Glomerular transcriptomics predicts long term outcome and identifies therapeutic strategies for patients with assumed benign IgA nephropathy.

Some patients diagnosed with benign IgA nephropathy (IgAN) develop a progressive clinical course, not predictable by known clinical or histopathological parameters. To assess if gene expression can differentiate between progressors and non-progressors with assumed benign IgAN, we tested microdissected glomeruli from archival kidney biopsy sections from adult patients with stable clinical remission (21 non-progressors) or from 15 patients that had undergone clinical progression within a 25-year time frame. Based on 1 240 differentially expressed genes from patients with suitable sequencing results, we identified eight IgAN progressor and nine non-progressor genes using a two-component classifier. These genes, including APOL5 and ZXDC, predicted disease progression with 88% accuracy, 75% sensitivity and 100% specificity on average 21.6 years before progressive disease was clinically documented. APOL lipoproteins are associated with inflammation, autophagy and kidney disease while ZXDC is a zinc-finger transcription factor modulating adaptive immunity. Ten genes from our transcriptomics data overlapped with an external genome wide association study dataset, although the gene set enrichment test was not statistically significant. We also identified 45 drug targets in the DrugBank database, including angiotensinogen, a target of sparsentan (dual antagonist of the endothelin type A receptor and the angiotensin II type 1 receptor) currently investigated for IgAN treatment. Two validation cohorts were used for substantiating key results, one by immunohistochemistry and the other by nCounter technology. Thus, glomerular mRNA sequencing from diagnostic kidney biopsies from patients with assumed benign IgAN can differentiate between future progressors and non-progressors at the time of diagnosis.

Racial Disparities in Invasive ICU Treatments Among Septic Patients: High Resolution Electronic Health Records Analysis from MIMIC-IV.

Background: Low-resolution administrative databases can give biased results, whereas high-resolution, time-stamped variables from clinical databases like MIMIC-IV might provide nuanced insights. We evaluated racial-ethnic disparities in life-sustaining ICU-treatments (Invasive Mechanical Ventilation (IMV), Renal Replacement Therapy (RRT), and Vasopressors (VP)) among patients with sepsis. Methods: In this observational retrospective cohort study, patients fulfilling sepsis-3 criteria were categorized by treatment assignment within the first 4 days. The outcomes were treatment allocations. The likelihood of receiving treatment was calculated by race-ethnicity (Racial-ethnic group (REG) or White group (WG)) using 5-fold sub-sampling nested logistic regression and XGBoost. Results: In 23,914 admissions, 82% were White, 42% were women. REG were less likely to receive IMV across all eligibility days (day 1 odds ratio (OR) 0.87, 95% confidence interval (CI) 0.83-0.94, day 4 OR 0.80, 95% CI 0.72 - 0.87). There were no differences in RRT (day 1 OR 1.00, 95% CI 0.96-1.09, day 4 OR 1.00, 95% CI 0.94-1.06). REG were also less likely to be treated with VP at days 1 to 3 (day 1 OR 0.87, 95% CI 0.76-0.94), but not at day 4 (OR 0.95, 95% CI 0.87-1.01). These findings remained robust when relaxing eligibility criteria for treatment allocation. Conclusion: Our findings reveal significant disparities in the use of invasive life-saving ICU treatments among septic patients from racial and ethnic minority backgrounds, particularly with respect to IMV and VP use. These disparities underscore not only the need to address inequality in critical care settings, but also highlight the importance of high-resolution data.

Sex differences in treatment patterns for non-advanced muscle-invasive bladder cancer: a descriptive analysis of 3484 patients of the Netherlands Cancer Registry.

PURPOSE: Bladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy). METHODS: A retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses. RESULTS: A total of 3484 patients were diagnosed with non-advanced MIBC in 2018-2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant. CONCLUSIONS: Considerable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient's sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes.

Gastrointestinal symptoms and diagnosis preceding ovarian cancer diagnosis: Effects on treatment allocation and potential diagnostic delay.

