Psychiatric and psychosocial morbidity 1 year after epilepsy surgery.

OBJECTIVES: There is a high rate of psychiatric comorbidity in patients with epilepsy. However, the impact of surgical treatment of refractory epilepsy on psychopathology remains under investigation. We aimed to examine the impact of epilepsy surgery on psychopathology and quality of life at 1-year post-surgery in a population of patients with epilepsy refractory to medication. METHODS: This study initially assessed 48 patients with refractory epilepsy using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life in Epilepsy Inventory 89 (QOLIE-89) on admission to an Epilepsy Monitoring Unit (EMU) as part of their pre-surgical assessment. These patients were again assessed using the SCID-I, QOLIE-89 and HADS at 1-year follow-up post-surgery. RESULTS: There was a significant reduction in psychopathology, particularly psychosis, following surgery at 1-year follow-up (p < 0.021). There were no new cases of de novo psychosis and surgery was also associated with a significant improvement in the quality of life scores (p < 0.001). CONCLUSIONS: This study demonstrates the impact of epilepsy surgery on psychopathology and quality of life in a patient population with refractory surgery. The presence of a psychiatric illness should not be a barrier to access surgical treatment.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

The impact of the COVID-19 pandemic on the Ontario Cervical Screening Program, colposcopy and treatment services in Ontario, Canada: a population-based study.

OBJECTIVE: To describe the immediate impact of the COVID-19 pandemic on cervical screening, colposcopy and treatment volumes in Ontario, Canada. DESIGN: Population-based retrospective observational study. SETTING: Ontario, Canada. POPULATION: People with a cervix age of 21-69 years who completed at least one cervical screening cytology test, colposcopy or treatment procedure for cervical dysplasia between January 2019 and August 2020. METHODS: Administrative databases were used to compare cervical screening cytology, colposcopy and treatment procedure volumes before (historical comparator) and during the first 6 months of the COVID-19 pandemic (March-August 2020). MAIN OUTCOME MEASURES: Changes in cervical screening cytology, colposcopy and treatment volumes; individuals with high-grade cytology awaiting colposcopy. RESULTS: During the first 6 months of the COVID-19 pandemic, the monthly average number of cervical screening cytology tests, colposcopies and treatments decreased by 63.8% (range: -92.3 to -41.0%), 39.7% (range: -75.1 to -14.3%) and 31.1% (range: -43.5 to -23.6%), respectively, when compared with the corresponding months in 2019. Between March and August 2020, on average 292 (-51.0%) fewer high-grade cytological abnormalities were detected through screening each month. As of August 2020, 1159 (29.2%) individuals with high-grade screening cytology were awaiting follow-up colposcopy. CONCLUSIONS: The COVID-19 pandemic has had a substantial impact on key cervical screening and follow-up services in Ontario. As the pandemic continues, ongoing monitoring of service utilisation to inform system response and recovery is required. Future efforts to understand the impact of COVID-19-related disruptions on cervical cancer outcomes will be needed. TWEETABLE ABSTRACT: COVID-19 has had a substantial impact on cervical screening and follow-up services in Ontario, Canada.

The impact of cannabis use on vasomotor symptoms, mood, insomnia and sexuality in perimenopausal and postmenopausal women: a systematic review.

OBJECTIVE: This study aimed to evaluate the published data on the effect of cannabis use in perimenopausal and postmenopausal women to alleviate menopausal symptoms, insomnia and anxiety. METHODS: Databases searched included Ovid MEDLINE, PubMed, Ovid Embase, Web of Science, Scopus, CINAHL, PsycINFO, Cochrane, LILACS and AMED. Selected studies assessed perimenopausal or postmenopausal women, cannabis use impact and menopausal symptoms. RESULTS: A total of 564 studies were retrieved. Three studies met the inclusion criteria. One study controlled for participant cannabis use and reported on the effects of cannabis and placebo cigarette smoking on mood in 10 postmenopausal women. Another study assessed associations between drug use with hot flashes and insomnia in 120 HIV-infected women and found that menopausal status and cannabis use was crudely associated with the presence of hot flashes. The last study evaluated expectancies of 115 menopausal patients who endorsed lifetime cannabis use and reported that women expected cannabis to improve depression, anxiety, hot flashes and problems with sleep. None of these studies assessed quality of life as an outcome. CONCLUSION: There is a paucity of literature on the impact of cannabis use in menopause. Research into cannabis consumption in menopause is essential, as it is frequently used to alleviate symptoms without evidence of its benefits.

