EATING DISORDER TREATMENT: WHAT FORMER PATIENTS ATTRIBUTE TO THEIR PERSONAL RECOVERY

The purpose of this study was to explore the personal experience of people who have an eating disorder with a specific focus on what they attributed to their recovery. Eating disorders are a mental illness that affect one in 20 people. Thus, this prevalence coupled with a lack of significant research about eating disorders in the field of social work uncovered the need for this study. Qualitative interviews were completed with five female students from a university in California. Each transcript was coded using conventional content analysis to uncover themes and subthemes, which included barriers to recovery, the need to uncover the root cause of the eating disorder, the value of support, and hope and resilience. The findings indicated that control is an important component in eating disorders and that change in weight should not be indicative of full recovery because recovery is an ongoing process. Furthermore, stigma and shame attached to eating disorders, a lack of knowledge by professionals, and access to care all served as detriments to seeking or receiving treatment. The study provided valuable insight into the field of social work for those who service clients in the most prevalent age group for eating disorders, adolescents, and young adults, which includes child protective services. It is extremely important for social workers to know the risk factors and behaviors of an eating disorder and include them in their assessment because increasing knowledge and decreasing stigma will help strengthen social work practice by increasing awareness, a greater understanding, and access to treatment

PHARMACOKINETIC AND PHARMCODYNAMIC STUDIES OF APOMORPHINE IN THE TREATMENT OF IDIOPATHIC PARKINSON'S DISEASE

There were two aspects to the study of apomorphine in the treatment of Parkinson' s disease: (i) a clinical pharmacokinetic-pharmacodynamic (PK-PD) study was designed and implemented in response to the challenges of apomorphine dose-titration in Parkinson's disease, and in view of the scarcity of available literature on the PK-PD relationships of apomorphine in Parkinson's disease, (ii) the PK(and tolerability)of apomorphine dosing using novel delivery/formulation combinations were explored in view of the inherent limitations associated with the conventional (ie. subcutaneous) route of administration of apomorphine (e.g. cutaneous nodule formation, needle-phobia). An HPLC assay was developed for the quantification of apomorphine in plasma, and stability issues relating to sample storage and assay were investigated. With regards to the first aspect of the research, simultaneous PK-PD modelling was performed, using an effect compartment model to account for counterclockwise hysteresis in a sub-group of patients. According to the traditional two-stage approach to data analysis, mean (standard deviation) clearance following subcutaneous bolus was 2.2 (0.5) L/kg/h, (apparent) volume of distribution was 1.9 (0.8) L/kg, absorption half-life was 4.1 (2.1) minutes and elimination half-life was 69.5 (21.1)minutes (n=7). Equilibration half-life was estimated for two patients at 8.3 and 16.5 minutes. Focus was given to investigating the relevance of a potential correlation (which had previously been identified using in-house pilot data) between post-distributional apomorphine PK and apomorphine-induced anti-parkinsonian response in patients with Parkinson's disease. It was hypothesised that this particular correlation may be of use in a dose-optimisation scheme. However it was demonstrated that, in the patients studied, the concept could not be applied to apomorphine dose-optimisation. The novel delivery systems under scrutiny were: (i) Britaject® (Britannia Pharmaceuticals Ltd.) apomorphine formulation administered subcutaneously using a needle-free (jet) injector (J-TIP®, National Medical Products Inc.), (ii) an intranasal apomorphine powder formulation delivered using a turbospin insufflator (CDFS), and (iii) an apomorphine hydrogel co-polymer produced as a dosage-form for buccal delivery (Controlled Therapeutics (Scotland) Ltd.). As a result of this work, a rationale for subsequent development of the novel systems was provided. Indeed, the needle-free and buccal systems were, in their existing format, shown not to convey a net advantage over the existing system. However the intranasal formulation, with a mean (standard deviation) relative bioavailability of 41 (18)% (n=16) compared to subcutaneous bolus administration (and with a favourable outcome as regards to tolerability), was considered to be potentially suitable for further development

