Multi-institutional evaluation of a Pareto navigation guided automated radiotherapy planning solution for prostate cancer.

BACKGROUND: Current automated planning solutions are calibrated using trial and error or machine learning on historical datasets. Neither method allows for the intuitive exploration of differing trade-off options during calibration, which may aid in ensuring automated solutions align with clinical preference. Pareto navigation provides this functionality and offers a potential calibration alternative. The purpose of this study was to validate an automated radiotherapy planning solution with a novel multi-dimensional Pareto navigation calibration interface across two external institutions for prostate cancer. METHODS: The implemented 'Pareto Guided Automated Planning' (PGAP) methodology was developed in RayStation using scripting and consisted of a Pareto navigation calibration interface built upon a 'Protocol Based Automatic Iterative Optimisation' planning framework. 30 previous patients were randomly selected by each institution (IA and IB), 10 for calibration and 20 for validation. Utilising the Pareto navigation interface automated protocols were calibrated to the institutions' clinical preferences. A single automated plan (VMATAuto) was generated for each validation patient with plan quality compared against the previously treated clinical plan (VMATClinical) both quantitatively, using a range of DVH metrics, and qualitatively through blind review at the external institution. RESULTS: PGAP led to marked improvements across the majority of rectal dose metrics, with Dmean reduced by 3.7 Gy and 1.8 Gy for IA and IB respectively (p < 0.001). For bladder, results were mixed with low and intermediate dose metrics reduced for IB but increased for IA. Differences, whilst statistically significant (p < 0.05) were small and not considered clinically relevant. The reduction in rectum dose was not at the expense of PTV coverage (D98% was generally improved with VMATAuto), but was somewhat detrimental to PTV conformality. The prioritisation of rectum over conformality was however aligned with preferences expressed during calibration and was a key driver in both institutions demonstrating a clear preference towards VMATAuto, with 31/40 considered superior to VMATClinical upon blind review. CONCLUSIONS: PGAP enabled intuitive adaptation of automated protocols to an institution's planning aims and yielded plans more congruent with the institution's clinical preference than the locally produced manual clinical plans.

Evaluation of Quantitative Pupillometry in Acute Postinjury Pediatric Concussion.

BACKGROUND: Although millions of children sustain concussions each year, a rapid and objective test for concussion has remained elusive. The aim of this study was to investigate quantitative pupillometry in pediatric patients in the acute, postinjury setting. METHODS: This was a prospective case-control study of concussed patients presenting to the emergency department within 72 hours of injury. Pupillary measurements were gathered using NeurOptics' PLR 3000; evaluation included a symptom checklist and neurocognitive assessment. Data were analyzed using descriptive statistics and regression models. RESULTS: A total of 126 participants were enrolled. One significant difference in pupillometry between concussed and control participants was found: left minimum pupil diameter in 12- to 18 year-olds (P = 0.02). Models demonstrating odds of a concussion revealed significant associations for time to 75% recovery (T75) of the left pupil in five- to 11-year-olds and average dilation velocity of the left pupil in 12- to 18-year-olds (P = 0.03 and 0.02 respectively). Models predicting symptom improvement showed one significant association: percent change of the right pupil in five-to-11-year-olds (P = 0.02). Models predicting neurocognitive improvement in 12- to 18-year-olds demonstrated significant association in T75 in the left pupil for visual memory, visual motor processing speed, and reaction time (P = 0.002, P = 0.04, P = 0.04). CONCLUSIONS: The limited statistically significant associations found in this study suggest that pupillometry may not be useful in pediatrics in the acute postinjury setting for either the diagnosis of concussion or to stratify risk for prolonged recovery.

Evaluating a radiotherapy deep learning synthetic CT algorithm for PET-MR attenuation correction in the pelvis.

BACKGROUND: Positron emission tomography-magnetic resonance (PET-MR) attenuation correction is challenging because the MR signal does not represent tissue density and conventional MR sequences cannot image bone. A novel zero echo time (ZTE) MR sequence has been previously developed which generates signal from cortical bone with images acquired in 65 s. This has been combined with a deep learning model to generate a synthetic computed tomography (sCT) for MR-only radiotherapy. This study aimed to evaluate this algorithm for PET-MR attenuation correction in the pelvis. METHODS: Ten patients being treated with ano-rectal radiotherapy received a [Formula: see text]F-FDG-PET-MR in the radiotherapy position. Attenuation maps were generated from ZTE-based sCT (sCTAC) and the standard vendor-supplied MRAC. The radiotherapy planning CT scan was rigidly registered and cropped to generate a gold standard attenuation map (CTAC). PET images were reconstructed using each attenuation map and compared for standard uptake value (SUV) measurement, automatic thresholded gross tumour volume (GTV) delineation and GTV metabolic parameter measurement. The last was assessed for clinical equivalence to CTAC using two one-sided paired t tests with a significance level corrected for multiple testing of [Formula: see text]. Equivalence margins of [Formula: see text] were used. RESULTS: Mean whole-image SUV differences were -0.02% (sCTAC) compared to -3.0% (MRAC), with larger differences in the bone regions (-0.5% to -16.3%). There was no difference in thresholded GTVs, with Dice similarity coefficients [Formula: see text]. However, there were larger differences in GTV metabolic parameters. Mean differences to CTAC in [Formula: see text] were [Formula: see text] (± standard error, sCTAC) and [Formula: see text] (MRAC), and [Formula: see text] (sCTAC) and [Formula: see text] (MRAC) in [Formula: see text]. The sCTAC was statistically equivalent to CTAC within a [Formula: see text] equivalence margin for [Formula: see text] and [Formula: see text] ([Formula: see text] and [Formula: see text]), whereas the MRAC was not ([Formula: see text] and [Formula: see text]). CONCLUSION: Attenuation correction using this radiotherapy ZTE-based sCT algorithm was substantially more accurate than current MRAC methods with only a 40 s increase in MR acquisition time. This did not impact tumour delineation but did significantly improve the accuracy of whole-image and tumour SUV measurements, which were clinically equivalent to CTAC. This suggests PET images reconstructed with sCTAC would enable accurate quantitative PET images to be acquired on a PET-MR scanner.

Impact of attenuation correction of radiotherapy hardware for positron emission tomography-magnetic resonance in ano-rectal radiotherapy patients.

