Higher education reform: getting the incentives right

This study is a joint effort by the Netherlands Bureau for Economic Policy Analysis (CPB) and the Center for Higher Education Policy Studies. It analyses a number of `best practices¿ where the design of financial incentives working on the system level of higher education is concerned. In Chapter 1, an overview of some of the characteristics of the Dutch higher education sector is presented. Chapter 2 is a refresher on the economics of higher education. Chapter 3 is about the Australian Higher Education Contribution Scheme (HECS). Chapter 4 is about tuition fees and admission policies in US universities. Chapter 5 looks at the funding of Danish universities through the so-called taximeter-model, that links funding to student performance. Chapter 6 deals with research funding in the UK university system, where research assessments exercises underlie the funding decisions. In Chapter 7 we study the impact of university-industry ties on academic research by examining the US policies on increasing knowledge transfer between universities and the private sector. Finally, Chapter 8 presents food for thought for Dutch policymakers: what lessons can be learned from our international comparison

The role of microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals

This observational, cross-sectional study describes the role played by clinical microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals. A total of 170 acute care hospitals from 32 European countries returned a questionnaire on antibiotic policies and practices implemented in 2001. Data on antibiotic use, expressed as De.ned Daily Doses per 100 occupied bed-days (DDD/100 BD) were provided by 139 hospitals from 30 countries. A total of 124 hospitals provided both datasets. 121 (71%) of Clinical Microbiology departments and 66 (41%) of Pharmacy departments provided out of hours clinical advice. 70 (41%) of microbiology/infectious disease specialists and 28 (16%) of pharmacists visited wards on a daily basis. The majority of laboratories provided monitoring of blood cultures more than once per day and summary data of antibiotic susceptibility testing (AST) for empiric prescribing (86% and 73% respectively). Most of the key laboratory and pharmacy-led initiatives examined did not vary signi.cantly by geographical location. Hospitals from the North and West of Europe were more likely to examine blood cultures more than once daily compared with other regions (p < 0.01). Hospitals in the North were least likely routinely to report susceptibility results for restricted antibiotics compared to those in the South-East and Central/Eastern Europe (p < 0.01). Hospital wards in the North were more likely to hold antibiotic stocks (100%) compared with hospitals in the South-East which were least likely (39%) (p < 0.001). Conversely, hospital pharmacies in the North were least likely to dispense antibiotics on an individual patient basis (16%) compared with hospital pharmacies from Southern Europe (60%) (p = 0.01). Hospitals that routinely reported susceptibility results for restricted antibiotics had signi.cantly lower median total antibiotic use in 2001 (p < 0.01). Hospitals that provided prescribing advice outside normal working hours had signi.cantly higher antibiotic use compared with institutions that did not provide this service (p = 0.01). A wide range of antibiotic stewardship measures was practised in the participating hospitals in 2001, although there remains great scope for expansion of those overseen by pharmacy departments. Most hospitals had active antibiotic stewardship programmes led by specialists in infection, although there is no evidence that these were associated with reduced antibiotic consumption. There was also no evidence that pharmacy services reduced the amount of antibiotics prescribed.The ARPAC study was funded by the European Commission (project QLK2-CT-2001-00915). F.M. MacKenzie was supported by the European Study Group on Antibiotic Policies to write this manuscript

Interleukin-1 as a mediator of fatigue in disease: a narrative review

Fatigue is commonly reported in a variety of illnesses, and it has major impact on quality of life. Previously, it was thought that fatigue originates in the skeletal muscles, leading to cessation of activity. However, more recently, it has become clear that the brain is the central regulator of fatigue perception. It has been suggested that pro-inflammatory cytokines, especially interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β), play a prominent role in the development of central fatigue, and several studies have been performed to elucidate the connection between inflammation and these central processes.In this narrative review, mechanisms of action of IL-1 are described, with special attention to its effect on the central nervous system. In addition, we present a summary of studies that (i) investigated the relationship between circulating IL-1α and IL-1β and fatigue severity and/or (ii) evaluated the effect of inhibiting IL-1 on fatigue. We aim to improve the understanding of fatigue in both inflammatory and non-inflammatory illnesses, which could help develop strategies to treat fatigue more effectively.Reviewing the studies that have been performed, it appears that there is a limited value of measuring circulating IL-1. However, inhibiting IL-1 has a positive effect on severe fatigue in most studies that have been conducte

Drug Burden Index and Cognitive and Physical Function in Aged Care Residents:A Longitudinal Study

