Retrospective analysis of factors influencing the implementation of a program to address unprofessional behaviour and improve culture in Australian hospitals.

BACKGROUND: Unprofessional behaviour among hospital staff is common. Such behaviour negatively impacts on staff wellbeing and patient outcomes. Professional accountability programs collect information about unprofessional staff behaviour from colleagues or patients, providing this as informal feedback to raise awareness, promote reflection, and change behaviour. Despite increased adoption, studies have not assessed the implementation of these programs utilising implementation theory. This study aims to (1) identify factors influencing the implementation of a whole-of-hospital professional accountability and culture change program, Ethos, implemented in eight hospitals within a large healthcare provider group, and (2) examine whether expert recommended implementation strategies were intuitively used during implementation, and the degree to which they were operationalised to address identified barriers. METHOD: Data relating to implementation of Ethos from organisational documents, interviews with senior and middle management, and surveys of hospital staff and peer messengers were obtained and coded in NVivo using the Consolidated Framework for Implementation Research (CFIR). Implementation strategies to address identified barriers were generated using Expert Recommendations for Implementing Change (ERIC) strategies and used in a second round of targeted coding, then assessed for degree of alignment to contextual barriers. RESULTS: Four enablers, seven barriers, and three mixed factors were found, including perceived limitations in the confidential nature of the online messaging tool ('Design quality and packaging'), which had downstream challenges for the capacity to provide feedback about utilisation of Ethos ('Goals and Feedback', 'Access to Knowledge and Information'). Fourteen recommended implementation strategies were used, however, only four of these were operationalised to completely address contextual barriers. CONCLUSION: Aspects of the inner setting (e.g., 'Leadership Engagement', 'Tension for Change') had the greatest influence on implementation and should be considered prior to the implementation of future professional accountability programs. Theory can improve understanding of factors affecting implementation, and support strategies to address them.

Experiences of peer messengers as part of a professional accountability culture change program to reduce unprofessional behaviour: a cross-sectional study across eight hospitals.

Objective Professional accountability programs are designed to promote professional behaviours between co-workers and improve organisational culture. Peer messengers play a key role in professional accountability programs by providing informal feedback to hospital staff about their behaviour. Little is known about the experiences of messengers. This study examined the experiences of staff who delivered messages to peers as part of a whole-of-hospital professional accountability program called 'Ethos'. Methods Ethos messengers (EMs) across eight Australian hospitals were invited to complete an online survey. The survey consisted of 17 close-ended questions asking respondents about their experiences delivering messages to peers and their perceptions of the Ethos program. Four open-ended questions asked respondents about rewarding and challenging aspects of being a peer messenger and what they would change about the program. Results Sixty EMs provided responses to the survey (response rate, 41.4%). The majority were from nursing and medical groups (53.4%) and had delivered 1-5 messages to staff (57.7%). Time as an EM ranged from less than 3 months to more than 12 months. A majority had been an EM for more than 12 months (80%; n = 40). Most agreed they had received sufficient training for the role (90.1%; n = 48) and had the skills (90.1%; n = 48), access to support (84.9%; n = 45) and time to fulfil their responsibilities (70.0%; n = 30). Approximately a third (34.9%; n = 15) of respondents indicated that recipients were 'sometimes' or 'never' receptive to messages. Challenging aspects of the role included organising a time to talk with staff, delivering feedback effectively and communicating with peers who lacked insight and were unable to reflect on their behaviour. Conclusions Skills development for peer messengers is key to ensuring the effectiveness and sustainability of professional accountability programs. Training in how to deliver difficult information and respond to negative reactions to feedback was identified by EMs as essential to support their ongoing effectiveness in their role.

Speaking up as an extension of socio-cultural dynamics in hospital settings: a study of staff experiences of speaking up across seven hospitals.

PURPOSE: The study aimed to understand the significance of how employee personhood and the act of speaking up is shaped by factors such as employees' professional status, length of employment within their hospital sites, age, gender and their ongoing exposure to unprofessional behaviours. DESIGN/METHODOLOGY/APPROACH: Responses to a survey by 4,851 staff across seven sites within a hospital network in Australia were analysed to interrogate whether speaking up by hospital employees is influenced by employees' symbolic capital and situated subjecthood (SS). The authors utilised a Bourdieusian lens to interrogate the relationship between the symbolic capital afforded to employees as a function of their professional, personal and psycho-social resources and their self-reported capacity to speak up. FINDINGS: The findings indicate that employee speaking up behaviours appear to be influenced profoundly by whether they feel empowered or disempowered by ongoing and pre-existing personal and interpersonal factors such as their functional roles, work-based peer and supervisory support and ongoing exposure to discriminatory behaviours. ORIGINALITY/VALUE: The findings from this interdisciplinary study provide empirical insights around why culture change interventions within healthcare organisations may be successful in certain contexts for certain staff groups and fail within others.

Unprofessional behaviours experienced by hospital staff: qualitative analysis of narrative comments in a longitudinal survey across seven hospitals in Australia.

BACKGROUND: Unprofessional behaviours of healthcare staff have negative impacts on organisational outcomes, patient safety and staff well-being. The objective of this study was to undertake a qualitative analysis of narrative responses from the Longitudinal Investigation of Negative Behaviours survey (LION), to develop a comprehensive understanding of hospital staff experiences of unprofessional behaviours and their impact on staff and patients. The LION survey identified staff experiences and perceptions related to unprofessional behaviours within hospitals. METHODS: Two open-ended questions within the LION survey invited descriptions of unprofessional staff behaviours across seven hospitals in three Australian states between December 2017 and November 2018. Respondents were from medical, nursing, allied health, management, and support services roles in the hospitals. Data were qualitatively analysed using Directed Content Analysis (DCA). RESULTS: From 5178 LION survey responses, 32% (n = 1636) of participants responded to the two open-ended questions exploring staff experiences of unprofessional behaviours across the hospital sites surveyed. Three primary themes and 11 secondary themes were identified spanning, i) individual unprofessional behaviours, ii) negative impacts of unprofessional behaviours on staff well-being, psychological safety, and employee experience, as well as on patient care, well-being, and safety, and iii) organisational factors associated with staff unprofessional behaviours. CONCLUSION: Unprofessional behaviours are experienced by hospital staff across all professional groups and functions. Staff conceptualise, perceive and experience unprofessional behaviours in diverse ways. These behaviours can be understood as enactments that either negatively impact other staff, patients or the organisational outcomes of team cohesion, work efficiency and efficacy. A perceived lack of organisational action based on existing reporting and employee feedback appears to erode employee confidence in hospital leaders and their ability to effectively address and mitigate unprofessional behaviours.

Are operating room distractions, interruptions and disruptions associated with performance and patient safety? A systematic review and meta-analysis.

OBJECTIVE: The operating room is a complex environment in which distractions, interruptions and disruptions (DIDs) are frequent. Our aim was to synthesize research on the relationships between DIDs and (i) operative duration, (ii) team performance, (iii) individual performance and (iv) patient safety outcomes in order to better understand how interventions can be designed to mitigate the negative effects of DIDs. METHODS: Electronic databases (MEDLINE, Embase, CINAHL and PsycINFO) and reference lists were systematically searched. Included studies were required to report the quantitative outcomes of the association between DIDs and team performance, individual performance and patient safety. Two reviewers independently screened articles for inclusion, assessed study quality and extracted data. A random-effects meta-analysis was performed on a subset of studies reporting total operative time and DIDs. RESULTS: Twenty-seven studies were identified. The majority were prospective observational studies (n = 15) of moderate quality. DIDs were often defined, measured and interpreted differently in studies. DIDs were significantly associated with extended operative duration (n = 8), impaired team performance (n = 6), self-reported errors by colleagues (n = 1), surgical errors (n = 1), increased risk and incidence of surgical site infection (n = 4) and fewer patient safety checks (n = 1). A random-effects meta-analysis showed that the proportion of total operative time due to DIDs was 22.0% (95% confidence interval 15.7-29.9). CONCLUSION: DIDs in surgery are associated with a range of negative outcomes. However, significant knowledge gaps exist about the mechanisms that underlie these relationships, as well as the potential clinical and non-clinical benefits that DIDs may deliver. Available evidence indicates that interventions to reduce the negative effects of DIDs are warranted, but current evidence is not sufficient to make recommendations about potentially useful interventions.

The prevalence and impact of unprofessional behaviour among hospital workers: a survey in seven Australian hospitals.

OBJECTIVE: To identify individual and organisational factors associated with the prevalence, type and impact of unprofessional behaviours among hospital employees. DESIGN, SETTING, PARTICIPANTS: Staff in seven metropolitan tertiary hospitals operated by one health care provider in three states were surveyed (Dec 2017 - Nov 2018) about their experience of unprofessional behaviours - 21 classified as incivility or bullying and five as extreme unprofessional behaviour (eg, sexual or physical assault) - and their perceived impact on personal wellbeing, teamwork and care quality, as well as about their speaking-up skills. MAIN OUTCOME MEASURES: Frequency of experiencing 26 unprofessional behaviours during the preceding 12 months; factors associated with experiencing unprofessional behaviour and its impact, including self-reported speaking-up skills. RESULTS: Valid surveys (more than 60% of questions answered) were submitted by 5178 of an estimated 15 213 staff members (response rate, 34.0%). 4846 respondents (93.6%; 95% CI, 92.9-94.2%) reported experiencing at least one unprofessional behaviour during the preceding year, including 2009 (38.8%; 95% CI, 37.5-40.1%) who reported weekly or more frequent incivility or bullying; 753 (14.5%; 95% CI, 13.6-15.5%) reported extreme unprofessional behaviour. Nurses and non-clinical staff members aged 25-34 years reported incivility/bullying and extreme behaviour more often than other staff and age groups respectively. Staff with self-reported speaking-up skills experienced less incivility/bullying (odds ratio [OR], 0.53; 95% CI, 0.46-0.61) and extreme behaviour (OR, 0.80; 95% CI, 0.67-0.97), and also less frequently an impact on their personal wellbeing (OR, 0.44; 95% CI, 0.38-0.51). CONCLUSIONS: Unprofessional behaviour is common among hospital workers. Tolerance for low level poor behaviour may be an enabler for more serious misbehaviour that endangers staff wellbeing and patient safety. Training staff about speaking up is required, together with organisational processes for effectively eliminating unprofessional behaviour.

Changes in medication administration error rates associated with the introduction of electronic medication systems in hospitals: a multisite controlled before and after study.

BACKGROUND: Electronic medication systems (EMS) have been highly effective in reducing prescribing errors, but little research has investigated their effects on medication administration errors (MAEs). OBJECTIVE: To assess changes in MAE rates and types associated with EMS implementation. METHODS: This was a controlled before and after study (three intervention and three control wards) at two adult teaching hospitals. Intervention wards used an EMS with no bar-coding. Independent, trained observers shadowed nurses and recorded medications administered and compliance with 10 safety procedures. Observational data were compared against medication charts to identify errors (eg, wrong dose). Potential error severity was classified on a 5-point scale, with those scoring ≥3 identified as serious. Changes in MAE rates preintervention and postintervention by study group, accounting for differences at baseline, were calculated. RESULTS: 7451 administrations were observed (4176 pre-EMS and 3275 post-EMS). At baseline, 30.2% of administrations contained ≥1 MAE, with wrong intravenous rate, timing, volume and dose the most frequent. Post-EMS, MAEs decreased on intervention wards relative to control wards by 4.2 errors per 100 administrations (95% CI 0.2 to 8.3; p=0.04). Wrong timing errors alone decreased by 3.4 per 100 administrations (95% CI 0.01 to 6.7; p<0.05). EMS use was associated with an absolute decline in potentially serious MAEs by 2.4% (95% CI 0.8 to 3.9; p=0.003), a 56% reduction in the proportion of potentially serious MAEs. At baseline, 74.1% of administrations were non-compliant with ≥1 of 10 procedures and this rate did not significantly improve post-EMS. CONCLUSIONS: Implementation of EMS was associated with a modest, but significant, reduction in overall MAE rate, but halved the proportion of MAEs rated as potentially serious.

Observational Tools That Quantify Nontechnical Skills in the Operating Room: A Systematic Review.

BACKGROUND: Errors and adverse events in the operating room (OR) are associated with not only poor technical performance but also deficits in nontechnical skills (NTSs). Numerous tools have been developed to assess NTS in the OR. Our aim was to conduct a systematic review of observational tools and report on their implementation and psychometric properties to guide healthcare professionals, educators, and researchers in tool selection and use. METHODS: A systematic literature search (January 1, 1990-May 28, 2019) was conducted across databases (MEDLINE, Embase, CINAHL, and PsycINFO) and reference lists of included studies. Reviewers independently screened articles for inclusion, assessed study quality, and extracted data. RESULTS: Thirty-one tools were identified across 88 studies, most commonly conducted in a real-world OR (n = 50), involving two observers (n = 50). The NTS of individuals (n = 62) were assessed more often than that of subteams (n = 21) or entire teams (n = 20). The NOn-Technical Skills for Surgeons demonstrated content validity, concurrent validity, predictive validity, and face validity across a range of studies. Oxford NOn-TECHnical Skills demonstrated content validity, concurrent validity, and predictive validity with good inter-rater reliability and test-retest validity. CONCLUSIONS: The NOn-Technical Skills for Surgeons has the strongest evidence of validity and reliability for assessing individuals, whereas the most robust tool for evaluating teams was Oxford NOn-TECHnical Skills. We recommend continued investigation of these observational tools regarding their feasibility and reproducibility of methods. Further research is needed to determine the training requirements for observers and the potential of video and audio recordings in the OR.