BACKGROUND: Positron Emission Tomography-Magnetic Resonance (PET-MR) scanners could improve ano-rectal radiotherapy planning through improved Gross Tumour Volume (GTV) delineation and enabling dose painting strategies using metabolic measurements. This requires accurate quantitative PET images acquired in the radiotherapy treatment position. PURPOSE: This study aimed to evaluate the impact on GTV delineation and metabolic parameter measurement of using novel Attenuation Correction (AC) maps that included the radiotherapy flat couch, coil bridge and anterior coil to see if they were necessary. METHODS: Seventeen ano-rectal radiotherapy patients received a 18 F $\mathrm{^{18}F}$ -FluoroDeoxyGlucose PET-MR scan in the radiotherapy position. PET images were reconstructed without ( CTAC std $\mathrm{CTAC_{std}}$ ) and with ( CTAC cba $\mathrm{CTAC_{cba}}$ ) the radiotherapy hardware included. Both AC maps used the same Computed Tomography image for patient AC. Semi-manual and threshold GTVs were delineated on both PET images, the volumes compared and the Dice coefficient calculated. Metabolic parameters: Standardized Uptake Values SUV max $\mathrm{SUV_{max}}$ , SUV mean $\mathrm{SUV_{mean}}$ and Total Lesion Glycolysis (TLG) were compared using paired t-tests with a Bonferroni corrected significance level of p = 0.05 / 8 = 0.006 $p = 0.05/8 = 0.006$ . RESULTS: Differences in semi-manual GTV volumes between CTAC cba $\mathrm{CTAC_{cba}}$ and CTAC std $\mathrm{CTAC_{std}}$ were approaching statistical significance (difference - 15.9 % ± 1.6 % $-15.9\%\pm 1.6\%$ , p = 0.007 $p = 0.007$ ), with larger differences in low FDG-avid tumours ( SUV mean < 8.5 g mL - 1 $\mathrm{SUV_{mean}} < 8.5\;\mathrm{g\: mL^{-1}}$ ). The CTAC cba $\mathrm{CTAC_{cba}}$ and CTAC std $\mathrm{CTAC_{std}}$ GTVs were concordant with Dice coefficients 0.89 ± 0.01 $0.89 \pm 0.01$ (manual) and 0.98 ± 0.00 $0.98 \pm 0.00$ (threshold). Metabolic parameters were significantly different, with SUV max $\mathrm{SUV_{max}}$ , SUV mean $\mathrm{SUV_{mean}}$ and TLG differences of - 11.5 % ± 0.3 % $-11.5\%\ \pm 0.3\%$ ( p < 0.001 $p < 0.001$ ), - 11.6 % ± 0.3 % $-11.6\% \pm 0.3\%$ ( p < 0.001 $p < 0.001$ ) and - 13.7 % ± 0.6 % $-13.7\%\ \pm 0.6\%$ ( p = 0.003 $p = 0.003$ ) respectively. The TLG difference resulted in 1/8 rectal cancer patients changing prognosis group, based on literature TLG cut-offs, when using CTAC cba $\mathrm{CTAC_{cba}}$ rather than CTAC std $\mathrm{CTAC_{std}}$ . CONCLUSIONS: This study suggests that using AC maps with the radiotherapy hardware included is feasible for patient imaging. The impact on tumour delineation was mixed and needs to be evaluated in larger cohorts. However using AC of the radiotherapy hardware is important for situations where accurate metabolic measurements are required, such as dose painting and treatment prognostication.

Perfusion MRI in the evaluation of brain metastases: current practice review and rationale for study of baseline MR perfusion imaging prior to stereotactic radiosurgery (STARBEAM-X).

Stereotactic radiosurgery is an established focal treatment for brain metastases with high local control rates. An important side-effect of stereotactic radiosurgery is the development of radionecrosis. On conventional MR imaging, radionecrosis and tumour progression often have similar appearances, but have contrasting management approaches. Perfusion MR imaging is often used in the post-treatment setting in order to help distinguish between the two, but image interpretation can be fraught with challenges.Perfusion MR plays an established role in the baseline and post-treatment evaluation of primary brain tumours and a number of studies have concentrated on the value of perfusion imaging in brain metastases. Of the parameters generated, relative cerebral blood volume is the most widely used variable in terms of its clinical value in differentiating between radionecrosis and tumour progression. Although it has been suggested that the relative cerebral blood volume tends to be elevated in active metastatic disease following treatment with radiosurgery, but not with treatment-related changes, the literature available on interpretation of the ratios provided in the context of defining tumour progression is not consistent.This article aims to provide an overview of the role perfusion MRI plays in the assessment of brain metastases and introduces the rationale for the STARBEAM-X study (Study of assessment of radionecrosis in brain metastases using MR perfusion extra imaging), which will prospectively evaluate baseline perfusion imaging in brain metastases. We hope this will allow insight into the vascular appearance of metastases from different primary sites, and aid in the interpretation of post-treatment perfusion imaging.

Comprehensive dose evaluation of a Deep Learning based synthetic Computed Tomography algorithm for pelvic Magnetic Resonance-only radiotherapy.

