Adverse drug reactions in hospitalized children in Germany are decreasing: results of a nine year cohort-based comparison

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SU(3) Gauge Family Symmetry and Prediction for the Lepton-Flavor Mixing and Neutrino Masses with Maximal Spontaneous CP Violation

A model for the lepton-flavor mixing and CP violation is proposed based on the SU$_F$(3) gauge family symmetry and the Majorana feature of neutrinos. A consistent prediction for the lepton-flavor mixing and masses is shown to be resulted from the appropriate vacuum structure of SU$_F$(3) gauge symmetry breaking. By choosing the SU$_F$(3) gauge fixing condition to possess a residual $Z_2$ symmetry and requiring the vacuum structure of spontaneous symmetry breaking to have approximate global U(1) family symmetries, we obtain naturally the tri-bimaximal mixing matrix and largely degenerate neutrino masses in the neutrino sector and the small mixing matrix in the charged-lepton sector. With a simple ansatz that all the smallness due to the approximate global U(1) family symmetries is characterized by a single Wolfenstein parameter $\lambda \simeq 0.22$, and the charged-lepton mixing matrix has a similar hierarchy structure as the CKM quark mixing matrix, we arrive at a consistent prediction for the MNSP lepton-flavor mixing with a maximal spontaneous CP violation: $\delta =\pi/2$, $\sin^2\theta_{13} \simeq 1/2\lambda^2 \simeq 0.024$ ($\sin^22\theta_{13} \simeq 0.094$), $\sin^2\theta_{12} \simeq 1/3{3}(1 - 2\lambda^3) \simeq 0.326$ and $\sin^2\theta_{23} \simeq 1/2(1 - \lambda^2) \simeq 0.48$, which agree well with the current experimental data. The CP-violating Jarlskog-invariant is obtained to be $J_{CP} \simeq 1/6\lambda(1-\lambda^2/2-\lambda^3)\sin\delta \simeq 0.035$, which is detectable in next generation neutrino experiment. The largely degenerate neutrino masses with the normal hierarchy and inverse hierarchy are discussed and found be at the order $m_{\nu_i} \simeq O(\lambda^2) \simeq 0.04\sim 0.06$ eV with a total mass $\sum m_{\nu} \sim 0.15$ eV, which is testable in future precision astrophysics and cosmology.Comment: 14 pages, it is explicitly shown that the smallness for both the charged-lepton mixing and neutrino masses with the standard seesaw mechanism can naturally be explained by the approximate global U(1) family symmetries of vacuum structure in the SU(3) gauge family model, references added, published version in PL

Standardised concentrations of morphine infusions for nurse/patient-controlled analgesia use in children

BACKGROUND: Standardizing concentrations of intravenous infusions enables pre-preparation and is effective in improving patient safety by avoiding large deviations from the prescribed concentration that can occur when infusions are made individually in wards and theatres. The use of pre-prepared morphine standardized concentration infusions for paediatric nurse/patient-controlled analgesia (N/PCA) has not been previously investigated. We aimed to establish, implement and evaluate standardized concentrations of morphine in pre-filled syringes (PFS) for use in paediatric N/PCA. METHODS: Concentrations of morphine in PFS for N/PCA were identified that accommodated dosage variation across a 1-50 kg weight range. The use of infusions in PFS was implemented and evaluated using mixed methods involved direct observation of healthcare professionals (HCPs), focus groups and failure mode and effects analysis, a HCP survey and medication incident reports analysis. RESULTS: Standardized concentrations, 3 mg, 10 mg and 50 mg morphine in 50 mL sodium chloride 0.9%, delivered prescribed continuous and bolus doses using programmable smart pumps with variable infusion rates. During the implementation, 175 morphine pre-prepared infusions were administered to 157 children (9.4 ± 5.1 years) in theatres and wards. Time taken to set up a N/PCA was 3.7 ± 1.7 min, a reduction of one third compared with the previous system. The number of incidents associated with N/PCA infusions was reduced by 41.2%, and preparation errors were eliminated. HCPs reported using morphine PFS was an easier and safer system. CONCLUSION: A system using pre-prepared standardized concentrations of morphine for paediatric N/PCA was implemented successfully and sustainably

Analgesic Drug Prescription Patterns On Five International Paediatric Wards

Aim: Analgesic and anti-inflammatory drugs are frequently prescribed in paediatrics. Prescribing and dosing patterns in hospitalised children are not well known. This study explores analgesic drug utilisation on five paediatric wards and discusses its findings in comparison with World Health Organization (WHO) guidelines. / Method: A sub-analysis of a prospective, multicentre, observational cohort study was undertaken. Prescription data of children aged up to ≤18 years were collected between October 2008 and December 2009 on paediatric general medical wards in five hospitals in Australia, Germany, the United Kingdom (UK), Hong Kong (HK) and Malaysia. Analgesic drug prescriptions were analysed for prescribing patterns in terms of dosing, frequency and route of administration. Dosing data were compared with local recommendations and WHO guidelines for children. / Results: In the study cohort, 56.8 % (726/1278) of paediatric patients received at least one analgesic drug prescription (1227 prescriptions). The median age of patients with analgesics was 2.2 years [interquartile range (IQR) 0.8–7.3], and the median number of prescriptions per patient was one (IQR 1–2). The most commonly prescribed drugs were oral paracetamol (45.9 %, 563/1227) and oral ibuprofen (19.9 %, 244/1227). Daily doses of paracetamol ranged from 30 mg/kg/day in Germany to 67–68 mg/kg/day in the UK and HK (p < 0.05). For ibuprofen, single doses ranged from 5–6 mg/kg in HK and the UK to 10 mg/kg in Germany and Australia (p < 0.001). Opioid use prevalence was statistically different between the centres and ranged from 0 to 17.6 % (p < 0.001). / Conclusion: This study provides a comprehensive overview of analgesic drug use of hospitalised children. Similar to primary care data, paracetamol is the most commonly used analgesic. As recommended by WHO guidelines, oral medication was favoured and opioids used in addition to paracetamol and ibuprofen. Overall drug utilisation was in line with local recommendations and WHO guidelines. Differences in use of paracetamol and ibuprofen among countries were seen, indicating that safety concerns are perceived differently. More large-scale safety studies are needed

GAPPS (Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies) a critical appraisal system for antimicrobial PKPD studies - development and application in pediatric antibiotic studies

Introduction: There are limited data on optimal dosing of antibiotics in different age groups for neonates and children. Clinicians usually consult pediatric formularies or online databases for dose selection, but these have variable recommendations, are usually based on expert opinion and are not graded based on the existing pharmacokinetic-pharmacodynamic (PKPD) studies. We describe here a potential new tool that could be used to grade the strength of evidence emanating from PKPD studies. Areas covered: A scoring system was developed (GAPPS tool) to quantify the strength of each PK assessment and rate the studies quality in already published articles. GAPPS was evaluated by applying it to pediatric PKPD studies of antibiotics from the 2019 Essential Medicines List for children (EMLC), identified through a search of PubMed. Expert opinion: Evidence for most antibiotic dose selection decisions was generally weak, coming from individual PK studies and lacked PKPD modeling and simulations. However, the quality of evidence appears to have improved over the last two decades. Incorporating a formal grading system, such as GAPPS, into formulary development will provide a transparent tool to support decision-making in clinical practice and guideline development, and guide PKPD authors on study designs most likely to influence guidelines

“There's very little that you can do other than refer them to the doctor if you think they've got postnatal depression”: Scoping the potential for perinatal mental health care by community pharmacists: Community pharmacists and perinatal mental health

Background: Twenty percent of women in the UK develop perinatal mental health (PMH) problems, which have widespread effects on maternal and child health. Community pharmacists are ideally placed to identify PMH problems and refer to other trained healthcare professionals. Objective: This study explored community pharmacists’ attitudes, current counselling practices, and barriers to providing mental health advice to perinatal women. Methods: A qualitative focus group study was performed virtually with community pharmacists (n = 11), working in urban settings across London. A topic guide was used to cover current counselling practice, barriers to and confidence in counselling women, and thoughts on potential pharmacist-led perinatal mental health services. The focus groups were recorded, transcribed, and analysed using thematic analysis. Results: Three themes were identified: Doing Mental Health Care; Willing, but Unable; and Introspection and reflection, which were related through a central organising concept of ‘Perinatal mental health care as a new frontier for community pharmacy’. It was found that while community pharmacists provide mental health advice to perinatal women and their partners, they lacked confidence, which was related to a lack of knowledge and inadequate training opportunities. Organisational barriers were identified including a lack of a formal referral pathway to existing mental health services and other trained healthcare professionals. Perceptions of opportunities and recommendations for service improvement and change were also garnered. Conclusion: This study demonstrates community pharmacists have a potential role within community mental healthcare in identification of PMH problems and providing appropriate advice and support. Upskilling community pharmacists in mental health should be considered to increase knowledge and confidence while formal referral pathways to other trained healthcare professionals and existing services should be established and made available to pharmacists

