Pilot study demonstrates that placental histology can provide an additional tool for diagnosing early-onset neonatal sepsis.

AIM: We explored whether placental histology could help to diagnose early-onset neonatal sepsis (EONS), guide clinical decision-making 48 hours after birth and reduce antibiotic use. METHODS: This study comprised 109 infants born at less than 32 weeks of gestation, who were admitted to the neonatal intensive care unit of Isala, Zwolle, The Netherlands, between January 2013 and December 2013. EONS was defined as clinical symptoms plus raised serial C-reactive protein (CRP) >10 mg/L and a positive (proven EONS) or a negative (suspected EONS) blood culture. Placentas were studied for a histological inflammatory response and scored according to Redline's criteria. RESULTS: A histological inflammatory response was seen in 15/88 (17%) placentas and this occurred significantly more often in infants with a high suspicion of EONS (p < 0.05). No histological inflammatory response was seen if maternal risk factors for EONS were absent, despite a raised CRP level. Based on placental histology, the duration of antibiotic therapy was reduced from more than five days to 48 hours in 20/27 infants (74%). CONCLUSION: Histological examination of the placenta helped to diagnose EONS and guide clinical decision-making 48 hours after birth and led to a clinically relevant reduction in antibiotic use.

Rehabilitation Enablement in Chronic Heart Failure-a facilitated self-care rehabilitation intervention in patients with heart failure with preserved ejection fraction (REACH-HFpEF) and their caregivers: rationale and protocol for a single-centre pilot randomised controlled trial.

INTRODUCTION: The Rehabilitation EnAblement in CHronic Heart Failure in patients with Heart Failure (HF) with preserved ejection fraction (REACH-HFpEF) pilot trial is part of a research programme designed to develop and evaluate a facilitated, home-based, self-help rehabilitation intervention to improve self-care and quality of life (QoL) in heart failure patients and their caregivers. We will assess the feasibility of a definitive trial of the REACH-HF intervention in patients with HFpEF and their caregivers. The impact of the REACH-HF intervention on echocardiographic outcomes and bloodborne biomarkers will also be assessed. METHODS AND ANALYSIS: A single-centre parallel two-group randomised controlled trial (RCT) with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention) or usual care alone (control) in 50 HFpEF patients and their caregivers. The REACH-HF intervention comprises a REACH-HF manual with supplementary tools, delivered by trained facilitators over 12 weeks. A mixed methods approach will be used to assess estimation of recruitment and retention rates; fidelity of REACH-HF manual delivery; identification of barriers to participation and adherence to the intervention and study protocol; feasibility of data collection and outcome burden. We will assess the variance in study outcomes to inform a definitive study sample size and assess methods for the collection of resource use and intervention delivery cost data to develop the cost-effectiveness analyses framework for any future trial. Patient outcomes collected at baseline, 4 and 6 months include QoL, psychological well-being, exercise capacity, physical activity and HF-related hospitalisation. Caregiver outcomes will also be assessed, and a substudy will evaluate impact of the REACH-HF manual on resting global cardiovascular function and bloodborne biomarkers in HFpEF patients. ETHICS AND DISSEMINATION: The study is approved by the East of Scotland Research Ethics Service (Ref: 15/ES/0036). Findings will be disseminated via journals and presentations to clinicians, commissioners and service users. TRIAL REGISTRATION NUMBER: ISRCTN78539530; Pre-results .

Clinical effectiveness and cost-effectiveness of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) facilitated self-care rehabilitation intervention in heart failure patients and caregivers: rationale and protocol for a multicentre randomised controlled trial.

INTRODUCTION: The Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) trial is part of a research programme designed to develop and evaluate a health professional facilitated, home-based, self-help rehabilitation intervention to improve self-care and health-related quality of life in people with heart failure and their caregivers. The trial will assess the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in patients with systolic heart failure and impact on the outcomes of their caregivers. METHODS AND ANALYSIS: A parallel two group randomised controlled trial with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention group) or usual care alone (control group) in 216 patients with systolic heart failure (ejection fraction <45%) and their caregivers. The intervention comprises a self-help manual delivered by specially trained facilitators over a 12-week period. The primary outcome measure is patients' disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure questionnaire at 12 months' follow-up. Secondary outcomes include survival and heart failure related hospitalisation, blood biomarkers, psychological well-being, exercise capacity, physical activity, other measures of quality of life, patient safety and the quality of life, psychological well-being and perceived burden of caregivers at 4, 6 and 12 months' follow-up. A process evaluation will assess fidelity of intervention delivery and explore potential mediators and moderators of changes in health-related quality of life in intervention and control group patients. Qualitative studies will describe patient and caregiver experiences of the intervention. An economic evaluation will estimate the cost-effectiveness of the REACH-HF intervention plus usual care versus usual care alone in patients with systolic heart failure. ETHICS AND DISSEMINATION: The study is approved by the North West-Lancaster Research Ethics Committee (ref 14/NW/1351). Findings will be disseminated via journals and presentations to publicise the research to clinicians, commissioners and service users. TRIAL REGISTRATION NUMBER: ISRCTN86234930; Pre-results.

Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants.

AIM: The therapeutic options available to treat neonatal pain are limited, and one alternative for nonopioid systemic treatment is paracetamol. However, pharmacokinetic data from prolonged administration of intravenous paracetamol in neonates are limited. The aim of this study was to present pharmacokinetics after multiple dose of intravenous paracetamol in very preterm infants of <32 weeks' gestation. METHODS: Fifteen very preterm infants received five, six-hourly doses of intravenous paracetamol (7.5 mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites. RESULTS: A two-compartment pharmacokinetic model gave the best fit for all individual patients and resulted in a predictable pharmacokinetic profile. The estimated pharmacokinetic population parameters were volume of distribution 0.764 ± 0.225 L/kg, elimination rate constant (ke ) 0.117 ± 0.091/h and intercompartment rate constants k12 0.607 ± 0.734/h and k21 1.105 ± 0.762/h. CONCLUSION: Our study found that multiple doses of intravenous paracetamol resulted in a predictable pharmacokinetic profile in very preterm infants. Increases in postmenstrual age and weight were associated with increased clearance. No evidence of hepatotoxicity was found.

Feasibility and reliability of PRISMA-medical for specialty-based incident analysis.

AIMS AND OBJECTIVES: In this study, the feasibility and reliability of the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method for systematic, specialty-based analysis and classification of incidents in the neonatal intensive care unit (NICU) were determined. METHODS: After the introduction of a Neonatology System for Analysis and Feedback on Medical Events (NEOSAFE) in eight tertiary care NICUs and one paediatric surgical ICU, PRISMA-Medical was started to be used to identify root causes of voluntary reported incidents by multidisciplinary unit patient safety committees. Committee members were PRISMA-trained and familiar with the department and its processes. In this study, the results of PRISMA-analysis of incidents reported during the first year are described. At t = 3 months and t = 12 months after introduction, test cases were performed to measure agreement at three levels of root cause classification using PRISMA-Medical. Inter-rater reliability was determined by calculating generalised kappa values for each level of classification. RESULTS: During the study period, 981 out of 1786 eligible incidents (55%) were analysed for underlying root causes. In total, 2313 root causes were identified and classified, giving an average of 2.4 root causes for every incident. Although substantial agreement (kappa 0.70-0.81) was reached at the main level of root cause classification of the test cases (discrimination between technical, organisational and human failure) and agreement among the committees at the second level (discrimination between skill-based, rule-based and knowledge-based errors) was acceptable (kappa 0.53-0.59), discrimination between rule-based errors (the third level of classification) was more difficult to assess (kappa 0.40-0.47). CONCLUSION: With some restraints, PRISMA-Medical proves to be both feasible and acceptably reliable to identify and classify multiple causes of medical events in the NICU.

Neonatal procedural pain exposure and pain management in ventilated preterm infants during the first 14 days of life.

OBJECTIVES: Ventilated preterm infants are at high risk for procedural pain exposure. In Switzerland there is a lack of knowledge about the pain management in this highly vulnerable patient population. The aims of this study were to describe the type and frequency of procedures and to determine the amount of analgesia given to this patient group in two Swiss neonatal intensive care units. METHOD: A retrospective cohort study was performed examining procedural exposure and pain management of a convenience sample of 120 ventilated preterm infants (mean age = 29.7 weeks of gestation) during the first 14 days of life after delivery and born between May 1st 2004 and March 31st 2006. RESULTS: The total number of procedures all the infants underwent was 38,626 indicating a mean of 22.9 general procedures performed per child and day. Overall, 75.6% of these procedures are considered to be painful. The most frequently performed procedure is manipulation on the CPAP prongs. Pain measurements were performed four to seven times per day. In all, 99.2% of the infants received either non-pharmacological and/or pharmacological agents and 70.8% received orally administered glucose as pre-emptive analgesia. Morphine was the most commonly used pharmacological agent. DISCUSSION: The number of procedures ventilated preterm infants are exposed to is disconcerting. Iatrogenic pain is a serious problem, particularly in preterm infants of low gestational age. The fact that nurses assessed pain on average four to seven times daily per infant indicates a commitment to exploring a painful state in a highly vulnerable patient population. In general, pharmacological pain management and the administration of oral glucose as a non-pharmacological pain relieving intervention appear to be adequate, but there may be deficiencies, particularly for extremely low birth weight infants born <28 weeks of gestation.

Loss of triglycerides and carotenoids in human milk after processing.

OBJECTIVE: Human milk (HM) is considered to be the best nutrition for preterm infants. However, storage, heating or tube feeding can cause a decline in essential nutrients, which can lead to the loss of antioxidant vitamins, resulting in an increased risk for oxygen radical diseases. Recently we found that carotenoids, present in human milk, can play a role in the antioxidant protection of preterm infants. In this study we evaluated the effect of processing HM and infant formula on the triglycerides and carotenoid concentrations. DESIGN: The triglyceride, alpha- and beta-carotene, lutein and lycopene concentrations of 30 samples of mature HM of mothers who delivered a term infant and 10 samples of infant formula were measured after refrigeration, freezing, microwave heating and tube feeding with and without exposure to normal light and phototherapy, imitating the clinical feeding routine in the NICU. RESULTS: After tube feeding triglyceride, lutein and beta-carotene concentrations decreased with 33%, 35% and 26% respectively. The decrease in triglycerides in HM accounts for 16% of the total caloric intake of neonates. Triglyceride and carotenoid concentrations in HM remained stable after refrigeration, freezing or low temperature microwave heating, except for lutein which decreased after refrigeration and freezing. In infant formula no differences were found. CONCLUSIONS: Mature human milk can be stored safely in a freezer and heated in a microwave oven without loss of fat or carotenoids. The clinically important loss of fat during tube feeding is probably the most important contributing factor to the decrease in lutein and beta-carotene in tube feeding, with only a small role for peroxidation during light-exposure.

Prognostic and accuracy data of multidetector CT coronary angiography in an established clinical service.

AIM: To assess the accuracy of clinical coronary computed tomography angiography (CTA) data compared to invasive coronary angiography, and to determine the prognostic value of a negative coronary CTA examination in symptomatic, intermediate-risk patients. METHODS: Thirty-seven months of coronary CTA data were audited. Seventy-eight patients were identified who had undergone coronary CTA followed by invasive coronary angiography (ICA) to determine the accuracy of CTA versus ICA. One hundred and seventy-eight patients were identified who had a "negative" coronary CTA to enable evaluation of the prognostic value of a negative CTA examination. RESULTS: Of the 78 patients in the accuracy analysis group there were 43 true-negative, two false-negative, 26 true-positive, and seven false-positive results producing a sensitivity of 92.9%, specificity of 86%, negative predictive value of 95.6%, and positive predictive value of 78.8%. The 178 patients who had a negative coronary CTA examination were followed up for a mean of 366 days and were all alive (0% mortality) with no episodes of myocardial infarction or unstable angina; two patients underwent elective revascularization procedures (1.1%). CONCLUSION: According to medium-term analysis, the accuracy of the clinical coronary CTA programme is in line with published trial data, producing excellent sensitivity and negative predictive values. The finding of a negative coronary CTA in symptomatic, intermediate-risk patients appears to confer a good prognosis, at mean follow-up of 1 year, with no deaths or episodes of myocardial infarction or unstable angina. This suggests that the prognostic value of a negative coronary CTA may be similar to that conferred by negative myocardial perfusion scintigraphy or stress echocardiography.

Body temperature measurement in VLBW infants by continuous skin measurement is a good or even better alternative than continuous rectal measurement.

BACKGROUND: An inadequate body temperature in preterm infants influences morbidity and mortality. Continuous rectal measurement is a reliable method to measure body temperature but might have adverse effects and is even contra-indicated in case of low platelets or necrotising enterocolitis. A save and non-invasive method to measure body temperature is the transcutaneous 'zero heat flow' method. AIM: We hypothesised that for monitoring body temperature in very low birth weight (VLBW) infants, central measurement of temperature by way of the zero heat flow principle is just as reliable as rectal temperature. METHODS: Twenty-six infants, birth weight between 520 g and 1250 g, gestational age 25.28-32.28 weeks were provided with an insulated continuous skin probe with 'zero heat flow' and a continuous rectal probe. Both measurements were registered every hour over a period of 48 h. The sample size was calculated to detect a difference of less than or equal to 0.20 degrees C. RESULTS: 1205 of the 1248 temperature measurements were analysed. At any moment, skin temperature was higher or equal when compared to rectal temperature. Mean skin temperature was 0.13 degrees C (SD 0.33) higher than mean rectal temperature (t-test, p < 0.001). Correlation between rectal and skin temperature was 0.82 (p

Specialty-based, voluntary incident reporting in neonatal intensive care: description of 4846 incident reports.

OBJECTIVES: To examine the characteristics of incidents reported after introduction of a voluntary, non-punitive incident reporting system for neonatal intensive care units (NICUs) in the Netherlands; and to investigate which types of reported incident pose the highest risk to patients in the NICU. DESIGN: Prospective multicentre survey. METHODS: Voluntary, non-punitive incident reporting was introduced in eight level III NICUs and one paediatric surgical ICU. An incident was defined as any unintended event which (could have) reduced the safety margin for the patient. Multidisciplinary, unit-based patient safety committees systematically collected and analysed incident reports, and assigned risk scores to each reported incident. Data were centrally collected for specialty-based analysis. This paper describes the characteristics of incidents reported during the first year. Bivariate logistic regression analysis was conducted to identify high-risk incident categories. RESULTS: There were 5225 incident reports on 3859 admissions, of which 4846 were eligible for analysis. Incidents with medication were most frequently reported (27%), followed by laboratory (10%) and enteral nutrition (8%). Severe harm was described in seven incident reports, and moderate harm in 63 incident reports. Incidents involving mechanical ventilation and blood products were most likely to be assigned high-risk scores, followed by those involving parenteral nutrition, intravascular lines and medication dosing errors. CONCLUSIONS: Incidents occur much more frequently in Dutch NICUs than has been previously observed, and their impact on patient morbidity is considerable. Reported incidents concerning mechanical ventilation, blood products, intravascular lines, parenteral nutrition and medication dosing errors pose the highest risk to patients in the NICU.

Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies.

BACKGROUND: Therapies targeting the T cell-mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T-cell counts in both compartments have been conducted in order to confirm or refute the hypothesized shifts between them. OBJECTIVES: To gain more insight in the dynamics of compartmentalization of T cells between PB and lesional skin of patients with psoriasis, in response to immune-targeted antipsoriatic therapies. METHODS: Eighteen patients with psoriasis received either efalizumab (n = 9) or etanercept (n = 9) for 12 weeks. Biopsies were taken for immunohistochemical analysis of T-cell subsets and simultaneously T-cell subsets were isolated from PB specimens by flow cytometry. RESULTS: The Psoriasis Area and Severity Index declined significantly after 12 weeks of etanercept, but not for efalizumab. After treatment with efalizumab, a significantly decreased number of all T-cell subsets was found in the dermis. In the epidermis, CD4+, CD8+, CD25+, CD45RO+ and CD161+ T-cell subsets were significantly decreased. With respect to etanercept, few significant changes in T-cell subsets were found. The percentage of lymphocytes in PB was significantly elevated after efalizumab treatment regardless of responder status. CONCLUSIONS: Treatment with efalizumab establishes successful recompartmentalization of T-cell subsets with modest clinical efficacy after 12 weeks, whereas in etanercept-treated patients, a significant clinical response is no guarantee for significant changes in T-cell subsets in the different compartments. Reductions in T-cell subsets cannot be used as predictive markers for the clinical response to therapy. Interference with the studied T-cell populations in its own right seems not to be responsible for the clinical efficacy of efalizumab and etanercept.

Distribution of dipeptidyl-peptidase IV on keratinocytes in the margin zone of a psoriatic lesion: a comparison with hyperproliferation and aberrant differentiation markers.

The inflammation process in psoriatic skin is characterized by influx of leukocytes, hyperproliferation and aberrant differentiation of keratinocytes regulated via cytokines. Dipeptidyl-peptidase IV (DPPIV) is known to be upregulated on keratinocytes in the psoriatic lesion. The objective was to gain insight into dynamics of DPPIV expression and enzyme activity together with keratinocyte proliferation and differentiation markers during development of a psoriatic lesion, in order to investigate coherence in mechanisms behind the upregulation of DPPIV in psoriatic skin. The expression of DPPIV, Ki-67 antigen and keratin-16 (K16) was studied in the dynamic margin zone of the psoriatic lesion, examining skin sections of the clinically uninvolved skin, the early lesion and the chronic lesion of psoriatic patients compared to healthy volunteers using immunohistochemical and enzymehistochemical staining methods. DPPIV-expression and enzyme activity, Ki-67 antigen and K16 are significantly upregulated in the centre and inner margin of the lesion compared to clinically uninvolved skin and the healthy volunteers skin. Mutually between the centre and inner margin, this upregulation did not differ significantly. The clinical symptomless skin proved to have significantly elevated DPPIV enzyme activity compared to the skin of healthy volunteers. We demonstrate that DPPIV is expressed and enzymatically active well before the development of an overt psoriatic lesion. The abnormal DPPIV distribution in psoriatic skin does not coincide with known markers of aberrant growth and differentiation of keratinocytes, which makes DPPIV (expression and enzyme activity) a marker standing on its own.

[Guideline for imminent preterm birth: insufficient adherence and implementation]. / Richtlijnen bij dreigende vroeggeboorte: onvoldoende afstemming en implementatie.

The guideline for referral to perinatology centres in cases of imminent preterm birth at 24-26 weeks gestation, is poorly adhered to by Dutch gynaecologists. Unfortunately, the guideline can be interpreted in various ways and the reasons for non-adherence remain unclear. In addition, no measures were taken to implement the guideline when it was published. This means that the usefulness of the finding that the guideline is poorly adhered to is limited.

CD26/dipeptidyl-peptidase IV in psoriatic skin: upregulation and topographical changes.

