Limited effect of patient and disease characteristics on compliance with hospital antimicrobial guidelines

Objective: Physicians frequently deviate from guidelines that promote prudent use of antimicrobials. We explored to what extent patient and disease characteristics were associated with compliance with guideline recommendations for three common infections. Methods: In a 1-year prospective observational study, 1,125 antimicrobial prescriptions were analysed for compliance with university hospital guidelines. Results: Compliance varied significantly between and within the groups of infections studied. Compliance was much higher for lower respiratory tract infections (LRTIs; 79%) than for sepsis (53%) and urinary tract infections (UTIs; 40%). Only predisposing illnesses and active malignancies were associated with more compliant prescribing, whereas alcohol/ intravenous drug abuse and serum creatinine levels > 130 mu mol/l were associated with less compliant prescribing. Availability of culture results had no impact on compliance with guidelines for sepsis but was associated with more compliance in UTIs and less in LRTIs. Narrowing initial broad-spectrum antimicrobial therapy to cultured pathogens was seldom practised. Most noncompliant prescribing concerned a too broad spectrum of activity when compared with guideline-recommended therapy. Conclusion: Patient characteristics had only a limited impact on compliant prescribing for a variety of reasons. Physicians seemed to practise defensive prescribing behaviour, favouring treatment success in current patients over loss of effectiveness due to resistance in future patients

Economic-demographic interactions in long-run growth

Cliometrics confirms that Malthus’ model of the pre-industrial economy, in which increases in productivity raise population but higher population drives down wages, is a good description for much of demographic/economic history. A contributor to the Malthusian equilibrium was the Western European Marriage Pattern, the late age of female first marriage, which promised to retard the fall of living standards by restricting fertility. The demographic transition and the transition from Malthusian economies to modern economic growth attracted many Cliometric models surveyed here. A popular model component is that lower levels of mortality over many centuries increased the returns to, or preference for, human capital investment so that technical progress eventually accelerated. This initially boosted birth rates and population growth accelerated. Fertility decline was earliest and most striking in late eighteenth century France. By the 1830s the fall in French marital fertility is consistent with a response to the rising opportunity cost of children. The rest of Europe did not begin to follow until end of the nineteenth century. Interactions between the economy and migration have been modelled with Cliometric structures closely related to those of natural increase and the economy. Wages were driven up by emigration from Europe and reduced in the economies receiving immigrants

Observing interactions between children and adolescents and their parents: the effects of anxiety disorder and age

Parental behaviors, most notably overcontrol, lack of warmth and expressed anxiety, have been implicated in models of the development and maintenance of anxiety disorders in children and young people. Theories of normative development have proposed that different parental responses are required to support emotional development in childhood and adolescence, yet age has not typically been taken into account in studies of parenting and anxiety disorders. In order to identify whether associations between anxiety disorder status and parenting differ in children and adolescents, we compared observed behaviors of parents of children (7–10 years) and adolescents (13–16 years) with and without anxiety disorders (n=120), while they undertook a series of mildly anxiety-provoking tasks. Parents of adolescents showed significantly lower levels of expressed anxiety, intrusiveness and warm engagement than parents of children. Furthermore, offspring age moderated the association between anxiety disorder status and parenting behaviors. Specifically, parents of adolescents with anxiety disorders showed higher intrusiveness and lower warm engagement than parents of non-anxious adolescents. A similar relationship between these parenting behaviors and anxiety disorder status was not observed among parents of children. The findings suggest that theoretical accounts of the role of parental behaviors in anxiety disorders in children and adolescents should distinguish between these different developmental periods. Further experimental research to establish causality, however, would be required before committing additional resources to targeting parenting factors within treatment

