Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies

Antifúngic; Candidèmia; DesescaladaAntifúngico; Candidemia; DesescaladaAntifungal; Candidemia; De-escalationBackground There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. Methods This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007–2016). The impact of ED and factors associated with mortality were assessed. Results Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48–10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94–9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14–5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48–10.61), and prior surgery (OR, 0.29; 95% CI, 0.08–0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16–1.53). Conclusions Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.This research forms part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Program. This study has been cofunded by the European Regional Development Fund. E. M.-G. (PI18/01061), P. P.-A. (“Rio Hortega” contract CM18/00132), M. F.-R. (“Miguel Servet” contract CP18/00073), and C. G.-V. (FIS PI18/01061) have received research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders

Targeted Intervention to Improve Monitoring of Antipsychotic-Induced Weight Gain and Metabolic Disturbance in First Episode Psychosis

OBJECTIVE: International guidelines recommend monitoring for weight gain and metabolic disturbance in patients prescribed second generation antipsychotics. We aimed to investigate whether a targeted intervention could improve levels of monitoring in a first episode psychosis clinic. METHOD: A pre-intervention audit of both metabolic screening rates and specific monitoring of weight and metabolic indices following the initiation of antipsychotic medication was performed in our first episode psychosis clinic. This was repeated 18 months later, following an intervention that included a number of targeted improvement strategies based on an analysis of barriers and enablers to performing monitoring within the clinic. The intervention included provision of monitoring equipment, interactive educational events, reminders and prompts and embedding processes for monitoring within team structure. RESULTS: There were significant improvements in both the screening of metabolic indices and the monitoring of indices following initiation of antipsychotic medications. There were also improvements in the number of active interventions offered to clients by clinicians. However, the level of guideline concordant monitoring remains low within our service. CONCLUSIONS: A comprehensive programme of implementation strategies can improve both screening and monitoring of the metabolic side-effects of antipsychotic medications. Further focused strategies are necessary to continue to improve monitoring to guideline concordant levels

Targeted intervention to improve monitoring of antipsychotic-induced weight gain and metabolic disturbance in first episode psychosis

Objective: International guidelines recommend monitoring for weight gain and metabolic disturbance in patients prescribed second generation antipsychotics. We aimed to investigate whether a targeted intervention could improve levels of monitoring in a first episode psychosis clinic. Method: A pre-intervention audit of both metabolic screening rates and specific monitoring of weight and metabolic indices following the initiation of antipsychotic medication was performed in our first episode psychosis clinic. This was repeated 18 months later, following an intervention that included a number of targeted improvement strategies based on an analysis of barriers and enablers to performing monitoring within the clinic. The intervention included provision of monitoring equipment, interactive educational events, reminders and prompts and embedding processes for monitoring within team structure. Results: There were significant improvements in both the screening of metabolic indices and the monitoring of indices following initiation of antipsychotic medications. There were also improvements in the number of active interventions offered to clients by clinicians. However, the level of guideline concordant monitoring remains low within our service. Conclusions: A comprehensive programme of implementation strategies can improve both screening and monitoring of the metabolic side-effects of antipsychotic medications. Further focused strategies are necessary to continue to improve monitoring to guideline concordant levels

Correction to: Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

[This corrects the article DOI: 10.1093/ofid/ofab250.]

Understanding the social construction of the democratic deficit in CSDP: a Foucauldian approach

Drawing upon the Foucauldian approach of governmentality, this article argues that the democratic deficit of the EU's Common Security and Defence Policy (CSDP) is the outcome of how governmental power flows in CSDP governance and more precisely within the governance practices of the policy. To support this argument, the narrative explores the secrecy/confidentiality, informality and normalisation of the exercise of governmental power in a concrete example of CSDP governance, the recent pooling and sharing initiative. The example shows that the official makers of CSDP pursue efficiency of governance to the detriment of the democratic quality of the policy, and this is related with the productive and expansive rationality of governmental power flowing in and between the EU institutions. Despite the fact that governmentality usually links to structural explanations, allowing limited space for the role of agency in politics, the article concludes with reflections on how the political agency of the governing EU political subjects contributes to the social construction of the democratic deficit of CSDP

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia : A Post Hoc Analysis of Three Cohort Studies

There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies. Early de-escalation (within 5 days of candidemia onset) was proven to be safe in episodes caused by fluconazole-susceptible strains with a controlled source of candidemia and hemodynamic stability. These results might help strengthen antifungal stewardship strategies