Understanding the role of oncogenic human papillomavirus (HPV) status on adherence behaviors among women with abnormal cervical cytology.

BACKGROUND: With the introduction of oncogenic Human Papillomavirus (HPV) testing into cervical screening there is a renewed focus on primary prevention among high-risk groups. To date, little is known about the effectiveness of this program, and the extent to which individual-level factors, such as psychosocial health and agency, may play a role. In particular, it is unclear if knowledge of one's oncogenic HPV status impacts on adherence behaviors amongst women with screening abnormalities. The purpose of this study was to identify if clinical, demographic or psychosocial factors predict non-adherence with recommended colposcopy follow-up. METHODS: This prospective pilot study included 145 women referred to a large Toronto colposcopy clinic between December, 2013 and September, 2014. Demographic, clinical and psychosocial characteristics were collected at three points in time: (1) at initial colposcopy consultation; (2) 4-6 weeks following initial consultation, and; (3) at time of follow-up appointment (within 12 months of initial consultation). RESULTS: Overall, 13% (n = 145) of the women were classified as non-adherent. Older women (OR = 0.73, p < 0.01) and those with higher-grade lesions (OR = 0.10, p < 0.01) were less likely to be non-adherent, whereas current smokers (OR = 22.46, p < 0.01) were more likely to be non-adherent. While not statistically significant, variation in rates of non-adherence amongst the various HPV status groups (untested; 15.3%, HPV positive; 5.3%, HPV negative; 6.7%) warrants further study. CONCLUSION: Findings of this study indicate that younger women, those with higher-grade lesions and current smokers were more likely to be non-adherent to recommended colposcopy follow-up. While HPV status did not reach statistical significance, the direction of this finding suggests that testing for HPV may have a positive reinforcing role on adherence to follow-up. The direction of this finding warrants further study, and potentially a practical clinical goal as HPV testing for women becomes standard of care.

Endoscopic Botulinum toxin as a treatment for delayed gastric emptying following oesophagogastrectomy.

INTRODUCTION: The incidence of delayed gastric emptying (DGE) following oesophagogastrectomy with gastric conduit reconstruction is reported to be between 1.7% and 50%. This variation is due to differing practices of intraoperative pylorus drainage procedures, which increase the risk of postoperative biliary reflux and dumping syndrome, resulting in significant morbidity. The aim of our study was to establish rates of DGE in people undergoing oesophagogastrectomy without routine intraoperative drainage procedures, and to evaluate outcomes of postoperative endoscopically administered Botulinum toxin into the pylorus (EBP) for people with DGE resistant to systemic pharmacological treatment. METHODS: All patients undergoing oesophagogastrectomy between 1 January 2016 and 31 March 2018 at our unit were included. No intraoperative pyloric drainage procedures were performed, and DGE resistant to systemic pharmacotherapy was managed with EBP. RESULTS: Ninety-seven patients were included. Postoperatively, 29 patients (30%) were diagnosed with DGE resistant to pharmacotherapy. Of these, 16 (16.5%) were diagnosed within 30 days of surgery. The median pre-procedure nasogastric tube aspirate was 780ml; following EBP, this fell to 125ml (p<0.001). Median delay from surgery to EBP in this cohort was 13 days (IQR 7-16 days). Six patients required a second course of EBP, with 100% successful resolution of DGE before discharge. There were no procedural complications. CONCLUSIONS: This is the largest series of patients without routine intraoperative drainage procedures. Only 30% of patients developed DGE resistant to pharmacotherapy, which was managed safely with EBP in the postoperative period, thus minimising the risk of biliary reflux in people who would otherwise be at risk following prophylactic pylorus drainage procedures.

Same-Day Discharge Among Patients With Obesity Undergoing Laparoscopic Gynaecologic Oncology Surgery.

OBJECTIVES: To determine the likelihood of same-day discharge (SDD) among patients with obesity undergoing laparoscopic gynaecologic oncology surgery and identify predictors of SDD. METHODS: We conducted a retrospective cohort study of gynaecologic oncology patients who underwent laparoscopic procedures between January 2012 and June 2016. Patients were categorized as non-obese, obese class I/II and obese class III (BMI <30, 30-39.9, and ≥40 kg/m2, respectively). We used univariate and multivariable logistic regression to identify variables associated with SDD. RESULTS: Of 496 patients, 288 were non-obese, 161 were obese class I/II, and 47 were obese class III. Overall, 182 patients (36.7%) were discharged same day; 44% of these were non-obese, 30% class I/II and 15% class III. On multivariable analysis, we found negative predictors for SDD to be obesity (OR 0.54; P = 0.03), procedure length (OR 0.51; P < 0.01), and higher American Society of Anesthesiologists (ASA) score (OR 0.63; P < 0.01), while we found being pre-booked for SDD (OR 9.16; P <0.01) was a positive predictor of SDD. Among all patients with obesity, only procedure length (OR 0.47; P < 0.01) and being pre-booked for SDD (OR 9.67; P < 0.01) were associated with SDD when we controlled for BMI, ASA score, intraoperative complications, type of surgery, and surgical start time. Patients discharged same day were less likely to present to the emergency department within 30 days of surgery (OR 0.48; P = 0.01). CONCLUSION: Among the study cohort and after controlling for potential confounders, women with class I, II, and III obesity had a much lower likelihood of SDD than non-obese women. The only significant predictors of SDD among patients with obesity were duration of procedure and pre-booking for SDD. Further study is needed to identify strategies to improve SDD rates among patients with obesity.

Risk of Cervical Dysplasia After Colposcopy Care and Risk-Informed Return to Population-Based Screening: A Systematic Review.

This systematic review examined the risk of cervical dysplasia among women who have undergone a colposcopy episode of care to inform their return to population-based cervical screening. PubMed, Embase, and grey literature were searched between January 2000 and 2018. One reviewer screened citations against pre-defined eligibility criteria. A second reviewer verified 10% and 100% of exclusions at title and abstract and at full-text screening, respectively. One reviewer extracted data and assessed methodological quality of included articles; a second reviewer verified these in full. The primary outcome was incidence of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) subsequent to initial colposcopy evaluation. Secondary outcomes included incidence of CIN2+ after negative follow-up test results and performance of follow-up strategies. Results were synthesized narratively. A total of 48 studies were included. The 1- to 5-year CIN2+ risks after colposcopy evaluation ranged from 2.4% to 16.5% among women treated for CIN2+ and from 0.7% to 16.8% among women untreated for CIN grade 1 or less (≤CIN1). Follow-up strategies included single or repeat cytology, human papillomavirus (HPV) testing, or combined HPV/cytology co-testing at various intervals. After negative follow-up test results, risk varied by follow-up strategy for both groups and by referral cytology severity for untreated women. Performance of follow-up strategies varied among treated women. Among untreated women, co-testing demonstrated greater sensitivity than cytology alone. In conclusion, women treated during colposcopy for CIN2+ and women with ≤CIN1 who were referred to colposcopy for low-grade cytology and who did not receive treatment may be able to return to population-based screening after negative co-testing results. Current evidence does not suggest that women untreated for ≤CIN1 who are referred for high-grade cytology be returned to screening at an average risk interval. The optimal strategy for colposcopy discharge needs ongoing evaluation as implementation of HPV testing evolves.

Assessment of isocenter alignment during CT colonography: Implications for clinical practice.

INTRODUCTION: Optimization of image quality and patient radiation dose is achieved in part by positioning the patient at the isocenter of the CT gantry. The aim of this study was to establish whether there was increased isocenter misalignment (IM) in CT colonography (CTC) scans by comparing patient position during the prone part of a CTC to patient position during renal stone protocol CT (CT-KUB) and patient position during the supine part of a CTC to patient position during abdominopelvic CT (CT-AP). METHODS: Two hundred and twenty two consecutive outpatient adult CTC studies performed between January and December 2016 were retrospectively analyzed. Automated dose-tracking software was used to quantify IM in the x and y planes. Renal stone CT-KUB (n = 100) and standard CT-AP (n = 100) were used as comparison studies. RESULTS: IM during CTC was significantly greater in the y-axis compared with the x-axis for both prone (p = 0.002) and supine (p < 0.001) scanning. IM was significantly greater during prone CTC compared with CT-KUB (p = 0.008) and during supine CTC compared with CT-AP (p = 0.0001). IM was shown to be slightly greater in studies performed by more experienced radiographers (p = 0.04). IM was not associated with patient age, gender or size (p > 0.05 for all). CONCLUSION: Isocenter misalignment is greater during CT colonography compared with CT-KUB or CT-AP. Strategies for improving patient positioning could include radiographer education and automated patient centering solutions.

BRCA1 Mutation Status and Follicular Fluid Exposure Alters NFκB Signaling and ISGylation in Human Fallopian Tube Epithelial Cells.

Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed epithelial ovarian cancer histotype. Other identified risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation, during which the FTE cells become transiently exposed to follicular fluid (FF). To test whether mtBRCA1 or mtBRCA2 nonmalignant FTE cells respond differently to periovulatory FF exposure than control patient FTE cells, gene expression profiles from primary FTE cultures derived from BRCA1 or BRCA2 mutation carriers or control patients were compared at baseline, 24 hours after FF exposure, and 24 hours after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Gene set enrichment analysis revealed increased NFκB and EGFR signaling at baseline in mtBRCA1 samples, with increased interferon target gene expression, including members of the ISGylation pathway, observed after recovery from FF exposure. Gene set enrichment analysis did not identify altered pathway signaling in mtBRCA2 samples. An inverse relationship between EGFR signaling and ISGylation with BRCA1 protein levels was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1 cDNA. Suppression of ISG15 and ISGylated protein levels by increased BRCA1 expression was found to be mediated by decreased NFκB signaling. These studies indicate that increased NFκB signaling associated with decreased BRCA1 expression results in increased ISG15 and protein ISGylation following FF exposure, which may be involved in predisposition to HGSOC.

Short- and long-term outcomes of patients with solid tumours following non-surgical intensive care admission.

BACKGROUND: There has been a significant increase in the number of patients presenting with cancer related emergencies and potentially requiring critical care admission. AIM: To analyse the short and long-term outcomes of patients with solid tumours requiring unplanned medical admission to a specialist cancer intensive care unit (ICU). DESIGN: An unplanned cohort study. METHODS: A retrospective analysis of patients admitted to a UK specialist tertiary oncology CCU between September 2009 and September 2015. The primary outcome measures were survival to CCU discharge and 1-year survival. RESULTS: 687 patients had an unplanned medical admission. The most frequent primary tumours were lymphoma (22.1%), lung (15.2%) and colorectal (13.0%), and 181 (44.4%) were known to have metastases. The median Acute Physiology and Chronic Health Evaluation (APACHE) II and Intensive Care National Audit and Research Centre (ICNARC) scores were 21 and 17, respectively. ICU mortality was 26.7%, with total hospital mortality of 41.9%. The median survival of the total cohort was 56 days after ICU admission, with 107 patients surviving 365 days. Patients with metastatic disease were almost twice as likely to die within the year following ICU admission compared with their counterparts without metastases. Only pancreatic and lung primaries were shown to have a statistically significant impact on survival at 1 year. Pneumonia carried with it the worst prognosis (cumulative survival 0.11), followed by sepsis (0.25) and non-infective respiratory disease (0.26). CONCLUSIONS: The stage and type of cancer appear to have minimal impact on short-term ICU outcomes and only confer poorer long-term prognosis related to the disease.

Can 5-methylcytosine analogues with extended alkyl side chains guide DNA methylation?

