Clinician-targeted interventions to influence antibiotic prescribing behaviour for acute respiratory infections in primary care: An overview of systematic reviews

Background: Antibiotic resistance is a worldwide health threat. Interventions that reduce antibiotic prescribing by clinicians are expected to reduce antibiotic resistance. Disparate interventions to change antibiotic prescribing behaviour for acute respiratory infections (ARIs) have been trialled and meta-analysed, but not yet synthesised in an overview. This overview synthesises evidence from systematic reviews, rather than individual trials. Objectives: To systematically review the existing evidence from systematic reviews on the effects of interventions aimed at influencing clinician antibiotic prescribing behaviour for ARIs in primary care. Methods: We searched the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Science Citation Index to June 2016. We also searched the reference lists of all included reviews. We ran a pre-publication search in May 2017 and placed additional studies in 'awaiting classification'. We included both Cochrane and non-Cochrane reviews of randomised controlled trials evaluating the effect of any clinician-focussed intervention on antibiotic prescribing behaviour in primary care. Two overview authors independently extracted data and assessed the methodological quality of included reviews using the ROBIS tool, with disagreements reached by consensus or by discussion with a third overview author. We used the GRADE system to assess the quality of evidence in included reviews. The results are presented as a narrative overview. Main results: We included eight reviews in this overview: five Cochrane Reviews (33 included trials) and three non-Cochrane reviews (11 included trials). Three reviews (all Cochrane Reviews) scored low risk across all the ROBIS domains in Phase 2 and low risk of bias overall. The remaining five reviews scored high risk on Domain 4 of Phase 2 because the 'Risk of bias' assessment had not been specifically considered and discussed in the review Results and Conclusions. The trials included in the reviews varied in both size and risk of bias. Interventions were compared to usual care. Moderate-quality evidence indicated that C-reactive protein (CRP) point-of-care testing (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.66 to 0.92, 3284 participants, 6 trials), shared decision making (odds ratio (OR) 0.44, 95% CI 0.26 to 0.75, 3274 participants, 3 trials; RR 0.64, 95% CI 0.49 to 0.84, 4623 participants, 2 trials; risk difference -18.44, 95% CI -27.24 to -9.65, 481,807 participants, 4 trials), and procalcitonin-guided management (adjusted OR 0.10, 95% CI 0.07 to 0.14, 1008 participants, 2 trials) probably reduce antibiotic prescribing in general practice. We found moderate-quality evidence that procalcitonin-guided management probably reduces antibiotic prescribing in emergency departments (adjusted OR 0.34, 95% CI 0.28 to 0.43, 2605 participants, 7 trials). The overall effect of these interventions was small (few achieving greater than 50% reduction in antibiotic prescribing, most about a quarter or less), but likely to be clinically important. Compared to usual care, shared decision making probably makes little or no difference to reconsultation for the same illness (RR 0.87, 95% CI 0.74 to 1.03, 1860 participants, 4 trials, moderate-quality evidence), and may make little or no difference to patient satisfaction (RR 0.86, 95% CI 0.57 to 1.30, 1110 participants, 2 trials, low-quality evidence). Similarly, CRP testing probably has little or no effect on patient satisfaction (RR 0.79, 95% CI 0.57 to 1.08, 689 participants, 2 trials, moderate-quality evidence) or reconsultation (RR 1.08, 95% CI 0.93 to 1.27, 5132 participants, 4 trials, moderate-quality evidence). Procalcitonin-guided management probably results in little or no difference in treatment failure in general practice compared to normal care (adjusted OR 0.95, 95% CI 0.73 to 1.24, 1008 participants, 2 trials, moderate-quality evidence), however it probably reduces treatment failure in the emergency department compared to usual care (adjusted OR 0.76, 95% CI 0.61 to 0.95, 2605 participants, 7 trials, moderate-quality evidence). The quality of evidence for interventions focused on clinician educational materials and decision support in reducing antibiotic prescribing in general practice was either low or very low (no pooled result reported) and trial results were highly heterogeneous, therefore we were unable draw conclusions about the effects of these interventions. The use of rapid viral diagnostics in emergency departments may have little or no effect on antibiotic prescribing (RR 0.86, 95% CI 0.61 to 1.22, 891 participants, 3 trials, low-quality evidence) and may result in little to no difference in reconsultation (RR 0.86, 95% CI 0.59 to 1.25, 200 participants, 1 trial, low-quality evidence). None of the trials in the included reviews reported on management costs for the treatment of an ARI or any associated complications. Authors' conclusions: We found evidence that CRP testing, shared decision making, and procalcitonin-guided management reduce antibiotic prescribing for patients with ARIs in primary care. These interventions may therefore reduce overall antibiotic consumption and consequently antibiotic resistance. There do not appear to be negative effects of these interventions on the outcomes of patient satisfaction and reconsultation, although there was limited measurement of these outcomes in the trials. This should be rectified in future trials. We could gather no information about the costs of management, and this along with the paucity of measurements meant that it was difficult to weigh the benefits and costs of implementing these interventions in practice. Most of this research was undertaken in high-income countries, and it may not generalise to other settings. The quality of evidence for the interventions of educational materials and tools for patients and clinicians was either low or very low, which prevented us from drawing any conclusions. High-quality trials are needed to further investigate these interventions. </p

Onset of main Phanerozoic marine radiation sparked by emerging Mid Ordovician icehouse

This is the final version. Available on open access from Springer Nature via the DOI in this recordThe Great Ordovician Biodiversification Event (GOBE) was the most rapid and sustained increase in marine Phanerozoic biodiversity. What generated this biotic response across Palaeozoic seascapes is a matter of debate; several intrinsic and extrinsic drivers have been suggested. One is Ordovician climate, which in recent years has undergone a paradigm shift from a text-book example of an extended greenhouse to an interval with transient cooling intervals - at least during the Late Ordovician. Here, we show the first unambiguous evidence for a sudden Mid Ordovician icehouse, comparable in magnitude to the Quaternary glaciations. We further demonstrate the initiation of this icehouse to coincide with the onset of the GOBE. This finding is based on both abiotic and biotic proxies obtained from the most comprehensive geochemical and palaeobiological dataset yet collected through this interval. We argue that the icehouse conditions increased latitudinal and bathymetrical temperature and oxygen gradients initiating an Early Palaeozoic Great Ocean Conveyor Belt. This fuelled the GOBE, as upwelling zones created new ecospace for the primary producers. A subsequent rise in δ(13)C ratios known as the Middle Darriwilian Isotopic Carbon Excursion (MDICE) may reflect a global response to increased bioproductivity encouraged by the onset of the GOBE.Our expeditions to Russia were mainly funded by the Carlsberg Foundation. C.M.Ø.R. and D.A.T.H. are particularly grateful to the Danish Council for Independent Research | Natural Sciences for their support of this specific project. C.M.Ø.R. further acknowledge support from the VILLUM Foundations Young Investigator Programme. A.L. was funded by the Royal Swedish Physiographic Society in Lund

A measurement of the 4He(g,n) reaction from 23 < Eg < 70 MeV

A comprehensive set of 4He(g,n) absolute cross-section measurements has been performed at MAX-lab in Lund, Sweden. Tagged photons from 23 < Eg < 70 MeV were directed toward a liquid 4He target, and neutrons were identified using pulse-shape discrimination and the Time-of-flight Technique in two liquid-scintillator detector arrays. Seven-point angular distributions have been measured for fourteen photon energies. The results have been subjected to complementary Transition-coefficient and Legendre-coefficient analyses. The results are also compared to experimental data measured at comparable photon energies as well as Recoil-Corrected Continuum Shell Model, Resonating Group Method, and Effective Interaction Hyperspherical-Harmonic Expansion calculations. For photon energies below 29 MeV, the angle-integrated data are significantly larger than the values recommended by Calarco, Berman, and Donnelly in 1983.Comment: 16 pages, 14 figures, some more revisions, submitted to Physical Review

Creation of a multiple-use recombinant inbred line population for the development of molecular markers in soft white winter wheat

