Clinicians' delirium treatment practice, practice change, and influences: A national online survey.

BACKGROUND: Recent studies cast doubt on the net effect of antipsychotics for delirium. AIM: To investigate the influence of these studies and other factors on clinicians' delirium treatment practice and practice change in palliative care and other specialties using the Theoretical Domains Framework. DESIGN: Australia-wide online survey of relevant clinicians. SETTING/PARTICIPANTS: Registered nurses (72%), doctors (16%), nurse practitioners (6%) and pharmacists (5%) who cared for patients with delirium in diverse settings, recruited through health professionals' organisations. RESULTS: Most of the sample (n = 475): worked in geriatrics/aged (31%) or palliative care (30%); in hospitals (64%); and saw a new patient with delirium at least weekly (61%). More (59%) reported delirium practice change since 2016, mostly by increased non-pharmacological interventions (53%). Fifty-five percent reported current antipsychotic use for delirium, primarily for patient distress (79%) and unsafe behaviour (67%). Common Theoretical Domains Framework categories of influences on respondents' delirium practice were: emotion (54%); knowledge (53%) and physical (43%) and social (21%) opportunities. Palliative care respondents more often reported: awareness of any named key study of antipsychotics for delirium (73% vs 39%, p < 0.001); changed delirium treatment (73% vs 53%, p = 0.017); decreased pharmacological interventions (60% vs 15%, p < 0.001); off-label medication use (86% vs 51%, p < 0.001: antipsychotics 79% vs 44%, p < 0.001; benzodiazepines 61% vs 26%, p < 0.001) and emotion as an influence (82% vs 39%, p < 0.001). CONCLUSION: Clinicians' use of antipsychotic during delirium remains common and is primarily motivated by distress and safety concerns for the patient and others nearby. Supporting clinicians to achieve evidence-based delirium practice requires further work.

Modelling the cost of place of birth: a pathway analysis.

BACKGROUND: In New South Wales (NSW), Australia there are three settings available for women at low risk of complications to give birth: home, birth centre and hospital. Between 2000 and 2012, 93.6% of babies were planned to be born in hospital, 6.0% in a birth centre and 0.4% at home. Availability of alternative birth settings is limited and the cost of providing birth at home or in a birth centre from the perspective of the health system is unknown. OBJECTIVES: The objective of this study was to model the cost of the trajectories of women who planned to give birth at home, in a birth centre or in a hospital from the public sector perspective. METHODS: This was a population-based study using linked datasets from NSW, Australia. Women included met the following selection criteria: 37-41 completed weeks of pregnancy, spontaneous onset of labour, and singleton pregnancy at low risk of complications. We used a decision tree framework to depict the trajectories of these women and Australian Refined-Diagnosis Related Groups (AR-DRGs) were applied to each trajectory to estimate the cost of birth. A scenario analysis was undertaken to model the cost for 30 000 women in one year. FINDINGS: 496 387 women were included in the dataset. Twelve potential outcome pathways were identified and each pathway was costed using AR-DRGs. An overall cost was also calculated by place of birth: $AUD4802 for homebirth, $AUD4979 for a birth centre birth and $AUD5463 for a hospital birth. CONCLUSION: The findings from this study provides some clarity into the financial saving of offering more options to women seeking an alternative to giving birth in hospital. Given the relatively lower rates of complex intervention and neonatal outcomes associated with women at low risk of complications, we can assume the cost of providing them with homebirth and birth centre options could be cost-effective.

Creating the first national linked dataset on perinatal and maternal outcomes in Australia: Methods and challenges.

BACKGROUND: Data linkage offers a powerful mechanism for examining healthcare outcomes across populations and can generate substantial robust datasets using routinely collected electronic data. However, it presents methodological challenges, especially in Australia where eight separate states and territories maintain health datasets. This study used linked data to investigate perinatal and maternal outcomes in relation to place of birth. It examined data from all eight jurisdictions regarding births planned in hospitals, birth centres and at home. Data linkage enabled the first Australia-wide dataset on birth outcomes. However, jurisdictional differences in data collection created challenges in obtaining comparable cohorts of women with similar low-risk pregnancies in all birth settings. The objective of this paper is to describe the techniques for managing previously linked data, and specifically for ensuring the resulting dataset contained only low-risk pregnancies. METHODS: This paper indicates the procedures for preparing and merging linked perinatal, inpatient and mortality data from different sources, providing technical guidance to address challenges arising in linked data study designs. RESULTS: We combined data from eight jurisdictions linking four collections of administrative healthcare and civil registration data. The merging process ensured that variables were consistent, compatible and relevant to study aims. To generate comparable cohorts for all three birth settings, we developed increasingly complex strategies to ensure that the dataset eliminated women with pregnancies at risk of complications during labour and birth. It was then possible to compare birth outcomes for comparable samples, enabling specific examination of the impact of birth setting on maternal and infant safety across Australia. CONCLUSIONS: Data linkage is a valuable resource to enhance knowledge about birth outcomes from different settings, notwithstanding methodological challenges. Researchers can develop and share practical techniques to address these challenges. Study findings suggest that jurisdictions develop more consistent data collections to facilitate future data linkage.

Inclusion, characteristics and outcomes of people requiring palliative care in studies of non-pharmacological interventions for delirium: A systematic review.

BACKGROUND: Delirium is common, distressing, serious and under-researched in specialist palliative care settings. OBJECTIVES: To examine whether people requiring palliative care were included in non-pharmacological delirium intervention studies in inpatient settings, how they were characterised and what their outcomes were. DESIGN: Systematic review (PROSPERO 2017 CRD42017062178). DATA SOURCES: Systematic search in March 2017 for non-pharmacological delirium intervention studies in adult inpatients. Database search terms were 'delirium', 'hospitalisation', 'inpatient', 'palliative care', 'hospice', 'critical care' and 'geriatrics'. Scottish Intercollegiate Guidelines Network methodological checklists guided risk of bias assessment. RESULTS: The 29 included studies were conducted between 1994 and 2015 in diverse settings in 15 countries (9136 participants, mean age = 76.5 years (SD = 8.1), 56% women). Most studies tested multicomponent interventions (n = 26) to prevent delirium (n = 19). Three-quarters of the 29 included studies (n = 22) excluded various groups of people requiring palliative care; however, inclusion criteria, participant diagnoses, illness severity and mortality indicated their presence in almost all studies (n = 26). Of these, 21 studies did not characterise participants requiring palliative care or report their specific outcomes (72%), four reported outcomes for older people with frailty, dementia, cancer and comorbidities, and one was explicitly focused on people receiving palliative care. Study heterogeneity and limitations precluded definitive determination of intervention effectiveness and only allowed interpretations of feasibility for people requiring palliative care. Acceptability outcomes (intervention adverse events and patients' subjective experience) were rarely reported overall. CONCLUSION: Non-pharmacological delirium interventions have frequently excluded and under-characterised people requiring palliative care and infrequently reported their outcomes.

Mapping the trajectories for women and their babies from births planned at home, in a birth centre or in a hospital in New South Wales, Australia, between 2000 and 2012.

BACKGROUND: In New South Wales (NSW) Australia, women at low risk of complications can choose from three birth settings: home, birth centre and hospital. Between 2000 and 2012, around 6.4% of pregnant women planned to give birth in a birth centre (6%) or at home (0.4%) and 93.6% of women planned to birth in a hospital. A proportion of the woman in the home and birth centre groups transferred to hospital. However, their pathways or trajectories are largely unknown. AIM: The aim was to map the trajectories and interventions experienced by women and their babies from births planned at home, in a birth centre or in a hospital over a 13-year period in NSW. METHODS: Using population-based linked datasets from NSW, women at low risk of complications, with singleton pregnancies, gestation 37-41 completed weeks and spontaneous onset of labour were included. We used a decision tree framework to depict the trajectories of these women and estimate the probabilities of the following: giving birth in their planned setting; being transferred; requiring interventions and neonatal admission to higher level hospital care. The trajectories were analysed by parity. RESULTS: Over a 13-year period, 23% of nulliparous and 0.8% of multiparous women planning a home birth were transferred to hospital. In the birth centre group, 34% of nulliparae and 12% of multiparas were transferred to a hospital. Normal vaginal birth rates were higher in multiparous women compared to nulliparous women in all settings. Neonatal admission to SCN/NICU was highest in the planned hospital group for nulliparous women (10.1%), 7.1% for nulliparous women planning a birth centre birth and 5.1% of nulliparous women planning a homebirth. Multiparas had lower admissions to SCN/NICU for all thee settings (hospital 6.3%, BC 3.6%, home 1.6%, respectively). CONCLUSIONS: Women who plan to give birth at home or in a birth centre have high rates of vaginal birth, even when transferred to hospital. Evidence on the trajectories of women who choose to give birth at home or in birth centres will assist the planning, costing and expansion of models of care in NSW.

PerCEN trial participant perspectives on the implementation and outcomes of person-centered dementia care and environments.

BACKGROUND: Well-being and various forms of agitation in people with dementia can be improved in a person-centered long-term care setting. Data obtained during the Person-Centered Dementia Care and Environment (PerCEN) randomized controlled trial shed light on the factors that influenced the adoption and outcomes of person-centered interventions in long-term care from the perspective of study participants. METHODS: Data were obtained from PerCEN participants: individual semi-structured interviews with care managers (29), nurses and care staff (70); telephone surveys with family members (73); staff reports of care approaches; and 131 field note entries recorded by the person-centered care and environment facilitators. Data were interpreted inductively using content analysis, code building, theme development, and synthesis of findings. RESULTS: All data sources confirmed that, when adopted, the person-centered model increased the number and variety of opportunities for resident interaction, improved flexibility in care regimens, enhanced staff's attention to resident needs, reduced resident agitation, and improved their well-being. Barriers and enablers for the person-centered model related to leadership, manager, staff and family appreciation of the model, staff's capacity, effective communication and team work among direct care staff, care service flexibility, and staff education on how to focus care on the person's well-being. CONCLUSIONS: Successful knowledge translation of the person-centered model starts with managerial leadership and support; it is sustained when staff are educated and assisted to apply the model, and, along with families, come to appreciate the benefits of flexible care services and teamwork in achieving resident well-being. The Australian New Zealand Clinical Trials Registry number is ACTRN 12608000095369.

Improving Healthcare Quality and Clinical Outcomes for Persons with Dementia in the Sub-Acute Hospital Through Person-Centered Care Practice.

Background: Person-centered care is considered beneficial for persons with dementia. Objective: To evaluate the impact of a person-centered knowledge translation intervention on the quality of healthcare and outcomes for persons with dementia. Methods: Over nine months, sub-acute hospital nursing, allied health, and medical staff (n = 90) participated in online and/or face-to-face person-centered education and were supported by senior nursing, allied health, and medical staff champions (n = 8) to implement person-centered healthcare. The quality of healthcare service, ward climate and care delivery were evaluated pre/post study intervention. In the week following hospital admission (Time 1) and week of discharge (Time 3), agitation incidence (co-primary outcome) was assessed in participants with dementia (n = 80). Participant delirium (co-primary outcome), accidents/injuries, psychotropic medicines, length of stay, readmission and discharge destination (secondary outcomes) were compared with a retrospective group (n = 77) matched on demographics, cognition and function in activities of daily living. Results: Improvements occurred post-intervention in service quality by 17.5% (p = 0.369, phi = 0.08), ward climate by 18.1% (p = 0.291, phi = 0.08), and care quality by 50% (p = 0.000, phi = 0.37). Participant agitation did not change from Time 1 to Time 3 (p = 0.223). Relative to the retrospective group, significant reductions occurred in participant delirium (p = 0.000, phi = 0.73), incidents/injuries (p = 0.000, phi = 0.99), psychotropic medicine use (p = 0.030, phi = 0.09), and hospital readmissions within 30 days (p = 0.002, phi = 0.25), but not in discharge to home (p = 0.171). Conclusions: When person-centered healthcare knowledge is translated through staff education and practice support, persons with dementia can experience improved healthcare services and clinical outcomes, while healthcare services can benefit through reductions in unplanned service use.

Treatment patterns and out-of-hospital healthcare resource utilisation by patients with advanced cancer living with pain: An analysis from the Stop Cancer PAIN trial.