Appropriate management of acute gastroenteritis in Australian children: A population-based study.

OBJECTIVES: To determine the proportion of care provided to children with acute gastroenteritis (AGE) in Australia consistent with clinical practice guidelines. METHODS: Indicators were developed from national and international clinical practice guideline (CPG) recommendations and validated by an expert panel. Medical records from children ≤15 years presenting with AGE in three healthcare settings-Emergency Department (ED), hospital admissions and General Practitioner (GP) consultations-from randomly selected health districts across three Australian States were reviewed. Records were audited against 35 indicators by trained paediatric nurses, to determine adherence to CPGs during diagnosis, treatment, and ongoing management. RESULTS: A total of 14,434 indicator assessments were performed from 854 healthcare visits for AGE by 669 children, across 75 GPs, 34 EDs and 26 hospital inpatient services. Documented adherence to guidelines across all healthcare settings was 45.5% for indicators relating to diagnosis (95% CI: 40.7-50.4), 96.1% for treatment (95% CI: 94.8-97.1) and 57.6% for ongoing management (95% CI: 51.3-63.7). Adherence varied by healthcare setting, with adherence in GPs (54.6%; 95% CI: 51.1-58.1) lower than for either ED settings (84.7%; 95% CI: 82.4-86.9) or for inpatients (84.3%; 95% CI: 80.0-87.9); p<0.0001 for both differences. The difference between settings was driven by differences in the diagnosis and ongoing management phases of care. CONCLUSIONS: Adherence to clinical guidelines for children presenting to healthcare providers with AGE varies according to phase of care and healthcare setting. Although appropriate diagnostic assessment and ongoing management phase procedures are not well documented in medical records (particularly in the GP setting), in the treatment phase children are treated in accordance with guidelines over 90% of the time.

Increased salt sensitivity in offspring of pregnancies complicated by experimental preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy known to increase the risk of cardiovascular disease in mothers and offspring. Offspring exposed to a suboptimal intrauterine environment may experience altered fetal programming and subsequent long-term cardiovascular changes. This study investigated changes in the vascular response in offspring from experimental preeclampsia (EPE) induced by uterine artery ligation, in the absence of fetal growth restriction, compared to normal baboon pregnancies (controls), following a high salt diet challenge. After 1 week of standard diet (containing <1% salt), animals were fed a high salt diet (6%) for 2 weeks. Systolic and diastolic blood pressure (SBP, DBP), aldosterone, renin and creatinine clearance were evaluated in EPE (n = 6, 50% male) and control (n = 6, 50% male) offspring. A repeated measures analysis was performed, and P < 0.05 was considered significant. At baseline, there were no differences between the groups in any parameter (EPE, mean age and weight 3.2 ± 1.2 years, 6.8 ± 1.0 kg, respectively; Control, 2.9 ± 0.8 years, 7.1 ± 1.5 kg). After salt loading the EPE group had significantly higher SBP (92 ± 5 mm Hg) compared to the control group (83 ± 4 mm Hg, P = 0.03). Aldosterone concentration was higher in the EPE group despite the same salt excretion and no difference in renal function. Salt sensitivity may differ in offspring from hypertensive pregnancies due to fetal programming. This could have long-term consequences for cardiovascular health of EPE offspring and further research is required to determine the exact pathological mechanisms.

CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma.

Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. Herein, we demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and, interestingly, the trogocytosing CD83+T cells expressed significantly more programmed death-1 compared to CD83-T cells. Hodgkin lymphoma tumor cells secreted soluble CD83 that inhibited T-cell proliferation, and anti-CD83 antibody partially reversed the inhibitory effect. High levels of soluble CD83 were detected in Hodgkin lymphoma patient sera, which returned to normal in patients who had good clinical responses to chemotherapy confirmed by positron emission tomography scans. We generated a human anti-human CD83 antibody, 3C12C, and its toxin monomethyl auristatin E conjugate, that killed CD83 positive Hodgkin lymphoma cells but not CD83 negative cells. The 3C12C antibody was tested in dose escalation studies in non-human primates. No toxicity was observed, but there was evidence of CD83 positive target cell depletion. These data establish CD83 as a potential biomarker and therapeutic target in Hodgkin lymphoma.