Mice Infected with Low-virulence Strains of Toxoplasma gondii Lose their Innate Aversion to Cat Urine, Even after Extensive Parasite Clearance

Toxoplasma gondii chronic infection in rodent secondary hosts has been reported to lead to a loss of innate, hard-wired fear toward cats, its primary host. However the generality of this response across T. gondii strains and the underlying mechanism for this pathogen mediated behavioral change remain unknown. To begin exploring these questions, we evaluated the effects of infection with two previously uninvestigated isolates from the three major North American clonal lineages of T. gondii, Type III and an attenuated strain of Type I. Using an hour-long open field activity assay optimized for this purpose, we measured mouse aversion toward predator and non-predator urines. We show that loss of innate aversion of cat urine is a general trait caused by infection with any of the three major clonal lineages of parasite. Surprisingly, we found that infection with the attenuated Type I parasite results in sustained loss of aversion at times post infection when neither parasite nor ongoing brain inflammation were detectable. This suggests that T. gondii-mediated interruption of mouse innate aversion toward cat urine may occur during early acute infection in a permanent manner, not requiring persistence of parasitecysts or continuing brain inflammation.Comment: 14 pages, 3 figure

Adding web-based support to exercise referral schemes improves symptoms of depression in people with elevated depressive symptoms:A secondary analysis of the e-coachER randomised controlled trial

Background: Exercise referral schemes (ERS) reduce depression but the additional effect on mental health from web-based behavioural support is unknown. The e-coachER trial reported no effect of augmenting usual ERS with theory-driven web-based behavioural support on moderate to vigorous physical activity (MVPA) at 12 months for patients with chronic physical and mental health conditions. The present study reports the effects of the e-coachER intervention on depression, anxiety and MVPA only among participants with elevated depressive symptoms and investigates whether these were mediated by changes in MVPA and hypothesised cognitive and behavioural processes. Methods: Of the original 450 adults recruited into the e-coachER trial, 205 had at least mild depression, based on the Hospital Anxiety and Depression Scale (HADS), and were included in the present analysis. Data collected included the HADS, accelerometer measured and self-reported MVPA and survey process measures on physical activity action planning, self-monitoring and goal reviewing, and perceived importance, confidence, competence, autonomy and support. Linear mixed models were used to compare groups for change in depression and anxiety at 4 and 12 months using intention-to-treat complete case analysis, controlling for baseline. We also examined whether changes in physical activity and process variables at 4 months mediated changes in depression and anxiety at 12 months. Results: Of the 205 participants, 138 (67%) provided follow-up data at four months and 126 (61%) at 12 months. For those that provided follow-up data, those randomised to e-coachER reported improved levels of depression (−1.36, 95% CI: −2.55 to −0.18) but not anxiety, or MVPA, compared with controls at four months. No differences were observed at 12 months for depression, anxiety or MVPA. Intervention effects on accelerometer-measured or self-reported MVPA did not mediate improvements in depression or anxiety. However, intervention effects on confidence, competence and self-monitoring at four months significantly mediated the reduction in depression scores at four months. Intervention effects on competence and self-monitoring at four months also significantly mediated improvements in anxiety scores at four months. Interpretation: Adding web-based support to usual ERS leads to reductions in depression but not anxiety at four months. Changes in depression and anxiety were influenced by changing people's motivational regulations toward physical activity. The benefit of adding web-based support to usual ERS on mental health appears to be from increasing a sense of confidence, competence and self-monitoring rather than from increasing physical activity in people with elevated depression. ERS should focus more on strengthening motivational regulations than just doing more exercise. Trial registration: ISRCTN15644451.</p

Adding web-based support to exercise referral schemes improves symptoms of depression in people with elevated depressive symptoms:A secondary analysis of the e-coachER randomised controlled trial

Background: Exercise referral schemes (ERS) reduce depression but the additional effect on mental health from web-based behavioural support is unknown. The e-coachER trial reported no effect of augmenting usual ERS with theory-driven web-based behavioural support on moderate to vigorous physical activity (MVPA) at 12 months for patients with chronic physical and mental health conditions. The present study reports the effects of the e-coachER intervention on depression, anxiety and MVPA only among participants with elevated depressive symptoms and investigates whether these were mediated by changes in MVPA and hypothesised cognitive and behavioural processes. Methods: Of the original 450 adults recruited into the e-coachER trial, 205 had at least mild depression, based on the Hospital Anxiety and Depression Scale (HADS), and were included in the present analysis. Data collected included the HADS, accelerometer measured and self-reported MVPA and survey process measures on physical activity action planning, self-monitoring and goal reviewing, and perceived importance, confidence, competence, autonomy and support. Linear mixed models were used to compare groups for change in depression and anxiety at 4 and 12 months using intention-to-treat complete case analysis, controlling for baseline. We also examined whether changes in physical activity and process variables at 4 months mediated changes in depression and anxiety at 12 months. Results: Of the 205 participants, 138 (67%) provided follow-up data at four months and 126 (61%) at 12 months. For those that provided follow-up data, those randomised to e-coachER reported improved levels of depression (−1.36, 95% CI: −2.55 to −0.18) but not anxiety, or MVPA, compared with controls at four months. No differences were observed at 12 months for depression, anxiety or MVPA. Intervention effects on accelerometer-measured or self-reported MVPA did not mediate improvements in depression or anxiety. However, intervention effects on confidence, competence and self-monitoring at four months significantly mediated the reduction in depression scores at four months. Intervention effects on competence and self-monitoring at four months also significantly mediated improvements in anxiety scores at four months. Interpretation: Adding web-based support to usual ERS leads to reductions in depression but not anxiety at four months. Changes in depression and anxiety were influenced by changing people's motivational regulations toward physical activity. The benefit of adding web-based support to usual ERS on mental health appears to be from increasing a sense of confidence, competence and self-monitoring rather than from increasing physical activity in people with elevated depression. ERS should focus more on strengthening motivational regulations than just doing more exercise. Trial registration: ISRCTN15644451.</p

Mobile technology supporting trainee doctors' workplace learning and patient care: an evaluation

Background The amount of information needed by doctors has exploded. The nature of knowledge (explicit and tacit) and processes of knowledge acquisition and participation are complex. Aiming to assist workplace learning, Wales Deanery funded “iDoc”, a project offering trainee doctors a Smartphone library of medical textbooks. Methods Data on trainee doctors’ (Foundation Year 2) workplace information seeking practice was collected by questionnaire in 2011 (n = 260). iDoc baseline questionnaires (n = 193) collected data on Smartphone usage alongside other workplace information sources. Case reports (n = 117) detail specific instances of Smartphone use. Results Most frequently (daily) used information sources in the workplace: senior medical staff (80% F2 survey; 79% iDoc baseline); peers (70%; 58%); and other medical/nursing team staff (53% both datasets). Smartphones were used more frequently by males (p < 0.01). Foundation Year 1 (newly qualified) was judged the most useful time to have a Smartphone library because of increased responsibility and lack of knowledge/experience. Preferred information source varied by question type: hard copy texts for information-based questions; varied resources for skills queries; and seniors for more complex problems. Case reports showed mobile technology used for simple (information-based), complex (problem-based) clinical questions and clinical procedures (skills-based scenarios). From thematic analysis, the Smartphone library assisted: teaching and learning from observation; transition from medical student to new doctor; trainee doctors’ discussions with seniors; independent practice; patient care; and this ‘just-in-time’ access to reliable information supported confident and efficient decision-making. Conclusion A variety of information sources are used regularly in the workplace. Colleagues are used daily but seniors are not always available. During transitions, constant access to the electronic library was valued. It helped prepare trainee doctors for discussions with their seniors, assisting the interchange between explicit and tacit knowledge. By supporting accurate prescribing and treatment planning, the electronic library contributed to enhanced patient care. Trainees were more rapidly able to medicate patients to reduce pain and more quickly call for specific assessments. However, clinical decision-making often requires dialogue: what Smartphone technology can do is augment, not replace, discussion with their colleagues in the community of practice

Neurological updates: neurological complications of CAR-T therapy

Chimeric antigen receptor (CAR) expressing T-cells now offer an effective treatment option for people with previously refractory B-cell malignancies and are under development for a wide range of other tumours. However, neurological toxicity is a common complication of CAR T-cell therapy, seen in over 50% of recipients in some cohorts. Since 2018, the term immune effector cell-associated neurotoxicity syndrome (ICANS) has been used to describe and grade neurotoxicity seen after CAR T-cells and other similar therapies. ICANS following CAR-T therapy is usually self-limiting but can necessitate admission to the intensive care unit and is rarely fatal. As CAR-T therapies enter routine clinical practice, it is important for neurologists to be aware of the nature of neurological complications. Here we summarise the clinical manifestations, mechanisms, investigations and recommended treatment of CAR-T related neurotoxicity, focusing on the licensed CD19 products

A process evaluation, with mediation analysis, of a web-based intervention to augment primary care exercise referral schemes:the e-coachER randomised controlled trial

BACKGROUND: The e-coachER trial aimed to determine whether adding web-based behavioural support to exercise referral schemes (ERS) increased long-term device-measured physical activity (PA) for patients with chronic conditions, compared to ERS alone, within a randomised controlled trial. This study explores the mechanisms of action of the e-coachER intervention using measures of the behaviour change processes integral to the intervention's logic model.METHODS: Four hundred fifty adults with obesity, diabetes, hypertension, osteoarthritis or history of depression referred to an ERS were recruited in Plymouth, Birmingham and Glasgow. The e-coachER intervention comprising 7-Steps to Health was aligned with Self-Determination Theory and mapped against evidence-based behaviour change techniques (BCTs). Participants completed questionnaires at 0, 4, and 12 months to assess PA and self-reported offline engagement with core BCTs in day-to-day life (including action planning and self-monitoring) and beliefs relating to PA (including perceived importance, confidence, competence, autonomy and support). We compared groups at 4 and 12 months, controlling for baseline measures and other covariates. Mediation analysis using the product of coefficients method was used to determine if changes in process variables mediated intervention effects on moderate to vigorous physical activity (MVPA) recorded by accelerometer and self-report at 4- and 12-months.RESULTS: The internal reliability (Cronbach's alpha) for all multi-item scales was &gt; 0.77. At 4-months, those randomised to e-coachER reported higher levels of PA beliefs relating to importance (1.01, 95% confidence interval (CI): 0.42 to 1.61, p = 0.001), confidence (1.28, 95% CI: 0.57 to 1.98, p &lt; 0.001), competence (1.61, 95% CI: .68 to 2.54, p = 0.001), availability of support (0.77, 95% CI: 0.07 to 1.48, p = 0.031), use of action planning (1.54, 95% CI: 0.23 to 2.85, p = 0.021) and use of self-monitoring (0.76, 95% CI: 0.19 to 1.32, p = 0.009) compared to ERS alone. There were no intervention effects on autonomous beliefs or perceived frequency of support, compared to ERS alone. At the 12-month follow-up, participants belief in the importance of PA was the only process measure to remain significantly higher in the e-coachER group when compared to ERS alone (0.75, 95% CI: 0.05 to 1.45). Intervention effects on perceived importance (2.52, 95% CI: 0.45 to 5.39), action planning (1.56, 95% CI: 0.10 to 3.54) and self-monitoring (1.92, 95% CI: 0.21 to 4.33) at 4-months significantly mediated change in accelerometer measured MVPA at 12-months (recorded in ≥ 10-min bouts).CONCLUSIONS: e-coachER led to some short-term changes in most process outcomes. Some of these processes also appeared to mediate e-coachER effects on changes in accelerometer measured MVPA. Further work should be carried out to understand how best to design and implement theoretically underpinned web-based physical activity promotion interventions within ERS.TRIAL REGISTRATION: ISRCTN, ISRCTN15644451 . Registered 12 February 2015.</p

Proteomic profiling of high risk medulloblastoma reveals functional biology

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior