Effect of audit and feedback with peer review on general practitioners' prescribing and test ordering performance: a cluster-randomized controlled trial.

BACKGROUND: Much research worldwide is focussed on cost containment and better adherence to guidelines in healthcare. The research focussing on professional behaviour is often performed in a well-controlled research setting. In this study a large-scale implementation of a peer review strategy was tested on both test ordering and prescribing behaviour in primary care in the normal quality improvement setting. METHODS: We planned a cluster-RCT in existing local quality improvement collaboratives (LQICs) in primary care. The study ran from January 2008 to January 2011. LQICs were randomly assigned to one of two trial arms, with each arm receiving the same intervention of audit and feedback combined with peer review. Both arms were offered five different clinical topics and acted as blind controls for the other arm. The differences in test ordering rates and prescribing rates between both arms were analysed in an intention-to-treat pre-post analysis and a per-protocol analysis. RESULTS: Twenty-one LQIC groups, including 197 GPs working in 88 practices, entered the trial. The intention-to-treat analysis did not show a difference in the changes in test ordering or prescribing performance between intervention and control groups. The per-protocol analysis showed positive results for half of the clinical topics. The increase in total tests ordered was 3% in the intervention arm and 15% in the control arm. For prescribing the increase in prescriptions was 20% in the intervention arm and 66% in the control group. It was observed that the groups with the highest baseline test ordering and prescription volumes showed the largest improvements. CONCLUSIONS: Our study shows that the results from earlier work could not be confirmed by our attempt to implement the strategy in the field. We did not see a decrease in the volumes of tests ordered or of the drugs prescribed but were able to show a lesser increase instead. Implementing the peer review with audit and feedback proved to be not feasible in primary care in the Netherlands. TRIAL REGISTRATION: This trial was registered at the Dutch trial register under number ISRCTN40008171 on August 7th 2007.

[Prospective comparison of the flow chart for laboratory investigations for anaemia from the Dutch College of General Practitioners' guideline 'Anaemia' with a self-developed, substantive and logistical alternative flow chart]. / Prospectieve vergelijking van het stroomschema voor laboratoriumonderzoek van anemie uit de NHG-standaard 'Anemie' met een eigen, inhoudelijk en logistiek alternatief stroomschema.

OBJECTIVE: To compare the flow diagram for the diagnosis of anaemia from the guideline 'Anaemia' from the Dutch College of General Practitioners (NHG) with a substantive and logistical alternative protocol. DESIGN: Prospective. METHOD: For evaluation of anaemia, 124 patients from primary care reported to the laboratories of the St. Elisabeth Hospital in Tilburg (n = 94) and the Scheper Hospital in Emmen (n = 30), the Netherlands. Two flow charts were used: the NHG's flow chart and a self-developed chart in which not mean corpuscular volume, but ferritin concentration occupies the central position. All the laboratory tests mentioned in both flow charts were carried out in every patient with, for practical reasons, the exception of Hgb electrophoresis and bone marrow investigations. General practitioners were approached and patient dossiers were consulted to obtain further clinical data. RESULTS: According to the NHG protocol, on the grounds of the laboratory investigations, 64 (52%) of patients could not be put in a specific category. The majority were patients with normocytary anaemia who did not fulfil the criteria for iron deficiency anaemia or the anaemia of chronic disease. According to the alternative chart, in 36 (29%) patients no diagnosis was made. These were patients in whom no abnormal laboratory findings were observed, other than low haemoglobin values. The majority of the patients had normocytary anaemia, in some cases this was interpreted as the anaemia of chronic disease, but more often the anaemia could not be assigned to a particular category. A large number ofpatients had a raised creatinine value. This value did not appear in the NHG protocol. In 15% of patients, more than one cause for anaemia was found. The NHG protocol did not enable these multiple diagnoses to be made. Accordingly, the NHG protocol was difficult to implement in the laboratory. CONCLUSION: Using the NHG flow diagram a large percentage of patients could not be assigned to a particular category. Using the alternative flow diagram, which procedure is easier to carry out in the laboratory, it was possible to make multiple diagnoses.

Evaluation of LabRespond, a new automated validation system for clinical laboratory test results.

BACKGROUND: Manual validation of laboratory test results is time-consuming, creating a demand for expert systems to automate this process. We have started to set up the program "LabRespond", which covers five validation levels: administrative, technical, sample, patient, and clinical validation. We present the evaluation of a prototype of an automated patient validation system based on statistical methods, in contrast to the commercially available program "VALAB", a rule-based automated validation system. METHODS: In the present study, 163 willfully altered, erroneous test results out of 5421 were submitted for validation to LabRespond, VALAB, and to a group of clinical chemists (n = 9) who validated these test results manually. The test results rejected by three or more clinical chemists (n = 281) served as a secondary reference standard. RESULTS: The error recovery rates of clinical chemists ranged from 23.9% to 71.2%. The recovery rates of LabRespond and VALAB were 77.9% and 71.8%, respectively (difference not significant). The false-positive rates were 82.7% for LabRespond, 83.6% for VALAB, and 27.8-86.7% for clinical chemists. Using the consensus of three or more clinical chemists as the secondary reference standard, we found error recovery rates of 64.8% for LabRespond and 72.2% for VALAB (P = 0.06). Compared with VALAB, LabRespond detected more (P = 0.003) erroneous test results of the type that were changed from abnormal to normal. CONCLUSIONS: The statistical plausibility check used by LabRespond offers a promising automated validation method with a higher error recovery rate than the clinical chemists participating in this study, and a performance comparable to VALAB.

A re-appraisal of the tri-axial chart for monitoring arterial acid-base values.

OBJECTIVE: To demonstrate the practicability of a tri-axial chart for the graphical and quantitative monitoring of arterial pH, arterial carbon dioxide partial pressure (PaCO2) and actual arterial bicarbonate-ion concentration (a[HCO3-]) in intensive care patients. DESIGN: Case report. SETTING: A general intensive care unit (ICU). METHODS: Using a standard mathematical transformation, a data set of pH, log PaCO2 and log a[HCO3-] values can be transformed in such a way that a graphical display of all three variables is possible while being faithful to their linear relationship. Remarkably, the graphical display closely resembles the tri-axial chart that Hastings and Steinhaus described in 1931 for studying displacements of the acid-base balance. Two new monitoring parameters based on the chart and the transformation are described. One monitors the abnormality of the acid-base status while the other monitors the rate of acid-base changes. CONCLUSIONS: With the tri-axial acid-base chart, the complete acid-base status can be faithfully monitored. Moreover, the proposed monitoring parameters provide extra information about the arterial acid-base status that, otherwise, would remain hidden.

Effects of ciliary neurotrophic factor on retrograde cell reaction after facial nerve crush in young adult rats.

Locally applied ciliary neurotrophic factor (CNTF) has a powerful effect on retrograde axonal reaction following facial nerve crush in neonatal rats. We examined whether it also exerts a strong effect on retrograde axonal reaction in young adult rats when administered subcutaneously. The dose was 1 mg/kg body weight, three times a week, similar to that used in a previous experiment in which CNTF was reported to have an effect. We studied changes in the morphology of the motor nerve cell bodies, in the number of perineuronal microglial cells and in the expression of five proteins. It appeared that CNTF prevented swelling of the facial motoneuron cell bodies but it did not influence the swelling of the nucleus nor the shift of the nucleus towards the periphery. In saline-treated rats, facial nerve crush resulted from day two to day six in a marked increase in the number of perineuronal glial cells. This increase was neither diminished nor augmented by CNTF. Following facial nerve crush, the immunoreactivity of the proteins C3bi, GFAP, B-50 and CGRP increased in the glial cells and motoneuron cell bodies, whilst the immunoreactivity of synaptophysin at the membrane of the motoneuron cell bodies decreased. CNTF had no obvious effect on these changes. It was concluded that in young adult rats under the present conditions, CNTF had only a small effect on a specific aspect of the retrograde cell reaction. The small effects might be explained by the minor availability of CNTF to the motoneuron cell bodies. The gain in body weight of rats treated with CNTF was less than that of saline-treated rats.