5-Methylcytosine (MeC) is an endogenous modification of DNA that plays a crucial role in DNA-protein interactions, chromatin structure, epigenetic regulation, and DNA repair. MeC is produced via enzymatic methylation of the C-5 position of cytosine by DNA-methyltransferases (DNMT) which use S-adenosylmethionine (SAM) as a cofactor. Hemimethylated CG dinucleotides generated as a result of DNA replication are specifically recognized and methylated by maintenance DNA methyltransferase 1 (DNMT1). The accuracy of DNMT1-mediated methylation is essential for preserving tissue-specific DNA methylation and thus gene expression patterns. In the present study, we synthesized DNA duplexes containing MeC analogues with modified C-5 side chains and examined their ability to guide cytosine methylation by the human DNMT1 protein. We found that the ability of 5-alkylcytosines to direct cytosine methylation decreased with increased alkyl chain length and rigidity (methyl > ethyl > propyl ∼ vinyl). Molecular modeling studies indicated that this loss of activity may be caused by the distorted geometry of the DNA-protein complex in the presence of unnatural alkylcytosines.

ZEB1-repressed microRNAs inhibit autocrine signaling that promotes vascular mimicry of breast cancer cells.

During normal tumor growth and in response to some therapies, tumor cells experience acute or chronic deprivation of nutrients and oxygen and induce tumor vascularization. While this occurs predominately through sprouting angiogenesis, tumor cells have also been shown to directly contribute to vessel formation through vascular mimicry (VM) and/or endothelial transdifferentiation. The extrinsic and intrinsic mechanisms underlying tumor cell adoption of endothelial phenotypes, however, are not well understood. Here we show that serum withdrawal induces mesenchymal breast cancer cells to undergo VM and that knockdown of the epithelial-to-mesenchymal transition (EMT) regulator, Zinc finger E-box binding homeobox 1 (ZEB1), or overexpression of the ZEB1-repressed microRNAs (miRNAs), miR-200c, miR-183, miR-96 and miR-182 inhibits this process. We find that secreted proteins Fibronectin 1 (FN1) and serine protease inhibitor (serpin) family E member 2 (SERPINE2) are essential for VM in this system. These secreted factors are upregulated in mesenchymal cells in response to serum withdrawal, and overexpression of VM-inhibiting miRNAs abrogates this upregulation. Intriguingly, the receptors for these secreted proteins, low-density lipoprotein receptor-related protein 1 (LRP1) and Integrin beta 1 (ITGB1), are also targets of the VM-inhibiting miRNAs, suggesting that autocrine signaling stimulating VM is regulated by ZEB1-repressed miRNA clusters. Together, these data provide mechanistic insight into the regulation of VM and suggest that miRNAs repressed during EMT, in addition to suppressing migratory and stem-like properties of tumor cells, also inhibit endothelial phenotypes of breast cancer cells adopted in response to a nutrient-deficient microenvironment.

Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia.

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin-5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.

Large scale accelerator production of 225Ac: Effective cross sections for 78-192MeV protons incident on 232Th targets.

Actinium-225 and 213Bi have been used successfully in targeted alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of 225Ac. The high-energy proton spallation reaction on natural thorium metal targets has been utilized to produce millicurie quantities of 225Ac. The results of sixteen irradiation experiments of thorium metal at beam energies between 78 and 192MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while target dissolution and processing was carried out at Oak Ridge National Laboratory (ORNL). Excitation functions for actinium and thorium isotopes, as well as for some of the fission products, are presented. The cross sections for production of 225Ac range from 3.6 to 16.7mb in the incident proton energy range of 78-192MeV. Based on these data, production of curie quantities of 225Ac is possible by irradiating a 5.0gcm-2 232Th target for 10 days in either BNL or LANL proton irradiation facilities.

Hypertensive disorders of pregnancy and outcomes of preterm infants of 24 to 28 weeks' gestation.

