Content and Mechanism of Action of National Antimicrobial Stewardship Interventions on Management of Respiratory Tract Infections in Primary and Community Care

A major modifiable factor contributing to antimicrobial resistance (AMR) is inappropriate use and overuse of antimicrobials, such as antibiotics. This study aimed to describe the content and mechanism of action of antimicrobial stewardship (AMS) interventions to improve appropriate antibiotic use for respiratory tract infections (RTI) in primary and community care. This study also aimed to describe who these interventions were aimed at and the specific behaviors targeted for change. Evidence-based guidelines, peer-review publications, and infection experts were consulted to identify behaviors relevant to AMS for RTI in primary care and interventions to target these behaviors. Behavior change tools were used to describe the content of interventions. Theoretical frameworks were used to describe mechanisms of action. A total of 32 behaviors targeting six different groups were identified (patients; prescribers; community pharmacists; providers; commissioners; providers and commissioners). Thirty-nine interventions targeting the behaviors were identified (patients = 15, prescribers = 22, community pharmacy staff = 8, providers = 18, and commissioners = 18). Interventions targeted a mean of 5.8 behaviors (range 1–27). Influences on behavior most frequently targeted by interventions were psychological capability (knowledge and skills); reflective motivation (beliefs about consequences, intentions, social/professional role and identity); and physical opportunity (environmental context and resources). Interventions were most commonly characterized as achieving change by training, enabling, or educating and were delivered mainly through guidelines, service provision, and communications & marketing. Interventions included a mean of four Behavior Change Techniques (BCTs) (range 1–14). We identified little intervention content targeting automatic motivation and social opportunity influences on behavior. The majority of interventions focussed on education and training, which target knowledge and skills though the provision of instructions on how to perform a behavior and information about health consequences. Interventions could be refined with the inclusion of relevant BCTs, such as goal-setting and action planning (identified in only a few interventions), to translate instruction on how to perform a behavior into action. This study provides a platform to refine content and plan evaluation of antimicrobial stewardship interventions

Ovarian ageing: the role of mitochondria in oocytes and follicles

BACKGROUND: There is a great inter-individual variability of ovarian ageing, and almost 20% of patients consulting for infertility show signs of premature ovarian ageing. This feature, taken together with delayed childbearing in modern society, leads to the emergence of age-related ovarian dysfunction concomitantly with the desire for pregnancy. Assisted reproductive technology is frequently inefficacious in cases of ovarian ageing, thus raising the economic, medical and societal costs of the procedures. OBJECTIVE AND RATIONAL: Ovarian ageing is characterized by quantitative and qualitative alteration of the ovarian oocyte reserve. Mitochondria play a central role in follicular atresia and could be the main target of the ooplasmic factors determining oocyte quality adversely affected by ageing. Indeed, the oocyte is the richest cell of the body in mitochondria and depends largely on these organelles to acquire competence for fertilization and early embryonic development. Moreover, the oocyte ensures the uniparental transmission and stability of the mitochondrial genome across the generations. This review focuses on the role played by mitochondria in ovarian ageing and on the possible consequences over the generations. SEARCH METHODS: PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews concerning mitochondria and ovarian ageing, in animal and human species. Searches were performed using keywords belonging to three groups: \u27mitochondria\u27 or \u27mitochondrial DNA\u27; \u27ovarian reserve\u27, \u27oocyte\u27, \u27ovary\u27 or \u27cumulus cells\u27; and \u27ageing\u27 or \u27ovarian ageing\u27. These keywords were combined with other search phrases relevant to the topic. References from these articles were used to obtain additional articles. OUTCOMES: There is a close relationship, in mammalian models and humans, between mitochondria and the decline of oocyte quality with ageing. Qualitatively, ageing-related mitochondrial (mt) DNA instability, which leads to the accumulation of mtDNA mutations in the oocyte, plays a key role in the deterioration of oocyte quality in terms of competence and of the risk of transmitting mitochondrial abnormalities to the offspring. In contrast, some mtDNA haplogroups are protective against the decline of ovarian reserve. Quantitatively, mitochondrial biogenesis is crucial during oogenesis for constituting a mitochondrial pool sufficiently large to allow normal early embryonic development and to avoid the untimely activation of mitochondrial biogenesis. Ovarian ageing also seriously affects the dynamic nature of mitochondrial biogenesis in the surrounding granulosa cells that may provide interesting alternative biomarkers of oocyte quality. WIDER IMPLICATIONS: A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future

