bone measurements and produced sufficient intra-rater reliability for qualitative assessment; therefore dose reduction can be achieved without compromising diagnostic decision- making.

Management of Severe Bleeding in Patients Treated with Direct Oral Anticoagulants: An Observational Registry Analysis.

BACKGROUND: The use of prothrombin complex concentrates and the role of plasma concentration of anticoagulants in the management of bleeding in patients treated with direct oral anticoagulants are still debated. Our aim was to describe management strategies and outcomes of severe bleeding events in patients treated with direct oral anticoagulants. METHODS: We performed a prospective cohort study of 732 patients treated with dabigatran, rivaroxaban, or apixaban hospitalized for severe bleeding, included prospectively in the registry from June 2013 to November 2015. RESULTS: Bleeding was gastrointestinal or intracranial in 37% (212 of 732) and 24% (141 of 732) of the cases, respectively. Creatinine clearance was lower than 60 ml/min in 61% (449 of 732) of the cases. The plasma concentration of direct oral anticoagulants was determined in 62% (452 of 732) of the cases and was lower than 50 ng/ml or higher than 400 ng/ml in 9.2% (41 of 452) and in 6.6% (30 of 452) of the cases, respectively. Activated or nonactivated prothrombin complex concentrates were administered in 38% of the cases (281 of 732). Mortality by day 30 was 14% (95% CI, 11 to 16). CONCLUSIONS: Management of severe bleeding in patients treated with direct oral anticoagulants appears to be complex. The use of prothrombin complex concentrates differs depending on bleeding sites and direct oral anticoagulant plasma concentrations. Mortality differs according to bleeding sites and was similar to previous estimates.

Prevention of syncopal-type reactions after whole blood donation: a cluster-randomized trial assessing hydration and muscle tension exercise.

BACKGROUND: The prevention of presyncopal and syncopal reactions to whole blood donation is important for both the donor's safety and their retention as blood donors. The best strategy to achieve this remains debated. STUDY DESIGN AND METHODS: A prospective cluster-randomized trial comparing three hydration modes (500 mL of an isotonic drink, 500 mL of water, just before phlebotomy, or advice to drink [control arm]) coupled or not with light muscle tensing exercises, was carried out in mobile and fixed units of two regional blood centers in southeast France between January and July 2014. The main outcome was the cumulative incidence of presyncope (feeling faint) and syncope (fainting) at the donation site or in the 48 hours after leaving the site. Secondary outcomes were the cumulative incidence of these adverse events during donation, immediately after blood donation, or within 48 hours. RESULTS: Overall, presyncope or syncope occurred in 5.5% of the 4576 donors. Compared to controls, drinking 500 mL (isotonic solution or water) significantly reduced the rate of events (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.55-0.99; p = 0.041) independently of muscle tensing exercise. Muscle tensing exercises significantly reduced syncopal-type reactions during the donation (OR, 0.64; 95% CI, 0.42-0.98; p = 0.041), and an isotonic drink significantly reduced delayed off-site syncopal-type reactions (OR, 0.62; 95% CI, 0.40-0.98; p = 0.040) and tiredness after donation (OR, 0.75; 95% CI, 0.59-0.94; p = 0.014). CONCLUSIONS: Drinking 500mL of water or isotonic drink close to phlebotomy is useful in preventing presyncopal or syncopal reactions in blood donors. Isotonic drinks have the advantage of preventing delayed reactions and tiredness after whole blood donation.

Transcranial Doppler to Predict Neurologic Outcome after Mild to Moderate Traumatic Brain Injury.

BACKGROUND: To assess the performance of transcranial Doppler (TCD) in predicting neurologic worsening after mild to moderate traumatic brain injury. METHODS: The authors conducted a prospective observational study across 17 sites. TCD was performed upon admission in 356 patients (Glasgow Coma Score [GCS], 9 to 15) with mild lesions on cerebral computed tomography scan. Normal TCD was defined as a pulsatility index of less than 1.25 and diastolic blood flow velocity higher than 25 cm/s in the two middle cerebral arteries. The primary endpoint was secondary neurologic deterioration on day 7. RESULTS: Twenty patients (6%) developed secondary neurologic deterioration within the first posttraumatic week. TCD thresholds had 80% sensitivity (95% CI, 56 to 94%) and 79% specificity (95% CI, 74 to 83%) to predict neurologic worsening. The negative predictive values and positive predictive values of TCD were 98% (95% CI, 96 to 100%) and 18% (95% CI, 11to 28%), respectively. In patients with minor traumatic brain injury (GCS, 14 to 15), the sensitivity and specificity of TCD were 91% (95% CI, 59 to 100%) and 80% (95% CI, 75 to 85%), respectively. The area under the receiver operating characteristic curve of a multivariate predictive model including age and GCS was significantly improved with the adjunction of TCD. Patients with abnormal TCD on admission (n = 86 patients) showed a more altered score for the disability rating scale on day 28 compared to those with normal TCD (n = 257 patients). CONCLUSIONS: TCD measurements upon admission may provide additional information about neurologic outcome after mild to moderate traumatic brain injury. This technique could be useful for in-hospital triage in this context. (Anesthesiology 2016; 125:346-54).