Objectives: Anticholinergic/antimuscarinic and sedative medications (eg, benzodiazepines) have been found to be associated with poorer cognitive and physical function and mobility impairment in older age. However, previous studies were mostly conducted among community-dwelling older individuals and had often a cross-sectional design. Accordingly, our aim was to examine longitudinal associations between cumulative exposure to anticholinergic and sedative medications and cognitive and physical function among residents from aged care homes. Design: Longitudinal study. Setting and Participants: A total of 4624 residents of Dutch aged care homes of whom data were collected between June 2005 and April 2014. Methods: Outcome measures were collected with the Long-Term Care Facilities assessment from the international Residential Assessment Instrument (interRAI-LTCF) and included the Cognitive Performance Scale, the Activities of Daily Living (ADL) Hierarchy scale, a timed 4-meter walk test, distance walked, hours of physical activity, and days being outside. Cumulative exposure to anticholinergic and sedative medications was calculated with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. Associations were examined with linear mixed models to take the potential dependence of observations into account (ie, data were collected at repeated assessment occasions of residents who were clustered in aged care homes). Analyses were adjusted for sex, age, dementia, comorbidity (neurological, psychiatric, cardiovascular, oncological, and pulmonary), fractures, depressive symptoms, and medications excluded from the DBI. Results: We observed significant longitudinal associations between a higher DBI and poorer ADLs, fewer hours of physical activity, and fewer days being outside. We found no significant longitudinal association between a higher DBI and poorer cognitive function. Conclusions and Implications: Over time, cumulative exposure to anticholinergic and sedative medications is associated with poorer physical but not cognitive function in aged care residents. Careful monitoring of aged care residents with high cumulative anticholinergic and sedative medication exposure is needed

Anticholinergic and Sedative Medications and Dynamic Gait Parameters in Older Patients

BACKGROUND: Anticholinergic and sedative medications are associated with poorer physical function in older age. Gait and physical function have traditionally been assessed with the time needed to execute objective function tests. Accelerometer-based gait parameters provide a precise capturing of gait dynamics and patterns and as such have added value. OBJECTIVES: This study examined the associations between cumulative exposure to anticholinergic and sedative medications and gait dimensions as assessed with accelerometer-based dynamic gait parameters. METHODS: Data were collected from outpatients of a diagnostic geriatric day clinic who underwent a comprehensive geriatric assessment (CGA). Cumulative exposure to anticholinergic and sedative medications was quantified with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. From a total of 22 dynamic gait parameters, the gait dimensions 'Regularity', 'Complexity', 'Stability', 'Pace', and 'Postural Control' were derived using factor analysis (and standardized total scores for these dimensions were calculated accordingly). Data were analyzed with multivariable linear regression analysis, in which adjustment was made for the covariates age, gender, body mass index (BMI), Mini Mental State Examination (MMSE) score, Charlson Comorbidity Index (CCI) including dementia, and number of medications not included in the DBI. RESULTS: A total of 184 patients participated, whose mean age was 79.8 years (± SD 5.8), of whom 110 (60%) were women and of whom 88 (48%) had polypharmacy (i.e., received treatment with ≥5 medications). Of the 893 medications that were prescribed in total, 157 medications (17.6%) had anticholinergic and/or sedative properties. Of the patients, 100 (54%) had no exposure (DBI = 0), 42 (23%) had moderate exposure (0 > DBI ≤ 1), while another 42 (23%) had high exposure (DBI >1) to anticholinergic and sedative medications. Findings showed that high cumulative exposure to anticholinergic and sedative medications was related with poorer function on the Regularity and Pace dimensions. Furthermore, moderate and high exposure were associated with poorer function on the Complexity dimension. CONCLUSIONS: These findings show that in older patients with comorbidities, cumulative anticholinergic and sedative exposure is associated with poorer function on multiple gait dimensions

Trained immunity or tolerance : opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors

Article Accepted Date: 29 January 2014. ACKNOWLEDGMENTS D.C.I. received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-2010-260338 (“Fungi in the setting of inflammation, allergy and autoimmune diseases: translating basic science into clinical practices” [ALLFUN]) (awarded to M.G.N.). M.G.N. and J.Q. were supported by a Vici grant of the Netherlands Organization of Scientific Research (awarded to M.G.N.). This work was supported, in part, by National Institutes of Health grant GM53522 to D.L.W. N.A.R.G. was supported by the Wellcome Trust.Peer reviewedPublisher PD

Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

Background: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS. Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS. In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo. To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion. Findings: Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states. ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition. Conclusions: These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS. Trial registration: ISRCTN0751814

Differential Expression of Proinflammatory Cytokines and Their Inhibitors during the Course of Meningococcal Infections

Circulating concentrations of tumor necrosis factor-α (TNF), interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors p55 (sTNFr-55) and p75 (sTNFr-75) and ex vivo production ofTNF, IL-1, IL-6, and IL-1ra using a whole blood culture system were measured during the acute and convalescent stages of meningococcal infection. Circulating TNF and IL-1 were below detection level, whereas IL-6 and IL-1ra, sTNFr-55, and sTNFr-75 were increased at admission. The ex vivo production of proinflammatory cytokines TNF, IL-1, and IL-6 was suppressed at admission and restored gradually during recovery. On the contrary, the production of the antiinflammatory IL-1ra was increased at admission. The elevated concentrations of both IL-1ra and sTNFr early in the course of infection suggest a regulatory role for these antiinflammatory compounds. The observed down-regulation of the ex vivo production of TNF, IL-1, and IL-6 and up-regulation of the production of IL-1 ra in the acute stage may indicate a protective regulation mechanis