No evidence for enhancement of recovery from a crush lesion of a motor nerve in rats by Org2766.

The present study was undertaken to investigate the effect of Org2766 on the recovery of lesioned motor nerve fibres. The facial nerve of Wistar rats was crush lesioned and the process of recovery was assessed by functional and histological methods. Functional recovery was examined in two experiments and was assessed by quantifying blind the return of eyelid and whisker movements. No difference could be demonstrated between Org2766-treated and saline-treated groups of animals. The histological investigations involved quantifying the number of reinnervated motor endplates in the whisker muscle. On days 10 to 12 in male rats and on days 12 and 13 in female rats, there was no difference in reinnervation between the two treatment groups. It was concluded that with the methods used in this study, no significant effect of Org2766 on the axonal regeneration of motor nerve fibres could be established.

Ciliary neurotrophic factor improves muscle fibre reinnervation after facial nerve crush in young rats.

In the present study we examined the effect of recombinant human ciliary neurotrophic factor (rH-CNTF) on muscle fibre reinnervation. After facial nerve crush, rats were treated systemically with either rH-CNTF (1 mg/kg per 48 h) or saline and were killed on days 10-13 after nerve crush when muscle fibre reinnervation becomes apparent. Blind counting of the number of reinnervated motor endplates and the length of the synaptophysin-positive staining was used to assess the effect of CNTF treatment on muscle fibre reinnervation in the whisker muscle. On day 10, both treatment groups showed a limited number of reinnervated motor endplates. Both the saline- and CNTF-treated rats showed a significant increase in the percentage of reinnervated motor endplates and in the length of the synaptophysin-positive staining with time. On days 10 and 11, there was no difference in muscle fibre reinnervation between the treated groups. On days 12 and 13, the CNTF-treated rats showed an increased muscle fibre reinnervation which was significant compared to the saline-treated rats. These results suggest that after facial nerve crush in young rats, CNTF enhances muscle fibre reinnervation, most probably by stimulating the intramuscular branching. There is no support for an effect of CNTF on nerve sprouting in the proximal axonal part or on axonal elongation; the CNTF effect on intramuscular branching might be mediated by the muscle fibres.

The neurotrophic analogue of ACTH(4-9) reduces the perineuronal microglial reaction after rat facial nerve crush.

Following peripheral nerve crush, microglial cells proliferate and migrate to motoneuron cell bodies of the injured nerves. Newly formed glial processes displace nerve terminals from the cell bodies. This process is known as synaptic stripping. In animal models of peripheral nerve diseases, the ACTH(4-9) analogue, ORG2766, was shown to facilitate axonal regeneration and to protect against experimental neuropathy. In the present study we examined the effect of ORG2766 on the microglial reaction. After facial nerve crush, rats were treated with either ORG2766 (75 micrograms/kg/48 h) or saline and were killed on day 2-6 after operation. Blind counting of the number of perineuronal glial cells in the facial nucleus was used to assess the effect of ORG2766 treatment on the microglial reaction. In the saline-treated animals the number of perineuronal glial cells per motoneuron cell body on the crushed side increased significantly. This number increased up to day 5 after operation and decreased significantly from day 5 to 6. After an initial increase in the peptide-treated animals, however, the number of perineuronal glial cells remained constant from day 3 onwards. Hence, on post-operation days 4 and 5, this number was significantly less than that seen in saline-treated animals. Microglial cells proliferate, presumably through signalling by injured motoneurons. It is suggested that the decrease in the number of perineuronal glial cells in the ORG2766-treated animals is the result of a peptide-induced reduction in the release of mediating signals/cytokines or, alternatively, increased protection of motoneurons by stress proteins. Further research should address the mechanism of action of ORG2766 in animal models of motoneuron disease.