BACKGROUND: Psoriasis is known to affect 2-3% of the population and can be considered an organ-specific autoimmune disease. CD26/dipeptidyl-peptidase IV (DPP-IV) is a membrane-bound protease with diverse properties. In theory, the expression of CD26/DPP-IV has common grounds with three principal key players of the psoriatic pathogenesis: keratinocytes, T cells and cytokines. OBJECTIVES: To assess CD26/DPP-IV expression in psoriasis in order to expand on the search for complementary biomarkers related to inflammation and proliferation in psoriasis. METHODS: The pattern of expression of CD26/DPP-IV was investigated on the mRNA-, protein- and enzyme-functionality level using immunohistochemical, immunofluorescent and enzyme activity labelling techniques. RESULTS: An 11-fold significant increase of CD26/DPP-IV on the mRNA level was demonstrated in psoriatic epidermal sheets compared with normal skin. Immunohistochemistry on psoriatic sections showed a distinct patchy honeycomb-like CD26/DPP-IV staining in the suprapapillary layers. Moreover, a clearly distinguishable column-like staining pattern throughout the suprabasal compartment along the rete ridges was seen, whereas in normal skin these patterns were absent. Strikingly, CD26/DPP-IV enzyme activity correlated with this immunohistochemical reactivity pattern for the CD26/DPP-IV protein. The T-cell bound expression of CD26/DPP-IV in psoriatic skin was explicitly present, albeit in small quantities. CONCLUSIONS: Our data provide clear evidence for a versatile upregulation of CD26/DPP-IV expression in psoriatic (epi)dermis. Although the exact functional contribution remains speculative, the topographical distribution of this complex multifunctional protein suggests a suitable role as a complementary biomarker in psoriasis.

Imaging the heart valves using ECG-gated 64-detector row cardiac CT.

Multi-detector row cardiac CT imaging demonstrates clinical usefulness in valvular heart disease, for which CT has not been traditionally used. Electrocardiographic (ECG)-gated CT coronary angiography also has an established clinical role with an increasingly solid evidence base, and the same data set in these patients also provides valuable information about chamber and valvular structure and function; this information should also be considered when interpreting cardiac CT and non-ECG gated thoracic imaging. Although true flow data cannot be achieved using CT, as with echocardiography and MRI, there are a number of imaging features that may be used when interpreting and inferring valve pathology. This article discusses the role of currently available imaging modalities and the rationale for cardiac CT, while focusing on the CT interpretation of valvular heart disease with respect to the relevant pathophysiology and management options that have importance to the radiologist. A suggested method of post-processing image review is provided with reference to a variety of normal and pathological pictorial illustrations.

Incidents and errors in neonatal intensive care: a review of the literature.

OBJECTIVES: To examine the characteristics of incident reporting systems in neonatal intensive care units (NICUs) in relation to type, aetiology, outcome and preventability of incidents. METHODS: Systematic review. SEARCH STRATEGY: Medline, Embase, Cochrane Library. Included: relevant systematic reviews, randomised controlled trials, observational studies and qualitative research. Excluded: non-systematic reviews, expert opinions, case reports and letters. PARTICIPANTS: hospital units supplying neonatal intensive care. INTERVENTION: none. OUTCOME: characteristics of incident reporting systems; type, aetiology, outcome and preventability of incidents. RESULTS: No relevant systematic reviews or randomised controlled trials were found. Eight prospective and two retrospective studies were included. Overall, medication incidents were most frequently reported. Available data in the NICU showed that the total error rate was much higher in studies using voluntary reporting than in a study using mandatory reporting. Multi-institutional reporting identified rare but important errors. A substantial number of incidents were potentially harmful. When a system approach was used, many contributing factors were identified. Information about the impact of system changes on patient safety was scarce. CONCLUSIONS: Multi-institutional, voluntary, non-punitive, system based incident reporting is likely to generate valuable information on type, aetiology, outcome and preventability of incidents in the NICU. However, the beneficial effects of incident reporting systems and consecutive system changes on patient safety are difficult to assess from the available evidence and therefore remain to be investigated.

Epidemiology of neonatal group B streptococcal disease in the Netherlands before and after introduction of guidelines for prevention.