Contribution of the ELFG test in algorithms of non-invasive markers towards the diagnosis of significant fibrosis in chronic hepatitis C.

BACKGROUND AND AIMS: We aimed to determine the best algorithms for the diagnosis of significant fibrosis in chronic hepatitis C (CHC) patients using all available parameters and tests. PATIENTS AND METHODS: We used the database from our study of 507 patients with histologically proven CHC in which fibrosis was evaluated by liver biopsy (Metavir) and tests: Fibrometer®, Fibrotest®, Hepascore®, Apri, ELFG, MP3, Forn's, hyaluronic acid, tissue inhibitor of metalloproteinase-1 (TIMP1), MMP1, collagen IV and when possible Fibroscan™. For the first test we used 90% negative predictive value to exclude patients with F≤1, next an induction algorithm was applied giving the best tests with at least 80% positive predictive value for the diagnosis of F≥2. The algorithms were computed using the R Software C4.5 program to select the best tests and cut-offs. The algorithm was automatically induced without premises on the part of the investigators. We also examined the inter-observer variations after independent review of liver biopsies by two pathologists. A medico-economic analysis compared the screening strategies with liver biopsy. RESULTS: In "intention to diagnose" the best algorithms for F≥2 were Fibrometer ®, Fibrotest®, or Hepascore® in first intention with the ELFG score in second intention for indeterminate cases. The percentage of avoided biopsies varied between 50% (Fibrotest® or Fibrometer®+ELFG) and 51% (Hepascore®+ELFG). In "per-analysis" Fibroscan™+ELFG avoided liver biopsy in 55% of cases. The diagnostic performance of these screening strategies was statistically superior to the usual combinations (Fibrometer® or Fibrotest®+Fibroscan™) and was cost effective. We note that the consensual review of liver biopsies between the two pathologists was mainly in favor of F1 (64-69%). CONCLUSION: The ELFG test could replace Fibroscan in most currently used algorithms for the diagnosis of significant fibrosis including for those patients for whom Fibroscan™ is unusable.

Including osteoprotegerin and collagen IV in a score-based blood test for liver fibrosis increases diagnostic accuracy.

BACKGROUND: Noninvasive methods for liver fibrosis evaluation in chronic liver diseases have been recently developed, i.e. transient elastography (Fibroscan™) and blood tests (Fibrometer®, Fibrotest®, and Hepascore®). In this study, we aimed to design a new score in chronic hepatitis C (CHC) by selecting blood markers in a large panel and we compared its diagnostic performance with those of other noninvasive methods. METHODS: Sixteen blood tests were performed in 306 untreated CHC patients included in a multicenter prospective study (ANRS HC EP 23 Fibrostar) using METAVIR histological fibrosis stage as reference. The new score was constructed by non linear regression using the most accurate biomarkers. RESULTS: Five markers (alpha-2-macroglobulin, apolipoprotein-A1, AST, collagen IV and osteoprotegerin) were included in the new function called Coopscore©. Using the Obuchowski Index, Coopscore© shows higher diagnostic performances than for Fibrometer®, Fibrotest®, Hepascore® and Fibroscan™ in CHC. Association between Fibroscan™ and Coopscore© might avoid 68% of liver biopsies for the diagnosis of significant fibrosis. CONCLUSION: Coopscore© provides higher accuracy than other noninvasive methods for the diagnosis of liver fibrosis in CHC. The association of Coopscore© with Fibroscan™ increases its predictive value.

Non-cardiac surgery in patients with coronary stents: the RECO study.

CONTEXT: Interruption or maintenance of oral antiplatelet therapy (OAT) during an invasive procedure may result in ischaemic and/or haemorrhagic complications. There is currently a lack of clear guidance regarding the issue of treatment interruption during surgical procedures. OBJECTIVE: To evaluate the rate of major adverse cardiac and cerebrovascular events (MACCEs) and major or minor bleeding complications and their associated independent correlates in coronary stented patients undergoing urgent or planned non-cardiac surgery. DESIGN, SETTING, AND PATIENTS: Prospective, multicentre, observational cohort study of 1134 consecutive patients with coronary stents. MAIN OUTCOME MEASURES: The co-primary endpoints consisted of the incidence of MACCE and major bleeding within the first 30 days of an invasive procedure. RESULTS: MACCE and haemorrhagic complications were observed in 124 (10.9%) and 108 (9.5%) patients, respectively, within an average time delay from invasive procedure to event of 3.3±3.9 and 5.3±5.3 days. Independent preoperative correlates for MACCE were complete OAT interruption for more than 5 days prior to surgery, preoperative haemoglobin <10 g/dl, creatinine clearance of <30 ml/min and emergency or high-risk surgery. Independent factors for haemorrhagic complications were preoperative haemoglobin <10 g/dl, creatinine clearance between 30 and 60 ml/min, a delay from stent implantation to surgery <3 months and high-risk surgery according to the Lee classification. CONCLUSIONS: Patients with coronary stents undergoing an invasive procedure are at high risk of perioperative myocardial infarction including stent thrombosis irrespective of the stent type and major bleeding. Interruption of OAT more than 5 days prior to an invasive procedure is a key player for MACCE. CLINICAL TRIAL REGISTRATION: NCT01045850.