Upregulation of B-50/GAP-43 in Schwann cells at denervated motor endplates and in motoneurons after rat facial nerve crush.

Crush or transection of peripheral nerves of the adult rat is accompanied by changes in protein expression, including the growth associated protein (GAP-43) B-50. Following peripheral nerve crush in rat enhanced B-50 immunoreactivity was observed in regenerating nerve fibres and in newly formed axon terminals. However, before reinnervation was apparent, an unexpected transient increase in B-50 immunoreactivity was observed at denervated motor endplates [J. Neurosci. 8 (1988) 1759]. This study was performed to clarify this observation. Four days following facial nerve crush B-50 immunoreactivity was detected by double immunofluorescence microscopy in Sl00-positive Schwann cells covering the denervated endplates. Using diluted polyclonal and monoclonal B-50 antibodies we found that B-50 immunoreactivity at the denervated motor endplates was strongly increased in comparison to innervated motor endplates in which B-50 immunoreactivity was hardly detectable. However, when a high concentration of B-50 antibodies was applied the normal innervated motor endplates were also B-50 immunoreactive. Muscle fibres did not display B-50 immunoreactivity. Northern blot analysis revealed elevated B-50 mRNA in denervated muscle and in degenerating nerve with respect to the controls. The B-50 mRNA levels in these non-neuronal tissues were very low compared to the intact and injured facial nucleus containing the neuronal cell bodies. Electron microscopy demonstrated that the B-50 protein was localized in the processes of Schwann cells covering axon terminals of intact and vacant motor endplates and in axon varicosities of sympathetic nerves. This study has confirmed that prior to reinnervation B-50 immunoreactivity is increased at denervated motor endplates and shows that B-50 is co-localized with S100 in Schwann cells. Therefore, upregulation of B-50 expression in Schwann cells may explain the early occurrence of B-50 immunoreactivity at the motor endplate.

Basal and electrically stimulated release of [3H]noradrenaline and [3H]dopamine from rat amygdala slices in vitro: effects of 4 beta-phorbol 12,13-dibutyrate, 4 alpha-phorbol 12,13-didecanoate and polymyxin B.

The protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDB) enhanced in a concentration-dependent manner the electrically stimulated release of [3H]noradrenaline ([3H]NA) and [3H]dopamine ([3H]DA) from rat amygdala slices in vitro. PDB enhanced the basal release of [3H]NA and [3H]DA as well. 4 alpha-Phorbol 12,13-didecanoate, which lacks the capacity to activate protein kinase C, was without effect on either basal or electrically stimulated release of [3H]NA and [3H]DA. Polymyxin B, which is a relatively selective protein kinase C inhibitor, decreased in a concentration-dependent manner the electrically stimulated release of both [3H]NA and [3H]DA from amygdala slices, whereas it enhanced the basal release of both neuromessengers. In the presence of 1.5 X 10(-7) M PDB, a concentration which when added to the superfusion medium alone doubled the electrically stimulated release of both [3H]NA and [3H]DA, polymyxin B again decreased in a concentration-dependent manner the release of both neuromessengers. At all polymyxin B concentrations used, the effect of the PKC inhibitor, expressed as percent inhibition, in the presence of PDB was approximately the same as that observed in the absence of PDB. This suggests that the antagonism between PDB and polymyxin B at the level of protein kinase C is not a competitive one. The effects of PDB and polymyxin B on basal release were additive. Taken together, these data suggest that in the amygdala presynaptically localized protein kinase C plays a role in signal transduction processes related to the exocytotic secretion of NA and DA from their nerve terminals.