BACKGROUND:Pre-dialysis and dialysis patients are at risk for drug related problems (DRPs) due to a high incidence of comorbidities. Pharmacist-led medication reviews might reduce the number of DRPs. OBJECTIVES:The aim of this study was to evaluate pharmacist-led medication reviews in pre-dialysis and dialysis patients by determining the number and type of DRPs, nephrologist acceptance of pharmacist interventions and time investment. METHODS:From September 2017 until December 2018, pharmacist-led medication reviews were performed on pre-dialysis and dialysis patients. DRPs (medication discrepancies, prescribing issues related to drug and dose selection, drug use problems) were identified using the pharmacists' expert opinion and the STOPP/START criteria. Number and type of accepted pharmacist interventions, sustainability of interventions after at least 1 month and time investment were determined. Practical barriers in the process were appraised. RESULTS:One-hundred twenty five patients were reviewed: 37 pre-dialysis and 88 dialysis patients. In 100 (80%) patients 277 medication discrepancies were identified of which 224 (81%) were accepted by the nephrologist. Pharmacists suggested 422 interventions concerning drug or dose selection for 115 patients; 106 interventions were accepted by the nephrologist, which resulted in 60 patients having medication changed. Ninety percent of those changes remained implemented on follow-up after at least 1 month. In 46 (37%) patients, the clinical pharmacist detected DRPs concerning the drug use process and performed patient counseling. The average time investment was 85 min per patient for the clinical pharmacist and 15 min for the nephrologist. Besides time investment, unclear responsibility for medication management due to multiple prescribers was an important barrier in the process and the main reason for nephrologists to reject pharmacist interventions. CONCLUSION:Pharmacist-led medication reviews in pre-dialysis and dialysis patients led to medication changes in half of the patients. However, efficiency should be improved before adopting pharmacist-led medication reviews into clinical practice.

Introduction: Developments in outcome-based medical education led to the introduction of time-variable medical training (TVMT). Although this idea of training may be a consequence of competency-based training that calls for individualized learning, its implementation has posed significant challenges. As a new paradigm it is likely to have repercussions on the organization of teaching hospitals. The purpose of this study is therefore to explore how hospital administrators cope with this implementation process. Methods: We conducted an exploratory qualitative study for which we interviewed administrators of hospitals who were actively implementing TVMT in their postgraduate programs. Results: Several problems of implementation were identified: existing governance structures proved unfit to cope with the financial and organizational implications of TVMT. Administrators responded to these problems by delegating responsibilities to departments, reallocating tasks, learning from other hospitals and scaling up their teaching facilities. Conclusions: Hospital administrators perceived the implementation of TVMT as challenging. TVMT affects the existing equilibrium between education and clinical service. Administrators' initial attempts to regain control, using steering strategies that were based on known concepts and general outcomes, including cutting departmental budgets did not work, nor did their subsequent wait-and-see approach of leaving the implementation to the individual departments.

Introduction: As competency-based education has gained currency in postgraduate medical education, it is acknowledged that trainees, having individual learning curves, acquire the desired competencies at different paces. To accommodate their different learning needs, time-variable curricula have been introduced making training no longer time-bound. This paradigm has many consequences and will, predictably, impact the organization of teaching hospitals. The purpose of this study was to determine the effects of time-variable postgraduate education on the organization of teaching hospital departments.Methods: We undertook exploratory case studies into the effects of time-variable training on teaching departments' organization. We held semi-structured interviews with clinical teachers and managers from various hospital departments.Results: The analysis yielded six effects: (1) time-variable training requires flexible and individual planning, (2) learners must be active and engaged, (3) accelerated learning sometimes comes at the expense of clinical expertise, (4) fast-track training for gifted learners jeopardizes the continuity of care, (5) time-variable training demands more of supervisors, and hence, they need protected time for supervision, and (6) hospital boards should support time-variable training.Conclusions: Implementing time-variable education affects various levels within healthcare organizations, including stakeholders not directly involved in medical education. These effects must be considered when implementing time-variable curricula.