BACKGROUND AND PURPOSE: Magnetic Resonance (MR)-only radiotherapy enables the use of MR without the uncertainty of MR-Computed Tomography (CT) registration. This requires a synthetic CT (sCT) for dose calculations, which can be facilitated by a novel Zero Echo Time (ZTE) sequence where bones are visible and images are acquired in 65 seconds. This study evaluated the dose calculation accuracy for pelvic sites of a ZTE-based Deep Learning sCT algorithm developed by GE Healthcare. MATERIALS AND METHODS: ZTE and CT images were acquired in 56 pelvic radiotherapy patients in the radiotherapy position. A 2D U-net convolutional neural network was trained using pairs of deformably registered CT and ZTE images from 36 patients. In the remaining 20 patients the dosimetric accuracy of the sCT was assessed using cylindrical dummy Planning Target Volumes (PTVs) positioned at four different central axial locations, as well as the clinical treatment plans (for prostate (n = 10), rectum (n = 4) and anus (n = 6) cancers). The sCT was rigidly and deformably registered, the plan recalculated and the doses compared using mean differences and gamma analysis. RESULTS: Mean dose differences to the PTV D98% were ≤ 0.5% for all dummy PTVs and clinical plans (rigid registration). Mean gamma pass rates at 1%/1 mm were 98.0 ± 0.4% (rigid) and 100.0 ± 0.0% (deformable), 96.5 ± 0.8% and 99.8 ± 0.1%, and 95.4 ± 0.6% and 99.4 ± 0.4% for the clinical prostate, rectum and anus plans respectively. CONCLUSIONS: A ZTE-based sCT algorithm with high dose accuracy throughout the pelvis has been developed. This suggests the algorithm is sufficiently accurate for MR-only radiotherapy for all pelvic sites.

Acute Hospital Management of Pediatric Stroke.

The field of pediatric stroke has historically been hampered by limited evidence and small patient cohorts. However the landscape of childhood stroke is rapidly changing due in part to increasing awareness of the importance of pediatric stroke and the emergence of dedicated pediatric stroke centers, care pathways, and alert systems. Acute pediatric stroke management hinges on timely diagnosis confirmed by neuroimaging, appropriate consideration of recanalization therapies, implementation of neuroprotective measures, and attention to secondary prevention. Because pediatric stroke is highly heterogenous in etiology, management strategies must be individualized. Determining a child's underlying stroke etiology is essential to appropriately tailoring hyperacute stroke management and determining best approach to secondary prevention. Herein, we review the methods of recognition, diagnosis, management, current knowledge gaps and promising research for pediatric stroke.

Does hospital variation in intrapartum-related perinatal mortality among caesarean births reflect differences in quality of care? Cross-sectional study in 21 hospitals in Burkina Faso.

OBJECTIVES: To examine hospital variation in crude and risk-adjusted rates of intrapartum-related perinatal mortality among caesarean births. DESIGN: Secondary analysis of data from the DECIDE (DECIsion for caesarean DElivery) cluster randomised trial postintervention phase. SETTING: 21 district and regional hospitals in Burkina Faso. PARTICIPANTS: All 5134 women giving birth by caesarean section in a 6-month period in 2016. PRIMARY OUTCOME MEASURE: Intrapartum-related perinatal mortality (fresh stillbirth or neonatal death within 24 hours of birth). RESULTS: Almost 1 in 10 of 5134 women giving birth by caesarean experienced an intrapartum-related perinatal death. Crude mortality rates varied substantially from 21 to 189 per 1000 between hospitals. Variation was markedly reduced after adjusting for case mix differences (the median OR decreased from 1.9 (95% CI 1.5 to 2.5) to 1.3 (95% CI 1.2 to 1.7)). However, higher and more variable adjusted mortality persisted among hospitals performing fewer caesareans per month. Additionally, adjusting for caesarean care components did not further reduce variation (median OR=1.4 (95% CI 1.2 to 1.8)). CONCLUSIONS: There is a high burden of intrapartum-related perinatal deaths among caesarean births in Burkina Faso and sub-Saharan Africa more widely. Variation in adjusted mortality rates indicates likely differences in quality of caesarean care between hospitals, particularly lower volume hospitals. Improving access to and quality of emergency obstetric and newborn care is an important priority for improving survival of babies at birth. TRIAL REGISTRATION NUMBER: ISRCTN48510263.