Tese de doutoramento em Física (Pré-Bolonha), especialidade de Física Experimental, apresentada à Faculdade de Ciências e Tecnologia da Universidade de CoimbraPositron emission tomography based on resistive plate chambers (RPC-PET) has been proposed for both preclinical and clinical applications. We firstly present imaging results of needle-like and planar 22Na sources obtained with a prototype of a high-acceptance small-animal RPC-PET. The two detector modules utilized in this experiment had an effective front face of 6.4 x 6.4 cm^2 and consisted of 5 gas gaps and 6 glass electrodes with a total thickness of 5 mm. The data included lines of response (LORs) inclined up to 58º, and the depth of interaction (DOI) was accurately measured, demonstrating the parallax-free property inherent to RPC-PET. The maximum likelihood expectation-maximization (MLEM) reconstruction of the acquired data yielded an excellent and stable resolution of 0.4 mm full width at half maximum (FWHM). Concurrently, we pursued studies of a suggested whole-body single-bed RPC-PET. It has been shown by simulation that RPC-PET with an axial field-of-view (AFOV) of 2.4 m is feasible and yields an absolute sensitivity at least one order of magnitude superior to that of typical crystal-based PET scanners. In addition, RPC-PET offers an important time-of-flight (TOF) advantage and provides a potentially very-high spatial resolution at the detector level. In the second part of this work, a fully three-dimensional reconstruction algorithm capable of processing the very inclined LORs from large AFOV systems such as RPC-PET is demonstrated. It relies on the application of a TOF-based-kernel into the MLEM algorithm. With the 300 ps FWHM time resolution, already experimentally demonstrated, a rejection of 63% of the body-scattered events is obtained. We present reconstructed results from blind simulations corresponding to the anthropomorphic phantom, NCAT, with oncological lesions introduced into different locations within the human body. A comparison between 300 and 600 ps FWHM TOF reconstructed images is performed, with an increasing detectability being observed for a better TOF resolution. We finally compare issues related to image convergence speed. An alternative new approach, which consists in dividing the full-body data into nine different image regions that are reconstructed independently with graphical processing unit (GPU) assistance, provides a six times faster reconstruction compared with a GPU-based whole-body reconstruction. For a 300 ps FWHM RPC-PET scanner, this allows reaching a reconstructed image, that results from 1.6 x 10^10 annihilations within 7 minutes and upon injection of 2 mCi, just 4 minutes after the end of data acquisition. We conclude that RPC-PET is well oriented to compete with other commercial PET scanners in the global market.A tomografia por emissão de positrões baseada em detectores do tipo câmaras de placas resistivas (RPC-PET) foi proposta para aplicação em ensaios com pequenos animais e na prática clínica. Neste trabalho, apresentamos primeiramente resultados experimentais obtidos a partir de um protótipo RPC-PET de alta aceitação para pequenos animais. Foram obtidas imagens de fontes do radioisótopo 22Na, uma quase pontual e outra planar. Usámos dois módulos de detectores RPC com uma área activa de 6.4 x 6.4 cm^2 e uma espessura de 5 mm, constituída por 6 vidros empilhados e 5 espaços gasosos definidos entre eles. Os dados adquiridos incluíram linhas de coincidência (LORs) inclinadas até um ângulo de 58º, tornando essencial a medida precisa da profundidade de interacção. A identificação dos espaços gasosos onde ocorreram as avalanches permitiu demonstrar a ausência de erro de paralaxe nas medidas realizadas com o RPC-PET para pequenos animais. A partir da reconstrução dos dados processados com o algoritmo maximum likelihood expectation-maximization (MLEM), obtivemos uma resolução espacial com largura a meia altura (FWHM) de 0.4 mm, excelente e estável. Em paralelo, continuámos a estudar as potencialidades de um protótipo RPC-PET de corpo inteiro e cama única, orientado para pessoas. Já foi anteriormente demonstrado por simulação que um scanner RPC-PET com 2.4 m de campo de visão axial (AFOV) é viável e permitirá o aumento de sensibilidade de pelo menos uma ordem de grandeza em relação aos scanners PET com cristais. Duas outras virtudes do RPC-PET são a sua capacidade de medição do tempo de voo (TOF) dos fotões e a elevada resolução espacial ao nível do detector. Na segunda parte deste trabalho apresentamos um algoritmo de reconstrução, totalmente tridimensional, capaz de processar LORs muito inclinadas em sistemas com um AFOV longo, como é o caso do RPC-PET. Este algoritmo acrescenta um kernel ao algoritmo MLEM, baseado na informação de TOF. Com uma resolução temporal de 300 ps FWHM, já experimentalmente comprovada, é possível rejeitar 63% dos eventos dispersados no corpo humano. Exibimos imagens reconstruídas obtidas a partir de simulações do fantoma antropomórfico, NCAT, com lesões oncológicas situadas em diferentes locais do corpo humano. A comparação entre imagens conseguidas com resoluções temporais de 300 ps e 600 ps FWHM, permite observar uma detectabilidade acrescida associada à melhor resolução de TOF. Por último, são estudados os tempos de convergência da reconstrução. Um método inovador e alternativo, que consiste na divisão dos dados do corpo humano em nove regiões e na reconstrução independente desses dados com recurso a unidades de processamento gráfico (GPUs), permite uma reconstrução seis vezes mais rápida do que a reconstrução de corpo inteiro também com o auxílio de GPUs. A partir de dados de 1.6 x 10^10 aniquilações ocorridas durante uma aquisição de 7 minutos e para uma actividade injectada de 2 mCi, um scanner RPC-PET com uma resolução temporal de 300 ps FWHM permitirá obter uma imagem reconstruída apenas 4 minutos após o fim da aquisição. Podemos assim concluir que o RPC-PET está bem colocado para competir no mercado dos scanners PET comerciais