OBJECTIVE: To examine the relationship between hypertensive disorders of pregnancy (HDPs) and mortality and major morbidities in preterm neonates born at 24 to 28 weeks of gestation. STUDY DESIGN: Using an international cohort, we retrospectively studied 27 846 preterm neonates born at 240 to 286 weeks of gestation during 2007 to 2010 from 6 national neonatal databases. The incidence of HDP was compared across countries, and multivariable logistic regression analyses were conducted to examine the association of HDP and neonatal outcomes including mortality to discharge, bronchopulmonary dysplasia, severe brain injury, necrotizing enterocolitis and treated retinopathy of prematurity. RESULTS: The incidence of HDP in the entire cohort was 13% (range 11 to 16% across countries). HDP was associated with reduced odds of mortality (adjusted odds ratio (aOR) 0.77; 95% confidence interval (CI) 0.67 to 0.88), severe brain injury (aOR 0.74; 95% CI 0.62 to 0.89) and treated retinopathy (aOR 0.82; 95% CI 0.70 to 0.96), but increased odds of bronchopulmonary dysplasia (aOR 1.16; 95% CI 1.05 to 1.27). CONCLUSIONS: In comparison with neonates born to mothers without HDP, neonates of HDP mothers had lower odds of mortality, severe brain injury and treated retinopathy, but higher odds of bronchopulmonary dysplasia. The impact of maternal HDP on newborn outcomes was inconsistent across outcomes and among countries; therefore, further international collaboration to standardize terminology, case definition and data capture is warranted.

What effect do substorms have on the content of the radiation belts?

Substorms are fundamental and dynamic processes in the magnetosphere, converting captured solar wind magnetic energy into plasma energy. These substorms have been suggested to be a key driver of energetic electron enhancements in the outer radiation belts. Substorms inject a keV "seed" population into the inner magnetosphere which is subsequently energized through wave-particle interactions up to relativistic energies; however, the extent to which substorms enhance the radiation belts, either directly or indirectly, has never before been quantified. In this study, we examine increases and decreases in the total radiation belt electron content (TRBEC) following substorms and geomagnetically quiet intervals. Our results show that the radiation belts are inherently lossy, shown by a negative median change in TRBEC at all intervals following substorms and quiet intervals. However, there are up to 3 times as many increases in TRBEC following substorm intervals. There is a lag of 1-3 days between the substorm or quiet intervals and their greatest effect on radiation belt content, shown in the difference between the occurrence of increases and losses in TRBEC following substorms and quiet intervals, the mean change in TRBEC following substorms or quiet intervals, and the cross correlation between SuperMAG AL (SML) and TRBEC. However, there is a statistically significant effect on the occurrence of increases and decreases in TRBEC up to a lag of 6 days. Increases in radiation belt content show a significant correlation with SML and SYM-H, but decreases in the radiation belt show no apparent link with magnetospheric activity levels.

A rare case of ischaemic pneumatosis intestinalis and hepatic portal venous gas in an elderly patient with good outcome following conservative management.

INTRODUCTION: Pneumatosis intestinalis (PI) and hepatic portal venous gas (HPVG) are typically associated and are likely to represent a spectrum of the same disease. The causes of both entities range from benign to life-threatening conditions. Ischaemic causes are known to be fatal without emergency surgical intervention. PRESENTATION OF CASE: In this case a 93year old male experienced acute abdominal pain radiating to his back, with nausea and vomiting and a 2-week history of altered bowel habit. Examination revealed abdominal tenderness and distension. He had deranged white cell count (WCC) and renal function. Computed tomography (CT) revealed PI with associated HPVG. The cause was due to ischaemic pathology. The patient was managed conservatively with antibiotics and was discharged 7days later with resolution of his abdominal pain and WCC. DISCUSSION: The pathogenesis of HPVG secondary to PI is poorly understood but usually indicates intestinal ischaemia, thought to carry a mortality of around 75%. HPVG in the older patient usually necessitates emergency surgery however this is not always in the patient's best interest. CONCLUSION: There are few reported cases of patient survival following conservative management of PI and HPVG secondary to ischaemic pathology. This case demonstrates the possibility of managing this condition without aggressive surgical intervention especially when surgery would likely result in mortality due to frailty and morbidity. Further work is required to identify suitable patients.