OBJECTIVE: To determine whether gastrointestinal (GI) disorder insurance claims in the year preceding a diagnosis of ovarian cancer (OC) lead to differing treatment allocations. The hypothesis is that GI disorders may be indicative of advanced OC. METHODS: This retrospective study identified patients with newly diagnosed OC from January 2015 to January 2019 in the IBM® MarketScan® US commercial insurance and Medicare databases. Analysis was limited to patients with primary or interval debulking surgery or chemotherapy, with or without GI claims in the year prior to diagnosis, with commercial or Medicare coverage for ≥12 months prior and ≥1 month after the index date. Patients were compared in terms of the odds of treatment with neoadjuvant chemotherapy (NCT) or primary debulking surgery (PDS) (logistic regression analysis). Median treatment-free interval in the subset of patients with antineoplastic treatment was compared (Kaplan-Meier analysis). RESULTS: Of the 6286 patients, 22% had a diagnosis of ≥1 GI disorder before their OC diagnosis. Of these patients, 39% were diagnosed with a GI disorder between 6 and 12 months before OC diagnosis and 61% were diagnosed <6 months prior. Women with a GI diagnosis were more likely to undergo NCT than PDS (odds ratio [OR], 1.37; P < 0.0001); this remained significant even when controlling for age, region, insurance plan type, and index year (OR, 1.24; P = 0.001). CONCLUSIONS: In this database, ≈25% of women with OC had a GI claim within the past year and were more likely treated with NCT, an indicator of more advanced disease with a worse prognosis. This suggests that OC should be considered in the differential diagnosis among women with GI complaints, which could alter treatment allocation.

Intra-observer agreements in multidisciplinary team assessments of pancreatic cancer patients.

BACKGROUND AND METHODS: Treatment strategies for pancreatic cancer patients are made by a multidisciplinary team (MDT) board. We aimed to assess intra-observer variance at MDT boards. Participating units staged, assessed resectability, and made treatment allocations for the same patients as they did two years earlier. We disseminated clinical information and CT images of pancreatic cancer patients judged by one MDT board to have nonmetastatic pancreatic cancer to the participating units. All units were asked to re-assess the TNM stage, resectability, and treatment allocation for each patient. To assess intra-observer variance, we computed %-agreements for each participating unit, defined as low (<50%), moderate (50%-75%), and high (>75%) agreement. RESULTS: Eighteen patients were re-assessed by six MDT boards. The overall agreement was moderate for TNM-stage (ranging from 50%-70%) and resectability assessment (53%) but low for treatment allocation (46%). Agreement on resectability assessments was low to moderate. Findings were similar but more pronounced for treatment allocation. We observed a shift in treatment strategy towards increasing use of neoadjuvant chemotherapy, particularly in patients with borderline resectable and locally advanced tumors. CONCLUSIONS: We found substantial intra-observer agreement variations across six different MDT boards of 18 pancreatic cancer patients with two years between the first and second assessment.

Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool.

Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.

Patient selection for a developmental therapeutics program using whole genome and Transcriptome analysis.

Introduction Given the high level of uncertainty surrounding the outcomes of early phase clinical trials, whole genome and transcriptome analysis (WGTA) can be used to optimize patient selection and study assignment. In this retrospective analysis, we reviewed the impact of this approach on one such program. Methods Patients with advanced malignancies underwent fresh tumor biopsies as part of our personalized medicine program (NCT02155621). Tumour molecular data were reviewed for potentially clinically actionable findings and patients were referred to the developmental therapeutics program. Outcomes were reviewed in all patients, including those where trial selection was driven by molecular data (matched) and those where there was no clear molecular rationale (unmatched). Results From January 2014 to January 2018, 28 patients underwent WGTA and enrolled in clinical trials, including 2 patients enrolled in two trials. Fifteen patients were matched to a treatment based on a molecular target. Five patients were matched to a trial based upon single-gene DNA changes, all supported by RNA data. Ten cases were matched on the basis of genome-wide data (n = 4) or RNA gene expression only (n = 6). With a median follow-up of 6.7 months, the median time on treatment was 8.2 weeks. Discussion When compared to single-gene DNA-based data alone, WGTA led to a 3-fold increase in treatment matching. In a setting where there is a high level of uncertainty around both the investigational agents and the biomarkers, more data are needed to fully evaluate the impact of routine use of WGTA.

Predictors of allocation to surgery in patients older than 50 years with partial-thickness rotator cuff tear.

BACKGROUND: The purpose of this study was to determine the predictive factors for allocation to surgery in patients older than 50 years with symptomatic chronic partial-thickness rotator cuff tear (PTRCT). METHODS: Patients older than 50 years with a confirmed diagnosis of unilateral isolated PTRCT were included in this retrospective study. In the minimum follow-up of 2 years, eventual allocation to surgical or nonsurgical treatment was determined individually. Patients who underwent surgery were defined as failed conservative management and allocation to surgery. Data pertaining to patients' demographics, functional comorbidity index values, duration of symptoms, and American Shoulder and Elbow Surgeons scores were collected from our medical records. Tear side and Ellman classification, subacromial spur, and acromiohumeral intervals were also noted. A regression analysis was performed to determine the major predictors of allocation to surgery. RESULTS: There were 202 patients with a mean age of 62 years in group I (no-surgery group) and 70 patients with a mean age of 57 years in group II (surgery group). The mean age and functional comorbidity index values were significantly higher in group I than in group II (P < .001 and P < .001, respectively). Bursal-sided tears were significantly more common in group II (P = .026). According to the findings of regression analysis, tear side and functional comorbidity index were the major predictors of allocation to surgery (P = .015 and P < .001, respectively). CONCLUSION: Our study results indicate that in patients older than 50 years with PTRCTs, those with fewer comorbidities and bursal-sided PTRCTs were significantly more likely to undergo surgery.

The Shiny Balancer - software and imbalance criteria for optimally balanced treatment allocation in small RCTs and cRCTs.

BACKGROUND: In randomised controlled trials with only few randomisation units, treatment allocation may be challenging if balanced distributions of many covariates or baseline outcome measures are desired across all treatment groups. Both traditional approaches, stratified randomisation and allocation by minimisation, have their own limitations. A third method for achieving balance consists of randomly choosing from a preselected list of sufficiently balanced allocations. As with minimisation, this method requires that heterogeneity between treatment groups is measured by specified imbalance metrics. Although certain imbalance measures are more commonly used than others, to the author's knowledge there is no generally accepted "gold standard", neither for categorical and even less so for continuous variables. METHODS: An intuitive and easily accessible web-based software tool was developed which allows for balancing multiple variables of different types and using various imbalance metrics. Different metrics were compared in a simulation study. RESULTS: Using simulated data, it could be shown that for categorical variables, χ2-based imbalance measures seem to be viable alternatives to the established "quadratic imbalance" metric. For continuous variables, using the area between the empirical cumulative distribution functions or the largest difference in the three pairs of quartiles is recommended to measure imbalance. Another imbalance metric suggested in the literature for continuous variables, the (symmetrised) Kullback-Leibler divergence, should be used with caution. CONCLUSION: The Shiny Balancer offers the possibility to visually explore the balancing properties of several well established or newly suggested imbalance metrics, and its use is particularly advocated in clinical studies with few randomisation units, as it is typically the case in cluster randomised trials.

Selection Processes in Prison-Based Treatment Referrals: A Street-Level Bureaucracy Perspective.

Studies indicated that detainees are not always allocated to treatment programs based on official guidelines. Street-level bureaucracy theory suggests that this is because government employees do not always perform policies as prescribed. This study aimed to assess whether this also applies to the allocation of offenders to treatment in Dutch penitentiary institutions, and aimed to determine which factors influenced this. The proposed questions were addressed by studying a group of 541 male prisoners who participated in the Dutch prison-based Prevention of Recidivism program. Results showed that official guidelines were, in most cases, not leading when referring detainees to programs. Instead, treatment referrals were influenced by a broad range of risk factors, as well as the length of an offender's sentence.

Clinical care for severe and persistent eating disorders in pediatric populations: Perspectives of health professionals.

OBJECTIVE: Models of treatment for adults with severe and enduring eating disorders focus on harm reduction and improving quality of life. However, there is a notable gap in the pediatric literature in this area. The current study set out to assess the perspectives of health professionals regarding clinical care for young people (e.g., ages 10-25 years) with severe and enduring eating disorders, and to explore perceptions about appropriate treatment options for these presentations. METHODS: Health professionals were invited to complete a two-stage online survey about their experiences with clinical care for pediatric eating disorders through Canadian and Australian professional eating disorder networks. Survey 1 included questions about their experiences in supporting individuals with severe and enduring presentations. Participants who completed Survey 2 reviewed clinical vignettes and shared their perspectives about treatment recommendations and models of care, including for a severe and enduring presentation. RESULTS: A total of 85 clinicians responded to questions on Survey 1 about severe and enduring eating disorder presentations. A portion of these respondents (n = 25) also participated in Survey 2. The majority of respondents to Survey 1 reported providing clinical care for pediatric severe and enduring eating disorder presentations. Amongst respondents to Survey 2, there was low consensus amongst respondents for the clinical care that would be most appropriate for young people with a severe and enduring eating disorder presentation. Numerous challenges in models of care for severe and enduring presentations in pediatric settings were raised in responses on Survey 2, with clinicians sharing their awareness of models focusing on quality of life, while also raising concerns about the appropriateness of these models for young people. CONCLUSIONS: The preliminary results of this study demonstrate that the majority of clinicians report that they have provided care to young people with severe and enduring presentations. There is a clear need for establishing guidance for clinicians working in pediatric eating disorder settings around models of care focused on quality of life. Engagement with interested parties, including those with lived experience, can clarify the development of terminology and clinical pathways for severe and enduring presentations of pediatric eating disorders.

Treatment models focusing on harm reduction and quality of life (as opposed to eating disorder recovery) are available for adults with severe and enduring eating disorders. However, these models are not widely available for young people. In fact, there is very limited research on severe and enduring eating disorder presentations in pediatric populations. We assessed the views of health professionals regarding clinical care for young people with severe and enduring eating disorder presentations, and asked professionals about what treatment options might be most appropriate for these presentations. Most participants reported providing clinical care for pediatric severe and enduring eating disorder presentations. However, clinicians had diverse views about the treatment that would be most appropriate for a severe and enduring eating disorder presentation in a young person. Further research and engagement with clinicians and those with lived experience is needed to clarify the terminology and clinical pathways for severe and enduring presentations of pediatric eating disorders.

Effectiveness and cost-effectiveness of sector-independent treatment coordination for people with substance-related disorders following an online assessment (ASSIST): study protocol for a randomized controlled trial.

BACKGROUND: The implementation of person-centred, need-oriented and flexible care for people with substance-related problems is often insufficient, in large part due to the complexity of addiction support services among different providers. A standardized online assessment and subsequent sector-independent treatment coordination could provide individuals with more appropriate services, thereby making better use of individual services and leading to a more effective addiction support system as a whole. The aim of this study is to determine the effectiveness and cost-effectiveness of sector-independent treatment coordination following an online assessment, in comparison with the current standard of care and treatment process in Germany. METHODS: The sample size of this randomized, controlled trial has been set to a total of 400 participants with substance-related problems. Participants living in Stuttgart, Germany, will be randomly allocated to (1) the intervention group with immediate online assessment and subsequent sector-independent treatment coordination (ASSIST) or (2) the waitlist group. Participants in the waitlist group will initially remain in usual care and only be provided with the online assessment 6 months later. Short-term effects (over 2 months) and medium-term effects (over 6 months) of ASSIST will be compared between the intervention and the waitlist groups. The primary outcome is improved treatment satisfaction. Secondary outcomes include improved subjective quality of life and empowerment, reductions in patients' substance use, unmet needs and illness-related clinical and social impairment. Health economic evaluation as well as quantitative and qualitative process evaluations will be conducted. DISCUSSION: The results of this study are expected to provide information on whether sector-independent treatment coordination following an online assessment contributes to improved health care service provision for people with substance-related problems. This randomized controlled trial will help identify facilitators and barriers to the sustainable implementation of a cross-sectoral care concept in substance abuse services. TRIAL REGISTRATION: German Clinical Trial Register DRKS00026996 . Registered on 29 October 2021.

Intimate Partner Violence: Variations in Perpetrators and Treatment Allocation.

The division of batterers into subtypes is hardly ever used, neither to describe the type of perpetrator nor to indicate in the clinical decision-making process what treatment should be offered. In this study, a sample of male perpetrators of intimate partner violence (IPV) who had been advised to seek treatment at a community-based Dutch forensic psychiatric facility (N = 110), either voluntarily or mandatorily, have been divided into four subtypes based on a model reported by Holtzworth-Munroe and Stuart (1994). The four subtypes are Family-Only (FO), Borderline-Dysphoric (BD), Generally Violent Antisocial (GVA), and Low-Level Antisocial (LLA). The aim of the study was to identify the subtypes and to compare the different groups on descriptive dimensions and treatment allocation. In the first part of the study, aside from identifying the batterer subtypes, important differences between the subtypes were encountered in the nature of the violence (structural vs. incidental). The characteristics of the BD subtype were found to be similar to the model except for the psychopathological dimension. Differences in allocation of treatment types between batterer subtypes were not substantial raising questions about the correspondence between typological subtypes and the judgment of clinicians. These results do suggest that more attention should be paid to the heterogeneity of the batterer population, which could improve treatment and advance our understanding of IPV.

Response-adaptive treatment allocation for clinical studies with ordinal responses.

Ordinal responses are common in clinical studies. Although the proportional odds model is a popular option for analyzing ordered-categorical data, it cannot control the type I error rate when the proportional odds assumption fails to hold. The latent Weibull model was recently shown to be a superior candidate for modeling ordinal data, with remarkably better performance than the latent normal model when the data are highly skewed. In clinical trials with ordinal responses, a balanced design is common, with equal sample allocation for each treatment. However, a more ethical approach is to adopt a response-adaptive allocation scheme in which more patients receive the better treatment. In this paper, we propose the use of the doubly adaptive biased coin design to generate treatment allocations that benefit the trial participants. The proposed treatment allocation scheme not only allows more patients to receive the better treatment, it also maintains compatible test power for the comparison of treatment efficiencies. A clinical example is used to illustrate the proposed procedure.

Treatment allocation of ruptured anterior communicating artery aneurysms: The influence of aneurysm morphology.

OBJECTIVES: Since publication of the ISAT study, the majority of neurovascular centers adhere to "coil first" policy for patients with subarachnoid hemorrhage (SAH). However, final allocation in favor of coiling or clipping is based on anatomic features of ruptured intracranial aneurysms with respect to clinical characteristics of SAH. In this study, we analyzed the parameters relevant for treatment allocation of ruptured anterior communicating artery aneurysms (AComAA). PATIENTS AND METHODS: From our institutional SAH database, all cases with ruptured AComAA, which underwent diagnostic subtraction angiography (DSA) with subsequent treatment allocation, were included. The radiographic features of AComAA were collected from pre-treatment DSA. In addition, demographic, clinical and radiographic parameters of SAH were recorded. The variables selected through univariate analyses were subsequently evaluated using multivariate regression analysis. RESULTS: Of 300 SAH patients in the final analysis, the majority of the cases underwent endovascular coiling (n = 221, 73.7%). The following aneurysm features were associated with treatment modality in the univariate analysis: maximal sack size (p = 0.034), perpendicular height (p = 0.007), aspect ratio (p < 0.001) and sack/neck-ratio (p = 0.001). Accordingly, the following cutoffs for these variables were defined upon the receiver operating characteristics curves: 5 mm for sack size, 6 mm for perpendicular height, 1.6 for aspect ratio and sack/neck-ratio. In the multivariate analysis, aspect ratio of 1.6 was the only independent predictor of treatment allocation (p = 0.005; aOR = 2.57; 95% CI 1.33-4.96), which remained significant (p = 0.003; aOR = 2.77; 95% CI 1.41-5.45) after adjusting for patients' age, WFNS & Fisher grades, as well as intracerebral hematoma volume. CONCLUSION: Although not-routinely assessed during initial allocation treatment, our retrospective analysis proved that aspect ratio is a reliable predictor of treatment allocation of ruptured AComAA. Except for large space-occupying ICH commonly obligating the microsurgical treatment, other clinical and radiographic characteristics of SAH do not seem to be of clinical relevance for the selection of treatment modality.

Adaptive Designs for Non-inferiority Trials with Multiple Experimental Treatments.

The increase in the popularity of non-inferiority clinical trials represents the increasing need to search for substitutes for some reference (standard) treatments. A new treatment would be preferred to the standard treatment if the benefits of adopting it outweigh a possible clinically insignificant reduction in treatment efficacy (non-inferiority margin). Statistical procedures have recently been developed for treatment comparisons in non-inferiority clinical trials that have multiple experimental (new) treatments. An ethical concern for non-inferiority trials is that some patients undergo the less effective treatments; this problem is more serious when multiple experimental treatments are included in a balanced trial in which the sample sizes are the same for all experimental treatments. With the aim of giving fewer patients the inferior treatments, we propose a response-adaptive treatment allocation scheme that is based on the doubly adaptive biased coin design. The proposed adaptive design is also shown to be superior to the balanced design in terms of testing power.

Factors associated with use of psychiatric intensive care and seclusion in adult inpatient mental health services.

AIMS: Within acute psychiatric inpatient services, patients exhibiting severely disturbed behaviour can be transferred to a psychiatric intensive care unit (PICU) and/or secluded in order to manage the risks posed to the patient and others. However, whether specific patient groups are more likely to be subjected to these coercive measures is unclear. Using robust methodological and statistical techniques, we aimed to determine the demographic, clinical and behavioural predictors of both PICU and seclusion. METHODS: Data were extracted from an anonymised database comprising the electronic medical records of patients within a large South London mental health trust. Two cohorts were derived, (1) a PICU cohort comprising all patients transferred from general adult acute wards to a non-forensic PICU ward between April 2008 and April 2013 (N = 986) and a randomly selected group of patients admitted to general adult wards within this period who were not transferred to PICU (N = 994), and (2) a seclusion cohort comprising all seclusion episodes occurring in non-forensic PICU wards within the study period (N = 990) and a randomly selected group of patients treated in these wards who were not secluded (N = 1032). Demographic and clinical factors (age, sex, ethnicity, diagnosis, admission status and time since admission) and behavioural precursors (potentially relevant behaviours occurring in the 3 days preceding PICU transfer/seclusion or random sample date) were extracted from electronic medical records. Mixed effects, multivariable logistic regression analyses were performed with all variables included as predictors. RESULTS: PICU cases were significantly more likely to be younger in age, have a diagnosis of bipolar disorder and to be held on a formal section compared with patients who were not transferred to PICU; female sex and longer time since admission were associated with lower odds of transfer. With regard to behavioural precursors, the strongest predictors of PICU transfer were incidents of physical aggression towards others or objects and absconding or attempts to abscond. Secluded patients were also more likely to be younger and legally detained relative to non-secluded patients; however, female sex increased the odds of seclusion. Likelihood of seclusion also decreased with time since admission. Seclusion was significantly associated with a range of behavioural precursors with the strongest associations observed for incidents involving restraint or shouting. CONCLUSIONS: Whilst recent behaviour is an important determinant, patient age, sex, admission status and time since admission also contribute to risk of PICU transfer and seclusion. Alternative, less coercive strategies must meet the needs of patients with these characteristics.

Optimal treatment allocations in space and time for on-line control of an emerging infectious disease.

A key component in controlling the spread of an epidemic is deciding where, when and to whom to apply an intervention. We develop a framework for using data to inform these decisions in realtime. We formalize a treatment allocation strategy as a sequence of functions, one per treatment period, that map up-to-date information on the spread of an infectious disease to a subset of locations where treatment should be allocated. An optimal allocation strategy optimizes some cumulative outcome, e.g. the number of uninfected locations, the geographic footprint of the disease or the cost of the epidemic. Estimation of an optimal allocation strategy for an emerging infectious disease is challenging because spatial proximity induces interference between locations, the number of possible allocations is exponential in the number of locations, and because disease dynamics and intervention effectiveness are unknown at out-break. We derive a Bayesian on-line estimator of the optimal allocation strategy that combines simulation-optimization with Thompson sampling. The estimator proposed performs favourably in simulation experiments. This work is motivated by and illustrated using data on the spread of white nose syndrome, which is a highly fatal infectious disease devastating bat populations in North America.

The Short Treatment Allocation Tool for Eating Disorders: current practices in assigning patients to level of care.

OBJECTIVE: The Short Treatment Allocation Tool for Eating Disorders (STATED) is a new evidence-based algorithm developed to match patients to the most clinically appropriate and cost-effective level of care (Geller et al., 2016). The objective of this research was to examine the extent to which current practices are in alignment with STATED recommendations. METHOD: Participants were 179 healthcare professionals providing care for youth and/or adults with eating disorders. They completed an online survey and rated the extent to which three patient dimensions (medical stability, symptom severity, and readiness) were used in assigning patients to each of five levels of care. RESULTS: The majority of analyses testing a priori hypotheses based on the STATED were statistically significant (all p's < .001), in the direction of STATED recommendations. However, a strict coding scheme evaluating the extent to which ratings were fully consistent with the STATED showed inconsistency rates ranging from 17 to 55% across the five levels of care, with the greatest inconsistencies involving the use of readiness information, and the lowest involving the use of medical stability information. DISCUSSION: Although practices were generally aligned with the STATED recommendations, readiness information was used least consistently in assigning patients to level of care.