Johannes G. M. Burgerhof

Self-medication with antimicrobial drugs in Europe

Antimicrobial drug self-medication occurs most often in eastern and southern Europe and least often in northern and western Europe.

Determinants of self-medication with antibiotics in Europe: the impact of beliefs, country wealth and the healthcare system

BACKGROUND Self-medication with antibiotics occurs among the population in Europe, particularly in southern and eastern countries. We studied the impact of predisposing factors (e.g. attitudes and knowledge concerning antibiotic use and self-medication) and enabling factors (country wealth and healthcare system factors) on self-medication with antibiotics in Europe. METHODS In this follow-up of a previous European survey, we interviewed a subsample of 1101 respondents. A multilevel analysis with two levels (respondent and country) was performed. Variables that were statistically significantly different between users and non-users of self-medication were considered for inclusion into the multilevel regression analyses. RESULTS Predisposing factors included individual-level characteristics. High perceived appropriateness of self-medication with antibiotics for bronchitis and an attitude favouring antibiotic use for minor ailments were related to a higher likelihood of self-medication. Enabling factors included individual and country data. At the individual level, perceived availability of antibiotics without a prescription was related to increased probability of self-medication. At the country level, higher gross domestic product (wealth) and exact dispensation of prescribed tablet quantities by pharmacies were independently associated with lower likelihood of self-medication. CONCLUSIONS Interventions aimed at preventing self-medication should include public education, enforcing regulations regarding the sale of antibiotics, and implementing laws for dispensing exact prescribed tablet quantities in pharmacies. With the included determinants, we explained almost all the variance at the country level, but not at the individual level. Future studies to increase our understanding of determinants of self-medication with antibiotics should focus on individual-level factors such as doctor-patient relationships and patient satisfaction.

C-Reactive Protein Modifies the Relationship Between Blood Pressure and Microalbuminuria

Abstract—C-reactive protein (CRP) and microalbuminuria reflect intimately related components of the atherosclerotic disease process. Epidemiological studies found only modest associations between CRP and microalbuminuria. Blood pressure, one of the components of the metabolic syndrome in the general population, is the main determinant of microalbuminuria in diabetes and hypertension. We questioned whether CRP modifies the relationship of blood pressure and other cardiovascular risk factors with microalbuminuria in a cross-sectional study in 8592 inhabitants from Groningen, The Netherlands. The crude data showed an increase in the prevalence of microalbuminuria with increasing CRP quartiles (4.8, 9.6, 14.5, and 18.6%, P <0.0001). On stratification for cardiovascular risk factors, the data revealed a significant and positive interaction between mean arterial pressure (MAP) and quartiles of CRP with respect to the risk of microalbuminuria (Wald statistic 9.2, P =0.03). In subjects with a MAP <90 mm Hg, a nonsignificant trend in the association between CRP quartiles and microalbuminuria was found (prevalence: 3.9%, 5.8%, 6.6%, 8.7%; P =0.11). This trend was much steeper and significant in subjects with an MAP >90 mm Hg (prevalence: 6.7%, 13.6%, 20.4%, 25.1%; P <0.0001). Controlling for other risk factors in multivariate analyses, the positive interaction persisted (P =0.0004). No significant interactions between other risk factors and CRP with respect to the risk of microalbuminuria were encountered. Thus, CRP modifies the relation between blood pressure and microalbuminuria.

Serum levels of BAFF, but not APRIL, are increased after rituximab treatment in patients with primary Sjögren's syndrome: data from a placebo-controlled clinical trial

B cell depletion therapy with rituximab (RTX; 2 weekly infusions of 1000 mg, premedication: 100 mg prednisolone) in primary Sjogrens syndrome (pSS) patients is effective in reducing subjective and objective symptoms.1 As B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are important cytokines involved in B cell survival and activation, we assessed in pSS patients included in a double-blind, randomised, placebo-controlled trial1 the effects of RTX on serum BAFF and APRIL levels up to 48 weeks after RTX. Serum concentrations of BAFF and APRIL were measured by ELISA using kits from RD median 1277 pg/ml (range 907–3802 pg/ml)) compared with healthy controls (n=10; median 983 pg/ml (range 600–1564 pg/ml)); p<0.01; figure 1A). Also, baseline serum APRIL levels were significantly higher in pSS patients (median 15 098 pg/ml (range 1891–228 591 pg/ml)) than in healthy controls (median 1965 pg/ml (range 889–4567 pg/ml); p<0.05; …

Automatic feedback control of relative blood volume changes during hemodialysis improves blood pressure stability during and after dialysis

Automatic feedback systems have been designed to control relative blood volume changes during hemodialysis (HD) as hypovolemia plays a major role in the development of dialysis hypotension. Of these systems, one is based on the concept of blood volume tracking (BVT). BVT has been shown to improve intra‐HD hemodynamic stability. We first questioned whether BVT also improves post‐HD blood pressure stability in hypotension‐prone patients and second, whether BVT is effective in reducing the post‐HD weight as many hypotension‐prone patients are overhydrated because of an inability to reach dry weight. After a 3‐week period on standard HD, 12 hypotension‐prone patients were treated with two consecutive BVT treatment protocols. During the first BVT period of 3 weeks, the post‐HD target weight was kept identical compared with the standard HD period (BVT‐constant weight; BVT‐cw). During the second BVT period of 6 weeks, we gradually tried to lower the post‐HD target weight (BVT‐reduced weight; BVT‐rw). In the last week of each period, we studied intra‐HD and 24 hr post‐HD blood pressure behavior by ambulatory blood pressure measurement (ABPM). Pre‐ and post‐HD weight did not differ between standard HD and either BVT‐cw or BVT‐rw. Heart size on a standing pre‐dialysis chest X‐ray did not change significantly throughout the study. There were less episodes of dialysis hypotension during BVT compared with standard HD (both BVT periods: p<0.01). ABPM data were complete in 10 patients. During the first 16 hr post‐HD, systolic blood pressure was significantly higher with BVT in comparison with standard HD (both BVT periods: p<0.05). The use of BVT in hypotension‐prone patients is associated with higher systolic blood pressures for as long as 16 hr post‐HD. BVT was not effective in reducing the post‐HD target weight in this patient group.

Outcome after resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia: Dutch nationwide retrospective cohort study

Objectives To evaluate the outcome of drowned children with cardiac arrest and hypothermia, and to determine distinct criteria for termination of cardiopulmonary resuscitation in drowned children with hypothermia and absence of spontaneous circulation. Design Nationwide retrospective cohort study. Setting Emergency departments and paediatric intensive care units of the eight university medical centres in the Netherlands. Participants Children aged up to 16 with cardiac arrest and hypothermia after drowning, who presented at emergency departments and/or were admitted to intensive care. Main outcome measure Survival and neurological outcome one year after the drowning incident. Poor outcome was defined as death or survival in a vegetative state or with severe neurological disability (paediatric cerebral performance category (PCPC) ≥4). Results From 1993 to 2012, 160 children presented with cardiac arrest and hypothermia after drowning. In 98 (61%) of these children resuscitation was performed for more than 30 minutes (98/160, median duration 60 minutes), of whom 87 (89%) died (95% confidence interval 83% to 95%; 87/98). Eleven of the 98 children survived (11%, 5% to 17%), but all had a PCPC score ≥4. In the 62 (39%) children who did not require prolonged resuscitation, 17 (27%, 16% to 38%) survived with a PCPC score ≤3 after one year: 10 (6%) had a good neurological outcome (score 1), five (3%) had mild neurological disability (score 2), and two (1%) had moderate neurological disability (score 3). From the original 160 children, only 44 were alive at one year with any outcome. Conclusions Drowned children in whom return of spontaneous circulation is not achieved within 30 minutes of advanced life support have an extremely poor outcome. Good neurological outcome is more likely when spontaneous circulation returns within 30 minutes of advanced life support, especially when the drowning incident occurs in winter. These findings question the therapeutic value of resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia.

Changes in nutritional status in childhood cancer patients: A prospective cohort study

BACKGROUND & AIMS Under- and overnutrition are linked to adverse outcomes during and after childhood cancer treatment. Therefore, understanding the timing of weight loss and weight gain and their contributory factors is essential for improving outcomes. We aimed to determine in which period of treatment changes in nutritional status occurred and which factors contributed to these changes. METHODS A prospective cohort study of 133 newly diagnosed cancer patients with hematological, solid, and brain malignancies was performed. Anthropometric data and related factors were assessed at 0, 3, 6 and 12 months after diagnosis. RESULTS Despite initial weight loss at the beginning of treatment in patients with hematological and solid malignancies, body mass index (BMI) and fat mass (FM) increased within 3 months with 0.13 SDS (P < 0.001) and 0.05 SDS (P = 0.021) respectively. Increase continued during the following months and resulted in a doubling of the number of overnourished patients. Fat free mass (FFM), which was already low at diagnosis, remained low. During the entire study period about 17% of the patients were undernourished on the basis of low FFM. Tube feeding and diminished activity level were related to increases in BMI and %FM respectively. No relationship was found between energy intake or corticosteroids and increase in BMI or %FM. CONCLUSIONS BMI and FM increased during and after the period of intensive treatment, while FFM remained low. Improvement of nutritional status might be accomplished by increasing physical activity from the early phase of treatment.

Tidal Volume and Mortality in Mechanically Ventilated Children: A Systematic Review and Meta-Analysis of Observational Studies

Objective:To determine whether tidal volume is associated with mortality in critically ill, mechanically ventilated children. Data Sources:MEDLINE, EMBASE, and CINAHL databases from inception until July 2013 and bibliographies of included studies without language restrictions. Study Selection:Randomized clinical trials and observational studies reporting mortality in mechanically ventilated PICU patients. Data Extraction:Two authors independently selected studies and extracted data on study methodology, quality, and patient outcomes. Meta-analyses were performed using the Mantel-Haenszel random-effects model. Heterogeneity was quantified using I2. Study quality was assessed using the Newcastle-Ottawa Score for cohort studies. Data Synthesis:Out of 142 citations, seven studies met the inclusion criteria, and additional two articles were identified from references of the found articles. One was excluded. These eight studies included 1,756 patients. Mortality rates ranged from 13% to 42%. There was no association between tidal volume and mortality when tidal volume was dichotomized at 7, 8, 10, or 12 mL/kg. Comparing patients ventilated with tidal volume less than 7 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg and tidal volume less than 8 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg also showed no association between tidal volume and mortality. Limiting the analysis to patients with acute lung injury/acute respiratory distress syndrome did not change these results. Heterogeneity was observed in all pooled analyses. Conclusions:A relationship between tidal volume and mortality in mechanically ventilated children could not be identified, irrespective of the severity of disease. The significant heterogeneity observed in the pooled analyses necessitates future studies in well-defined patient populations to understand the effects of tidal volume on patient outcome.

Predominantly proinflammatory cytokines decrease after B cell depletion therapy in patients with primary Sjögren's syndrome

Cytokines are critical in initiating and perpetuating the chronic inflammatory response in primary Sjogrens syndrome (pSS).1 Rituximab has beneficial effects on disease activity in pSS patients2 and results in a rise in B cell activating factor (BAFF) levels.3 Whether (elevated) levels of other (proinflammatory) cytokines are affected was addressed in this study. This information is important for understanding of the effect of rituximab in pSS. Twenty-eight patients with early-onset pSS2 treated with rituximab (n=18) or placebo (n=10), and 10 age-matched and sex-matched healthy controls (HCs) were assessed for presence of cytokines/chemokines in serum, using a multiplex-25 bead array assay (Invitrogen, Breda, The Netherlands). The following cytokines and chemokines were analysed: GM-CSF, IL-1β, IL-1Ra, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40/p70, IL-13, IL-15, IL-17, IFN-α, IFN-γ, TNF-α, MCP-1/CCL2, MIP-1α/CCL3; MIP-1β/CCL4, RANTES/CCL5, Eotaxin/CCL11, MIG/CXCL9 and IP-10/CXCL10. At baseline, levels for nearly all cytokines/chemokines were significantly higher in pSS patients than …

Transfusion of Leukocyte-Depleted RBCs Is Independently Associated With Increased Morbidity After Pediatric Cardiac Surgery

Objective: To test the hypothesis that transfusion of leukocyte-depleted RBC preparations within the first 48 hours of PICU stay was independently associated with prolonged duration of mechanical ventilation, irrespective of surgery type and disease severity. Design: Retrospective, observational study. Setting: Single-center PICU in The Netherlands. Patients: Children less than 18 years consecutively admitted after pediatric cardiac surgery between February 2007 and February 2010. Interventions: None. Measurements and Main Results: Data from 335 patients were used for analysis of whom 86 (25.7%) were transfused during the first 48 hours of PICU stay. Duration of mechanical ventilation (115 ± 19 hours vs. 25 ± 4 hours, p < 0.001) was longer among transfused patients. Ventilator-associated pneumonia (10.5% vs. 1.6%, odds ratio 7.2; 95% confidence interval 1.92–32.47; p < 0.001) was more frequent among transfused patients. New acute kidney injury after 48 hours of PICU admission (23.9% vs. 15.4%, p = 0.18) and mortality were comparable (2.3% vs. 4%, p = 0.16). The number of discrete transfusion events was significantly correlated with the duration of mechanical ventilation (Spearman’s rho 0.617, p < 0.001). Transfusion remained independently associated with prolonged duration of mechanical ventilation after adjusting for confounders using Cox proportional hazards regression analysis. Conclusions: Transfusion of leukocyte-depleted RBCs within the first 48 hours of PICU stay after cardiac surgery is independently associated with prolonged duration of mechanical ventilation.