Relationship between diminished ovarian reserve and mitochondrial biogenesis in cumulus cells

STUDY QUESTION: What part do mitochondria play in cases of diminished ovarian reserve (DOR)? SUMMARY ANSWER: Mitochondrial biogenesis in cumulus cells may be linked with impaired oocyte competence in patients with DOR. WHAT IS KNOWN ALREADY: DOR, one of the causes of infertility even in young women, is characterized by the depletion of the ovarian pool associated with a decline in oocyte competence. Mitochondria, which play a role in oocyte quality, could be involved in the pathogenesis of DOR. The study of cumulus cells offers an interesting non-invasive approach for evaluating oocyte quality and the metabolic processes on which it depends. If mitochondrial dysfunction is involved in DOR, it is likely to have an impact on the functioning of cumulus cells. STUDY DESIGN, SIZE, DURATION: This is an observational study of 74 immature oocyte-cumulus complexes retrieved from 47 women undergoing in vitro fertilization with intracytoplasmic sperm injection at the University Hospital of Angers, France, from March 2013 to March 2014. The women were divided into two groups: one group included 26 women with DOR, and the other, which included 21 women with a normal ovarian reserve (NOR), served as a control group. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The oocyte mitochondrial content and the average mitochondrial content of the cumulus cells were assessed by mitochondrial (mt)DNA quantification using a quantitative real-time PCR technique. Microfluidic-based quantitative RT-PCR assays were used to quantify the expression of 13 genes involved in mitochondrial functions such as apoptosis and antioxidant activity or in mitochondrial biogenesis. We used orthogonal partial least-squares discriminant analysis (OPLS-DA) to distinguish between the DOR group and the NOR group of patients, and an OPLS model to predict the value of the oocyte mtDNA content that could be used as a critical marker of oocyte quality. MAIN RESULTS AND THE ROLE OF CHANCE: The OPLS-DA model showed a good predictive capability (Q2 = 0.543). Using the variable importance in projection (VIP) metric we found three mitochondrial variables distinguishing the DOR group from the NOR group of patients, i.e. the oocyte mtDNA content (VIP = 0.92), the cumulus cell mtDNA content (VIP = 0.95) and the expression in cumulus cells of peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC-1A) (VIP = 1.10), all of which were lower in the DOR group than in the NOR group of patients. The OPLS model was able to satisfactorily predict the oocyte mtDNA content in only the NOR group of patients (Q2 = 0.506). We found four new variables positively linked to the oocyte mitochondrial mass, i.e. the cumulus cell mtDNA content (VIP = 1.19), and the expression in cumulus cells of three factors of mitochondrial biogenesis: polymerase gamma (POLG) (VIP = 2.13), optic atrophy 1 (OPA1) (VIP = 1.89) and the transcription factor associated with mitochondria (TFAM) (VIP = 1.32). LIMITATIONS, REASONS OF CAUTION: This is a descriptive study. Because of ethical concerns in human clinical practice, this study has been performed only on immature oocytes and corresponding cumulus cells, which are usually discarded during in vitro fertilization procedures. WIDER IMPLICATIONS OF THE FINDINGS: Cumulus cells may govern mitochondrial biogenesis, creating an adequate oocyte mitochondrial pool to promote embryonic development. The alteration of this process in patients with DOR may account for the impairment of oocyte quality. This suggests that some mitochondrial characteristics of cumulus cells may serve as indicators of oocyte competence and that oocyte quality may be improved by products enhancing mitochondrial biogenesis. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a grant from the University Hospital of Angers, France: \u27Appel d\u27offre interne à la recherche 2014\u27. TRIAL REGISTRATION NUMBER: N/A

A versatile method for simulating pp -> ppe+e- and dp -> pne+e-p_spec reactions

We have developed a versatile software package for the simulation of di-electron production in $pp$ and $dp$ collisions at SIS energies. Particular attention has been paid to incorporate different descriptions of the Dalitz decay $\Delta \to N e^+e^-$ via a common interface. In addition, suitable parameterizations for the virtual bremsstrahlung process $NN \to NN e^+e^-$ based on one-boson exchange models have been implemented. Such simulation tools with high flexibility of the framework are important for the interpretation of the di-electron data taken with the HADES spectrometer and the design of forthcoming experiments

Study of the quasi-free np→npπ+π−np \to np \pi^+\pi^- reaction with a deuterium beam at 1.25 GeV/nucleon

The tagged quasi-free $np \to np\pi^+\pi^-$ reaction has been studied experimentally with the High Acceptance Di-Electron Spectrometer (HADES) at GSI at a deuteron incident beam energy of 1.25 GeV/nucleon ($\sqrt s \sim$ 2.42 GeV/c for the quasi-free collision). For the first time, differential distributions for $\pi^{+}\pi^{-}$ production in $np$ collisions have been collected in the region corresponding to the large transverse momenta of the secondary particles. The invariant mass and angular distributions for the $np\rightarrow np\pi^{+}\pi^{-}$ reaction are compared with different models. This comparison confirms the dominance of the $t$-channel with $\Delta\Delta$ contribution. It also validates the changes previously introduced in the Valencia model to describe two-pion production data in other isospin channels, although some deviations are observed, especially for the $\pi^{+}\pi^{-}$ invariant mass spectrum. The extracted total cross section is also in much better agreement with this model. Our new measurement puts useful constraints for the existence of the conjectured dibaryon resonance at mass M$\sim$ 2.38 GeV and with width $\Gamma\sim$ 70 MeV

Deep sub-threshold Ξ−\Xi^- production in Ar+KCl reactions at 1.76A GeV

We report first results on a deep sub-threshold production of the doubly strange hyperon $\Xi^-$ in a heavy-ion reaction. At a beam energy of 1.76A GeV the reaction Ar+KCl was studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18/GSI. A high-statistics and high-purity $\Lambda$ sample was collected, allowing for the investigation of the decay channel $\Xi^- \to \Lambda \pi^-$. The deduced $\Xi^-/(\Lambda+\Sigma^0)$ production ratio of $(5.6 \pm 1.2 ^{+1.8}_{-1.7})\cdot 10^{-3}$ is significantly larger than available model predictions.Comment: 4 pages, including 4 figure

In-Medium Effects on K0 Mesons in Relativistic Heavy-Ion Collisions

We present the transverse momentum spectra and rapidity distributions of $\pi^{-}$ and K$^0_S$ in Ar+KCl reactions at a beam kinetic energy of 1.756 A GeV measured with the spectrometer HADES. The reconstructed K$^0_S$ sample is characterized by good event statistics for a wide range in momentum and rapidity. We compare the experimental $\pi^{-}$ and K$^0_S$ distributions to predictions by the IQMD model. The model calculations show that K$^0_S$ at low tranverse momenta constitute a particularly well suited tool to investigate the kaon in-medium potential. Our K$^0_S$ data suggest a strong repulsive in-medium K$^0$ potential of about 40 MeV strength.Comment: 10 pages, 10 figures, accepted by Phys. Rev.

Inclusive dielectron production in proton-proton collisions at 2.2 GeV beam energy

Data on inclusive dielectron production are presented for the reaction p+p at 2.2 GeV measured with the High Acceptance DiElectron Spectrometer (HADES). Our results supplement data obtained earlier in this bombarding energy regime by DLS and HADES. The comparison with the 2.09 GeV DLS data is discussed. The reconstructed e+e- distributions are confronted with simulated pair cocktails, revealing an excess yield at invariant masses around 0.5 GeV/c2. Inclusive cross sections of neutral pion and eta production are obtained

Production of Sigma{\pm}pi?pK+ in p+p reactions at 3.5 GeV beam energy

We study the production of Sigma^+-pi^+-pK^+ particle quartets in p+p reactions at 3.5 GeV kinetic beam energy. The data were taken with the HADES experiment at GSI. This report evaluates the contribution of resonances like Lambda(1405$, Sigma(1385)^0, Lambda(1520), Delta(1232), N^* and K^*0 to the Sigma^+- pi^-+ p K+ final state. The resulting simulation model is compared to the experimental data in several angular distributions and it shows itself as suitable to evaluate the acceptance corrections properly.Comment: 15 pages, 5 figure