Effect of a single acupuncture treatment on surgical wound healing in dogs: a randomized, single blinded, controlled pilot study

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to investigate the effect of acupuncture on wound healing after soft tissue or orthopaedic surgery in dogs.</p> <p>Methods</p> <p>29 dogs were submitted to soft tissue and/or orthopaedic surgeries. Five dogs had two surgical wounds each, so there were totally 34 wounds in the study. All owners received instructions for post operative care as well as antibiotic and pain treatment. The dogs were randomly assigned to treatment or control groups. Treated dogs received one dry needle acupuncture treatment right after surgery and the control group received no such treatment. A veterinary surgeon that was blinded to the treatment, evaluated the wounds at three and seven days after surgery in regard to oedema (scale 0-3), scabs (yes/no), exudate (yes/no), hematoma (yes/no), dermatitis (yes/no), and aspect of the wound (dry/humid).</p> <p>Results</p> <p>There was no significant difference between the treatment and control groups in the variables evaluated three and seven days after surgery. However, oedema reduced significantly in the group treated with acupuncture at seven days compared to three days after surgery, possibly due the fact that there was more oedema in the treatment group at day three (although this difference was nor significant between groups).</p> <p>Conclusions</p> <p>The use of a single acupuncture treatment right after surgery in dogs did not appear to have any beneficial effects in surgical wound healing.</p

Global antibiotic dosing strategies in hospitalised children: Characterising variation and implications for harmonisation of international guidelines

Background Paediatric global antibiotic guidelines are inconsistent, most likely due to the limited pharmacokinetic and efficacy data in this population. We investigated factors underlying variation in antibiotic dosing using data from five global point prevalence surveys. Methods & findings Data from 3,367 doses of the 16 most frequent intravenous antibiotics administered to children 1 month–12 years across 23 countries were analysed. For each antibiotic, we identified standard doses given as either weight-based doses (in mg/kg/day) or fixed daily doses (in mg/day), and investigated the pattern of dosing using each strategy. Factors underlying observed variation in weight-based doses were investigated using linear mixed effects models. Weight-based dosing (in mg/kg/day) clustered around a small number of peaks, and all antibiotics had 1–3 standard weight-based doses used in 5%-48% of doses. Dosing strategy was more often weight-based than fixed daily dosing for all antibiotics apart from teicoplanin, which had approximately equal proportions of dosing attributable to each strategy. No strong consistent patterns emerged to explain the historical variation in actual weight-based doses used apart from higher dosing seen in central nervous system infections, and lower in skin and soft tissue infections compared to lower respiratory tract infections. Higher dosing was noted in the Americas compared to the European region. Conclusions Antibiotic dosing in children clusters around a small number of doses, although variation remains. There is a clear opportunity for the clinical, scientific and public health communities to consolidate behind a consistent set of global antibiotic dosing guidelines to harmonise current practice and prioritise future research

Discrete family symmetry, Higgs mediators and theta_{13}

We present a new (supersymmetric) framework for obtaining an excellent description of quark, charged lepton and neutrino masses and mixings from a Delta(6n^2) family symmetry with multiplet assignments consistent with an underlying SO(10) Grand Unification. It employs a Higgs mediator sector in place of the usual Froggatt-Nielsen messengers, with quark and lepton messengers, and provides significant improvements over existing models of this type having unsuppressed Yukawa couplings to the third generation and a simplified vacuum alignment mechanism. The neutrino mass differences are naturally less hierarchical than those of the quarks and charged leptons. Similarly the lepton mixing angles are much larger than those in the quark sector and have an approximate tri-bi-maximal (TB) mixing form for theta_{12} and theta_{23}. However the mixing angle theta_{13} is naturally much larger than in pure TB mixing and can be consistent with the value found in recent experiments. The magnitude of theta_{13} is correlated with a the predicted deviation of theta_{23} from bi-maximal mixing. The model has light familon fields that can significantly modify the associated SUSY phenomenology.Comment: v3: accepted in JHE