Diurnal changes in seawater carbonate chemistry speciation at increasing atmospheric carbon dioxide

Natural variability in seawater pH and associated carbonate chemistry parameters is in part driven by biological activities such as photosynthesis and respiration. The amplitude of these variations is expected to increase with increasing seawater carbon dioxide (CO2) concentrations in the future, because of simultaneously decreasing buffer capacity. Here, we address this experimentally during a diurnal cycle in a mesocosm CO2 perturbation study. We show that for about the same amount of dissolved inorganic carbon (DIC) utilized in net community production diel variability in proton (H+) and CO2 concentrations was almost three times higher at CO2 levels of about 675 ± 65 in comparison with levels of 310 ± 30 μatm. With a simple model, adequately simulating our measurements, we visualize carbonate chemistry variability expected for different oceanic regions with relatively low or high net community production. Since enhanced diurnal variability in CO2 and proton concentration may require stronger cellular regulation in phytoplankton to maintain respective gradients, the ability to adjust may differ between communities adapted to low in comparison with high natural variability

Monitoring of IVF birth outcomes in Finland: a data quality study

BACKGROUND: The collection of information on infertility treatments is important for the surveillance of potential health consequences and to monitor service provision. STUDY DESIGN: We compared the coverage and outcomes of IVF children reported in aggregated IVF statistics, the Medical Birth Register (subsequently: MBR) and research data based on reimbursements for IVF treatments in Finland in 1996–1998. RESULTS: The number of newborns were nearly equal in the three data sources (N = 4331–4384), but the linkage between the MBR and the research data revealed that almost 40% of the reported IVF children were not the same individuals. The perinatal outcomes in the three data sources were similar, excluding the much lower incidence of major congenital anomalies in the IVF statistics (157/10 000 newborns) compared to other sources (409–422/10 000 newborns). CONCLUSION: The differences in perinatal outcomes in the three data sets were in general minor, which suggests that the observed non-recording in the MBR is most likely unbiased

Recent developments of the Hierarchical Reference Theory of Fluids and its relation to the Renormalization Group

The Hierarchical Reference Theory (HRT) of fluids is a general framework for the description of phase transitions in microscopic models of classical and quantum statistical physics. The foundations of HRT are briefly reviewed in a self-consistent formulation which includes both the original sharp cut-off procedure and the smooth cut-off implementation, which has been recently investigated. The critical properties of HRT are summarized, together with the behavior of the theory at first order phase transitions. However, the emphasis of this presentation is on the close relationship between HRT and non perturbative renormalization group methods, as well as on recent generalizations of HRT to microscopic models of interest in soft matter and quantum many body physics.Comment: 17 pages, 5 figures. Review paper to appear in Molecular Physic

The factor structure and psychometric properties of the Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM) in Norwegian clinical and non-clinical samples

Background The Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM) is a 34-item instrument developed to monitor clinically significant change in out-patients. The CORE-OM covers four domains: well-being, problems/symptoms, functioning and risk, and sums up in two total scores: the mean of All items, and the mean of All non-risk items. The aim of this study was to examine the psychometric properties of the Norwegian translation of the CORE-OM. Methods A clinical sample of 527 out-patients from North Norwegian specialist psychiatric services, and a non-clinical sample of 464 persons were obtained. The non-clinical sample was a convenience sample consisting of friends and family of health personnel, and of students of medicine and clinical psychology. Students also reported psychological stress. Exploratory factor analysis (EFA) was employed in half the clinical sample. Confirmatory (CFA) factor analyses modelling the theoretical sub-domains were performed in the remaining half of the clinical sample. Internal consistency, means, and gender and age differences were studied by comparing the clinical and non-clinical samples. Stability, effect of language (Norwegian versus English), and of psychological stress was studied in the sub-sample of students. Finally, cut-off scores were calculated, and distributions of scores were compared between clinical and non-clinical samples, and between students reporting stress or no stress. Results The results indicate that the CORE-OM both measures general (g) psychological distress and sub-domains, of which risk of harm separates most clearly from the g factor. Internal consistency, stability and cut-off scores compared well with the original English version. No, or only negligible, language effects were found. Gender differences were only found for the well-being domain in the non-clinical sample and for the risk domain in the clinical sample. Current patient status explained differences between clinical and non-clinical samples, also when gender and age were controlled for. Students reporting psychological distress during last week scored significantly higher than students reporting no stress. These results further validate the recommended cut-off point of 1 between clinical and non-clinical populations. Conclusions The CORE-OM in Norwegian has psychometric properties at the same level as the English original, and could be recommended for general clinical use. A cut-off point of 1 is recommended for both genders

The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management.

Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk