LC-MS-MS quantification of Δ8-THC, Δ9-THC, THCV isomers and their main metabolites in human plasma.

In recent years, potential therapeutic applications of several different cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC), its isomer Δ8-THC and Δ9-tetrahydrocannabivarin (Δ9-THCV), have been investigated. Nevertheless, to establish dose-effect relationship and to gain knowledge of their pharmacokinetics and metabolism, sensitive and specific analytical assays are needed to measure these compounds in patients. For this reason, we developed and validated an online extraction high-performance liquid/liquid chromatography-tandem mass spectrometry (LC/LC-MS-MS) method for the simultaneous quantification of 13 cannabinoids and metabolites including the Δ8 and Δ9 isomers of THC, THCV and those of their major metabolites in human plasma. Plasma was fortified with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL was extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC-atmospheric pressure chemical ionization-MS-MS running in the positive multiple reaction monitoring mode. The lower limit of quantification ranged from 0.5 to 2.5 ng/mL, and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 82.9% to 109% and 4.3% to 20.3% (coefficient of variance), respectively. Of 534 plasma samples following controlled oral administration of Δ8-THCV, 236 were positive for Δ8-THCV (median; interquartile ranges: 3.5 ng/mL; 1.8-11.9 ng/mL), 383 for the major metabolite (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabivarin (Δ8-THCV-COOH) (95.4 ng/mL; 20.7-328 ng/mL), 260 for (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (Δ9-THCV-COOH) (5.8 ng/mL; 2.5-16.1 ng/mL), 157 for (-)-11-hydroxy-Δ8-tetrahydrocannabivarin (11-OH-Δ8-THCV) (1.7 ng/mL; 1.0-3.7 ng/mL), 49 for Δ8-THC-COOH (1.7 ng/mL; 1.4-2.3 ng/mL) and 42 for Δ9-THCV (1.3 ng/mL; 0.8-1.6 ng/mL). We developed and validated the first LC/LC-MS-MS assay for the specific quantification of Δ8-THC, Δ9-THC and THCV isomers and their respective metabolites in human plasma. Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV and Δ9-THCV-COOH were the major Δ8-THCV metabolites in human plasma after oral administration of 98.6% pure Δ8-THCV.

Examining the referral of patients with elevated blood pressure to health resources in an under-resourced community in South Africa.

BACKGROUND: Low-and-middle income countries face a disproportionate burden of non-communicable diseases (NCDs) that threaten to overwhelm under-resourced health systems. Community health workers (CHWs) can promote NCD prevention, reach patients, and connect them to local community health resources; however, little has been done to examine how referrals to these resources are utilized by community members. The purpose of this study is to examine the use of referrals to community-based health resources and investigate the factors influencing patient utilization of referrals connecting them to appropriate health resources for elevated blood pressure (BP). METHODS: CHWs conducted home visits, which included BP screening and brief counseling, with community members in Soweto, South Africa. Participants with elevated (systolic BP: 121-139/ diastolic BP: 81-89 mmHg) or high (≥ 140/90 mmHg) BP were referred to either a local, community-based physical activity (PA) program managed by a non-governmental organization or local health clinics. The number of participants that received and utilized their referrals was tracked. Follow-up interviews were conducted with individuals given a referral who: (1) went to the PA program, (2) did not go to the PA program, (3) went to a clinic, and (4) did not go to a clinic. Interviews were transcribed and analyzed to identify common themes and differences between groups regarding their decisions to utilize the referrals. RESULTS: CHWs visited 1056 homes, with 1001 community members consenting to the screening; 29.2% (n = 292) of adults were classified as having optimal BP (≤120/80 mmHg), 35.8% (n = 359) had elevated BP, and 35.0% (n = 350) had high BP. One hundred and seventy-three participants accepted a referral to the PA program with 46 (26.6%) enrolling. Five themes emerged from the interviews: (1) prior knowledge and thoughts on BP, (2) psychosocial factors associated with BP control, (3) perception about receiving the referral, (4) contextual factors influencing referral utilization, and (5) perceived benefits of utilizing the referral. CONCLUSION: CHWs can successfully increase community members' access to health resources by providing appropriate referrals. However, greater attention needs to address community members' barriers and hesitancy to utilize health resources.

Emotion Controllability Beliefs and Young People's Anxiety and Depression Symptoms: A Systematic Review.

Emotion regulation is a powerful predictor of youth mental health and a crucial ingredient of interventions. A growing body of evidence indicates that the beliefs individuals hold about the extent to which emotions are controllable (emotion controllability beliefs) influence both the degree and the ways in which they regulate emotions. A systematic review was conducted that investigated the associations between emotion controllability beliefs and youth anxiety and depression symptoms. The search identified 21 peer-reviewed publications that met the inclusion criteria. Believing that emotions are relatively controllable was associated with fewer anxiety and depression symptoms, in part because these beliefs were associated with more frequent use of adaptive emotion regulation strategies. These findings support theoretical models linking emotion controllability beliefs with anxiety and depression symptoms via emotion regulation strategies that target emotional experience, like reappraisal. Taken together, the review findings demonstrate that emotion controllability beliefs matter for youth mental health. Understanding emotion controllability beliefs is of prime importance for basic science and practice, as it will advance understanding of mental health and provide additional targets for managing symptoms of anxiety and depression in young people.

A cognitive behavioural model of the bidirectional relationship between disordered eating and diabetes self care in adult men with Type 1 diabetes mellitus.

AIMS: This qualitative study aimed to develop the first cognitive behavioural (CBT) model outlining the development and maintenance of disordered eating in adult men living with Type 1 diabetes to improve on previous theoretical models of Type 1 diabetes and disordered eating and to draw comparisons to women with Type 1 diabetes and disordered eating. METHODS: Twenty-seven men (n = 16 with Type 1 diabetes and disordered eating, n = 11 with Type 1 diabetes without disordered eating) participated in semi-structured interviews. Data were analysed using thematic analysis and individual CBT formulations were developed for each participant to inform the model. RESULTS: Men with Type 1 diabetes and disordered eating experience negative thoughts about food, insulin, weight/shape and diabetes itself, which cause negative emotions such as fear and vulnerability and difficulties with diabetes self care such as problems with hyper and hypoglycaemia and problems accessing structured education and technology result in men feeling more dissatisfied about their body weight/shape. CONCLUSIONS: This CBT model of disordered eating in men with Type 1 diabetes can guide new interventions.

Protocol for the STEADY intervention for type 1 diabetes and disordered eating: Safe management of people with Type 1 diabetes and EAting Disorders studY.

This paper describes the protocol to test the feasibility of the Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY) intervention. STEADY is a novel complex intervention for people with type 1 diabetes and disordered eating (T1DE) of mild to moderate severity. The STEADY intervention integrates cognitive behavioural therapy (CBT) with diabetes education, and was developed using Experience-Based Co-Design. METHODS: The feasibility of STEADY will be tested using a randomised controlled feasibility trial. Forty adults with T1DE will be recruited and randomised into the STEADY intervention or treatment as usual control group. We will collect demographic, biomedical and psychometric data, routine glucose metrics and conduct the Structured Clinical Interview for DSM-5. Participants randomised to the STEADY intervention will receive 12 STEADY therapy sessions with a diabetes specialist nurse trained in CBT, delivered via videoconference and an optional smartphone app. The main outcome at 6 months will be the feasibility of STEADY (recruitment, dropout rates, feasibility of delivery). The secondary outcomes are biomedical (HbA1c and glucose time in range) and psychological (person-reported outcome measures in disordered eating, diabetes distress, depression and anxiety). A process evaluation will evaluate the fidelity, feasibility, acceptability and appropriateness of STEADY, and participant experiences. ETHICS AND DISSEMINATION: The protocol was approved by the East of England-Essex Research Ethics Committee (21/EE/0235). Study findings will be shared with study participants and disseminated through peer-reviewed publications and conference presentations.

A randomized, double-blind, placebo-controlled, repeated-dose pilot study of the safety, tolerability, and preliminary effects of a cannabidiol (CBD)- and cannabigerol (CBG)-based beverage powder to support recovery from delayed onset muscle soreness (DOMS).

BACKGROUND: Cannabinoid-containing products are marketed to athletes as promoting recovery, in spite of a lack of data on their safety and effects. This randomized, double-blind, placebo-controlled, repeated-dose pilot study tested the safety, tolerability, and preliminary effects on recovery of a formulation containing cannabidiol (CBD; 35 mg), cannabigerol (CBG; 50 mg), beta caryophyllene (BCP; 25 mg), branched-chain amino acids (BCAAs; 3.8 g), and magnesium citrate (420 mg). METHODS: Exercise-trained individuals (N = 40) underwent an experimental induction of delayed onset muscle soreness (DOMS) and completed follow-up visits 24-, 48-, and 72-hours post-DOMS. Participants were randomized to active or placebo formulation, and consumed the formulation twice per day for 3.5 days. RESULTS: There was one adverse event (AE) in the active group (diarrhea) and two AEs in placebo (dry mouth; eye rash/swollen eye). There was 100% self-reported compliance with formulation consumption across the two groups. For the primary outcome of interest, the estimate of effect for ratings of average soreness/discomfort 72 hours post-DOMS between active and placebo groups was -1.33 (85% confidence interval = -2.55, -0.10), suggesting moderate evidence of a treatment difference. The estimate of effect for the outcome of ratings of interference of soreness, discomfort, or stiffness on daily activities at work or home 48 hours post-DOMS was -1.82 (95% confidence interval = -3.64, -0.01), indicating a treatment difference of potential clinical importance. There was no significant effect between active and placebo groups on objective measures of recovery, sleep quality, or mood disturbance. CONCLUSIONS: The tested formulation reduced interference of DOMS on daily activities, demonstrating its improvement on a functional aspect of recovery.

Integrated feathering for craniospinal irradiation improves patient safety and departmental efficiency.

This paper presents to the dosimetrist audience an integrated feathering technique for craniospinal irradiation which improves dosimetry, physics, physician and therapist efficiencies while increasing patient safety and decreasing portal imaging time. This technique has been presented by other authors in physics journals stressing technical and quality assurance aspects, this article is presented to the treatment planners with a focus on the planning process including field design and weighting, efficiency improvements and patient safety.

A Two-Phase, Dose-Ranging, Placebo-Controlled Study of the Safety and Preliminary Test of Acute Effects of Oral Δ8-Tetrahydrocannabivarin in Healthy Participants.

Introduction: Tetrahydrocannabivarin (THCV) is an understudied cannabinoid that appears to have effects that vary as a function of dose. No human study has evaluated the safety and nature of effects in a wide range of THCV doses. Methods: This was a two-phase, dose-ranging, placebo-controlled trial of the Δ8 isomer of oral THCV in healthy adults. Phase 1 utilized an unblinded, single-ascending dose design (n=3). Phase 2 used a double-blind, randomized, within-participant crossover design (n=18). Participants received single acute doses of placebo and 12.5, 25, 50, 100, and 200 mg of THCV. Safety measures and subjective and cognitive effects were assessed predose and up to 8 h postdose. Results: Most adverse events (AEs; 55/60) were mild. Euphoric mood was the most common AE. The 12.5, 25, and 200 mg doses produced significantly lower minimum times to complete the digit vigilance test (ps=0.01). The 25 mg dose showed elevations on mean ratings of "energetic" at 1-, 2-, and 4-h postdose, but the maximum postdose rating for this dose did not achieve statistical significance relative to placebo ([95% confidence interval]=3.2 [-0.5 to 6.9], p=0.116). The 100 and 200 mg doses showed elevations on ratings of "feel a drug effect" and "like the drug effect." Almost all urine drug screens (78/79) at 8 h postdose in the active THCV conditions tested positive for tetrahydrocannabinol (THC). Conclusion: All THCV doses displayed a favorable safety profile. Several THCV doses showed a preliminary signal for improved sustained attention, but the effect was not dose dependent. Though mild and not associated with impairment, THC-like effects were observed at higher THCV doses. Oral THCV-containing products could lead to positive urine drug screens for THC. ClinicalTrials.gov ID: NCT05210634.

Oral Cannabidiol Treatment in Two Postmenopausal Women with Osteopenia: A Case Series.

Introduction: Cannabidiol (CBD), a nonintoxicating cannabinoid, may be involved in bone remodeling, but human studies are limited. In this case series, we explored the effects of oral CBD administration on bone turnover. Materials and Methods: Two postmenopausal women with osteopenia (T-score=-1 to -2.5) were randomized to receive 100 or 300 mg CBD daily (oral, bis in die [twice per day]) for 12 weeks. Serum markers of bone resorption (carboxyl-terminal collagen crosslinks [CTx]) and bone formation (procollagen type 1 N-terminal propeptide [P1NP], bone-specific alkaline phosphatase [BSAP], and osteocalcin [OC]); safety measures; plasma concentrations of CBD and metabolites; sleep disturbance; symptoms of depression, anxiety, and stress; and quality of life, were assessed. Results: CBD was well tolerated, with no clinically significant change in vital signs, hematology, chemistry, or urinalysis, and no adverse events reported. Reductions (% change vs. baseline) in CTx (-8.5%, -28.1%), P1NP (-9.9%, -39.5%), BSAP (-12.7%, -74.8%), and OC (-16.0%, -6.7%) were observed after 12 weeks of oral administration of 100 or 300 mg CBD daily, respectively. The two participants self-reported consuming 95.3% and 98.8% of CBD doses, respectively. CBD and select metabolites were measurable in plasma after 4 and 12 weeks of CBD treatment. No notable changes in sleep disturbance, depression, anxiety, stress, or quality of life were observed. Conclusions: CBD was well tolerated after 12 weeks of twice-daily oral administration and was associated with reduction in measured markers of bone turnover. Compliance with CBD treatment was good. Large-scale randomized clinical trials into the bone protective effects of CBD in postmenopausal women are warranted.

Exploring the Impact of COVID-19 on Individuals with Eating Disorders in Saudi Arabia: A Thematic Analysis.

Food and sleep are critical for human survival. However, for individuals with eating disorders, they face two critical disruptions in terms of abnormal feeding patterns as well as poor sleep. These difficulties are exacerbated as a result of the recent coronavirus pandemic, which caused drastic changes in daily life schedules and living arrangements. The current study therefore aims to explore, through qualitative means, how individuals with eating disorders are affected during the subsequent lockdowns, with a particular emphasis on the pandemic's impact on their sleep in Saudi Arabia. Two groups of participants were recruited: participants with eating disorders and healthy controls. Based on thematic analysis of focus group discussion data, it was found that both types of participants experienced poorer sleep and poorer mental health. Participants with eating disorders too showed a deterioration of their symptoms. However, healthy participants tended to show greater levels of recovery and coping. Based on the study findings, recommendations for future studies are made.

Decision-making difficulties mediate the association between poor emotion regulation and eating disorder symptoms in adolescence.

BACKGROUND: The emergence of eating problems during childhood increases the risk for eating disorders (EDs) during young adulthood. Previous studies highlight a relationship between poor self-regulation and onset of eating pathology. In this study, we investigated whether this association is mediated by decision-making difficulties. METHODS: To test this hypothesis, we used data from the Millennium Cohort Study. Decision-making performance was assessed with the Cambridge Gambling Task at age 11. Principal components analysis was used to derive an index of ED symptoms at age 14. The trajectories of scores of two subscales of the Child Social Behaviour Questionnaire, Independence and Self-Regulation (ISR) and Emotional Dysregulation (EmotDy), were modelled from ages 3 to 7 years in a latent growth curve analysis. The individual predicted values of the intercept (set at baseline, 3 years) and the slope (rate of annual change) were then used in the mediation analysis. RESULTS: In our sample of 11 303 individuals, there was evidence for mediation by three measures of decision-making at age 11 (poor quality of decision-making, delay aversion and low risk-adjustment) in the association between EmotDy across ages 3-7 and ED symptoms at age 14 even after the adjustment for relevant covariates. We found no evidence of association between ISR and ED symptoms. CONCLUSION: Our findings suggest that emotion regulation processes during childhood may be relevant for the future onset of ED symptoms via their association with decision-making skills. These findings, obtained from a large, representative, sample, shed light on the relationship between self-regulation, decision-making and symptoms of EDs.

Does decision-making at age 11 predict prodromal eating pathology at ages 14 and 17? A prospective, observational, UK population-based cohort study.

OBJECTIVES: We examined whether decision-making at age 11 and 14 is associated with prodromal eating pathology at age 14 and whether it would persist across adolescence and also be present at age 17. DESIGN: This prospective, observational, population-based cohort study used a longitudinal design. SETTING: Data from the Millennium Cohort Study (MCS), a UK longitudinal cohort study involving 19 244 families from England, Scotland, Wales and Northern Ireland, were analysed. PARTICIPANTS: We modelled data from 8922 boys and girls aged 11, 14 and 17 (MCS sweeps 5, 6 and 7). PRIMARY AND SECONDARY OUTCOMES: We investigated decision-making using the risk-taking, quality of decision-making, deliberation time, delay aversion and risk adjustment subscales of the Cambridge Gambling Task and prodromal eating pathology through binary response items measuring: body dissatisfaction (whether the participant perceived their body as being too overweight); intention to lose weight (whether participants reported a strong desire to lose weight); dietary restriction (whether participants reported actively eating less to influence their shape/weight) and excessive exercise (whether participants reported exercising in a driven way in order to influence weight/shape). Data were analysed using latent class analysis and logistic regression. RESULTS: Lower scores on quality of decision-making (OR=0.46) and deliberation time (OR=0.99) at age 14 were associated with prodromal eating pathology at both ages 14 and 17 (all p<0.05), indicating an association between less frequently opting to bet on the most likely outcome and taking less time to decide on which bet to choose and the persistence of prodromal eating pathology over adolescence. Lower deliberation time (OR=0.99) and delay aversion (OR=0.62) at 11 and lower risk-taking scores at 14 (OR=0.43) were associated with the absence of prodromal eating pathology at 14 and 17 (all p<0.05), indicating that a moderate approach under conditions of risk in childhood and mid-adolescence is associated with reduced eating pathology across adolescence. CONCLUSIONS: Training advantageous decision-making might protect from later prodromal eating pathology.

The Ability of Bumblebees Bombus terrestris (Hymenoptera: Apidae) to Detect Floral Humidity is Dependent Upon Environmental Humidity.

Flowers produce local humidity that is often greater than that of the surrounding environment, and studies have shown that insect pollinators may be able to use this humidity difference to locate and identify suitable flowers. However, environmental humidity is highly heterogeneous, and is likely to affect the detectability of floral humidity, potentially constraining the contexts in which it can be used as a salient communication pathway between plants and their pollinators. In this study, we use differential conditioning techniques on bumblebees Bombus terrestris audax (Harris) to explore the detectability of an elevated floral humidity signal when presented against different levels of environmental noise. Artificial flowers were constructed that could be either dry or humid, and individual bumblebees were presented with consistent rewards in either the humid or dry flowers presented in an environment with four levels of constant humidity, ranging from low (~20% RH) to highly saturated (~95% RH). Ability to learn was dependent upon both the rewarding flower type and the environment: the bumblebees were able to learn rewarding dry flowers in all environments, but their ability to learn humid rewarding flowers was dependent on the environmental humidity, and they were unable to learn humid rewarding flowers when the environment was highly saturated. This suggests that floral humidity might be masked from bumblebees in humid environments, suggesting that it may be a more useful signal to insect pollinators in arid environments.

A description of virtual skills workshops for supporters of loved ones with eating disorders: Indicators of benefit and acceptability, clinical reflections and consideration of neurodiversity.

OBJECTIVE: Providing information and support to those supporting a loved one with an eating disorder is a key part of evidence-based service provision. We report on how we took our workshops for supporters online during the Covid-19 Pandemic when country-side physical distancing restrictions meant we were unable to work face to face. METHODS: We outline the structure of an eight-session 2-h workshop series delivered fortnightly facilitated by a multidisciplinary team of clinicians, researchers and experts by experience. We use a repeated-measures design to understand the possible benefits of the workshops on supporter skills (n = 76). RESULTS: Measured using the Caregiver Skills Scale, we observed small-sized improvements in the overall skills (D = 0.43) of n = 17 supporters who provided data at the end of the intervention. Supporters gave largely positive feedback on the virtual format. They particularly liked the opportunity to interact with other supporters. As facilitators, we overcome our initial anxiety around workshop delivery using a new platform and reflected that having more time to cover key information and for skills practice over a period of 16 weeks offered opportunities to develop and reflect on new skill together as a group. We were also able to work with larger groups of supporters, as several barriers to access were removed. CONCLUSIONS: As the workshops reached a larger number of supporters than through face to face delivery and were of benefit to those who reported on their skills, we plan to continue offering workshops to supporters online in future.

Types of Eating Disorder Prodrome in Adolescence: The Role of Decision Making in Childhood.

Psychiatric disorders like eating disorders (EDs) might be underpinned by differences in decision making. However, little previous research has investigated this potential relationship using longitudinal data. This study aimed to understand how components of decision making (delay aversion, risk adjustment, risk taking, quality of decision making and deliberation time) measured by the Cambridge Gambling Task in the United Kingdom's Millennium Cohort Study (MCS; n = 11,303; female = 50.17%) at age 11 might explain clusters/types of ED prodrome involving body dissatisfaction, intention to lose weight, dietary restraint, excessive exercise and significant under/overweight measured in the MCS at age 14. Latent class analysis revealed two groups within the cohort: a non-prodromal eating pathology group, who were more likely to be of "average" weight, according to the UK90, with minimal disordered attitudes and behaviors in relation to eating and weight; and a second group with prodromal eating pathology, who had more body dissatisfaction, a desire to lose weight, were using dietary restriction and exercise to influence weight and were more likely to be "overweight" according to the UK90. Logistic regression showed that, after adjustment for confounding, higher risk-taking scores were associated with a 60% greater probability of being in the prodromal eating pathology group (b = 0.47, OR = 1.60, p < 0.01), and higher scores on quality of decision making were associated with a 30% lower probability of being in the prodromal eating pathology group (b = -0.34, OR = 0.70, p < 0.05). Helping young people to engage in moderate risk taking and improving decision making might reduce the later presence of ED prodromes.

Decision-Making in Childhood Predicts Prodromal Eating Pathology in Adolescence.

OBJECTIVE: Differences in decision-making under conditions of risk have been observed cross-sectionally in clinical groups of people with eating disorders but have never been studied longitudinally or in large cohorts. We investigated whether responses on the Cambridge Gambling Task (CGT), measured in the Millennium Cohort Study in childhood, would predict prodromal eating pathology in adolescence. METHOD: Regression models were built to explore relationships between CGT variables at age 11 years and prodromal eating pathology (body dissatisfaction, intention to lose weight, dietary restriction, significant under/overweight, and excessive exercise) at 14 years. RESULTS: In 11,303 boys and girls, those with better quality decision-making were 34% less likely to show an intention to lose weight (b = -0.40, odds ratio [OR] = 0.66, p < 0.05) and 34% less likely to be overweight (b = -0.41, relative risk ratio [RRR] = 0.66, p < 0.05). Those with higher risk-taking were 58% more likely to report dietary restriction (b = 0.45, OR = 1.58, p < 0.05) and 46% more likely to report excessive exercise (b = 0.38, OR = 1.46, p < 0.05). In the complete-cases sample, higher risk-adjustment scores were associated with a 47% increased risk of underweight (b = 0.39, RRR = 1.47, p < 0.05), and better quality of decision-making was associated with a 46% lower risk of overweight (b = -0.60, RRR = 0.54, p < 0.05). CONCLUSION: Disadvantageous decision-making in childhood may predict prodromal eating pathology in adolescence and might represent a prevention target.

