Amphotericin B with and without itraconazole for invasive aspergillosis: A three-year retrospective study

AbstractBackground: Treatment of invasive aspergillosis is frequently unsuccessful, so innovations in therapy are needed. Clinical studies demonstrate that itraconazole may be an effective alternative to amphotericin B. Itraconazole also has been combined with amphotericin B in animal models of aspergillosis, but this regimen produced antagonistic effects.Objectives: To determine the role of itraconazole in the adjunctive treatment of invasive aspergillosis.Methods: A review was conducted of all patients with definite or probable aspergillosis from January 1995 to December 1997 who were treated with conventional amphotericin B alone or in combination with itraconazole.Results: Of 21 patients, 10 received amphotericin B and 11 received the combination. The two groups of patients were comparable clinically at baseline (including similar mean APACHE III scores). Both groups received similar doses and days of amphotericin B treatment. Of the patients who received combination therapy, nine (82%) were cured or improved, and of those who received only amphotericin B, five (50%) were cured or improved.Conclusions: This study demonstrates that itraconazole and amphotericin B given together are not clinically antagonistic and that the promise of combination therapy for aspergillosis should be evaluated further in a randomized clinical trial

Development and Initial Findings of an Implementation Process Measure for Child Welfare System Change

This article describes a new measure designed to examine the process of implementation of child welfare systems change. The measure was developed to document the status of the interventions and strategies that are being implemented and the drivers that are being installed to achieve sustainable changes in systems. The measure was used in a Children’s Bureau-supported national effort to assess the ongoing implementation of 24 systems-change projects in child welfare jurisdictions across the country. The article describes the process for measure development, method of administration and data collection, and quantitative and qualitative findings

Temporal dynamics of hot desert microbial communities reveal structural and functional responses to water input

8 páginas, 4 figuras. -- The first publication is available at https://www.nature.comThe temporal dynamics of desert soil microbial communities are poorly understood. Given the implications for ecosystem functioning under a global change scenario, a better understanding of desert microbial community stability is crucial. Here, we sampled soils in the central Namib Desert on sixteen different occasions over a one-year period. Using Illumina-based amplicon sequencing of the 16S rRNA gene, we found that α-diversity (richness) was more variable at a given sampling date (spatial variability) than over the course of one year (temporal variability). Community composition remained essentially unchanged across the first 10 months, indicating that spatial sampling might be more important than temporal sampling when assessing β-diversity patterns in desert soils. However, a major shift in microbial community composition was found following a single precipitation event. This shift in composition was associated with a rapid increase in CO2 respiration and productivity, supporting the view that desert soil microbial communities respond rapidly to re-wetting and that this response may be the result of both taxon-specific selection and changes in the availability or accessibility of organic substrates. Recovery to quasi pre-disturbance community composition was achieved within one month after rainfall.We gratefully acknowledge financial support from the National Research Foundation of South Africa (grant no.81779 and TTK2008052000003), the Research Council of Norway (grant No. 180352) and the University of the Western Cape. Partial support was also provided under the Laboratory Directed Research and Development Program at PNNL, a multiprogram national laboratory operated by Battelle for the U.S. Department of Energy under contract DE-AC05-76RL01830.Peer reviewe

Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149741/1/hep41353.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149741/2/hep41353_am.pd

Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3

Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups

Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial

A three-arm randomized trial conducted among infants in Papua New Guinea estimates the preventive effect against malaria episodes of intermittent preventive treatment, in an area where children are exposed to both falciparum and vivax malaria

High intensity intermittent games-based activity and adolescents’ cognition: moderating effect of physical fitness

Background: An acute bout of exercise elicits a beneficial effect on subsequent cognitive function in adolescents. The effect of games-based activity, an ecologically valid and attractive exercise model for young people, remains unknown; as does the moderating effect of fitness on the acute exercise-cognition relationship. Therefore, the aim of the present study was to examine the effect of games-based activity on subsequent cognition in adolescents, and the moderating effect of fitness on this relationship. Methods: Following ethical approval, 39 adolescents (12.3 ± 0.7 year) completed an exercise and resting trial in a counterbalanced, randomised crossover design. During familiarisation, participants completed a multi-stage fitness test to predict VO2 peak. The exercise trial consisted of 60-min games-based activity (basketball), during which heart rate was 158 ± 11 beats∙min−1. A battery of cognitive function tests (Stroop test, Sternberg paradigm, trail making and d2 tests) were completed 30-min before, immediately following and 45-min following the basketball. Results: Response times on the complex level of the Stroop test were enhanced both immediately (p = 0.021) and 45-min (p = 0.035) post-exercise, and response times on the five item level of the Sternberg paradigm were enhanced immediately post-exercise (p = 0.023). There were no effects on the time taken to complete the trail making test or any outcome of the d2 test. In particular, response times were enhanced in the fitter adolescents 45-min post-exercise on both levels of the Stroop test (simple, p = 0.005; complex, p = 0.040) and on the three item level of the Sternberg paradigm immediately (p = 0.017) and 45-min (p = 0.008) post-exercise. Conclusions: Games-based activity enhanced executive function and working memory scanning speed in adolescents, an effect particularly evident in fitter adolescents, whilst the high intensity intermittent nature of games-based activity may be too demanding for less fit children

Supporting patients to get the best from their osteoporosis treatment: a rapid realist review of what works, for whom, and in what circumstance

Systematic reviews that examine effectiveness of interventions to improve medicines optimisation do not explain how or why they work. This realist review identified that interventions which effectively optimise medicines use in osteoporosis include opportunities to address patients' perceptions of illness and treatment and/or support primary care clinician decision making. INTRODUCTION: In people with osteoporosis, adherence to medicines is poorer than other diseases and patients report follow-up is lacking, and multiple unmet information needs. We conducted a rapid realist review to understand what contextual conditions and mechanisms enable interventions to support osteoporosis medication optimisation. METHODS: A primary search identified observational or interventional studies which aimed to improve medicines adherence or optimisation; a supplementary second search identified research of any design to gain additional insights on emerging findings. Extracted data was interrogated for patterns of context-mechanism-outcome configurations, further discussed in team meetings, informed by background literature and the Practicalities and Perception Approach as an underpinning conceptual framework. RESULTS: We identified 5 contextual timepoints for the person with osteoporosis (identifying a problem; starting medicine; continuing medicine) and the practitioner and healthcare system (making a diagnosis and giving a treatment recommendation; reviewing medicine). Interventions which support patient-informed decision making appear to influence long-term commitment to treatment. Supporting patients' practical ability to adhere (e.g. by lowering treatment burden and issuing reminders) only appears to be helpful, when combined with other approaches to address patient beliefs and concerns. However, few studies explicitly addressed patients' perceptions of illness and treatment. Supporting primary care clinician decision making and integration of primary and secondary care services also appears to be important, in improving rates of treatment initiation and adherence. CONCLUSIONS: We identified a need for further research to identify a sustainable, integrated, patient-centred, and cost- and clinically effective model of long-term care for people with osteoporosis

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc