Rush immunotherapy for wasp venom allergy seems safe and effective in patients with mastocytosis.

BACKGROUND: Patients with mastocytosis and wasp venom allergy (WA) may benefit from venom immunotherapy (VIT). However, fatal insect sting reactions have been described in mastocytosis patients despite previous immunotherapy. We investigated the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. OBJECTIVE: To investigate the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. METHODS: We describe nine patients with cutaneous mastocytosis and WA who received VIT. Cutaneous mastocytosis was confirmed by histopathology and systemic mastocytosis was diagnosed according to World Health Organization criteria. VIT was given according to a rush protocol. Given the difference in safety and efficacy of VIT in patients with WA and honeybee venom allergy, we reviewed the literature for VIT with the focus on WA patients with mastocytosis and addressed the difference between patients with cutaneous versus systemic mastocytosis. RESULTS: Nine patients had WA and mastocytosis, of whom six had cutaneous mastocytosis, two combined cutaneous and systemic mastocytosis and one systemic mastocytosis. All patients received rush IT with wasp venom. Most patients had only mild local side effects, with no systemic side effects during the course of VIT. One patient had a systemic reaction upon injection on one occasion, during the updosing phase, with dyspnoea and hypotension, but responded well to treatment. Immunotherapy was continued after temporary dose adjustment without problems. Two patients with a previous anaphylactic reaction were re-stung, without any systemic effects. CONCLUSIONS: VIT is safe in cutaneous mastocytosis patients with WA, while caution has to be made in case of systemic mastocytosis. VIT was effective in the patients who were re-stung.

A trend analysis in referrals during pregnancy and labour in Dutch midwifery care 1988-2004.

OBJECTIVE: To assess the trends and patterns of referral from midwives to obstetricians within the Dutch maternity care system from 1988 to 2004, and the differences in referral patterns between nulliparous and parous women. DESIGN: A descriptive study. SETTING: The Dutch midwifery database (LVR1), which monitored 74% (1988) to 94% (2004) of all midwifery care in the Netherlands between 1988 and 2004. POPULATION: A total of 1 977 006 pregnancies, attended by a primary care level midwife. METHODS: The indications for referral from midwifery to obstetric care were classified into fifteen groups (eight antepartum, six intrapartum and one postpartum). The trends in referrals of these indications were analysed by general linear models. MAIN OUTCOME MEASURES: Trends in the percentage of antepartum, intrapartum and postpartum referrals from midwifery care to obstetric care; trends in the specific indications for referral; contribution of different groups of the indications to the trend. RESULTS: From 1988 to 2004 an increase of 14.5% (from 36.9 to 51.4%) occurred in referrals from primary midwifery care to secondary obstetric care either during pregnancy, childbirth or in the postpartum period. The timing of the referrals was as follows: antepartum +9.0%, intrapartum +5.2% and postpartum +0.3%. In parous women, the increase in referrals was greater (+16.6%) than in nulliparous women (+12.3%) (P = 0.001). The commonest indications for referrals in nulliparous women were anticipated or evident complications due to 'failure to progress in the first or second stage' and 'fetal distress'. Parous women were most commonly referred for anticipated or evident complications due to 'medical history' and 'fetal distress'. In nulliparous women, 52% of the increase in referrals was related to the need of pain relief and occurrence of meconium-stained amniotic fluid; in parous women, 54% of the increase in referrals was related to the general medical and obstetrical history of the women, particularly previous caesarean section, and the occurrence of meconium-stained amniotic fluid. CONCLUSIONS: During a 17-year period, there was a continuous increase in the referral rate from midwives to obstetricians. Previous caesarean section, requirement for pain relief and the presence of meconium-stained amniotic fluid were the main contributors to the changes in referral rates. Primary prevention of caesarean section and antenatal preparation for childbirth are important interventions in the maintenance of primary obstetric care for low-risk pregnant women.

Perinatal mortality and morbidity in a nationwide cohort of 529,688 low-risk planned home and hospital births.

OBJECTIVE: To compare perinatal mortality and severe perinatal morbidity between planned home and planned hospital births, among low-risk women who started their labour in primary care. DESIGN: A nationwide cohort study. SETTING: The entire Netherlands. POPULATION: A total of 529,688 low-risk women who were in primary midwife-led care at the onset of labour. Of these, 321,307 (60.7%) intended to give birth at home, 163,261 (30.8%) planned to give birth in hospital and for 45,120 (8.5%), the intended place of birth was unknown. METHODS: Analysis of national perinatal and neonatal registration data, over a period of 7 years. Logistic regression analysis was used to control for differences in baseline characteristics. MAIN OUTCOME MEASURES: Intrapartum death, intrapartum and neonatal death within 24 hours after birth, intrapartum and neonatal death within 7 days and neonatal admission to an intensive care unit. RESULTS: No significant differences were found between planned home and planned hospital birth (adjusted relative risks and 95% confidence intervals: intrapartum death 0.97 (0.69 to 1.37), intrapartum death and neonatal death during the first 24 hours 1.02 (0.77 to 1.36), intrapartum death and neonatal death up to 7 days 1.00 (0.78 to 1.27), admission to neonatal intensive care unit 1.00 (0.86 to 1.16). CONCLUSIONS: This study shows that planning a home birth does not increase the risks of perinatal mortality and severe perinatal morbidity among low-risk women, provided the maternity care system facilitates this choice through the availability of well-trained midwives and through a good transportation and referral system.

Evaluation of 280,000 cases in Dutch midwifery practices: a descriptive study.

OBJECTIVE: To assess the nature and outcome of intrapartum referrals from primary to secondary care within the Dutch obstetric system. DESIGN: Descriptive study. SETTING: Dutch midwifery database (LVR1), covering 95% of all midwifery care and 80% of all Dutch pregnancies (2001-03). POPULATION: Low-risk women (280,097) under exclusive care of a primary level midwife at the start of labour either with intention to deliver at home or with a personal preference to deliver in hospital under care of a primary level midwife. METHODS: Women were classified into three categories (no referral, urgent referral and referral without urgency) and were related to maternal characteristics and to neonatal outcomes. MAIN OUTCOME MEASURES: Distribution of referral categories, main reasons for urgent referral, Apgar score at 5 minutes, perinatal death within 24 hours and referral to a paediatrician within 24 hours. RESULTS: In our study, 68.1% of the women completed childbirth under exclusive care of a midwife, 3.6% were referred on an urgency basis and 28.3% were referred without urgency. Of all referrals, 11.2% were on an urgency basis. The main reasons for urgent referrals were fetal distress and postpartum haemorrhage. The nonurgent referrals predominantly took place during the first stage of labour (73.6% of all referrals). Women who had planned a home delivery were referred less frequently than women who had planned a hospital delivery: 29.3 and 37.2%, respectively (P < 0.001). On average, the mean Apgar score at 5 minutes was high (9.72%) and the peripartum neonatal mortality was low (0.05%) in the total study group. No maternal deaths occurred. Adverse neonatal outcomes occurred most frequently in the urgent referral group, followed by the group of referrals without urgency and the nonreferred group. CONCLUSIONS: Risk selection is a crucial element of the Dutch obstetric system and continues into the postpartum period. The system results in a relatively small percentage of intrapartum urgent referrals and in overall satisfactory neonatal outcomes in deliveries led by primary level midwives.

[Ethnic differences in preference for home delivery and in pregnancy care received by pregnant women]. / Etnische verschillen in de voorkeur voor thuisbevallingen en het zorgtraject dat zwangeren doorlopen.

OBJECTIVE: To investigate differences among pregnant women from various ethnic groups in terms of pregnancy care and the place of delivery. DESIGN: Descriptive, retrospective study. METHOD: Data from the Dutch Perinatal Registries during the period 1995-2002, representing a total of 1,401,892 pregnancies, were linked and analysed for perinatal care, the place of the delivery and the ethnic group of the mother. The ethnic categories defined in the registries were: Dutch, Mediterranean, other European, African, Hindu, Asian and unknown. RESULTS: Other European women and Asian women often started pregnancy care with a midwife and were not often referred to secondary care with an obstetrician. These two groups most often completed the delivery under the care of a midwife (45.3% of other European women and 44.6% of Asian women). As Hindu and African women often started pregnancy care directly with an obstetrician due to medical reasons and were often referred to secondary care during pregnancy or birth, these two groups were least likely to complete their births under the primary care of a midwife (33.1% and 28.0%, respectively). 39% of the Dutch women completed delivery with a midwife. Of those women who started the delivery under the care of a midwife, 3 out of 4 Dutch women, 1 out of 3 Mediterranean women and only 1 out of 5 Hindu women ultimately elected for a home birth. CONCLUSION: Large ethnic differences exist in both pregnancy care and preference for place of delivery and, ultimately, place of birth. This should be taken into account in policy-making and in the provision of information regarding the Dutch midwifery system.

Resistive heating during off-pump coronary bypass surgery.

BACKGROUND: Maintaining normothermia during off-pump coronary artery bypass (OPCAB) surgery is difficult. The purpose of the present study is to determine the effect of the Inditherm Patient Warming System (IPWS) with standard institutional care during OPCAB surgery. METHODS: A control cohort of 10 patients undergoing OPCAB surgery received standard conventional therapy. A study cohort of another 10 patients then underwent similar procedures with the additional use of the IPWS. The nasopharyngeal and rectal temperatures of the two groups were compared during the 4-hour study period. RESULTS: During the 4-hour study period after induction, the Inditherm patients demonstrated significantly improved core body temperatures compared to the control group: lowest rectal temperature: 35.8 +/- 0.4 degrees C vs. 34.8 +/- 0.6 degrees C (p < 0.01) and lowest nasopharyngeal temperature : 35.5 +/- 0.4 degrees C vs. 34.7 +/- 0.5 degrees C (p < 0.01), respectively. The between-group rectal and nasopharyngeal temperature differences reached statistical significance after 70 minutes, 36.2 +/- 0.5 degrees C vs. 35.7 +/- 0.2 degrees C (p < 0.01) and after 60 minutes 35.8 +/- 0.4 degrees C vs. 35.4 +/- 0.1 degrees C (p < 0.01), respectively. At the end, the rectal core temperatures were 36.1 +/- 0.6 degrees C vs. 34.9 +/- 0.6 degrees C (p < 0.01) and the nasopharyngeal temperatures were 35.8 +/- 0.6 degrees C vs. 34.8 +/- 0.5 degrees C (p < 0.01) in the study and the control groups, respectively. CONCLUSION: The combination of the IPWS with standard thermal care provides higher core temperatures during OPCAB surgery.

[Systemic mastocytosis: a heterogeneous disease]. / Systemische mastocytose: een heterogene ziekte.

Systemic mastocytosis (SM) is an acquired myeloproliferative disease, which is caused by an uncontrolled proliferation of aberrant mast cells. SM patients can have very different clinical phenotypes and may therefore initially present to different specialties. Diagnosis is often delayed because many physicians are unfamiliar with this illness. This can lead to substantial morbidity and puts patients at risk of complications such as severe anaphylaxis. Measurement of serum tryptase levels is always a sensible first step in the diagnostic work-up, but a normal serum tryptase does not rule out SM completely, and a bone marrow biopsy is essential for a conclusive diagnosis. Here, we describe two patient cases to illustrate the heterogeneous nature of this disease, and provide an overview of the symptoms, diagnostic work-up and current treatments options for SM.

Gender-dependent regulation of glutamate dehydrogenase expression in periportal and pericentral zones of rat liver lobules.

We studied the level(s) at which glutamate dehydrogenase (GDH; EC 1.4.1.2) expression is regulated in the livers of fed male and female rats. The cellular content of GDH mRNA, protein, and enzyme activity was determined quantitatively using image analysis for measurement of the absorbance in consecutive serial sections that were processed for in situ hybridization, immunohistochemistry, and enzyme histochemistry. In both males and females, GDH protein and activity patterns were similar, with pericentral values being twice as high as periportal values. GDH mRNA distribution patterns in female liver lobules reflected those of GDH protein and activity, but GDH mRNA distribution patterns in male rat livers were found to be homogeneous owing to a more than twofold lower cellular mRNA content in pericentral zones than in female rats. We conclude that gender affects GDH expression selectively in pericentral zones at posttranscriptional and pretranslational levels.

Evidence of hemispheric specialization in marmosets (Callithrix penicillata) using tympanic membrane thermometry.

Recent studies have employed tympanic thermometry to assess lateralization of cognitive and emotional functions in primates. However, no studies using this technique have investigated the possibility of hemispheric specialization in New World monkeys. Therefore, the aim of the present study was to investigate tympanic membrane (TM) temperature asymmetries and their possible correlation with stress responses in marmosets (Callithrix penicillata). Infrared TM thermometry was completed bilaterally in 24 animals (14 males and 10 females) during a stressful situation of capture and restraint. There were no significant differences between gender. A significant negative correlation was observed between TM temperature of the right ear and the number of captures (r = -0.633; P<0.001). Subjects with a more frequent previous history of captures (5 to 9 captures; N = 11) showed lower TM temperature when compared to those with fewer previous captures (1 to 4 captures; N = 13). No differences were observed for the left TM temperature. These results suggest that under intense emotional challenge (capture and restraint) there is a stronger activation of the neural structures situated in the right brain hemisphere. Taken together, the data reveal for the first time evidence of hemispheric specialization in emotional physiological processing in a New World monkey.

Randomised clinical trial on the effect of the Dutch obstetric peer review system.

The project "Obstetric Peer Review Interventions" (Verloskundige Onderlinge Kwaliteitsspiegeling Interventies, VOKSINT) was set-up in The Netherlands in 1994. It provided annual comparison data (quality ranking, league tables) for secondary care obstetric departments adjusted for population differences, based on the data registered in the Perinatal Database of The Netherlands (Landelijke Verloskunde Registratie, LVR). The aim of the so-called VOKS reports was to influence obstetricians' interventions in such a way that they led to a more homogeneous policy. To assess this influence, a trial was set-up, with departments randomly assigned to be or not to be informed about the VOKS results. Obstetric intervention rates and the morbidity of newborns including neonatal neurological examinations (NNEs) were assessed. Obstetric intervention rates were similar in the report group and the control group. Practice in the report group became more homogeneous (adjusted for population differences) than in the control departments, but this was only statistically significant for term caesarean section.

Suboptimal care and perinatal mortality in ten European regions: methodology and evaluation of an international audit.

BACKGROUND: A European concerted action (the EuroNatal study) investigated differences in perinatal mortality between countries of Europe. This report describes the methods used in the EuroNatal international audit and discusses the validity of the results. METHODS: Perinatal deaths between 1993 and 1998 in regions of ten European countries were identified. The categories of death chosen for the study were singleton fetal deaths at 28 or more weeks of gestational age, all intrapartum deaths at 28 or more weeks of gestational age and neonatal deaths at 34 or more weeks of gestational age. Deaths with major congenital anomalies were excluded. An international audit panel used explicit criteria to review all cases, which were blinded for region. Subjective interpretation was used in cases of events or interventions where explicit criteria did not exist. Suboptimal factors were identified in the antenatal, intrapartum and neonatal periods, and classified as 'maternal/social', due to 'infrastructure/service organization', or due to 'professional care delivery'. The contribution of each suboptimal factor to the fatal outcome was listed and consensus was reached on a final grade using a procedure that included correspondence and plenary meetings. RESULTS: In all regions combined, 90% of all known or estimated cases in the selected categories were included in the audit. In total, 1619 cases of perinatal death were audited. Consensus was reached in 1543 (95%) cases. In 75% of all cases, the grade was based on explicit criteria. In the remaining cases, consensus was reached within subpanels without reference to predefined criteria. There was reasonable to good agreement between and within subpanels, and within panel members. CONCLUSIONS: The international audit procedure proved feasible and led to consistent results. The results that relate to suboptimal care will need to be studied in depth in order to reach conclusions about their implications for assessing the quality of perinatal care in the individual regions.

[Evaluation and validation of a perinatal death audit by means of feedback to the caregivers]. / Evaluatie en validatie van perinatale-sterfte-audit door terugkoppeling naar zorgverleners.

OBJECTIVE: To evaluate a perinatal audit procedure by communicating the results to the caregivers (midwives and obstetricians) involved, in order to determine whether the audit led to specific suggestions for improving practice and whether evaluation of the panel assessments by caregivers leads to a different evaluation of the audit process. DESIGN: Descriptive evaluation study. METHOD: Because of privacy regulations, the results of a recently published audit concerning perinatal mortality were reported at an aggregated level. At their own request, two participating hospitals received panel assessment reports of their own cases. The audit procedure, the 77 panel assessments and the care provided were then evaluated during closed meetings with the caregivers affiliated to the respective hospitals. RESULTS: In two audited cases of mortality the caregivers judged the panel's assessments as being too light and as too severe in one other case (Cohen's kappa: 0.98). Detailed case description was considered essential to the audit procedure. While aggregated reporting of audit results provides a general understanding of substandard factors in the care provided, feedback of results on an individual practice level led to specific suggestions for improvement (in relation to medical aspects, patient-caregiver relationship and collaboration between caregivers). Lack of anonymity appeared not to be an issue for the caregivers. CONCLUSION: The feedback of perinatal audit results to the caregivers involved as well as discussion of these results led to specific starting points in the areas of collaboration, documentation and policymaking at both individual and institutional level.

[Perinatal mortality assessed: results of a regional audit]. / Perinatale sterfte getoetst: resultaten van een regionale audit.

OBJECTIVE: To assess the level of suboptimal care prior to cases of perinatal death and the extent to which perinatal mortality can be reduced by further improvements in care. DESIGN: Retrospective panel audit investigation. METHOD: Cases of perinatal death occurring in 1996 and 1997 among women living in the region Zuid-Holland-Noord, the Netherlands, were identified by approaching midwives, obstetricians/gynaecologists and paediatricians/neonatologists. The medical records of the cases were studied by an expert panel using a checklist of evidence-based criteria for standard care in order to determine circumstances and actions that did not comply with professional protocols, or that indicated either low compliance of the mother or an inadequate healthcare infrastructure (so-called sub-standard factors). The panel also assessed whether the perinatal death could have been prevented. RESULTS: A total of 342 perinatal deaths were found. For 332 cases sufficient information was available for a panel assessment and for 318 cases the panel reached a consensus on the assessment. One or more sub-standard care factors were identified in more than half of the cases. In 19% of the cases the panel agreed that the sub-standard factor had 'possibly' contributed to the death, and in 6% they agreed that the sub-standard factor had 'probably' contributed to the death. In the last group the main problems involved were antenatal care (particularly a failure to detect or inadequate management of intrauterine growth retardation) and intrapartum care (too much of a 'wait and see' approach). CONCLUSIONS: This regional audit revealed that further quality improvement of obstetric care is possible if clinical practice guidelines for effective and safe care are better implemented. It is expected that these improvements could reduce the perinatal mortality rate by between 6% and 25%.

Are premature ventricular contractions always harmless?

INTRODUCTION: Premature ventricular contractions (PVCs) are among the most prevalent arrhythmias. PVCs lead to haemodynamically insufficient heartbeats. Their presence is considered rather insignificant, but this widespread assumption is not supported by research evidence. CASES: We present three cases of patients commonly seen in daily general practice, with a range of presentations, varying from incidental (harmless) PVCs to frequent and potentially symptomatic PVCs. DISCUSSION: In more frequent PVCs (> 10% heart beats) fatigue and exertional dyspnoea may occur. When > 20% of heart beats are PVCs, patients may develop cardiomyopathy and heart failure. Incidental PVCs are harmless. Anti-arrhythmic drug treatment should be considered in case of frequent PVCs but also catheter ablation appears an effective treatment option. CONCLUSION: Altogether, PVCs may not be harmless, depending on their occurrence rate. Research data from primary care settings on epidemiology and natural course is needed.

Cost-effectiveness of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal disease.

OBJECTIVE: To estimate the costs and effects of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal (GBS) disease in the Netherlands. The treatment strategies include a risk-based strategy, a screening-based strategy, a combined screening/risk-based strategy and the current Dutch guideline. DESIGN: Cost-effectiveness analysis based on decision model. SETTING: Obstetric care system in the Netherlands. POPULATION/SAMPLE: Hypothetical cohort of 200,000 neonates. METHODS: A decision analysis model was used to compare the costs and effects of different treatment strategies with no treatment. Baseline estimates were derived from literature and a survey among parents of children affected by GBS disease. The analysis was performed from a societal perspective, and costs and effects were discounted at a percentage of 3%. Main outcome measures Cost per quality adjusted of life-year (QALY). RESULT: The risk-based strategy will prevent 352 cases of early-onset GBS for 5.0 million Euros, indicating a cost-effectiveness ratio of 7600 Euros per QALY gained. The combined screening risk-based strategy has comparable results. The current Dutch guideline resulted in lower effects for higher costs. The screening-based strategy shows the highest reduction in cases of early-onset GBS, however, at a cost-effectiveness ratio of 59,300 Euros per QALY gained. Introducing the polymerase chain reaction (PCR) test may lead to a more favourable cost-effectiveness ratio. CONCLUSION: In the Dutch system, the combined screening/risk-based strategy and the risk-based strategy have reasonable cost-effectiveness ratios. If it becomes feasible to add the PCR test, the cost-effectiveness of the combined screening/risk-based strategy may even be more favourable.