The financing of postgraduate medical education (PGME) becomes an important topic. PGME is costly, and in most western countries is partly paid by public funding. One of the models that can help to reduce costs is time-variable PGME. Moving to true outcome-based education can lead to more efficient training programs while maintaining educational quality. We analyzed the financial effects of time-variable PGME by identifying the educational activities of PGME programs and comparing the costs and revenues of these activities in gynecology training as an example. This resulted in a revenue-cost balance of PGME activities in gynecology. As gynecology consists of both surgical and non-surgical parts, this specialty is a good starting point for a training cost analysis that can be used for a more general discussion. Shortening PGME programs without losing educational quality appears to be possible with time-variable structures. However, shortening is only safely possible on those areas in which residents have already obtained the desired level of competence. This means that time can be gained at the expense of those educational activities in which residents generate the highest revenues. We therefore conclude that shorter education with the help of time-variable training schemes leads to overall higher costs at the hospital level.

Innovation and change in postgraduate medical education programs affects teaching hospital organizations, since medical education and clinical service are interrelated.Recent trends towards flexible, time-independent and individualized educational programs put pressure on this relationship. This pressure may lead to organizational uncertainty, unbalance and friction making it an important issue to analyze.The last decade was marked by a transition towards outcome-based postgraduate medical education. During this transition competency-based programs made their appearance. Although competency-based medical education has the potential to make medical education more efficient, the effects are still under debate. And while this debate continues, the field of medical education is already introducing next level innovations: flexible and individualized training programs. Major organizational change, like the transition to flexible education programs, can easily lead to friction and conflict in teaching hospital organizations.This article analyses the organizational impact of postgraduate medical education innovations, with a particular focus on flexible training and competency based medical education. The characteristics of teaching hospital organizations are compared with elements of innovation and complexity theory.With this comparison the article argues that teaching hospital organizations have complex characteristics and behave in a non-linear way. This perspective forms the basis for further discussion and analysis of this unexplored aspect of flexible and competency based education.

Treatment goals for patients with CKD are often unrealized for many reasons, but support by nurse practitioners may improve risk factor levels in these patients. Here, we analyzed renal endpoints of the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study after extended follow-up to determine whether strict implementation of current CKD guidelines through the aid of nurse practitioners improves renal outcome. In total, 788 patients with moderate to severe CKD were randomized to receive nurse practitioner support added to physician care (intervention group) or physician care alone (control group). Median follow-up was 5.7 years. Renal outcome was a secondary endpoint of the MASTERPLAN study. We used a composite renal endpoint of death, ESRD, and 50% increase in serum creatinine. Event rates were compared with adjustment for baseline serum creatinine concentration and changes in estimated GFR were determined. During the randomized phase, there were small but significant differences between the groups in BP, proteinuria, LDL cholesterol, and use of aspirin, statins, active vitamin D, and antihypertensive medications, in favor of the intervention group. The intervention reduced the incidence of the composite renal endpoint by 20% (hazard ratio, 0.80; 95% confidence interval, 0.66 to 0.98; P=0.03). In the intervention group, the decrease in estimated GFR was 0.45 ml/min per 1.73 m(2) per year less than in the control group (P=0.01). In conclusion, additional support by nurse practitioners attenuated the decline of kidney function and improved renal outcome in patients with CKD.