A longitudinal analysis of angiotensin II type 1 receptor antibody and angiogenic markers in pregnancy.

BACKGROUND: Preeclampsia can be caused by shallow trophoblast invasion and results in endothelial dysfunction. Angiotensin II type 1 receptor antibodies may have a role in both processes. Other angiogenic markers (placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin) have been shown to alter before clinically evident preeclampsia. OBJECTIVE: The aim of this study is to assess the longitudinal changes and utility of biomarker angiotensin II type 1 receptor antibodies and angiogenic markers in hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia. STUDY DESIGN: A longitudinal prospective cohort observational study of angiogenic markers and a secondary retrospective case-control study of angiotensin II type 1 receptor antibody changes were conducted. The studies were conducted in a large tertiary metropolitan teaching hospital (Sydney, Australia). Sequential recruitment of women with a singleton pregnancy (N = 351) was undertaken. Plasma concentrations of angiotensin II type 1 receptor antibodies, placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin were measured using validated enzyme-linked immunosorbent assays at 12, 18, 28, 36, and 40 weeks' gestation and 6 weeks' postpartum. Clinical, demographic, and pregnancy data were prospectively collected. Pregnancy outcomes were classified as normotensive, gestational hypertension, or preeclampsia. Analyses were carried out using software and significance set at P < .05. RESULTS: In all, 351 women were recruited, 17 developed gestational hypertension, and 18 developed preeclampsia. Women with preeclampsia at baseline were heavier (P = .015), were taller (P = .046), and had higher systolic (P = .029) and diastolic (P = .006) blood pressure. The preeclampsia group had higher soluble fms-like tyrosine kinase-1 from ≥28 weeks (P = .003) and lower placental growth factor from 18 weeks (P = .004). Soluble endoglin and angiotensin II type 1 receptor antibodies did not vary over time or between groups. Angiotensin II type 1 receptor antibody (12 weeks) was positively correlated with serum pregnancy associated plasma protein A (P = .008) and human chorionic gonadotrophin (P = .04). CONCLUSION: Angiogenic markers vary longitudinally during pregnancy and placental growth factor and soluble fms-like tyrosine kinase-1 have a role for predicting and diagnosing preeclampsia later in disease. Our data show that angiotensin II type 1 receptor antibodies are not sensitive for disease and hence not useful as a biomarker. Larger studies are required to describe the role and functionality of angiotensin II type 1 receptor antibodies in preeclampsia.

Placental Growth Factor Reduces Blood Pressure in a Uteroplacental Ischemia Model of Preeclampsia in Nonhuman Primates.

An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia because of endothelial dysfunction. Circulating soluble fms-like tyrosine kinase 1 (sFLT-1) increases and placental growth factor (PlGF) reduces before and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a nonhuman primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of a 182-day pregnancy). Two weeks after uteroplacental ischemia, rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100 µg/kg per day) for 5 days. Blood pressure was monitored by intra-arterial radiotelemetry and sFLT-1 and PlGF by ELISA. Uteroplacental ischemia resulted in experimental preeclampsia evidenced by increased blood pressure, proteinuria, and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after uteroplacental ischemia. rhPlGF reduced systolic blood pressure in the treated group (-5.2±0.8 mm Hg; from 132.6±6.6 mm Hg to 124.1±7.6 mm Hg) compared with an increase in systolic blood pressure in controls (6.5±3 mm Hg; from 131.3±1.5 mm Hg to 138.6±1.5 mm Hg). Proteinuria reduced in the treated group (-72.7±55.7 mg/mmol) but increased in the control group. Circulating levels of total sFLT-1 were not affected by the administration of PlGF; however, a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference between the weights or lengths of the neonates in the rhPlGF or control group; however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia.

Comparison of indirect and direct blood pressure measurements in baboons during ketamine anaesthesia.

BACKGROUND: The aim of this study was to assess agreement between different methods of blood pressure measurement in anaesthetised baboons. METHODS: Systolic and diastolic blood pressure (SBP and DBP) were measured in anaesthetised baboons using intra-arterial radiotelemetry, automated oscillometry and mercury sphygmomanometry. Correlation between the different methods was assessed. RESULTS: The correlation between intra-arterial radiotelemetry and automated oscillometry was 0.9 (P < 0.001) for SBP and 0.9 (P < 0.001) for DBP. Between-method differences were -4.4 ± 7.2 mm Hg for SBP and -3.4 ± 7.1 mm Hg for DBP. For automated oscillometry vs. mercury sphygmomanometry, correlation was 0.4 for both SBP (P < 0.001) and DBP (P < 0.001). Between-method differences were 7.9 ± 12.7 mm Hg for SBP and 7.3 ± 12.6 mm Hg for DBP. CONCLUSIONS: Our study demonstrates that automated oscillometry may be an appropriate alternative to telemetry for measuring blood pressure in anaesthetised baboons.

Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas).

Preeclampsia is a common disease of pregnancy characterised by maternal hypertension and proteinuria. Abnormal placentation in early pregnancy and abnormal cytokine and anti-angiogenic factor expression are thought to contribute to the clinical syndrome of endothelial dysfunction evident in the second half of gestation. The mechanisms underlying both the placental pathology and its translation to the maternal clinical syndrome are not fully understood. A model of preeclampsia manifest by clinically evident endothelial dysfunction (increased blood pressure and proteinuria) was induced by administration of low-dose TNF-α for 2weeks at mid-gestation in pregnant baboons (Papio hamadryas). Blood pressure was monitored continuously and remotely by intra-arterial radiotelemetry. Following TNF-α infusion, there was an increase in systolic and diastolic blood pressure and development of proteinuria in pregnant treated animals, but not in pregnant saline controls nor in non-pregnant TNF-α treated animals. The treated pregnant animals also developed elevated plasma soluble FMS-like tyrosine kinase-1 (sFLT-1) and increased placental mRNA expression of sFLT-1 and soluble endoglin (sEng). These results clearly demonstrate that the cytokine TNF-α can induce the clinical and biochemical features of human preeclampsia. The results identify a link between cytokines, placental dysfunction and endothelial dysfunction resulting in a loss of maternal blood pressure control.

Animal models of pre-eclampsia.

The cardinal features of human pre-eclampsia, hypertension and proteinuria, are mimicked in animal models. Increasingly, the accuracy of inducing 'pure' systemic endothelial dysfunction is regarded as critical in differentiating mechanisms of pre-eclampsia from other conditions which induce hypertension (e.g. glomerulonephritis, renal denervation or manipulation of the renin-angiotensin system). A recent study in baboons has identified the timing of induction of maternal endothelial damage after acute uteroplacental ischaemia (UPI). The endothelial changes in the glomerulus are indicative of a direct endothelial toxin and mimic the lesions seen in human pre-eclampsia; the extent of hypertension and proteinuria are also similar. This animal model identifies systemic and placental sFLT-1 (soluble fms-like tyrosine kinase-1) as a potential mediator of endothelial damage. This research involving primates with haemomonochorial placentas makes translation of these results to humans very compelling for understanding the mechanisms of human disease. Similar endothelial dysfunction has been identified in baboons treated with anti-inflammatory inhibitors. Similar studies in rodents have identified a relationship between angiotensin II agonistic antibodies, UPI/reduced uteroplacental perfusion pressure, angiogenic markers, and cytokines. We can now identify vasoconstrictive mediators of the hypertensive and endothelial response such as endothelin 1, the renin-angiotensin system, or other hormones such as oestrogens in primate models.

Maternal parity affects neonatal survival rate in a colony of captive bred baboons (Papio hamadryas).

BACKGROUND: Non-human primates, particularly baboons, are valuable as animal models for reproductive research, because of their similarity to humans. Knowledge of colony-specific pregnancy and neonatal outcomes is essential for interpretation of such research. METHODS: A retrospective review of the reproductive records of the Australian National Baboon Colony (ANBC) from 1994 to 2006 was performed. RESULTS: The overall live birth rate was over 70% of recognized pregnancies. Pregnancy loss was due to equal proportions of spontaneous abortion and stillbirth, and was not affected by maternal age or parity. Stillbirth rates were increased by the use of animals in novel late pregnancy experimental protocols. Neonatal mortality rates were low overall, but significantly higher in primiparous compared with multiparous mothers (P < 0.05). There were no cases of maternal mortality. CONCLUSIONS: The success of the ANBC breeding programme is demonstrated by the low rate of pregnancy loss, high neonatal survival rate and lack of maternal mortality.