The implementation of unit-based perinatal mortality audit in perinatal cooperation units in the northern region of the Netherlands.

BACKGROUND: Perinatal (mortality) audit can be considered to be a way to improve the careprocess for all pregnant women and their newborns by creating an opportunity to learn from unwanted events in the care process. In unit-based perinatal audit, the caregivers involved in cases that result in mortality are usually part of the audit group. This makes such an audit a delicate matter. METHODS: The purpose of this study was to implement unit-based perinatal mortality audit in all 15 perinatal cooperation units in the northern region of the Netherlands between September 2007 and March 2010. These units consist of hospital-based and independent community-based perinatal caregivers. The implementation strategy encompassed an information plan, an organization plan, and a training plan. The main outcomes are the number of participating perinatal cooperation units at the end of the project, the identified substandard factors (SSF), the actions to improve care, and the opinions of the participants. RESULTS: The perinatal mortality audit was implemented in all 15 perinatal cooperation units. 677 different caregivers analyzed 112 cases of perinatal mortality and identified 163 substandard factors. In 31% of cases the guidelines were not followed and in 23% care was not according to normal practice. In 28% of cases, the documentation was not in order, while in 13% of cases the communication between caregivers was insufficient. 442 actions to improve care were reported for 'external cooperation' (15%), 'internal cooperation' (17%), 'practice organization' (26%), 'training and education' (10%), and 'medical performance' (27%). Valued aspects of the audit meetings were: the multidisciplinary character (13%), the collective and non-judgmental search for substandard factors (21%), the perception of safety (13%), the motivation to reflect on one's own professional performance (5%), and the inherent postgraduate education (10%). CONCLUSION: Following our implementation strategy, the perinatal mortality audit has been successfully implemented in all 15 perinatal cooperation units. An important feature was our emphasis on the delicate character of the caregivers evaluating the care they provided. However, the actual implementation of the proposed actions for improving care is still a point of concern.

Reboxetine and cytochrome P450--comparison with paroxetine treatment in humans.

OBJECTIVES: The noradrenaline-selective antidepressant reboxetine in vitro is a weak inhibitor of both cytochrome P450 (CYP) 2D6 and CYP3A4. Thus, in this study the pharmacokinetics of reboxetine in relation to pharmacogenetics and the effects of reboxetine compared to paroxetine treatment on the CYP2D6 and CYP3A4 phenotype were analyzed in healthy control subjects. METHODS: Healthy male volunteers were treated with either 6 mg reboxetine (n = 26) or 30 mg paroxetine (n = 25). On Days 10/11 of treatment, serum concentrations of the antidepressants were measured and pharmacokinetic parameters calculated. Volunteers were phenotyped at the end of treatment and after at least 3 weeks washout (true phenotype) using 30 mg dextromethorphan (DM) hydrobromide given orally and measuring DM and metabolites in serum 2 h after intake. CYP2D6 and CYP2C19 genotypes were determined in parallel. RESULTS AND CONCLUSION: Reboxetine serum concentrations showed no correlation with the CYP2D6 genotype and the CYP2D6 phenotype, whereas paroxetine concentrations showed some dependence on CYP2D6. In contrast to in vitro investigations, indicating a major role of CYP3A4 in reboxetine metabolism, reboxetine concentrations in serum showed no correlation with the respective DM metabolic ratios. There was also no correlation between paroxetine concentrations and the CYP3A4 phenotype data. The CYP2C19 genotype (only heterozygosity) had no influence on reboxetine and paroxetine pharmacokinetics. There were only minor changes in the DM metabolite pattern on treatment with reboxetine and no evidence of enzyme inhibition was obtained. In contrast and as expected, paroxetine strongly inhibited CYP2D6. Thus, reboxetine treatment has no effect on the CYP2D6 genotype and no clinically relevant drug interactions involving CYP2D6 are anticipated.

Increase of phosphodiesters during neuroleptic treatment of schizophrenics: a longitudinal 31P-magnetic resonance spectroscopic study.

BACKGROUND: Increased levels of phosphodiesters (PDE%) and reduced relative concentrations of phosphomonoesters (PME%) have been reported in unmedicated schizophrenics, whereas findings in brain of medicated patients were not consistent. METHODS: We determined in vivo the metabolism of phospholipids and high-energy phosphates in the left and right frontal lobes of 8 patients with schizophrenia using 31P-magnetic resonance spectroscopy (31P-MRS). Serial investigations were performed first after a neuroleptic-free period (mean 7.5 +/- 1.9 days) and second, after neuroleptic treatment (mean 20.6 +/- 11.1 days). RESULTS: PDE% increased significantly in the left frontal lobe (32.0 +/- 5.9% versus 36.9 +/- 5.6%, p = .009) after medication. All other parameters showed no significant differences. CONCLUSIONS: Our study suggests that neuroleptics do not decrease phospholipase A2 activity in schizophrenia. Individual neuroleptics may have different effects on phospholipase A2 activity as indicated by animal studies. An influence of neuroleptics on high-energy phosphates cannot be confirmed by our data.

Pentosidine and N(epsilon)-(carboxymethyl)-lysine in Alzheimer's disease and vascular dementia.

Increasing evidence suggests an interaction of oxidative stress and the formation of advanced glycation end products (AGE) in the onset and progression of Alzheimer's disease. We studied levels of pentosidine and N(epsilon)-(carboxymethyl)-lysine (CML) in serum and cerebrospinal fluid (CSF) of 15 patients with probable Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 31 control subjects (14 matched for age, and 17 younger patients). AGE protein concentrations in CSF did not differ within controls when divided into two subgroups by age. We found significantly elevated levels of CML in CSF of AD patients and of pentosidine in CSF of patients suffering from vascular dementia when compared to controls. The concentrations of pentosidine and CML in serum apparently did not relate directly to CSF values, suggesting influence of extra-cerebral factors in serum samples. It is concluded that AGE proteins are differentially affected in these types of dementia, depending on the specific neuropathology. Furthermore, measurements of AGE products in vivo should rely on CSF rather than blood samples.

[Perinatal audit in the North of the Netherlands: the first 2 years]. / Perinatale audit Noord-Nederland: de eerste 2 jaar.

OBJECTIVE: Description of the implementation of local audit meetings and the identified substandard factors, points of special interest, actions for improvement and the opinion of the participating health care providers. DESIGN: Descriptive study. METHOD: A new organisation and methodology for perinatal mortality audit meetings was introduced in 15 collaborative structures in the northern part of the Netherlands in the period September 2007 to March 2010. During these multidisciplinary audit meetings, cases of perinatal mortality selected by the obstetric collaborative group were discussed in a structured way under the direction of an independent chairman. RESULTS: In total 64 audit meetings were held, in which 677 perinatal health care providers took part at least once, and 112 cases of perinatal death were evaluated. 163 substandard factors were identified. These included : not following the protocol, guideline, standard (31%) or usual care (23%) and insufficient documentation (28%) and communication between health care providers (13%). 442 actions to improve care were reported divided over: 'external collaboration' (15%), 'internal collaboration' (17%), 'practice management' (26%) and 'training and education' (10%). The most valued aspects of the audit meetings were: their multidisciplinary character, the collaborative search for substandard factors, their security, the learning effect and the positive effect on collaboration. CONCLUSION: Cases of perinatal mortality were discussed in all 15 perinatal collaborative structures in the northern part of the Netherlands. Substandard factors were identified, but further analysis of these factors merits attention. The participants concluded that the multidisciplinary approach and the collaboration during the audit meetings improved the cooperation between perinatal health care providers.

[Phosphorus 31 magnetic resonance spectroscopy in schizophrenia research. Pathophysiology of cerebral metabolism of high-energy phosphate and membrane phospholipids]. / 31Phosphor-Magnetresonanzspektroskopie in der Schizophrenieforschung. Zur Pathophysiologie des zerebralen Stoffwechsels energiereicher Phosphate und Membranphospholipide.

31Phosphorus nuclear magnetic resonance spectroscopy (31P-MRS) has gained much interest in schizophrenia research in the last years, since it allows noninvasive measurement of high energy phosphates and phospholipids of the human brain in vivo. Thus, several studies have reported cerebral metabolic differences between patients and healthy controls as well as on lateralization effects and influences of epidemiological and psychopathological factors. This review gives a survey of the potential of 31P-MRS in schizophrenia research and summarizes and comments on the results of preceding studies. The discussion covers the reduction of phospholipids in patients in the context of the membrane phospholipid hypotheses, the question of an energetic hypometabolism in schizophrenics, and the influence of neuroleptic medication.

Frontal lobe in vivo (31)P-MRS reveals gender differences in healthy controls, not in schizophrenics.

Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) has gained much interest in schizophrenia research in recent years since it allows the non-invasive measurement of high-energy phosphates and phospholipids in vivo. However, until now only differences in metabolite concentrations between certain brain areas of schizophrenic patients and healthy controls have been examined. We investigated the influence of gender on the concentrations of different phosphorus compounds. For this purpose, well-defined volumes in the frontal lobe of 32 healthy controls and 51 schizophrenic in-patients were examined with an image selected in vivo spectroscopy (ISIS) sequence on a whole-body scanner at 1.5 T. Healthy females exhibited increased values of inorganic phosphate (P(i)) and decreased values of phosphocreatine (PCr) in comparison to their male counterparts. In schizophrenic patients such gender differences were not present. Thus, the results can be interpreted in the sense that frontal energy demanding processes are enhanced in female compared to male healthy volunteers; schizophrenia seems to reduce these gender differences.