Co-designing a virtual reality exposure therapy with students experiencing school anxiety: a proof-of-concept study.

BACKGROUND AND OBJECTIVES: Anxiety related school avoidance can affect up to 5% of a country's students each year. VRET (Virtual Reality Exposure Therapy) is a novel therapy proven to be as effective as conventional approaches for treating many anxiety disorders. The aim of this research is to co-design and evaluate a VRET intervention for students experiencing school related anxiety. METHOD: Eighteen adolescents participated in design thinking workshops where they developed a script and storyboard for the VRET. Using an iterative approach, a VRET prototype was developed based on this work. Eighteen teenagers were subsequently recruited to engage with the VRET for one session each and provide feedback on their experience via a structured questionnaire (supervised by a study coordinator) particularly focusing on the ability of the VR experience to reduce school related anxiety. RESULTS: Exposure therapy needs to produce an anxiety response to be effective. The VRET was effective in producing an anxiety response in 89% of participants. Results demonstrated that 93% of participants found the simulations immersive, 94% found the scenarios believable, and 83% could relate to 'Dala', the avatar in the videos. 100% of participants believed that VRET would help with school anxiety. CONCLUSION: This proof-of-concept study demonstrates favourable face validity indicating promise for this mode of intervention for delivering targeted support to anxious students. VRET could be used as a scalable, cost effective early intervention to reduce the severity of anxiety associated with school avoidance.

No evidence for metabolic adaptation during exercise-related energy compensation.

The constrained energy model posits that the increased total daily energy expenditure (TDEE) in response to exercise is often less than the energy cost of the exercise prescribed. The mechanisms behind this phenomenon, coined "exercise-related energy compensation" (ExEC), are poorly understood, and it is unknown if ExEC is coupled with metabolic adaptation. Using a randomized controlled 24-week exercise intervention, individuals who demonstrated ExEC were identified. Changes to all components of TDEE and metabolic adaptation were assessed using doubly labeled water over 14 days and room calorimetry over 24-h 48% of individuals exhibited ExEC (-308 ± 158 kcals/day). There were no statistically significant differences in sex, age, or BMI between ExEC and non-ExEC. ExEC was associated with baseline TDEE (r = -0.50, p = 0.006). There were no statistically significant differences in metabolic adaptations for 24 h, sleep, or resting expenditures. These findings reveal that ExEC occurs independent of metabolic adaptation in sedentary components of EE.

Implementation of the MiNDToolkit intervention for the management of behavioral symptoms in MND by healthcare professionals: a mixed-methods process evaluation.

OBJECTIVE: MiNDToolkit is a novel psychoeducational intervention for carers to support management of behavioral symptoms in people living with motor neuron disease (PlwMND). Implementation of MiNDToolkit involves delivery of an online intervention to carers, which is reinforced by trained healthcare professionals (HCPs). METHODS: A mixed-methods process evaluation of the MiNDToolkit feasibility trial was conducted, focusing on reinforcement of the intervention by HCPs. Quantitative data, descriptively analyzed, were included from platform analytics, questionnaire, and 10 semi-structured interviews with HCPs. Interviews were transcribed verbatim; data were inductively analyzed using Reflective Thematic Analysis. RESULTS: The MiNDToolkit training and platform is a beneficial and acceptable resource for HCPs with potential to increase knowledge and confidence in identifying and managing behavioral symptoms in MND. Implementation barriers included HCPs' perceptions that highlighting behavior changes would be burdensome to carers and assumptions that carers would take the initiative to ask for support from clinicians. Degree of intervention reinforcement varied, with most HCPs delegating intervention delivery solely to the online platform. CONCLUSIONS: Implementation of the MiNDToolkit was viewed to be feasible and the platform thought to increase accessibility of support to carers. The flexible approach to delivery (online platform and optional HCP reinforcement) is acceptable as an intervention for supporting carers of PlwMND with behavioral symptoms. However, MiNDToolkit should not negate HCP involvement in providing medical and practical information to PlwMND and families. Future research should explore ways to incorporate support for carers in the management of PlwMND alongside standard care, alongside tools such as the MiNDToolkit.

An online intervention for carers to manage behavioral symptoms in motor neuron disease (MiNDToolkit): a randomized parallel multi-center feasibility trial.

BACKGROUND: Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design: Randomized, parallel, multi-center, feasibility trial. SETTING: England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23. PARTICIPANTS: Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control. INTERVENTION: MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables. MAIN OUTCOMES: One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period. CONCLUSION: The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted.

Clinically available immunosuppression averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques.

A safe, efficacious, and clinically applicable immunosuppressive regimen is necessary for islet xenotransplantation to become a viable treatment option for diabetes. We performed intraportal transplants of wild-type adult porcine islets in 25 streptozotocin-diabetic cynomolgus monkeys. Islet engraftment was good in 21, partial in 3, and poor in 1 recipient. Median xenograft survival was 25 days with rapamycin and CTLA4Ig immunosuppression. Adding basiliximab induction and maintenance tacrolimus to the base regimen significantly extended median graft survival to 147 days (p < .0001), with three animals maintaining insulin-free xenograft survival for 265, 282, and 288 days. We demonstrate that this regimen suppresses non-Gal anti-pig antibody responses, circulating effector memory T cell expansion, effector function, and infiltration of the graft. However, a chronic systemic inflammatory state manifested in the majority of recipients with long-term graft survival indicated by increased neutrophil to lymphocyte ratio, IL-6, MCP-1, CD40, and CRP expression. This suggests that this immunosuppression regimen fails to regulate innate immunity and resulting inflammation is significantly associated with increased incidence and severity of adverse events making this regimen unacceptable for translation. Additional studies are needed to optimize a maintenance regimen for regulating the innate inflammatory response.

Imaging Review of Paraneoplastic Neurologic Syndromes.

Paraneoplastic syndromes are systemic reactions to neoplasms mediated by immunologic or hormonal mechanisms. The most well-recognized paraneoplastic neurologic syndrome, both clinically and on imaging, is limbic encephalitis. However, numerous additional clinically described syndromes affect the brain, spinal cord, and peripheral nerves. Many of these syndromes can have imaging findings that, though less well described, are important in making the correct diagnosis. Moreover, imaging in these syndromes frequently mimics more common pathology, which can be a diagnostic challenge for radiologists. Our goal is to review the imaging findings of paraneoplastic neurologic syndromes, including less well-known entities and atypical presentations of common entities. Specifically, we discuss limbic encephalitis, paraneoplastic cerebellar degeneration, paraneoplastic brain stem encephalitis, cranial neuropathy, myelitis, and polyneuropathy. We also demonstrate common diagnostic pitfalls that can be encountered when imaging these patients.

Variability in body temperature in healthy adults and in patients receiving chemotherapy: prospective observational cohort study.

Between-individual variability of body temperature has been little investigated, but is of clinical importance: for example, in detection of neutropenic sepsis during chemotherapy. We studied within-person and between-person variability in temperature in healthy adults and those receiving chemotherapy using a prospective observational design involving 29 healthy participants and 23 patients undergoing chemotherapy. Primary outcome was oral temperature. We calculated each patient's mean temperature, standard deviation within each patient (within-person variability), and between patients (between-person variability). Secondary analysis explored temperature changes in the three days before admission for neutropenic sepsis. 1,755 temperature readings were returned by healthy participants and 1,765 by chemotherapy patients. Mean participant temperature was 36.16 C (95% CI 36.07-36.26) in healthy participants and 36.32 C (95% CI 36.18-36.46) in chemotherapy patients. Healthy participant within-person variability was 0.40 C (95% CI 0.36-0.44) and between-person variability was 0.26 C (95% CI 0.16-0.35). Chemotherapy patient within-person variability was 0.39 C (95% CI 0.34-0.44) and between-person variability was 0.34 C (95% CI 0.26-0.48). Thus, use of a population mean rather than personalised baselines is probably sufficient for most clinical purposes as between-person variability is not large compared to within-person variability. Standardised guidance and provision of thermometers to patients might help to improve recording and guide management.