OBJECTIVE:Most of the biomedical research is performed in University Medical Centers (UMC's). Increasingly, however, biomedical research is also done in non-academic large teaching hospitals, united in the Organization for Topclinical Hospitals (STZ) in the Netherlands. The objective of this study was to compare citation scores of biomedical publications from UMC's and STZ hospitals.DESIGN:Bibliometric analysis.METHOD:The Center for Science and Technology Studies of the University of Leiden, the Netherlands, annually analyzes the volume and quality (reflected by normalized citation scores) of the publications of all UMC's in the Netherland. Recently, also for STZ hospitals a similar analysis has been performed.RESULTS:Research publications from UMC's in the Netherland have normalized mean citation scores that are far above the mean world average. The normalized mean citation score of publications from STZ hospitals is lower when research is done independent of a UMC, whereas research that is a combined effort of UMC's and STZ hospitals has a very high mean normalized citation score.CONCLUSION:The Netherlands produces a relatively large volume of biomedical research and publications. Based on citation analysis research done in collaboration between UMC's and STZ hospitals has a very high quality. As most STZ hospitals mostly collaborate with a neighbouring UMC, the formation of research networks that overlap with existing teaching and training networks, could provided the necessary infrastructure for further stimulating this collaborative research.

Most of the biomedical research is performed in University Medical Centers (UMC's). Increasingly, however, biomedical research is also done in non-academic large teaching hospitals, united in the Organization for Topclinical Hospitals (STZ) in the Netherlands. The objective of this study was to compare citation scores of biomedical publications from UMC's and STZ hospitals. Bibliometric analysis. The Center for Science and Technology Studies of the University of Leiden, the Netherlands, annually analyzes the volume and quality (reflected by normalized citation scores) of the publications of all UMC's in the Netherland. Recently, also for STZ hospitals a similar analysis has been performed. Research publications from UMC's in the Netherland have normalized mean citation scores that are far above the mean world average. The normalized mean citation score of publications from STZ hospitals is lower when research is done independent of a UMC, whereas research that is a combined effort of UMC's and STZ hospitals has a very high mean normalized citation score. The Netherlands produces a relatively large volume of biomedical research and publications. Based on citation analysis research done in collaboration between UMC's and STZ hospitals has a very high quality. As most STZ hospitals mostly collaborate with a neighbouring UMC, the formation of research networks that overlap with existing teaching and training networks, could provided the necessary infrastructure for further stimulating this collaborative research

Strict implementation of guidelines directed at multiple targets reduces vascular risk in diabetic patients. Whether this also applies to patients with chronic kidney disease (CKD) is uncertain. To evaluate this, the MASTERPLAN Study randomized 788 patients with CKD (estimated GFR 20-70 ml/min) to receive additional intensive nurse practitioner support (the intervention group) or nephrologist care (the control group). The primary end point was a composite of myocardial infarction, stroke, or cardiovascular death. During a mean follow-up of 4.62 years, modest but significant decreases were found for blood pressure, LDL cholesterol, anemia, proteinuria along with the increased use of active vitamin D or analogs, aspirin and statins in the intervention group compared to the controls. No differences were found in the rate of smoking cessation, weight reduction, sodium excretion, physical activity, or glycemic control. Intensive control did not reduce the rate of the composite end point (21.3/1000 person-years in the intervention group compared to 23.8/1000 person-years in the controls (hazard ratio 0.90)). No differences were found in the secondary outcomes of vascular interventions, all-cause mortality or end-stage renal disease. Thus, the addition of intensive support by nurse practitioner care in patients with CKD improved some risk factor levels, but did not significantly reduce the rate of the primary or secondary end points.

The criteria in the 2009 Dutch National Transmural Agreement (LTA) for chronic renal damage are used in patient care. But in 2012, patient referral patterns have not fully adhered to this guideline. This commentary indicates that the availability of a similar 2009 guideline used by nephrologists in in-hospital care may cause confusion. As new evidence accumulates, it is reasonable to expect a new 2014 guideline that will bring the two guidelines together. This will lead to even greater adherence in referral patterns in the Netherlands.