Deconstructing the outsider puzzle: The legitimation journey of novelty

The proposition that outsiders often are crucial carriers of novelty into an established institutional field has received wide empirical support. But an equally compelling proposition points to the following puzzle: the very same conditions that enhance outsiders' ability to make novel contributions also hinder their ability to carry them out. We seek to address this puzzle by examining the contextual circumstances that affect the legitimation of novelty originating from a noncertified outsider that challenged the status quo in an established institutional field. Our research case material is John Harrison's introduction of a new mechanical method for measuring longitude at sea-the marine chronometer- which challenged the dominant astronomical approach.We find that whether an outsider's new offer gains or is denied legitimacy is influenced by (1) the outsider's agency to further a new offer, (2) the existence of multiple audiences with different dispositions toward this offer, and (3) the occurrence of an exogenous jolt that helps create a more receptive social space. We organize these insights into a multilevel conceptual framework that builds on previouswork but attributes a more decisive role to the interplay between endogenous and exogenous variables in shaping a field's shifting receptiveness to novelty. The framework exposes the interdependencies between the micro-, meso-, and macro-level processes that jointly affect an outsider's efforts to introduce novelty into an existing field

Teasing apart the heterogeneity of autism: Same behavior, different brains in toddlers with fragile X syndrome and autism

To examine brain volumes in substructures associated with the behavioral features of children with FXS compared to children with idiopathic autism and controls. A cross-sectional study of brain substructures was conducted at the first time-point as part of an ongoing longitudinal MRI study of brain development in FXS. The study included 52 boys between 18–42 months of age with FXS and 118 comparison children (boys with autism-non FXS, developmental-delay, and typical development). Children with FXS and autistic disorder had substantially enlarged caudate volume and smaller amygdala volume; whereas those children with autistic disorder without FXS (i.e., idiopathic autism) had only modest enlargement in their caudate nucleus volumes but more robust enlargement of their amygdala volumes. Although we observed this double dissociation among selected brain volumes, no significant differences in severity of autistic behavior between these groups were observed. This study offers a unique examination of early brain development in two disorders, FXS and idiopathic autism, with overlapping behavioral features, but two distinct patterns of brain morphology. We observed that despite almost a third of our FXS sample meeting criteria for autism, the profile of brain volume differences for children with FXS and autism differed from those with idiopathic autism. These findings underscore the importance of addressing heterogeneity in studies of autistic behavior

Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants

Economic-demographic interactions in the European long run growth

Cliometrics confirms that Malthus’s model of the preindustrial economy is a good description for much of demographic-economic history; increases in productivity raise population, but higher population drives down wages. A contributor to the Malthusian equilibrium was the Western European marriage pattern, the late age of female first marriage, which promised to retard the fall of living standards by restricting fertility. The demographic transition and the transition from Malthusian economies to modern economic growth attracted many cliometric models surveyed here. A popular model component is that lower levels of mortality over many centuries increased the returns to, or preference for, human capital investment so that technical progress eventually accelerated. This initially boosted birth rates and population growth accelerated. Fertility decline was earliest and most striking in late-eighteenth-century France. By the 1830s, the fall in French marital fertility is consistent with a response to the rising opportunity cost of children. The rest of Europe did not begin to follow until near the end of the nineteenth century. Interactions between the economy and migration, mainly focused on the long nineteenth century, have been modeled with cliometric structures closely related to those of natural increase and the economy. Wages were driven up by emigration from Europe and reduced in the economies receiving immigrants

Explaining UK wage inequality in the past globalisation period, 1880–1913.

The current era of globalisation has witnessed a rising premium paid to skilled workers resulting in increasing wage inequality in most OECD countries. This pattern differs from that observed during the past globalisation period (1880–1913), in which wage inequality decreased in most of the Old World countries. The present debate over wage inequality focuses on the implications of globalisation, technological change, the role of labour market institutions and education. Similar factors were at work in the past globalisation process. In order to disentangle the main factors that contribute to wage inequality, we calibrate a general equilibrium model for the UK economy in the past globalisation period. The results show that a trade shock and a skilled-biased technology shock increased wage inequality. However, education and emigration had a more significant impact and led to a decrease in wage inequality.Wage inequality, Globalisation, Technological change, General equilibrium