Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks

Perioperative events influence cancer recurrence risk after surgery.

Surgery is a mainstay treatment for patients with solid tumours. However, despite surgical resection with a curative intent and numerous advances in the effectiveness of (neo)adjuvant therapies, metastatic disease remains common and carries a high risk of mortality. The biological perturbations that accompany the surgical stress response and the pharmacological effects of anaesthetic drugs, paradoxically, might also promote disease recurrence or the progression of metastatic disease. When cancer cells persist after surgery, either locally or at undiagnosed distant sites, neuroendocrine, immune, and metabolic pathways activated in response to surgery and/or anaesthesia might promote their survival and proliferation. A consequence of this effect is that minimal residual disease might then escape equilibrium and progress to metastatic disease. Herein, we discuss the most promising proposals for the refinement of perioperative care that might address these challenges. We outline the rationale and early evidence for the adaptation of anaesthetic techniques and the strategic use of anti-adrenergic, anti-inflammatory, and/or antithrombotic therapies. Many of these strategies are currently under evaluation in large-cohort trials and hold promise as affordable, readily available interventions that will improve the postoperative recurrence-free survival of patients with cancer

Measurement of charged particle spectra in minimum-bias events from proton-proton collisions at root s =13 TeV

Pseudorapidity, transverse momentum, and multiplicity distributions are measured in the pseudorapidity range vertical bar eta vertical bar 0.5 GeV in proton-proton collisions at a center-of-mass energy of root s = 13 TeV. Measurements are presented in three different event categories. The most inclusive of the categories corresponds to an inelastic pp data set, while the other two categories are exclusive subsets of the inelastic sample that are either enhanced or depleted in single diffractive dissociation events. The measurements are compared to predictions from Monte Carlo event generators used to describe high-energy hadronic interactions in collider and cosmic-ray physics.Peer reviewe

Call to restrict neonicotinoids

On 28 April 2018 the European Parliament voted for a complete and permanent ban on all outdoor uses of the three most commonly used neonicotinoid pesticides. With the partial exception of the state of Ontario, Canada, governments elsewhere have failed to take action. Below is a letter, signed by 232 scientists from around the world, urgently calling for global action by policy makers to address this issue

Search for resonant pair production of Higgs bosons decaying to bottom quark-antiquark pairs in proton-proton collisions at 13 TeV

A search for a narrow-width resonance decaying into two Higgs bosons, each decaying into a bottom quark-antiquark pair, is presented. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 35.9 fb$^{-1}$ at $\sqrt{s}=$ 13 TeV recorded by the CMS detector at the LHC. No evidence for such a signal is observed. Upper limits are set on the product of the production cross section for the resonance and the branching fraction for the selected decay mode in the resonance mass range from 260 to 1200 GeV

Search for supersymmetric partners of electrons and muons in proton–proton collisions at s=13TeV

A search for direct production of the supersymmetric (SUSY) partners of electrons or muons is presented in final states with two opposite-charge, same-flavour leptons (electrons and muons), no jets, and large missing transverse momentum. The data sample corresponds to an integrated luminosity of 35.9 fb−1 of proton–proton collisions at s=13TeV, collected with the CMS detector at the LHC in 2016. The search uses the MT2 variable, which generalises the transverse mass for systems with two invisible objects and provides a discrimination against standard model backgrounds containing W bosons. The observed yields are consistent with the expectations from the standard model. The search is interpreted in the context of simplified SUSY models and probes slepton masses up to approximately 290, 400, and 450 GeV, assuming right-handed only, left-handed only, and both right- and left-handed sleptons (mass degenerate selectrons and smuons), and a massless lightest supersymmetric particle. Limits are also set on selectrons and smuons separately. These limits show an improvement on the existing limits of approximately 150 GeV.0info:eu-repo/semantics/publishe

Evidence for X(3872) in Pb-Pb Collisions and Studies of its Prompt Production at sNN\sqrt {s_{NN}}=5.02 TeV

The first evidence for X(3872) production in relativistic heavy ion collisions is reported. The $X(3872)$ production is studied in lead-lead (Pb-Pb) collisions at a center-of-mass energy of $\sqrt {s_{NN}}$ 5.02 TeV per nucleon pair, using the decay chain $X(3872) → J/ψ π^+ π^− → μ^+ μ^- π^+ π^−$. The data were recorded with the CMS detector in 2018 and correspond to an integrated luminosity of 1.7 nb$^{-1}$. The measurement is performed in the rapidity and transverse momentum ranges $|y|<$ 1.6 and 15$< p_T <$ 50 GeV/c. The significance of the inclusive $X(3872)$ signal is 4.2 standard deviations. The prompt $X(3872)$ to $ψ2S$ yield ratio is found to be $ρ^{Pb-Pb} =1.08±0.49(stat)±0.52(syst)$, to be compared with typical values of 0.1 for pp collisions. This result provides a unique experimental input to theoretical models of the $X(3872)$ production mechanism, and of the nature of this exotic state