The Clavicle Trial A Multicenter Randomized Controlled Trial Comparing Operative with Nonoperative Treatment of Displaced Midshaft Clavicle Fractures

Background: The treatment of displaced midshaft clavicle fractures remains controversial. Methods: We undertook a multicenter randomized controlled trial to compare effectiveness and safety between nonoperative management and ORIF (open reduction and internal fixation) for displaced midshaft clavicle fractures in adults. Three hundred and one eligible adult patients were randomized to 1 of the 2 treatment groups and followed at 6 weeks, 3 months, and 9 months after recruitment. The primary outcome was the rate of radiographically evident nonunion at 3 months following treatment. Secondary outcomes were the rate of radiographically evident nonunion at 9 months, limb function measured using the Constant-Murley Score and DASH (Disabilities of the Arm, Shoulder and Hand) score, and patient satisfaction. Results: There was no difference in the proportion of patients with radiographic evidence of nonunion at 3 months between the operative (28%) and nonoperative (27%) groups, whereas at 9 months the proportion with nonunion was significantly lower (p < 0.001) in the operative group (0.8%) than in the nonoperative group (11%). The DASH and ConstantMurley scores and patient satisfaction were all significantly better in the operative group than in the nonoperative group at 6 weeks and 3 months. Conclusions: Although at 3 months there was no evidence that surgery had reduced the rate of nonunion of displaced midshaft clavicle fractures, at 9 months nonoperative treatment had led to a significantly higher nonunion rate (11% compared with <1%). The rate of secondary surgical intervention during the trial period was 12 (11%) of the 147 patients in the nonoperative group. ORIF is a safe and reliable intervention with superior early functional outcomes and should be considered for patients who sustain this common injury. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence

Inclusive top-pair production phenomenology with TOPIXS

We discuss various aspects of inclusive top-quark pair production based on TOPIXS, a new, flexible program that computes the production cross section at the Tevatron and LHC at next-to-next-to-leading logarithmic accuracy in soft and Coulomb resummation, including bound-state effects and the complete next-to-next-to-leading order result in the q-qbar channel, which has recently become available. We present the calculation of the top-pair cross section in pp collisions at 8 TeV centre-of-mass energy, as well as the cross sections for hypothetical heavy quarks in extensions of the standard model. The dependence on the parton distribution input is studied. Further we investigate the impact of LHC top cross section measurements at sqrt(s)=7 TeV on global fits of the gluon distribution using the NNPDF re-weighting method.Comment: 27 pages, 5 figures; v2: corrected typos in Eqs. (2.8) and (6.2) and the text, added footnote on page 4, matches published versio

Predictions for Higgs production at the Tevatron and the associated uncertainties

We update the theoretical predictions for the production cross sections of the Standard Model Higgs boson at the Fermilab Tevatron collider, focusing on the two main search channels, the gluon-gluon fusion mechanism $gg \to H$ and the Higgs-strahlung processes $q \bar q \to VH$ with $V=W/Z$, including all relevant higher order QCD and electroweak corrections in perturbation theory. We then estimate the various uncertainties affecting these predictions: the scale uncertainties which are viewed as a measure of the unknown higher order effects, the uncertainties from the parton distribution functions and the related errors on the strong coupling constant, as well as the uncertainties due to the use of an effective theory approach in the determination of the radiative corrections in the $gg \to H$ process at next-to-next-to-leading order. We find that while the cross sections are well under control in the Higgs--strahlung processes, the theoretical uncertainties are rather large in the case of the gluon-gluon fusion channel, possibly shifting the central values of the next-to-next-to-leading order cross sections by more than $\approx 40$. These uncertainties are thus significantly larger than the $\approx 10$ error assumed by the CDF and D0 experiments in their recent analysis that has excluded the Higgs mass range $M_H=$162-166 GeV at the 95% confidence level. These exclusion limits should be, therefore, reconsidered in the light of these large theoretical uncertainties.Comment: 40 pages, 12 figures. A few typos are corrected and some updated numbers are provide

Appropriateness of treatment recommendations for PPI in hospital discharge letters

International audienc

Nutrient adequacy during weight loss interventions: a randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group

<p>Abstract</p> <p>Background</p> <p>Safe and effective weight control strategies are needed to stem the current obesity epidemic. The objective of this one-year study was to document and compare the macronutrient and micronutrient levels in the foods chosen by women following two different weight reduction interventions.</p> <p>Methods</p> <p>Ninety-six generally healthy overweight or obese women (ages 25–50 years; BMI 25–35 kg/m²) were randomized into a Traditional Food group (TFG) or a Meal Replacement Group (MRG) incorporating 1–2 meal replacement drinks or bars per day. Both groups had an energy-restricted goal of 5400 kJ/day. Dietary intake data was obtained using 3-Day Food records kept by the subjects at baseline, 6 months and one-year. For more uniform comparisons between groups, each diet intervention consisted of 18 small group sessions led by the same Registered Dietitian.</p> <p>Results</p> <p>Weight loss for the 73% (n = 70) completing this one-year study was not significantly different between the groups, but was significantly different (p ≤ .05) within each group with a mean (± standard deviation) weight loss of -6.1 ± 6.7 kg (TFG, n = 35) vs -5.0 ± 4.9 kg (MRG, n = 35). Both groups had macronutrient (Carbohydrate:Protein:Fat) ratios that were within the ranges recommended (50:19:31, TFG vs 55:16:29, MRG). Their reported reduced energy intake was similar (5729 ± 1424 kJ, TFG vs 5993 ± 2016 kJ, MRG). There was an improved dietary intake pattern in both groups as indicated by decreased intake of saturated fat (≤ 10%), cholesterol (<200 mg/day), and sodium (< 2400 mg/day), with increased total servings/day of fruits and vegetables (4.0 ± 2.2, TFG vs 4.6 ± 3.2, MRG). However, the TFG had a significantly lower dietary intake of several vitamins and minerals compared to the MRG and was at greater risk for inadequate intake.</p> <p>Conclusion</p> <p>In this one-year university-based intervention, both dietitian-led groups successfully lost weight while improving overall dietary adequacy. The group incorporating fortified meal replacements tended to have a more adequate essential nutrient intake compared to the group following a more traditional food group diet. This study supports the need to incorporate fortified foods and/or dietary supplements while following an energy-restricted diet for weight loss.</p

Reference values of bone stiffness index and C-terminal telopeptide in healthy European children

BACKGROUND/OBJECTIVE: Quantitative ultrasound measurements and bone metabolic markers can help to monitor bone health and to detect impaired skeletal development. Population-based reference values for children may serve as a basis for preventive measures to reduce the risk of osteoporosis and osteoporotic fractures in later life. This is the first paper providing age-, sex-and height-specific reference values for bone stiffness index (SI) and serum carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in healthy, apparently prepubertal children. SUBJECTS/METHODS: In the population-based IDEFICS baseline survey (2007-2008) and follow-up (2009-2010), 18 745 children from eight European countries were newly recruited. A total of 10 791 2-10.9-year-old and 1646 3-8.9-year-old healthy children provided data on SI of the right and left calcaneus and serum CTX, respectively. Furthermore, height and weight were measured. Percentile curves were calculated using the General Additive Model for Location Scale and Shape (GAMLSS) to model the distribution of SI and CTX depending on multiple covariates while accounting for dispersion, skewness, and the kurtosis of this distribution. RESULTS: SI was negatively associated with age and height in children aged 2-5 years, whereas a positive association was observed in children aged 6-10 years. The dip in SI occurred at older age for higher SI percentiles and was observed earlier in taller children than in smaller children. The CTX reference curves showed a linear-positive association with age and height. No major sex differences were observed for the SI and CTX reference values. CONCLUSION: These reference data lay the ground to evaluate bone growth and metabolism in prepubertal children in epidemiological and clinical settings. They may also inform clinical practice to monitor skeletal development and to assess adverse drug reactions during medical treatments

Constraints on the gluon PDF from top quark pair production at hadron colliders

Using the recently derived NNLO cross sections \cite{Czakon:2013goa}, we provide NNLO+NNLL theoretical predictions for top quark pair production based on all the available NNLO PDF sets, and compare them with the most precise LHC and Tevatron data. In this comparison we study in detail the PDF uncertainty and the scale, $m_t$ and $\alpha_s$ dependence of the theoretical predictions for each PDF set. Next, we observe that top quark pair production provides a powerful direct constraint on the gluon PDF at large $x$, and include Tevatron and LHC top pair data consistently into a global NNLO PDF fit. We then explore the phenomenological consequences of the reduced gluon PDF uncertainties, by showing how they can improve predictions for Beyond the Standard Model processes at the LHC. Finally, we update to full NNLO+NNLL the theoretical predictions for the ratio of top quark cross sections between different LHC center of mass energies, as well as the cross sections for hypothetical heavy fourth-generation quark production at the LHC.Comment: 29 pages, 13 figures, accepted for publication in JHE

Gaviscon® vs. omeprazole in symptomatic treatment of moderate gastroesophageal reflux. a direct comparative randomised trial

<p>Abstract</p> <p>Background</p> <p>Medical management of GERD mainly uses proton pump inhibitors. Alginates also have proven efficacy. The aim of this trial was to compare short-term efficacy of an alginate (Gaviscon^®, 4 × 10 mL/day) and omeprazole (20 mg/day) on GERD symptoms in general practice.</p> <p>Methods</p> <p>A 14-day multicentre randomised double-blind double-dummy non-inferiority trial compared Gaviscon^®(4 × 10 mL/day) and omeprazole (20 mg/day) in patients with 2-6 day heartburn episodes weekly without alarm signals. The primary outcome was the mean time to onset of the first 24-h heartburn-free period after initial dosing. Secondary outcomes were the proportion of patients without heartburn by D7, pain relief by D7, and reduction in pain intensity by D7 and D14.</p> <p>Results</p> <p>278 patients were recruited; 120 were included in the Gaviscon^®group and 121 in the omeprazole group for the per protocol non-inferiority analysis. The mean time to onset of the first 24-h heartburn-free period after initial dosing was 2.0 (± 2.2) days for Gaviscon^®and 2.0 (± 2.3) days for omeprazole (<it>p </it>= 0.93); mean intergroup difference was 0.01 ± 1.55 days (95% CI = -0.41 to 0.43): i.e., less than the lower limit of the 95% CI of -0.5 days predetermined to demonstrate non-inferiority. The mean number of heartburn-free days by D7 was significantly greater in the omeprazole group: 3.7 ± 2.3 days vs. 3.1 ± 2.1 (<it>p </it>= 0.02). On D7, overall quality of pain relief was slightly in favour of omeprazole (<it>p </it>= 0.049). There was no significant difference in the reduction in pain intensity between groups by D7 (<it>p = </it>0.11) or D14 (<it>p = </it>0.08). Tolerance and safety were good and comparable in both groups.</p> <p>Conclusion</p> <p>Gaviscon^®was non-inferior to omeprazole in achieving a 24-h heartburn-free period in moderate episodic heartburn, and is a relevant effective alternative treatment in moderate GERD in primary care.</p> <p>Trial registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN62203233">ISRCTN62203233</a>.</p

Defective CFTR Expression and Function Are Detectable in Blood Monocytes: Development of a New Blood Test for Cystic Fibrosis

BACKGROUND: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes. DESCRIPTION: Western blot, PCR, immunofluorescence and cell membrane depolarization analysis by single-cell fluorescence imaging, using the potential-sensitive DiSBAC(2)(3) probe were utilized. Expression of PKA phosphorylated, cell membrane-localized CFTR was detected in non-CF monocytes, being undetectable or present in truncated form in monocytes derived from CF patients presenting with nonsense mutations. CFTR agonist administration induced membrane depolarization in monocytes isolated from non-CF donors (31 subjects) and, to a lesser extent, obligate CFTR heterozygous carriers (HTZ: 15 subjects), but it failed in monocytes from CF patients (44 subjects). We propose an index, which values in CF patients are significantly (p<0.001) lower than in the other two groups. Nasal Potential Difference, measured in selected subjects had concordant results with monocytes assay (Kappa statistic 0.93, 95%CI: 0.80-1.00). RESULTS AND SIGNIFICANCE: CFTR is detectable and is functional in human monocytes. We also showed that CFTR-associated activity can be evaluated in 5 ml of peripheral blood and devise an index potentially applicable for diagnostic purposes and both basic and translational research: from drug development to evaluation of functional outcomes in clinical trials