Sirolimus: Efficacy and Complications in Children With Hyperinsulinemic Hypoglycemia: A 5-Year Follow-Up Study.

INTRODUCTION: Sirolimus, a mammalian target of rapamycin inhibitor, has been used in congenital hyperinsulinism (CHI) unresponsive to diazoxide and octreotide. Reported response to sirolimus is variable, with high incidence of adverse effects. To the best of our knowledge, we report the largest group of CHI patients treated with sirolimus followed for the longest period to date. METHODS: Retrospective study of CHI patients treated with sirolimus in a tertiary service and review of the 15 publications reporting CHI patients treated with mammalian target of rapamycin inhibitors. Comparison was made between the findings of this study with those previously published. RESULTS: Twenty-two CHI patients treated with sirolimus were included in this study. Twenty showed partial response, one showed complete response, and one was unresponsive. Five of the partially/fully responsive patients had compound heterozygous ABCC8 mutations and five had heterozygous ABCC8 mutations. A total of 86.4% (19/22) developed complications, with infection being the most frequent (17/22), of which 11 were of bacterial etiology, followed by persistent diarrhea (3/22) and hyperglycemia (2/22). Seventeen patients stopped sirolimus: 13 from infections; 2 from hyperglycemia; and 2 from alternative treatment (lanreotide) response. Compared with data previously published, our study identified a higher number of partially sirolimus-responsive CHI cases, although the high rate of complications while on this medication limited its potential usefulness. CONCLUSION: Sirolimus candidates must be carefully selected given its frequent and potentially life-threatening side effects. Its use as a short-term, last-resort therapy until normoglycemia is achieved with other agents such as lanreotide could avoid pancreatectomy. Further studies evaluating the use of sirolimus in patients with CHI are required.

Isolated recurrent myelitis in a persistent MOG positive patient.

MOG-Ab positive CNS demyelination typically involves the optic nerve and spinal cord. Recurrent episodes of myelitis without optic neuritis are very rare and according to current literature review represent about 3-5% of positive MOG-Ab cases. We report a 30-year-old woman with positive serum MOG-Ab suffering two discrete episodes of transverse myelitis without ophthalmic involvement. Repeated serum MOG-Ab test after the second relapse was positive, correlating with high likelihood of relapsing disease. Of note, our patient relapsed under Rituximab therapy, which does not seem to be uncommon for MOG-Ab patients. Patients with isolated or recurrent myelitis without optic involvement should be screened for anti MOG IgG as a part of their workup.

A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis.

Cystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further.

First case of vaccine-strain varicella infection as manifestation of HIV in healthcare worker: a case report and review of the literature.

Live-attenuated varicella vaccination is safe in non-immunocompromised populations and is associated with rare non-serious adverse events. A healthcare worker (HCW) developed varicella infection, and exposure investigation led to immunization against varicella in an exposed non-immune HCW. Subsequently, vaccine-strain-induced disseminated varicella and progressive outer retinal necrosis in the exposed HCW resulted in identification of undiagnosed human immunodeficiency virus infection. This article reviews serious adverse events from varicella vaccination, and extreme caution is advised prior to live vaccination of HCWs.

Diagnosis and management of spinal cord emergencies.

Most spinal cord injury is seen with trauma. Nontraumatic spinal cord emergencies are discussed in this chapter. These myelopathies are rare but potentially devastating neurologic disorders. In some situations prior comorbidity (e.g., advanced cancer) provides a clue, but in others (e.g., autoimmune myelopathies) it may come with little warning. Neurologic examination helps distinguish spinal cord emergencies from peripheral nervous system emergencies (e.g., Guillain-Barré), although some features overlap. Neurologic deficits are often severe and may quickly become irreversible, highlighting the importance of early diagnosis and treatment. Emergent magnetic resonance imaging (MRI) of the entire spine is the imaging modality of choice for nontraumatic spinal cord emergencies and helps differentiate extramedullary compressive causes (e.g., epidural abscess, metastatic compression, epidural hematoma) from intramedullary etiologies (e.g., transverse myelitis, infectious myelitis, or spinal cord infarct). The MRI characteristics may give a clue to the diagnosis (e.g., flow voids dorsal to the cord in dural arteriovenous fistula). However, additional investigations (e.g., aquaporin-4-IgG) are often necessary to diagnose intramedullary etiologies and guide treatment. Emergency decompressive surgery is necessary for many extramedullary compressive causes, either alone or in combination with other treatments (e.g., radiation) and preoperative neurologic deficit is the best predictor of outcome.

A review of a GP registrar-run mobile health clinic for homeless people.

BACKGROUND: Homeless people have excessively high morbidity and mortality rates, yet they face barriers accessing primary care. A mobile health clinic, staffed by GP registrars, was developed to provide services to homeless people, particularly rough sleepers and sex workers. AIM: The aims were to improve access to primary care and to challenge the stereotypes and prejudices of GP registrars through direct contact with homeless people. DESIGN AND SETTING: This was a qualitative study; questionnaires were completed on the mobile health clinic and two focus groups were conducted. METHODS: All service users were asked to complete a questionnaire over a 3 month period. Two focus groups were conducted with 6 and 14 GP registrars who had worked on the bus. RESULTS: There was an 80% response rate (116 of 145). Fifty-two percent had no Medical Card meaning that they had no way to access the free primary care to which they are entitled. Had the clinic not been available, over half would not have sought further treatment and 16% would have gone to an Emergency Department. Ninety-one percent of users rated the service 10/10. The focus groups found that GP registrars who worked on the mobile health clinic had decreased negative stereotypes, increased empathy, and more knowledge of homeless issues. Furthermore, they intended to ensure that homeless people will not face discrimination in their future practice. CONCLUSION: A GP Registrar-run Mobile Health Clinic achieved its aims of improving access to primary care for rough sleepers and sex workers, and challenging stereotypes of GP Registrars.

The forgotten foot - An assessment of foot and ankle radiograph pathology in final year medical students.

INTRODUCTION: It has been shown that doctors in Emergency Departments (EDs) have inconsistent knowledge of musculoskeletal anatomy. This is most likely due to a deficiency in focused musculoskeletal modules at undergraduate level in medical school. The aims of this study were to evaluate the knowledge of final year medical students on foot anatomy and common foot and ankle pathology as seen on radiographs. METHODS: Final year medical students were asked to complete our short examination on a handout. The handout was anonymous and non-mandatory. There were four images. The first image is the anatomical section and the remaining images are the pathological section. RESULTS: All 235 students responded. 57% were females. For the identification of the normal bones of the foot as shown on an X-ray, the average score for the group was 2.69 (out of a maximum of 6) {SD 1.67}7. Only 8.3% achieved a 6/6 or 100% grade i.e. recognising all six bones correctly. A further 8.3% achieved 5/6 (83%). 8.3% failed to correctly identify any bone seen on the X-ray, a corresponding score of 0. DISCUSSION: This quick test showed normal anatomy of the foot and common pathology. One would expect final year medical students to be familiar with, especially two weeks before their finals in surgery. The curriculum should address the paucity of time spent in educating students in foot and ankle pathology.

Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility.

BACKGROUND: Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID). METHODS: Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006-February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). KEY RESULTS: Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). CONCLUSIONS & INFERENCES: This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy.

A pain in the neck--medical student attitudes to the Orthopaedic spine.

Considerable deficiencies exist in the teaching of Orthopaedic medicine. This study aimed (i) to determine if spinal surgery was the Orthopaedic specialty that students found most difficult, (ii) to appraise attitudes towards teaching of the spine, and (iii) to suggest ways teaching might be improved. A questionnaire on Orthopaedic teaching was given to 238 final year medical students in Ireland. Perceived difficulties with spinal surgery were compared to seven other Orthopaedic sub-specialties. Suggestions made on how to maximise teaching potential included 69 (29%) for more tutorials, 43 (18%) for more lectures, 26 (11%) suggested a more structured training programme and 17 (7%) for increased use of online resources. The spine is one of the least popular Orthopaedic subspecialties and considerable deficiencies exist in its education.