BACKGROUNDGuidelines have set goals for risk factor management in chronic kidney disease (CKD) patients. These goals are often not met. In this analysis, we set out to assess the quality of risk factor management in CKD and to identify factors that determine the quality of care (QoC). For that purpose, baseline data of the MASTERPLAN (Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse practitioners) study have been used. MASTERPLAN is a multicentre study which evaluates the effect of a multifactorial intervention in prevalent CKD patients on cardiovascular (CV) events and progression of kidney failure.METHODSQoC was quantified using a score based on the number of 11 defined treatment goals on target. The maximum score per patient was 11.RESULTSThe average (±SD) QoC score was 6.7 (±1.5). The average score per centre ranged from 5.9 to 6.9. In a multivariable analysis, centre proved to be a significant, independent determinant of QoC with a difference up to 0.7 between centres. This difference remained when adjustments were made for those risk factors primarily treated by pharmacotherapy. Other factors that were significantly related to the QoC were estimated glomerular filtration rate, Caucasian race, diabetes mellitus, diabetic nephropathy as cause of kidney disease and previous kidney transplantation.CONCLUSIONSIn CKD patients, risk factors for progression of kidney failure and CV events were inadequately controlled. Treatment centre proved to be an important determinant of QoC. This data may point towards the physician's interest and preference as important determinants of QoC. This is a potentially modifiable determinant of the quality of patient care [Trial registration ISRCTN registry: 73187232 (http://isrctn.org)].

SUMMARY Changes in systemic and renal hemodynamics and in the renin-angiotensin system caused by infusion of the calcium antagonist felodipine were investigated in a placebo-controlled study with 12 normotensive volunteers before and during a graded infusion of angiotensin II (AII). In spite of a fall in blood pressure through vasodilatation, felodipine had a natriuretic effect. There was only a transient rise in effective renal plasma flow (ERPF), whereas glomerular filtration rate (GFR) did not change. Urinary sodium excretion remained elevated when ERPF had normalized. Urinary potassium excretion did not change. All-induced reductions in ERPF, GFR, and sodium excretion were abolished by felodipine. Felodipine also partly antagonized the rise in plasma aldosterone levels caused by AII. We conclude that the natriuretic effect of dihydropyridine calcium antagonists is probably not caused by a single mechanism, but may be dependent on changes in renal hemodynamics together with a diminished sodium reabsorption at multiple tubular sites. Interference with All-mediated renal mechanisms and an impairment of the action of aldosterone may contribute to this natriuretic effect as well.

The effects of intravenous administration of a new calcium antagonist, felodipine, were studied in healthy subjects and hypertensive patients. Felodipine infused at a rate of 0.01 mg/min in 10 normotensive volunteers caused gradual haemodynamic and hormonal changes compatible with a direct vasodilatory mechanism of action; it also had a diuretic and natriuretic effect. When infused at a mean dose of 0.02 mg/kg body weight over 20 to 120 minutes in 7 patients with a hypertensive emergency, felodipine caused a rapid reduction in blood pressure with a maximal fall in mean arterial pressure of 30.4 ± 7.3% (mean ± 1 SD) in 30 minutes. No serious side effects were observed. The haemodynamic effectiveness of an infusion rate of 0.01 mg/min was confirmed in a pilot study of 5 patients with refractory hypertension. On the basis of these findings, a schedule for the treatment of acute hypertension with intravenous felodipine is proposed.

Felodipine and placebo were infused in a double- blind, crossover study in 10 healthy normotensive volunteers. Compared with placebo, felodipine caused a significant decrease in diastolic blood pressure and forearm vascular resistance, while there was no change in systolic blood pressure. The rises in heart rate, plasma renin activity and plasma nor- adrenaline (norepinephrine) concentration further demonstrated the vasodilating activity of felodipine. Plasma aldosterone, adrenaline (epinephrine) and antidiuretic hormone concentrations were similar after a 90- minute infusion of felodipine or placebo. The response of plasma aldosterone levels to exogenous adenocorticotrophic hormone showed evidence of a slight blunting during felodipine infusion. Felodipine had a marked diuretic effect, probably secondary to an increase in natriuresis, which might be due to a direct tubular effect of the drug.