OBJECTIVES: (1) To describe the epidemiology of neonatal group B streptococcal (GBS) disease over five years (1997-2001) in the Netherlands, stratified for proven and probable sepsis and for very early (<12 h), late early (12 h - <7 days) and late (7-90 days) onset sepsis. (2) To evaluate the effect of the introduction in January 1999 of guidelines for prevention of early onset GBS disease based on risk factors. METHODS: Data on cases were collected in collaboration with the Dutch Paediatric Surveillance Unit and corrected for under-reporting by the capture-recapture technique. RESULTS: Total incidence of proven very early onset, late early onset and late onset GBS sepsis was 0.32, 0.11 and 0.14 per 1000 live births, respectively, and of probable very early onset, late early onset and late onset GBS sepsis was 1.10, 0.18 and 0.02 per 1000 live births, respectively. Maternal risk factors were absent in 46% of the proven early onset cases. Considerably more infants with proven GBS sepsis were boys. 64% of the infants with proven very early onset GBS sepsis were first born compared with 47% in the general population. After the introduction of guidelines the incidence of proven early onset sepsis decreased considerably from 0.54 per 1000 live births in 1997-8 to 0.36 per 1000 live births in 1999-2001. However, there was no decrease in the incidence of meningitis and the case fatality rate in the first week of life. The incidence of late onset sepsis also remained unchanged. CONCLUSION: After the introduction prevention guidelines based on risk factors there has been a limited decrease in the incidence of proven early onset GBS sepsis in the Netherlands. This study therefore recommends changing the Dutch GBS prevention guidelines.

Morphine in ventilated neonates: its effects on arterial blood pressure.

OBJECTIVE: To study the effects of continuous morphine infusion on arterial blood pressure in ventilated neonates. DESIGN: Blinded randomised placebo controlled trial. SETTING: Level III neonatal intensive care unit in two centres. PATIENTS: A total of 144 ventilated neonates. Inclusion criteria were postnatal age <3 days, ventilation <8 hours, and indwelling arterial line. Exclusion criteria were severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers. INTERVENTION: Arterial blood pressure was measured before the start and during the first 48 hours of masked infusion of drug (morphine/placebo; 100 microg/kg + 10 microg/kg/h). OUTCOME MEASURES: Arterial blood pressure and blood pressure variability. RESULTS: There were no significant differences in overall mean arterial blood pressure between the morphine group (median (interquartile range) 36 mm Hg (6) and the placebo group (38 mm Hg (6)) (p = 0.11). Although significantly more morphine treated patients (70%) showed hypotension than the placebo group (47%) (p = 0.004), the use of volume expanders and vasopressor drugs was not significantly different (morphine group, 44%; placebo group, 48%; p = 0.87), indicating the limited clinical significance of this side effect. Blood pressure variability was not influenced by routine morphine analgesia (p = 0.81) or additional morphine (p = 0.80). Patients with and without intraventricular haemorrhage showed no differences in blood pressure (Mann-Whitney U test 1953; p = 0.14) or incidence of hypotension (chi(2) test 1.16; df 1; p = 0.28). CONCLUSIONS: Overall arterial blood pressure, use of inotropes, and blood pressure variability were not influenced by morphine infusion. Therefore the clinical impact of hypotension as a side effect of low dose morphine treatment in neonates is negligible.

Jaundice as a presentation of heart failure.

On rare occasions the first manifestation of heart disease is jaundice, caused by passive congestion of the liver or acute ischaemic hepatitis. We looked for this presentation retrospectively in 661 patients referred over fifty-six months to a 'jaundice hotline' (rapid access) service. The protocol included a full clinical history, examination and abdominal ultrasound. Those with no evidence of biliary obstruction had a non-invasive liver screen for parenchymal liver disease and those with suspected heart disease had an electrocardiogram, chest X-ray and echocardiogram. 8 patients (1.2%), bilirubin 31-79 micromol/L, mean 46 micromol/L, had a primary cardiac cause for their jaundice. All had dyspnoea, an increased cardiothoracic ratio on chest X-ray and an abnormal electrocardiogram. The jugular venous pressure was raised in the 3 in whom it was recorded. In 6 patients the jaundice was attributed to hepatic congestion and in 2 to ischaemic hepatitis. All patients had severe cardiac dysfunction. Jaundice due to heart disease tends to be mild, and a key feature is breathlessness. The most common mechanism is hepatic venous congestion; ischaemic hepatitis is suggested by a high aminotransferase.