Post-Concussive Orthostatic Tachycardia is Distinct from Postural Orthostatic Tachycardia Syndrome (POTS) in Children and Adolescents.

Background: Orthostatic tachycardia (OT) affects some patients after concussion/mild traumatic brain injury (mTBI). In this study, we sought to identify the factors associated with increased risk for OT in patients with mTBI. Methods: We conducted a retrospective review of 268 patients (8-25 years) with mTBI/concussion to determine the prevalence of OT, defined as orthostatic heart rate change ≥40 bpm for those ≤19 years of age and ≥30 bpm on active standing test for those >19 years of age. Results: Among the study population, 7% (n = 19) exhibited post-concussive OT. The only significant difference between OT and non-OT groups was that history of prior concussion was more prevalent in the OT group. Conclusion: A substantial subset (7%) of concussion clinic patients exhibit OT. While POTS literature describes female and adolescent predominance, post-concussive OT had similar prevalence across age and gender groups in this study, suggesting that it may be distinct from POTS.

Mental health service use among mothers involved in public family law proceedings: linked data cohort study in South London 2007-2019.

PURPOSE: Mental health problems and substance misuse are common among the mothers of children who experience court-mandated placement into care in England, yet there is limited research characterising these health needs to inform evidence-based policy. In this descriptive study, we aimed to generate evidence about the type, severity, and timing of mental health and substance misuse needs among women involved in public family law proceedings concerning child placement into care ('care proceedings'). METHODS: This is a retrospective, matched cohort study using linked family court and mental health service records for 2137 (66%) of the 3226 women involved in care proceedings between 2007 and 2019 in the South London and Maudsley NHS Mental Health Trust (SLaM) catchment area. We compared mental health service use and risk of dying with 17,096 female-matched controls who accessed SLaM between 2007 and 2019, aged 16-55 years, and were not involved in care proceedings. RESULTS: Most women (79%) were known to SLaM before care proceedings began. Women had higher rates of schizophrenia spectrum disorders (19% vs 11% matched controls), personality disorders (21% vs 11%), and substance misuse (33% vs 12%). They were more likely to have a SLaM inpatient admission (27% vs 14%) or to be sectioned (19% vs 8%). Women had a 2.15 (95% CI 1.68-2.74) times greater hazard of dying, compared to matched controls, adjusted for age. CONCLUSION: Women involved in care proceedings experience a particularly high burden of severe and complex mental health and substance misuse need. Women's increased risk of mortality following proceedings highlights that interventions responding to maternal mental health and substance misuse within family courts should offer continued, long-term support.

Spontaneous Intracranial Artery Dissection causing Subarachnoid Hemorrhage: Importance of Short-Term Surveillance.

Hemorrhagic intracranial artery dissections are unstable lesions, with a high propensity for rebleeding (up to 40%) in the acute period. Imaging plays an important role in the diagnosis and management of intracranial artery dissections. In this paper, we describe 2 cases in which the dissected intracranial artery underwent rapid morphological change within 3 days or less, highlighting the importance of short-term follow-up imaging in patients with these hemorrhagic lesions.

Cone beam computed tomography for dose calculation quality assurance for magnetic resonance-only radiotherapy.

BACKGROUND AND PURPOSE: Magnetic Resonance (MR)-only prostate radiotherapy using synthetic Computed Tomography (sCT) algorithms with high dose accuracy has been clinically implemented. MR images can suffer from geometric distortions so Quality Assurance (QA) using an independent, geometrically accurate, image could be required. The first-fraction Cone Beam CT (CBCT) has demonstrated potential but has not been evaluated in a clinical MR-only pathway. This study evaluated the clinical use of CBCT for dose accuracy QA of MR-only radiotherapy. MATERIALS AND METHODS: A total of 49 patients treated with MR-only prostate radiotherapy were divided into two cohorts. Cohort 1 (20 patients) received a back-up CT, whilst Cohort 2 (29 patients) did not. All patients were planned using the sCT and received daily CBCT imaging with MR-CBCT soft-tissue matching. Each CBCT was calibrated using a patient-specific stepwise Hounsfield Units-to-mass density curve. The treatment plan was recalculated on the first-fraction CBCT using the clinically applied soft-tissue match and the doses compared. For Cohort 1 the sCT was rigidly registered to the back-up CT, the plan recalculated and doses compared. RESULTS: Mean sCT-CBCT dose difference across both cohorts was - 0.6 ± 0.1 % (standard error of the mean, range - 2.3 % , 2.3 % ), with 47/49 patients within [ - 2 % , 1 % ]. The sCT-CBCT dose difference was systematically lower than the sCT-CT by - 0.7 ± 0.6 % ( ± 95 % limits of agreement). The mean sCT-CBCT gamma pass rate ( 2 % / 2 mm ) was 96.1 ± 0.4 % ( 85.4 % , 99.7 % ). CONCLUSIONS: CBCT-based dose accuracy QA for MR-only radiotherapy appears clinically feasible. There was a small systematic sCT-CBCT dose difference implying asymmetric tolerances of [ - 2 % , 1 % ] would be appropriate.

Are cone beam CT image matching skills transferrable from planning CT to planning MRI for MR-only prostate radiotherapy?

OBJECTIVES: Treatment verification for MR-only planning has focused on fiducial marker matching, however, these are difficult to identify on MR. An alternative is using the MRI for soft-tissue matching with cone beam computed tomography images (MR-CBCT). However, therapeutic radiographers have limited experience of MRI. This study aimed to assess transferability of therapeutic radiographers CT-CBCT prostate image matching skills to MR-CBCT image matching. METHODS: 23 therapeutic radiographers with 3 months-5 years' experience of online daily CT-CBCT soft-tissue matching prostate cancer patients participated. Each observer completed a baseline assessment of 10 CT-CBCT prostate soft-tissue image matches, followed by 10 MR-CBCT prostate soft-tissue image match assessment. A MRI anatomy training intervention was delivered and the 10 MR-CBCT prostate soft-tissue image match assessment was repeated. Limits of agreement were calculated as the disagreement of the observers with mean of all observers. RESULTS: Limits of agreement at CT-CBCT baseline were 2.8 mm, 2.8 mm, 0.7 mm (vertical, longitudinal, lateral). MR-CBCT matches prior to training were 3.3 mm, 3.1 mm, 0.9 mm, and after training 2.6 mm, 2.4 mm, 1.1 mm (vertical, longitudinal, lateral). Results show similar limits of agreement across the assessments, and variation reduced following the training intervention. CONCLUSION: This suggests therapeutic radiographers' prostate CBCT image matching skills are transferrable to a MRI planning scan, since MR-CBCT matching has comparable observer variation to CT-CBCT matching. ADVANCES IN KNOWLEDGE: This is the first publication assessing interobserver MR-CBCT prostate soft tissue matching in an MR-only pathway.

Baclofen Toxicity Mimicking Brain Death: A Case Report of a Pediatric Patient.

BACKGROUND: Baclofen is commonly used in both pediatric and adult patients to treat spasticity secondary to spinal cord and cerebral pathology. A broad range of symptoms and severity of baclofen toxicity have been described. However, to our knowledge, there are no reports to date of baclofen toxicity mimicking brain death in pediatric patients. OBJECTIVE: We reviewed the presentation, clinical course, diagnostic studies including imaging and electroencephalography, and outcome of a patient with transient coma and loss of brainstem reflexes mimicking brain death secondary to baclofen toxicity. METHODS: During a baclofen pump refill, a 12-year-old boy with cerebral palsy had inadvertent injection of 12,000 µg of baclofen into the pocket around his pump. Within an hour, he presented with acute altered mental status that rapidly progressed to a comatose state with absent brainstem reflexes. RESULTS: After appropriate management, the patient returned to his neurological baseline by hospital day 3. DISCUSSION: We reviewed the literature for varying presentations of baclofen toxicity and associated electroencephalography findings, mechanism of overdose, and different management options. In this case, the mechanism of baclofen toxicity was suspected to be secondary to extravasation from the pump pocket and subsequent systemic absorption. CONCLUSIONS: Patients with baclofen toxicity may have a dramatic presentation and an initial examination mimicking brain death. Given its rarity, this clinical entity may not be readily recognized, and there is potential for misinterpretation of diagnosis and prognosis. It is important for physicians to be familiar with this clinical scenario to avoid false declaration of brain death.

Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial.

INTRODUCTION: Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone. METHODS: A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. PRIMARY OUTCOME: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024. ETHICS AND DISSEMINATION: Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03763253; ISCRTN58401737.

Gender-based violence and its association with mental health among Somali women in a Kenyan refugee camp: a latent class analysis.

BACKGROUND: In conflict-affected settings, women and girls are vulnerable to gender-based violence (GBV). GBV is associated with poor long-term mental health such as anxiety, depression and post-traumatic stress disorder (PTSD). Understanding the interaction between current violence and past conflict-related violence with ongoing mental health is essential for improving mental health service provision in refugee camps. METHODS: Using data collected from 209 women attending GBV case management centres in the Dadaab refugee camps, Kenya, we grouped women by recent experience of GBV using latent class analysis and modelled the relationship between the groups and symptomatic scores for anxiety, depression and PTSD using linear regression. RESULTS: Women with past-year experience of intimate partner violence alone may have a higher risk of depression than women with past-year experience of non-partner violence alone (Coef. 1.68, 95% CI 0.25 to 3.11). Conflict-related violence was an important risk factor for poor mental health among women who accessed GBV services, despite time since occurrence (average time in camp was 11.5 years) and even for those with a past-year experience of GBV (Anxiety: 3.48, 1.85-5.10; Depression: 2.26, 0.51-4.02; PTSD: 6.83, 4.21-9.44). CONCLUSION: Refugee women who experienced past-year intimate partner violence or conflict-related violence may be at increased risk of depression, anxiety or PTSD. Service providers should be aware that compared to the general refugee population, women who have experienced violence may require additional psychological support and recognise the enduring impact of violence that occurred before, during and after periods of conflict and tailor outreach and treatment services accordingly.

Research challenges in evaluating gender-based violence response services in a refugee camp.

This article presents a case study of research in Dadaab, Kenya to highlight some of the relevant challenges encountered while conducting gender-based violence research in humanitarian settings. A longitudinal mixed-methods design was used to evaluate a comprehensive case-management intervention in the refugee complex near the border of Kenya and Somalia. We present an overview of both expected and unexpected challenges during preparation and implementation of the research, adaptations made to the research design, and lessons learned for future research in similar contexts. Some of the key challenges were attributed to the highly securitized and remote environment of Dadaab refugee camp, like many refugee camp settings, which created limitations for sampling designs, interview locations, and also created particular burdens for the research team members conducting interviews. In addition to the camp environment, the dynamic nature of events and trends in the camp setting created barriers to follow-up with longitudinal cohort participants as well as uncertainty on how to plan for future implementation of research design phases in response to camp changes. Conducting research in humanitarian settings requires a flexible approach to accommodate the challenges that can impact both service delivery and research activities. The discussion presented in this article contributes to the evolving practical guidance on conducting research in humanitarian settings.

Characterizing newborn and older infant entries into care in England between 2006 and 2014.

BACKGROUND: The risk of entry to state care during infancy is increasing, both here in England and abroad, with most entering within a week of birth ('newborns'). However, little is known about these infants or of their pathways through care over early childhood. OBJECTIVE: To characterize infant entries to care in England. PARTICIPANTS AND SETTING: All children in England who first entered care during infancy, between April 2006 and March 2014 (n = 42,000). METHODS: We compared sociodemographic and care characteristics for infants entering care over the study period by age at first entry (newborn: <1wks, older infant 1-51wks). Among those who entered before April 2010, we further characterized care over follow-up (i.e. 4 years from first entry) and employed latent class analysis to uncover any common pathways through care. RESULTS: Almost 40 % of infants first entered care as a newborn. Most infants first entered care under s 20 arrangements (i.e. out-of-court, 60 % of newborns vs 47 % of older infants). Among infants entering before April 2010, most were adopted over follow-up (60 % vs 37 %), though many were restored to parental care (20 % vs 32 %) or exited care to live with extended family (13 % vs 19 %). One in six infants (17.7 %) had particularly unstable care trajectories over early childhood, typified by three or more placements or failed reunification. CONCLUSIONS: Evidence-based strengthening of pre-birth social work support is needed to improve preventive interventions before birth, to more effectively target infant placement into care. Linkages between child protection records and information on parents are needed to inform preventive strategies.

Association between health indicators of maternal adversity and the rate of infant entry to local authority care in England: a longitudinal ecological study.

OBJECTIVE: Infants enter care at varying rates across local authorities (LAs) in England, but evidence is lacking on what is driving these differences. With this ecological study, we aimed to explore the extent to which adversity indicated within women's hospitalisation histories, predelivery, explained the rate of infant entry into care. METHODS: We used two longitudinal person-level data sets on hospitalisations and entries to care to create annual measures for 131 English LAs, between 2006/2007 and 2013/2014 (April-March). We combined these measures by LA and financial year, along with other publicly available data on LA characteristics. We used linear mixed-effects models to analyse the relationship between the outcome-LA-specific rate of infant entry into care (per 10 000 infants in the LA population) - and LA-specific percentage of live births with maternal history of adversity-related hospital admissions (ie, substance misuse, mental health problems or violence-related admissions in the 3 years before delivery), adjusted for other predictors of entry into care. RESULTS: Rate of infant entry into care (mean: 85.16 per 10 000, SD: 41.07) and percentage of live births with maternal history of adversity-related hospital admissions (4.62%, 2.44%) varied greatly by LA. The prevalence of maternal adversity accounted for 24% of the variation in rate of entry (95% CI 14% to 35%). After adjustment, a percentage point increase in prevalence of maternal adversity-both within and between LAs-was associated with an estimated 2.56 (per 10 000) more infants entering care (1.31-3.82). CONCLUSIONS: The prevalence of maternal adversity before birth helped to explain the variation in LA rates of infant entry into care. Preventive interventions are needed to improve maternal well-being before and during pregnancy, and potentially reduce risk of child maltreatment and therefore entries to care. Evidence on who to target and data to evaluate change require linkage between parent-child healthcare data and administrative data from children's social care.

Disability, violence, and mental health among Somali refugee women in a humanitarian setting.

BACKGROUND: There is limited evidence on the relationship between disability, experiences of gender-based violence (GBV), and mental health among refugee women in humanitarian contexts. METHODS: A cross-sectional analysis was conducted of baseline data (n = 209) collected from women enrolled in a cohort study of refugee women accessing GBV response services in the Dadaab refugee camps in Kenya. Women were surveyed about GBV experiences (past 12 months, before the last 12 months, before arriving in the refugee camps), functional disability status, and mental health (anxiety, depression, post-traumatic stress), and we explored the inter-relationship of these factors. RESULTS: Among women accessing GBV response services, 44% reported a disability. A higher proportion of women with a disability (69%) reported a past-year experience of physical intimate partner violence and/or physical or sexual non-partner violence, compared to women without a disability (54%). A higher proportion of women with a disability (32%) experienced non-partner physical or sexual violence before arriving in the camp compared to women without a disability (16%). Disability was associated with higher scores for depression (1.93, 95% confidence interval (CI) 0.54-3.33), PTSD (2.26, 95% CI 0.03-4.49), and anxiety (1.54, 95% CI 0.13-2.95) after adjusting for age, length of encampment, partner status, number of children, and GBV indicators. CONCLUSIONS: A large proportion of refugee women seeking GBV response services have disabilities, and refugee women with a disability are at high risk of poor mental health. This research highlights the need for mental health and disability screening within GBV response programming.