Tofacitinib-induced Progressive Multifocal Leukoencephalopathy with Immune Reconstitution Inflammatory Syndrome.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) with subsequent immune reconstitution inflammatory syndrome (IRIS) is a rare disease associated with compromised immune systems. It has never been described in a patient taking tofacitinib. CASE PRESENTATION: A 49-year-old woman with history of systemic lupus erythematous treated with tofacitinib presented with several weeks of intermittent fevers and altered mental status. MRI revealed multifocal T2-weighted FLAIR hyperintensities in the subcortical white matter, including the subcortical U-fibers, without mass effect or contrast enhancement, compatible with PML. Tofacitinib was stopped and the patient's symptoms initially improved. However, the patient presented again less than a week after discharge with three days of left arm weakness, left facial droop, dysarthria, and one day of confusion. Repeat MRI demonstrated interval progression in T2/FLAIR hyperintensities with development of patchy gadolinium enhancement on T1-post contrasted sequences, consistent with development of IRIS in the setting of tofacitinib cessation. DISCUSSION: This is the first case describing PML-IRIS in the setting of administration and subsequent cessation of tofacitinib.

Developing a novel intervention for type 1 diabetes and disordered eating using a participatory action design process: Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY).

AIMS: To develop a cognitive behavioural therapy-based intervention for people with type 1 diabetes and disordered eating using Experience-Based Co-Design as part of the Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY). METHODS: Fifteen people with type 1 diabetes and experience of disordered eating (33 ± 11 years old, 22 ± 12 years diabetes duration) and 25 healthcare professionals working in type 1 diabetes or eating disorders (44 ± 9 years old; 14 ± 10 years of professional experience) attended six Experience-Based Co-Design workshops from July 2019 to March 2020 to collaboratively develop intervention content. RESULTS: We developed a cognitive behaviour therapy intervention 'toolkit' that can be tailored for individual patient needs. Participants designed and revised toolkit materials to ensure acceptability and relevance for people with diabetes and disordered eating by engaging in guided discussion, brainstorming, and rapid testing to review toolkit prototypes in an iterative process. Workshop themes were 'Insulin titration'; 'Hypoglycaemia'; 'Coming to terms with diabetes'; 'Fear of weight gain'; 'Toolkit revision'; and 'Practical elements of STEADY therapy'. The intervention is focussed on improving diabetes self-care and embedded in a multidisciplinary healthcare approach. The intervention will be delivered in 12 sessions by a diabetes specialist nurse trained in cognitive behavioural therapy. CONCLUSIONS: Through an iterative co-design process, people with type 1 diabetes and healthcare professionals collaboratively developed a novel intervention toolkit that can be used with a wide range of disordered eating presentations. The intervention will be tested in the STEADY feasibility randomised controlled trial.

How to Respond to a Ransomware Attack? One Radiation Oncology Department's Response to a Cyber-Attack on Their Record and Verify System.

The digitization of healthcare for patient safety and efficiency introduced third party networks into closed hospital systems increasing the probability of cyberattacks and their consequences(1). In April 2021, a major vendor of a Radiation Oncology (RO) record and verify system (RVS) suffered a ransomware attack, affecting our department and many others across the United States. This article summarizes our response to the ransomware event including workflows, team member roles, responsibilities, communications and departmental recovery. The RVS created or housed accurate patient dose records for 6 locations. The immediate response to the ransomware attack was to shut down the system including the ability to treat patients. With the utilization of the hospital EMR and pre-existing interfaces with RVS, the department was able to safely continue patient radiotherapy treatments innovatively utilizing a direct Digital Imaging and Communications in Medicine (DICOM) transfer of patient data to the linear accelerators and implementing paper charting. No patients were treated in the first 24 hours of the attack. Within 48 hours of the ransomware event, 50% of patients were treated, and within 1 week, 95% of all patients were treated using direct DICOM transfer and paper charts. The RVS was completely unavailable for 2.5 weeks and full functionality was not restored for 4.5 weeks. A phased approach was adopted for re-introduction of patient treatments back into the RVS. Human capital costs included communication, outreach, workflow creation, quality assurance and extended clinical hours. Key lessons learned were to have a back-up of essential information, employ 'dry run' emergency training, having consistent parameter requirements across different vendor hardware and software, and having a plan for the recovery effort of restoring normal operations once software is operational. The provided report presents valuable information for the development of cyber-attack preparedness for RO departments.