The Lived Experience of Informal Caregivers of People Who Have Severe Mental Illness and Coexisting Long-Term Conditions: A Qualitative Study.

BACKGROUND: People with severe mental illness (SMI) experience higher rates and poorer outcomes of physical long-term conditions (LTCs). The management of SMI and LTCs is highly complex and many people with SMI rely on informal carers for support, which may lead to high levels of caregiver burden, and caregiver burnout. Caregiver burnout can result in poor health outcomes for informal carers and a reduction in the quality of care they are able to provide. Therefore, it is important to understand the caring experience to identify and address factors that contribute to burden and burnout. METHODS: This paper reports a secondary qualitative analysis of semistructured interviews and focus groups conducted with informal carers of people who have coexisting SMI and LTCs. We recruited 12 informal carers in England between December 2018 and April 2019. The transcripts were coded and analysed thematically. RESULTS: We identified two overarching themes and five subthemes. The themes included 'Fighting on all fronts: Mounting strain between demands and resources', which described the challenge of providing care in the context of coexisting SMI and LTCs, and 'Safekeeping: The necessity of chronic hypervigilance', which captured how informal carers' roles were defined by managing high-risk situations, leading to hypervigilance and paternalistic approaches to care. CONCLUSION: The experience of informal carers for people with SMI and coexisting LTCs is marked by limited access to support and the management of significant risk, which could contribute to high caregiver burden. Further primary research is needed to understand how the experiences of the caregiver role for people with SMI and LTCs influence caregiver burden. PATIENT OR PUBLIC CONTRIBUTION: Our PPI panel DIAMONDS Voice provided guidance on this study from conception, design and development of interview guides and recruitment materials to final write-up. DIAMONDS Voice consists of service users and carers who have experience of SMI and LTCs. Three carer members reviewed the final manuscript, and two are credited as authors.

Rituximab Chimeric Anti-CD20 Monoclonal Antibody Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a Four-Dose Treatment Program.

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.

The lived experience of severe mental illness and long-term conditions: a qualitative exploration of service user, carer, and healthcare professional perspectives on self-managing co-existing mental and physical conditions.

BACKGROUND: People with severe mental illness (SMI), such as schizophrenia, have higher rates of physical long-term conditions (LTCs), poorer health outcomes, and shorter life expectancy compared with the general population. Previous research exploring SMI and diabetes highlights that people with SMI experience barriers to self-management, a key component of care in long-term conditions; however, this has not been investigated in the context of other LTCs. The aim of this study was to explore the lived experience of co-existing SMI and LTCs for service users, carers, and healthcare professionals. METHODS: A qualitative study with people with SMI and LTCs, their carers, and healthcare professionals, using semi-structured interviews, focused observations, and focus groups across the UK. Forty-one interviews and five focus groups were conducted between December 2018 and April 2019. Transcripts were coded by two authors and analysed thematically. RESULTS: Three themes were identified, 1) the precarious nature of living with SMI, 2) the circularity of life with SMI and LTCs, and 3) the constellation of support for self-management. People with co-existing SMI and LTCs often experience substantial difficulties with self-management of their health due to the competing demands of their psychiatric symptoms and treatment, social circumstances, and access to support. Multiple long-term conditions add to the burden of self-management. Social support, alongside person-centred professional care, is a key facilitator for managing health. An integrated approach to both mental and physical healthcare was suggested to meet service user and carer needs. CONCLUSION: The demands of living with SMI present a substantial barrier to self-management for multiple co-existing LTCs. It is important that people with SMI can access person-centred, tailored support for their LTCs that takes into consideration individual circumstances and priorities.

The history of Rhoton's Lab.

The work performed in Dr. Rhoton's Lab, represented by over 500 publications on microneurosurgical anatomy, greatly contributed to improving the level of neurosurgical treatment throughout the world. The authors reviewed the development and activities of the Lab over 40 years. Dr. Albert L. Rhoton Jr., the founder of, and leader in, this field, displayed great creativity and ingenuity during his life. He devoted himself to perfecting his study methodology, employing high-definition photos and slides to enhance the quality of his published papers. He dedicated his life to the education of neurosurgeons. His "lab team," which included microneuroanatomy research fellows, medical illustrators, lab directors, and secretaries, worked together under his leadership to develop the methods and techniques of anatomical study to complete over 160 microneurosurgical anatomy projects. The medical illustrators adapted computer technologies and integrated art and science in the field of microneurosurgical anatomy. Dr. Rhoton's fellows established methods of injecting colors and pursued a series of projects to innovate surgical approaches and instruments over a 40-year period. They also continued to help Dr. Rhoton to conduct international educational activities after returning to their home countries. Rhoton's Lab became a world-renowned anatomical lab as well as a microsurgical training center and generated the knowledge necessary to perform accurate, gentle, and safe surgery for the sake of patients.

The microneurosurgical anatomy legacy of Albert L. Rhoton Jr., MD: an analysis of transition and evolution over 50 years.

The authors chronologically categorized the 160 original articles written by Dr. Rhoton and his fellows to show why they selected their themes and how they carried out their projects. The authors note that as neurosurgery progresses and new techniques and approaches are developed, accurate and safe treatment will depend upon continued clarification of microsurgical anatomy.

Variations of Occipital Artery-Posterior Inferior Cerebellar Artery Bypass: Anatomic Consideration.

BACKGROUND: Advances in diagnosis of posterior inferior cerebellar artery (PICA) aneurysms have revealed the high frequency of distal and/or dissecting PICA aneurysms. Surgical treatment of such aneurysms often requires revascularization of the PICA including but not limited to its caudal loop. OBJECTIVE: To examine the microsurgical anatomy involved in occipital artery (OA)-PICA anastomosis at various anatomic segments of the PICA. METHODS: Twenty-eight PICAs in 15 cadaveric heads were examined with the operating microscope to take morphometric measurements and explore the specific anatomy of bypass procedures. RESULTS: OA bypass to the p2, p3, p4, or p5 segment was feasible with a recipient vessel of sufficient diameter. The loop wandering near the jugular foramen in the p2 segment provided sufficient length without requiring cauterization of any perforating arteries to the brainstem. Wide dissection of the cerebellomedullary fissure provided sufficient exposure for the examination of some p3 segments and all p4 segments hidden by the tonsil. OA-p5 bypass was placed at the main trunk before the bifurcation in 5 hemispheres and at the larger hemispheric trunk in others. CONCLUSION: Understanding the possible variations of OA-PICA bypass may enable revascularization of the appropriate portion of the PICA when the parent artery must be occluded. A detailed anatomic understanding of each segment clarifies important technical nuances for the bypass on each segment. Dissection of the cerebellomedullary fissure helps to achieve sufficient exposure for the bypass procedures on most of the segments.

The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis.

Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a Center for International Blood and Marrow Transplant Research study evaluating the incidence, timing, prophylaxis agents, risk factors and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs controls (P=0.0004). After controlling for significant variables, the proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs matched controls (P<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes.

Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer: a phase II trial.

The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m2 ) + Cisplatin (30 mg/m2 ) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50Gy/25 fractions) on weeks 4-8. Sunitinib was commenced 4-13 weeks after surgery and continued for one year. Sixty-one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12-month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2-year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy (n = 43), median survival was 36 months, with a 2-year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer.

Mixed reality ventriculostomy simulation: experience in neurosurgical residency.

BACKGROUND: Medicine and surgery are turning toward simulation to improve on limited patient interaction during residency training. Many simulators today use virtual reality with augmented haptic feedback with little to no physical elements. In a collaborative effort, the University of Florida Department of Neurosurgery and the Center for Safety, Simulation & Advanced Learning Technologies created a novel "mixed" physical and virtual simulator to mimic the ventriculostomy procedure. The simulator contains all the physical components encountered for the procedure with superimposed 3-D virtual elements for the neuroanatomical structures. OBJECTIVE: To introduce the ventriculostomy simulator and its validation as a necessary training tool in neurosurgical residency. METHODS: We tested the simulator in more than 260 residents. An algorithm combining time and accuracy was used to grade performance. Voluntary postperformance surveys were used to evaluate the experience. RESULTS: Results demonstrate that more experienced residents have statistically significant better scores and completed the procedure in less time than inexperienced residents. Survey results revealed that most residents agreed that practice on the simulator would help with future ventriculostomies. CONCLUSION: This mixed reality simulator provides a real-life experience, and will be an instrumental tool in training the next generation of neurosurgeons. We have now implemented a standard where incoming residents must prove efficiency and skill on the simulator before their first interaction with a patient.

Degree of tumor shrinkage following neoadjuvant chemoradiotherapy: a potential predictor for complete pathological response in esophageal cancer?

Neoadjuvant chemoradiotherapy (CRT) before surgery results in a pathological complete response (pCR) rate in about 1/3 of the patients, which is correlated with survival. It was hypothesized that volumetric tumor response to CRT would correlate with outcomes. Patients who completed trimodality therapy, where planning, pre-, and post-CRT computed tomography scans were available, and pathology was reviewed by a central pathologist, were eligible for analysis. Absolute and relative tumor volume change pretreatment and post-treatment were correlated with pCR, locoregional recurrence (LRR), disease-free survival, and overall survival. Fifty-six patients were analyzed. pCR was observed in 30% of patients. Median follow up was 20.3 (range 4-89) months. The 2- and 4-year overall survival was 61.3% (95% confidence interval [CI]: 45-74) and 25.0% (95%CI: 11-41); proportion disease free was 32.1% (95% CI: 19-46) and 20.6% (9-36) at 2 and 4 years, respectively. The median relative volume reduction was 17% (95% CI: -24, -3%). Using 20% as the criteria, the proportion of patients with pCR of ≥20% versus <20% was 13/25 (52%) versus 4/31 (13%) for those who did not (odds ratio 7.3; 95% CI: 2-27). The LRR at 2 and 4 years were 29.5% (95% CI: 16-43) and 36.2% (95% CI: 23-50). The relative tumor reduction ≥20% was significantly correlated with LRR (hazard ratio 0.24; 95% CI: 0.07-0.8; p 0.02) at 2 and 4 years, respectively. Relative tumor volume reduction following CRT is correlated with pCR and LRR. Further investigations are warranted to examine the effect of volume change, alone or in conjunction with other factors as potential predictors for pathological response.

Mixed-reality simulation for neurosurgical procedures.

BACKGROUND: Surgical education is moving rapidly to the use of simulation for technical training of residents and maintenance or upgrading of surgical skills in clinical practice. To optimize the learning exercise, it is essential that both visual and haptic cues are presented to best present a real-world experience. Many systems attempt to achieve this goal through a total virtual interface. OBJECTIVE: To demonstrate that the most critical aspect in optimizing a simulation experience is to provide the visual and haptic cues, allowing the training to fully mimic the real-world environment. METHODS: Our approach has been to create a mixed-reality system consisting of a physical and a virtual component. A physical model of the head or spine is created with a 3-dimensional printer using deidentified patient data. The model is linked to a virtual radiographic system or an image guidance platform. A variety of surgical challenges can be presented in which the trainee must use the same anatomic and radiographic references required during actual surgical procedures. RESULTS: Using the aforementioned techniques, we have created simulators for ventriculostomy, percutaneous stereotactic lesion procedure for trigeminal neuralgia, and spinal instrumentation. The design and implementation of these platforms are presented. CONCLUSION: The system has provided the residents an opportunity to understand and appreciate the complex 3-dimensional anatomy of the 3 neurosurgical procedures simulated. The systems have also provided an opportunity to break procedures down into critical segments, allowing the user to concentrate on specific areas of deficiency.

Layer V perirhinal cortical ensemble activity during object exploration: a comparison between young and aged rats.

Object recognition memory requires the perirhinal cortex (PRC) and this cognitive function declines during normal aging. Recent electrophysiological recordings from young rats have shown that neurons in Layer V of the PRC are activated by three-dimensional objects. Thus, it is possible that age-related object recognition deficits result from alterations in PRC neuron activity in older animals. To examine this, the present study used cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) with confocal microscopy to monitor cellular distributions of activity-induced Arc RNA in layer V of the PRC. Activity was monitored during two distinct epochs of object exploration. In one group of rats (6 young/6 aged) animals were placed in a familiar testing arena and allowed to explore five different three-dimensional objects for two 5-min sessions separated by a 20-min rest (AA). The second group of animals (6 young/6 aged) also explored the same objects for two 5-min sessions, but the environment was changed between the first and the second epoch (AB). Behavioral data showed that both age groups spent less time exploring objects during the second epoch, even when the environment changed, indicating successful recognition. Although the proportion of active neurons between epochs did not change in the AA group, in the AB group more neurons were active during epoch 2 of object exploration. This recruitment of neurons into the active neural ensemble could serve to signal that familiar stimuli are being encountered in a new context. When numbers of Arc positive neurons were compared between age groups, the old rats had significantly lower proportions of Arc-positive PRC neurons in both the AA and AB behavioral conditions. These data support the hypothesis that age-associated functional alterations in the PRC contribute to declines in stimulus recognition over the lifespan.

Self-similar breakup of near-inviscid liquids.

The final stages of pinchoff and breakup of dripping droplets of near-inviscid Newtonian fluids are studied experimentally for pure water and ethanol. High-speed imaging and image analysis are used to determine the angle and the minimum neck size of the cone-shaped extrema of the ligaments attached to dripping droplets in the final microseconds before pinchoff. The angle is shown to steadily approach the value of 18.0 ± 0.4°, independently of the initial flow conditions or the type of breakup. The filament thins and necks following a τ(2/3) law in terms of the time remaining until pinchoff, regardless of the initial conditions. The observed behavior confirms theoretical predictions.

The central nervous system solitary fibrous tumor: a review of clinical, imaging and pathologic findings among all reported cases from 1996 to 2010.

OBJECTIVE: Central nervous system (CNS) solitary fibrous tumor (SFT) is a rare lesion first identified as a unique entity in 1996. We describe two cases treated at the University of Florida followed by a review of all reported cases of CNS SFT between 1996 and 2010. METHODS: A review of the literature was performed to identify all reported cases of CNS SFT. RESULTS: 189 cases (including the two presented herein) were discovered, of which 46 were spinal and 143 were intracranial. Demographic, imaging, and pathologic findings are presented. Roughly 6% of reported lesions are malignant. Subtotal resection (STR) was associated with a 16-fold increased odds of recurrence (OR 15.9, 95% CI 5.5-46.1), although mean follow-up was shorter in those cases of GTR without recurrence. CONCLUSION: CNS SFT is a rare lesion. Six percent of lesions are malignant. GTR is superior to STR although the degree of superiority is not clear.

Robust, globally consistent and fully automatic multi-image registration and montage synthesis for 3-D multi-channel images.

The need to map regions of brain tissue that are much wider than the field of view of the microscope arises frequently. One common approach is to collect a series of overlapping partial views, and align them to synthesize a montage covering the entire region of interest. We present a method that advances this approach in multiple ways. Our method (1) produces a globally consistent joint registration of an unorganized collection of three-dimensional (3-D) multi-channel images with or without stage micrometer data; (2) produces accurate registrations withstanding changes in scale, rotation, translation and shear by using a 3-D affine transformation model; (3) achieves complete automation, and does not require any parameter settings; (4) handles low and variable overlaps (5-15%) between adjacent images, minimizing the number of images required to cover a tissue region; (5) has the self-diagnostic ability to recognize registration failures instead of delivering incorrect results; (6) can handle a broad range of biological images by exploiting generic alignment cues from multiple fluorescence channels without requiring segmentation and (7) is computationally efficient enough to run on desktop computers regardless of the number of images. The algorithm was tested with several tissue samples of at least 50 image tiles, involving over 5000 image pairs. It correctly registered all image pairs with an overlap greater than 7%, correctly recognized all failures, and successfully joint-registered all images for all tissue samples studied. This algorithm is disseminated freely to the community as included with the Fluorescence Association Rules for Multi-Dimensional Insight toolkit for microscopy (http://www.farsight-toolkit.org).

Evaluation of a transition to practice program for neurosurgery residents: creating a safe transition from resident to independent practitioner.

BACKGROUND: In 2004, the Department of Neurosurgery at the University of Florida implemented a major curriculum innovation called the Transition to Practice program. This program was established to prepare residents to more safely transition to the role of independent practitioner. METHODS: A qualitative and quantitative evaluation of the program was conducted after its fifth year using online surveys and interviews. Study participants included Transition to Practice graduates, faculty, and current residents. RESULTS: Of the 26 respondents, 89% of faculty and all graduates were very satisfied with the program. Strengths identified included an independent yet mentored broad operative experience, the development of self-confidence, and a real sense of responsibility for patients. Medical billing and coding instruction and career mentoring were areas of the program that required additional attention. CONCLUSION: Overall, this program is meeting the stated objectives and is well received by the graduates and faculty. Based on the results of this evaluation, curricular changes such as instructions in practice management and implementation of a career-mentoring program have occurred. The Transition to Practice program is a unique curricular response to change that other surgical specialties may find useful in addressing the current-day stresses on graduate medical education.