BACKGROUND: About 70% of patients with advanced cancer experience pain. Few studies have investigated the use of healthcare in this population and the relationship between pain intensity and costs. METHODS: Adults with advanced cancer and scored worst pain ≥ 2/10 on a numeric rating scale (NRS) were recruited from 6 Australian oncology/palliative care outpatient services to the Stop Cancer PAIN trial (08/15-06/19). Out-of-hospital, publicly funded services, prescriptions and costs were estimated for the three months before pain screening. Descriptive statistics summarize the clinico-demographic variables, health services and costs, treatments and pain scores. Relationships with costs were explored using Spearman correlations, Mann-Whitney U and Kruskal-Wallis tests, and a gamma log-link generalized linear model. RESULTS: Overall, 212 participants had median worst pain scores of five (inter-quartile range 4). The most frequently prescribed medications were opioids (60.1%) and peptic ulcer/gastro-oesophageal reflux disease (GORD) drugs (51.6%). The total average healthcare cost in the three months before the census date was A$6,742 (95% CI $5,637, $7,847), approximately $27,000 annually. Men had higher mean healthcare costs than women, adjusting for age, cancer type and pain levels (men $7,872, women $4,493, p<0.01) and higher expenditure on prescriptions (men $5,559, women $2,034, p<0.01). CONCLUSIONS: In this population with pain and cancer, there was no clear relationship between healthcare costs and pain severity. These treatment patterns requiring further exploration including the prevalence of peptic ulcer/GORD drugs, and lipid lowering agents and the higher healthcare costs for men. TRIAL REGISTRATION: ACTRN12615000064505. World Health Organisation unique trial number U1111-1164-4649. Registered 23 January 2015.

Effect of Cancer Pain Guideline Implementation on Pain Outcomes Among Adult Outpatients With Cancer-Related Pain: A Stepped Wedge Cluster Randomized Trial.

Importance: An evidence-practice gap exists for cancer pain management, and cancer pain remains prevalent and disabling. Objectives: To evaluate the capacity of 3 cancer pain guideline implementation strategies to improve pain-related outcomes for patients attending oncology and palliative care outpatient services. Design, Setting, and Participants: A pragmatic, stepped wedge, cluster-randomized, nonblinded, clinical trial was conducted between 2014 and 2019. The clusters were cancer centers in Australia providing oncology and palliative care outpatient clinics. Participants included a consecutive cohort of adult outpatients with advanced cancer and a worst pain severity score of 2 or more out of 10 on a numeric rating scale (NRS). Data were collected between August 2015 and May 2019. Data were analyzed July to October 2019 and reanalyzed November to December 2021. Interventions: Guideline implementation strategies at the cluster, health professional, and patient levels introduced with the support of a clinical champion. Main Outcomes and Measures: The primary measure of effect was the percentage of participants initially screened as having moderate to severe worst pain (NRS ≥ 5) who experienced a clinically important improvement of 30% or more 1 week later. Secondary outcomes included mean average pain, patient empowerment, fidelity to the intervention, and quality of life and were measured in all participants with a pain score of 2 or more 10 at weeks 1, 2, and 4. Results: Of 8099 patients screened at 6 clusters, 1564 were eligible, and 359 were recruited during the control phase (mean [SD] age, 64.2 [12.1] years; 196 men [55%]) and 329 during the intervention phase (mean [SD] age, 63.6 [12.7] years; 155 men [47%]), with no significant differences between phases on baseline measures. The mean (SD) baseline worst pain scores were 5.0 (2.6) and 4.9 (2.6) for control and intervention phases, respectively. The mean (SD) baseline average pain scores were 3.5 (2.1) for both groups. For the primary outcome, the proportions of participants with a 30% or greater reduction in a pain score of 5 or more of 10 at baseline were similar in the control and intervention phases (31 of 280 participants [11.9%] vs 30 of 264 participants [11.8%]; OR, 1.12; 95% CI, 0.79-1.60; P = .51). No significant differences were found in secondary outcomes between phases. Fidelity to the intervention was low. Conclusions and Relevance: A suite of implementation strategies was insufficient to improve pain-related outcomes for outpatients with cancer-related pain. Further evaluation is needed to determine the required clinical resources needed to enable wide-scale uptake of the fundamental elements of cancer pain care. Ongoing quality improvement activities should be supported to improve sustainability.

Breast cancer in multiple endocrine neoplasia type 1 (MEN1).

SUMMARY: A 38-year-old female was identified as carrying a heterozygous pathogenic MEN1 variant (c.1304delG) through predictive genetic testing, following a diagnosis of familial hyperparathyroidism. Routine screening for parathyroid and pituitary disease was negative. However, cross-sectional imaging by CT revealed a 41 mm pancreatic tail mass. Biopsy via endoscopic ultrasound confirmed the lesion to be a well-differentiated (grade 1) pancreatic neuroendocrine tumour (pNET) with MIB1<1%. Biochemically, hyperinsulinaemic hypoglycaemia was confirmed following an overnight fast, which was subsequently managed by diet alone prior to definitive surgery. Pre-operative work-up with octreotide SPECT CT demonstrated avid tracer uptake in the pancreatic lesion and, unexpectedly, a focal area of uptake in the left breast. Further investigation, and subsequent mastectomy, confirmed ductal carcinoma in situ pT2 (23 mm) grade 1, N0 (ER positive; HER2 negative). Following mastectomy, our patient underwent a successful distal pancreatectomy to resect the pNET. Loss of heterozygosity (LOH) at the MEN1 locus was found in both the breast tumour and pNET, thereby in keeping with a 'two-hit' hypothesis of oncogenesis, a suggestive but non-definitive clue for causation. To obtain further support for a causative relationship between MEN1 and breast cancer, we undertook a detailed review of the published literature which overall supports the notion that breast cancer is a MEN1-related malignancy that presents at a younger age and histologically, is typically of ductal subtype. Currently, clinical guidance regarding breast cancer surveillance in MEN1 does not exist and further research is required to establish a clinical and cost-effective surveillance strategy). LEARNING POINTS: We describe a case of pNET and breast cancer diagnosed at a young age of 38 years in a patient who is heterozygous for a pathogenic MEN1 variant. Loss of the wild-type allele was seen in both breast tissue and pNET specimen. Breast cancer may be an under-recognised MEN1-associated malignancy that presents at a younger age than in the general population with a relative risk of 2-3. Further research is required to determine the cost-effectiveness of breast cancer surveillance approach at a younger age in MEN1 patients relative to the general population .

A Multicomponent Nonpharmacological Intervention to Prevent Delirium for Hospitalized People with Advanced Cancer: A Phase II Cluster Randomized Waitlist Controlled Trial (The PRESERVE Pilot Study).

Background: Delirium is a common debilitating complication of advanced cancer. Objective: To determine if a multicomponent nonpharmacological delirium prevention intervention was feasible for adult patients with advanced cancer, before a phase III (efficacy) trial. Design: Phase II (feasibility) cluster randomized controlled trial. All sites implemented delirium screening and diagnostic assessment. Strategies within sleep, vision and hearing, hydration, orientation, mobility, and family domains were delivered to enrolled patients at intervention site admission days 1-7. Control sites then implemented the intervention ("waitlist sites"). Setting: Four Australian palliative care units. Measurements: The primary outcome was adherence, with an a priori endpoint of at least 60% patients achieving full adherence. Secondary outcomes were interdisciplinary care delivery, delirium measures, and adverse events, analyzed descriptively and inferentially. Results: Sixty-five enrolled patients (25 control, 20 intervention, and 20 waitlist) had 98% delirium screens and 75% diagnostic assessments completed. Nurses (67%), physicians (16%), allied health (8.4%), family (7%), patients (1%), and volunteers (0.5%) delivered the intervention. There was full adherence for 5% patients at intervention sites, partial for 25%. Both full and partial adherence were higher at waitlist sites: 25% and 45%, respectively. One-third of control site patients (32%) became delirious within seven days of admission compared to one-fifth (20%) at both intervention and waitlist sites (p = 0.5). Mean (standard deviation) Delirium Rating Scale-Revised-1998 scores were 16.8 + 12.0 control sites versus 18.4 + 8.2 (p = 0.6) intervention and 18.7 + 7.8 (p = 0.5) waitlist sites. The intervention caused no adverse events. Conclusion: The intervention requires modification for optimal adherence in a phase III trial.

Maternal and perinatal outcomes by planned place of birth in Australia 2000 - 2012: a linked population data study.

OBJECTIVE: To compare perinatal and maternal outcomes for Australian women with uncomplicated pregnancies according to planned place of birth, that is, in hospital labour wards, birth centres or at home. DESIGN: A population-based retrospective design, linking and analysing routinely collected electronic data. Analysis comprised χ2 tests and binary logistic regression for categorical data, yielding adjusted ORs. Continuous data were analysed using analysis of variance. SETTING: All eight Australian states and territories. PARTICIPANTS: Women with uncomplicated pregnancies who gave birth between 2000 and 2012 to a singleton baby in cephalic presentation at between 37 and 41 completed weeks' gestation. Of the 1 251 420 births, 1 171 703 (93.6%) were planned in hospital labour wards, 71 505 (5.7%) in birth centres and 8212 (0.7%) at home. MAIN OUTCOME MEASURES: Mode of birth, normal labour and birth, interventions and procedures during labour and birth, maternal complications, admission to special care/high dependency or intensive care units (mother or infant) and perinatal mortality (intrapartum stillbirth and neonatal death). RESULTS: Compared with planned hospital births, the odds of normal labour and birth were over twice as high in planned birth centre births (adjusted OR (AOR) 2.72; 99% CI 2.63 to 2.81) and nearly six times as high in planned home births (AOR 5.91; 99% CI 5.15 to 6.78). There were no statistically significant differences in the proportion of intrapartum stillbirths, early or late neonatal deaths between the three planned places of birth. CONCLUSIONS: This is the first Australia-wide study to examine outcomes by planned place of birth. For healthy women in Australia having an uncomplicated pregnancy, planned births in birth centres or at home are associated with positive maternal outcomes although the number of homebirths was small overall. There were no significant differences in the perinatal mortality rate, although the absolute numbers of deaths were very small and therefore firm conclusions cannot be drawn about perinatal mortality outcomes.

Multicomponent non-pharmacological intervention to prevent delirium for hospitalised people with advanced cancer: study protocol for a phase II cluster randomised controlled trial.

INTRODUCTION: Delirium is a significant medical complication for hospitalised patients. Up to one-third of delirium episodes are preventable in older inpatients through non-pharmacological strategies that support essential human needs, such as physical and cognitive activity, sleep, hydration, vision and hearing. We hypothesised that a multicomponent intervention similarly may decrease delirium incidence, and/or its duration and severity, in inpatients with advanced cancer. Prior to a phase III trial, we aimed to determine if a multicomponent non-pharmacological delirium prevention intervention is feasible and acceptable for this specific inpatient group. METHODS AND ANALYSIS: The study is a phase II cluster randomised wait-listed controlled trial involving inpatients with advanced cancer at four Australian palliative care inpatient units. Intervention sites will introduce delirium screening, diagnostic assessment and a multicomponent delirium prevention intervention with six domains of care: preserving natural sleep; maintaining optimal vision and hearing; optimising hydration; promoting communication, orientation and cognition; optimising mobility; and promoting family partnership. Interdisciplinary teams will tailor intervention delivery to each site and to patient need. Control sites will first introduce only delirium screening and diagnosis, later implementing the intervention, modified according to initial results. The primary outcome is adherence to the intervention during the first seven days of admission, measured for 40 consecutively admitted eligible patients. Secondary outcomes relate to fidelity and feasibility, acceptability and sustainability of the study intervention, processes and measures in this patient population, using quantitative and qualitative measures. Delirium incidence and severity will be measured to inform power calculations for a future phase III trial. ETHICS AND DISSEMINATION: Ethical approval was obtained for all four sites. Trial results, qualitative substudy findings and implementation of the intervention will be submitted for publication in peer-reviewed journals, and reported at conferences, to study sites and key peak bodies. TRIAL REGISTRATION NUMBER: ACTRN12617001070325; Pre-results.

Refractory spontaneous hypoglycaemia: a diagnostic conundrum

A frail 79-year-old lady with dementia presented with a 2-year history of frequent falls. Recurrent hypoglycaemic episodes were diagnosed and treated with continuous glucose infusion in multiple hospital admissions. Hypoadrenalism and hypothyroidism were ruled out. Whilst hypoglycaemic (blood glucose 1.6 mmol/L), both plasma C-peptide and proinsulin concentrations, were inappropriately elevated at 4210 pmol/L (174­960) and >200 pmol/L (0­7) respectively with plasma insulin suppressed at 12 pmol/L (0­180). Whilst reported cases of proinsulinoma are typically pancreatic in origin, radiological investigations of the pancreas in this patient did not identify abnormalities. Unexpectedly contrast CT identified a heterogeneously enhancing mass (6.6 cm) at the lower pole of the left kidney consistent with renal cell carcinoma. Non-islet cell tumour-induced hypoglycaemia has been associated with renal malignancy; however, a serum IGF2:IGF1 ratio measured at <10 effectively excludes this diagnosis. Concomitantly on the CT, extensive peripherally enhancing heterogeneous mass lesions in the liver were identified, the largest measuring 12 cm. A palliative approach was taken due to multiple comorbidities. On post-mortem, the kidney lesion was confirmed as clear cell renal carcinoma, whilst the liver lesions were identified as proinsulin-secreting neuroendocrine tumours. In conclusion, the diagnosis of proinsulinoma can be missed if plasma proinsulin concentration is not measured at the time of hypoglycaemia. In this case, the plasma insulin:C-peptide ratio was too high to be accounted for by the faster relative clearance of insulin and was due to proinsulin cross-reactivity in the C-peptide assay. In addition, the concomitant malignancy proved to be a challenging red herring. Learning points: •• Even in non-diabetics, hypoglycaemia needs to be excluded in a setting of frequent falls. Insulin- or proinsulinsecreting tumours are potentially curable causes. •• Whilst investigating spontaneous hypoglycaemia, if plasma insulin concentration is appropriate for the hypoglycaemia, it is prudent to check proinsulin concentrations during the hypoglycaemic episode. •• Proinsulin cross-reacts variably with C-peptide and insulin assays; the effect is method dependent. In this case, the discrepancy between the insulin and C-peptide concentrations was too great to be accounted for by the faster relative clearance of insulin, raising the suspicion of assay interference. The C-peptide assay in question (Diasorin liaison) has been shown to be 100% cross reactive with proinsulin based on spiking studies with a proinsulin reference preparation. •• Whilst reported cases of proinsulinoma and 99% of insulinomas are of pancreatic origin, conventional imaging studies (CT, MRI or ultrasound) fail to detect neuroendocrine tumours <1 cm in 50% of cases. •• The concomitant renal mass identified radiologically proved to be a red herring. •• In view of the rarity of proinsulinoma, no conclusive association with renal cell carcinoma can be established.

Unilateral adrenal infarction in pregnancy secondary to elevated factor VIII.

Adrenal infarction in pregnancy is an extremely rare event. We report a case of a 29-year-old pregnant woman at the twenty-fourth week of gestation that presented with an acute episode of severe localized right upper quadrant pain. Her preliminary blood investigations and abdominal ultrasonography were essentially unremarkable. A diagnosis of right adrenal infarction was subsequently established on the basis of a non-enhanced swollen right adrenal gland on CT scanning of the abdomen with contrast, consistent with the clinical presentation. She was treated with subcutaneous low molecular weight heparin (LMWH) until 2 weeks postpartum. A thrombophilia screen post-partum revealed a significantly elevated factor VIII level and a hypercoagulable state that justified prolonged anticoagulation. This case highlights the importance of a high index of suspicion for adrenal infarction in pregnancy on the clinical grounds of otherwise unexplained acute abdominal pain accompanied by suggestive radiological findings, especially in the presence of thrombophilia.

Marked hyperandrogenicity in a 60-year-old woman.

Markedly elevated androgen levels can lead to clinical virilization in females. Clinical features of virilization in a female patient, in association with biochemical hyperandrogenism, should prompt a search for an androgen-producing tumor, especially of ovarian or adrenal origin. We herein report the case of a 60-year-old woman of Pakistani origin who presented with the incidental finding of male pattern baldness and hirsutism. Her serum testosterone level was markedly elevated at 21 nmol/L (normal range: 0.4-1.7 nmol/L), while her DHEAS level was normal, indicating a likely ovarian source of her elevated testosterone. Subsequently, a CT abdomen-pelvis was performed, which revealed a bulky right ovary, confirmed on MRI of the pelvis as an enlarged right ovary, measuring 2.9 × 2.2 cm transaxially. A laparoscopic bilateral salpingo-oophorectomy was performed, and histopathological examination and immunohistochemistry confirmed the diagnosis of a Leydig cell tumor, a rare tumor accounting for 0.1% of ovarian tumors. Surgical resection led to normalization of testosterone levels. LEARNING POINTS: Hirsutism in postmenopausal women should trigger suspicion of androgen-secreting tumorExtremely elevated testosterone level plus normal DHEAS level point toward ovarian sourceLeydig cell tumor is extremely rare cause of hyperandrogenicity.