Interventions to promote the health and well-being of children under 5s experiencing homelessness in high-income countries: a scoping review.

OBJECTIVES: Homelessness among families with children under 5 residing in temporary accommodation is a growing global concern, especially in high-income countries (HICs). Despite significant impacts on health and development, these 'invisible' children often fall through the gaps in policy and services. The study's primary objective is to map the content and delivery methods of culturally sensitive interventions for children under 5 experiencing homelessness in HICs. DESIGN: A scoping review guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist. DATA SOURCES: Databases include PubMed, Medline, SCOPUS, The Cochrane Library and Google Scholar were searched up to 24 March 2022. ELIGIBILITY CRITERIA: This scoping review includes studies that describe, measure or evaluate intervention strategies aimed at improving child health programmes, specifically those yielding positive outcomes in key areas like feeding, nutrition, care practices and parenting. DATA EXTRACTION AND SYNTHESIS: Articles were selected and evaluated by two independent reviewers, with a dispute resolution system involving a third reviewer for contested selections. The methodological quality of the studies was assessed using various tools including the Risk of Bias (RoB) tool, Cochrane RoB V.2.0, the Risk of Bias Assessment Tool for Non-randomized Studies (RoBANS) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), each selected according to the type of article. RESULTS: The database search yielded 951 results. After deduplication, abstract screening and full review, 13 articles met the inclusion criteria. Two predominant categories of intervention delivery methods were identified in this research: group-based interventions (educational sessions) and individual-based interventions (home visits). CONCLUSION: This review highlights effective interventions for promoting the health and well-being of children under 5 experiencing homelessness, including educational sessions and home visits. Research has supported the importance of home visiting to be instrumental in breaking down language, cultural and health literacy barriers.

Stigma and mental health problems in an Indian context. Perceptions of people with mental disorders in urban, rural and tribal areas of Kerala.

BACKGROUND: The concept of stigma has been widely used to understand patterns of discrimination and negative ideas surrounding people with mental health problems, yet we know little of the specific nuances of how this might operate beyond the 'Global North'. AIM: This paper aims to explore the notion of stigma in an Indian context by considering the lived experience of patients, carers and community members. METHODS: A sample of 204 participants, representing mental health patients, informal carers and community members was recruited from urban and rural areas in Kerala, India. Participants took part in interviews where they were encouraged to talk about their experiences of mental ill health, attitudes towards these problems, barriers encountered and sources of support. RESULTS: Experiences akin to the experience of stigma in Europe and the United States were elicited but there were important local dimensions specific to the Indian context. The difficulties faced by people with diagnoses of mental disorders in finding marriage partners was seen as an important problem, leading to marriage proposals being refused in some cases, and secrecy on the part of those with mental health problems. Rather than the 'self-stigma' identified in the US, participants were more likely to see this as a collective problem in that it could reflect badly on the family group as a whole rather than just the sufferer. CONCLUSIONS: In the Indian context, the idioms of stigma emphasised impairments in marriage eligibility and the implications for the family group rather than just the self.

Multiple Mental Health Literacies in a Traditional Temple Site in Kerala: The Intersection Between Beliefs, Spiritual and Healing Regimes.

The notion of 'mental health literacy' has been proposed as a way of improving mental health problem recognition, service utilisation and reducing stigma. Yet, the idea embodies a number of medical-model assumptions which are often at odds with diverse communities' spiritual traditions and local belief systems. Twenty participants were recruited to this study consisting of mental health service users (N = 7), family carers (N = 8) and community members (N = 5) in a temple town in Kerala, South India participated in semi-structured interviews exploring the variety of beliefs and practices relating to mental health. Our findings indicate that the issue may be better understood in terms of multiple mental health literacies which people deploy in different circumstances. Even those sceptical of traditional and spiritual approaches are knowledgeable about them, and the traditional practices themselves often involve detailed regimes of activities aimed at effecting an improvement in the person's mood or condition. Therefore, we argue it is appropriate to consider mental health literacy not as a unitary universal phenomenon but instead as a mosaic of different literacies which may be deployed in different settings and in line with different experiences and which may operate in synergy with each other to enable treatment but also facilitate a sense of meaning and purpose in life.

In-vitro and in-vivo performance studies of a porous infusion catheter designed for intraparenchymal delivery of therapeutic agents of varying size.

BACKGROUND: Limitations have previously existed for the use of brain infusion catheters with extended delivery port designs to achieve larger distribution volumes using convection-enhanced delivery (CED), due to poor transmittance of materials and uncontrolled backflow. The goal of this study was to evaluate a novel brain catheter that has been designed to allow for extended delivery and larger distribution volumes with limited backflow of fluid. It was characterized using a broad range of therapeutic pore sizes both for transmittance across the membranes to address possible occlusion and for distribution in short term infusion studies, both in-vitro in gels and in-vivo in canines. METHODS: Brain catheters with pore sizes of 10, 12, 15, 20 and 30 µm were evaluated using three infusates prepared in 0.9% sterile saline with diameters approximating 2, 5, and 30 nm, respectively. Magnevist™ was chosen as the small molecule infusate to mimic low-molecular weight therapeutics. Galbumin™ served as a surrogate for an assortment of proteins used for brain cancer and Parkinson's disease. Gadoluminate™ was used to assess the distribution of large therapeutics, such as adeno-associated viral particles and synthetic nanoparticles. The transmittance of the medium and large tracer particles through catheters of different pore size (15, 20 and 30 µm) was measured by MRI and compared with the measured concentration of the control. Infusions into 0.2% agarose gels were performed in order to evaluate differences in transmittance and distribution of the small, medium, and large tracer particles through catheters with different pore sizes (10, 12, 15, 20 and 30 µm). In-vivo infusions were performed in the canine in order to evaluate the ability of the catheter to infuse the small, medium, and large tracer particles into brain parenchyma at high flow rates through catheters with different pore sizes (10, 15, and 20 µm). Two catheters were stereotactically inserted into the brain for infusion, one per hemisphere, in each animal (N = 6). RESULTS: The transmittance of Galbumin and Gadoluminate across the catheter membrane surface was 100% to within the accuracy of the measurements. There was no evidence of any blockage or retardation of any of the infusates. Catheter pore size did not appear to significantly affect transmittance or distribution in gels of any of the molecule sizes in the range of catheter pore sizes tested. There were differences in the distributions between the different tracer molecules: Magnevist produced relatively large distributions, followed by Gadoluminate and Galbumin. We observed no instances of uncontrolled backflow in a total of 12 in-vivo infusions. In addition, several of the infusions resulted in substantial amounts remaining in tissue. We expect the in-tissue distributions to be substantially improved in the larger human brain. COMPARISON WITH EXISTING METHODS: The new porous brain catheter performed well in terms of both backflow and intraparenchymal infusion of molecules of varying size in the canine brain under CED flow conditions. CONCLUSIONS: Overall, the data presented in this report support that the novel porous brain catheter can deliver therapeutics of varying sizes at high infusion rates in the brain parenchyma, and resist backflow that can compromise the efficacy of CED therapy. Additional work is needed to further characterize the brain catheter, including animal toxicity studies of chronically implanted brain catheters to lay the foundation for its use in the clinic.

Experience-based investigation and codesign of approaches to prevent and reduce Mental Health Act use (CO-PACT): a protocol.

INTRODUCTION: The Independent Review of the Mental Health Act (MHA) in England and Wales confirmed increasing levels of compulsory detentions, especially for racialised communities. This research aims to: (a) understand the causes of and propose preventive opportunities to reduce the disproportionate use of the MHA, (b) use an adapted form of experience-based codesign (EBCD) to facilitate system-wide changes and (c) foreground the voices of service users at risk of detention to radically reform policy and implement new legislation to ensure the principles of equity are retained. METHODS AND ANALYSIS: This is a qualitative study, using a comparative case study design. This study is composed of five work packages; photovoice workshops will be conducted in eight local systems with service users and healthcare professionals separately (WP1); a series of three EBCD workshops in each local system to develop approaches that reduce detentions and improve the experience of people from racialised communities. This will inform a comparative analysis and national knowledge exchange workshop (WP2); an evaluation led by the patient and public involvement group to better understand what it is like for people to participate in photovoice, codesign and participatory research (WP3); an economic evaluation (WP4) and dissemination strategy (WP5). The impact of the involvement of patients and public will be independently evaluated. ETHICS AND DISSEMINATION: This study is sponsored by the University of Oxford and granted ethical approval from the NHS Research Ethics Committee and Health Research Authority (21/SC/0204). The outputs from this study will be shared through several local and national channels.

Developing a toolkit for increasing the participation of black, Asian and minority ethnic communities in health and social care research.

BACKGROUND: It is recognised that Black, Asian and Minority Ethnic (BAME) populations are generally underrepresented in research studies. The key objective of this work was to develop an evidence based, practical toolkit to help researchers maximise recruitment of BAME groups in research. METHODS: Development of the toolkit was an iterative process overseen by an expert steering group. Key steps included a detailed literature review, feedback from focus groups (including researchers and BAME community members) and further workshops and communication with participants to review the draft and final versions. RESULTS: Poor recruitment of BAME populations in research is due to complex reasons, these include factors such as inadequate attention to recruitment strategies and planning, poor engagement with communities and individuals due to issues such as cultural competency of researchers, historical poor experience of participating in research, and lack of links with community networks. Other factors include language issues, relevant expertise in research team and a lack of adequate resources that might be required in recruitment of BAME populations. CONCLUSIONS: A toolkit was developed with key sections providing guidance on planning research and ensuring adequate engagement of communities and individuals. Together with sections suggesting how the research team can address training needs and adopt best practice. Researchers highlighted the issue of funding and how best to address BAME recruitment in grant applications, so a section on preparing a grant application was also included. The final toolkit document is practical, and includes examples of best practice and 'top tips' for researchers.

Idioms of resilience: Mental health and migration in India.

BACKGROUND: Resilience has proved to be a versatile notion to explain why people are not defeated by hardship and adversity, yet so far, we know little of how it might apply to communities and cultures in low to middle income countries. AIM: This paper aims to explore the notion of resilience in cross-cultural context through considering the lived experience of internal migration. METHODS: A sample of 30 participants with experience of migration was recruited from a low-income slum dwelling neighbourhood in the city of Pune, India. These individuals participated in biographical narrative interviews in which they were encouraged to talk about their experience of migration, their adaptation to life in their new environment and making new lives for themselves. RESULTS: Participants referred to a variety of intra-individual and external factors that sustained their resilience, including acceptance of their circumstances, the importance of memory, hope for their children's futures as well as kindness from family friends and community members and aspects of the physical environment which were conducive to an improvement in their lives. CONCLUSIONS: By analogy with the widely used term 'idioms of distress', we advocate attention to the locally nuanced and culturally inflected 'idioms of resilience' or 'eudaemonic idioms' which are of crucial importance as migration and movement become ever more prominent in discussions of human problems. The nature and extent of people's coping abilities, their aspirations and strategies for tackling adversity, their idioms of resilience and eudaemonic repertoires merit attention so that services can genuinely support their adjustment and progress in their new-found circumstances.

Growth and form, Lie algebras and special functions.

The formation of a biological organism, or an organ within it, can often be regarded as the unfolding of successive equilibria of a mechanical system. In a mathematical model, these changes of equilibria may be considered to be responses of mechanically constrained systems to a change of a reference configuration and of a reference metric, which are in turn driven by genes and their expression. This paper brings together three major threads of research. These are: Lie-type symmetries of equations; models as well as data on growth and pattern formation; and the relation between Lie algebras (and groups) and special functions associated with them. We show that symmetry methods can be generalized to map between solutions to models with different reference metrics. In the case in which we attempt to obtain such equations, they seem too complicated to be of any immediate service to the community of researchers on cortical growth. However, models and data on growth may be used to obtain generators of these Lie algebras empirically and numerically. These generators result in new classes of special functions. The paper is an invitation to develop what we may call empirical Lie algebras and associated functions. The hypothesis that remains to be tested is whether the confluence of ideas described in the paper, namely the Lie algebraic-related consequences of pattern formation and growth, prove useful for deepened understanding of biological growth patterns.

Determinants of Intraparenchymal Infusion Distributions: Modeling and Analyses of Human Glioblastoma Trials.

Intra-parenchymal injection and delivery of therapeutic agents have been used in clinical trials for brain cancer and other neurodegenerative diseases. The complexity of transport pathways in tissue makes it difficult to envision therapeutic agent distribution from clinical MR images. Computer-assisted planning has been proposed to mitigate risk for inadequate delivery through quantitative understanding of infusion characteristics. We present results from human studies and simulations of intratumoral infusions of immunotoxins in glioblastoma patients. Gd-DTPA and 124I-labeled human serum albumin (124I-HSA) were co-infused with the therapeutic, and their distributions measured in MRI and PET. Simulations were created by modeling tissue fluid mechanics and physiology and suggested that reduced distribution of tracer molecules within tumor is primarily related to elevated loss rates computed from DCE. PET-tracer on the other hand shows that the larger albumin molecule had longer but heterogeneous residence times within the tumor. We found over two orders of magnitude variation in distribution volumes for the same infusion volumes, with relative error ~20%, allowing understanding of even anomalous infusions. Modeling and measurement revealed that key determinants of flow include infusion-induced expansion and loss through compromised BBB. Opportunities are described to improve computer-assisted CED through iterative feedback between simulations and imaging.

Ethnic variations in referrals to the Leicester memory and dementia assessment service, 2010 to 2017.

BACKGROUND: The incidence of dementia in Black, Asian and minority ethnic (BAME) groups is increasing in the UK, with concern about underdiagnosis and late presentation. AIMS: By reviewing referrals to memory clinics from Leicester City we examined whether the following differed by ethnicity: the proportion with a diagnosis of dementia, type of dementia and severity at presentation. METHOD: We examined referrals between 2010 and 2017: all those whose ethnicity was recorded as Black (n = 131) and a random sample of 260 Asian and 259 White British referrals. Severity of dementia was assessed by record review. Odds ratios (ORs) were adjusted for general practice, age, gender and year of referral. RESULTS: A diagnosis of dementia was recorded in 193 (74.5%) White British, 96 (73.3%) Black and 160 (61.5%) Asian referrals. Compared with Asians, White British had twice the adjusted odds of a dementia diagnosis (OR = 1.99 (1.23-3.22). Of those with dementia, Alzheimer's disease was more common in White British (57.0%) than in Asian (43.8%) and Black referrals (51.0%): adjusted OR White British versus Asian 1.76 (1.11-2.77). Of those with dementia, the proportion with moderate/severe disease was highest in White British (66.8%), compared with 61.9% in Asian and 45.8% in Black groups. The adjusted OR for the White versus Black groups was 2.03 (1.10-3.72), with no significant difference between Asian and White British groups. CONCLUSIONS: Differences in confirmed dementia suggest general practitioners have a lower threshold for referral for possible dementia in some BAME groups. Unlike other centres, we found no evidence of greater severity at presentation in Asian and Black groups.

What do we know about the health and health care of people with intellectual disabilities from minority ethnic groups in the United Kingdom? A systematic review.

BACKGROUND: People with from minority ethnic communities face inequalities in health and health care. This systematic review considers the question of what we know about the health and health care of children and adults with intellectual disabilities from ethnic minority communities in the UK. METHOD: Studies published from 1990 to 2018 were identified via electronic literature databases, email requests and cross-citations. Studies were reviewed narratively in relation to identified themes. RESULTS: Twenty-three studies were identified, most commonly focusing on South Asian communities. Very little information was identified on physical health or physical health care, with the identified evidence tending to focus on mental health care, access to specialist intellectual disability services, and inpatient services. CONCLUSION: Little is known about the health status of people with intellectual disabilities from minority ethnic groups in the UK. It is clear that they may experience barriers to accessing specialist intellectual disability services and other forms of health care.

Theory for acoustic streaming in soft porous matter and its applications to ultrasound-enhanced convective delivery.

This paper develops theory for bulk acoustic streaming in soft porous materials, with applications to biological tissue. The principal results of this paper are: (i) streaming equations for such porous media, which show interestingly significant differences from those that describe streaming in pure fluids; (ii) the Green functions obtained for these equations in isotropic, infinite media; and (iii) approximate evaluation of the sources in the streaming equations from acoustic wave forms often used, and the streaming velocities and particle trajectories resulting therefrom. People are now investigating acoustic enhancement of delivery of therapeutics such as drug molecules or other particulates, introduced directly into cellular tissue. A comparison of the predictions of the theory in this paper to available data is made and shown to be surprisingly good. Some macroscale effects of the ultrastructure of the tissue that are not contained in the current paper are pointed out for future studies.

Large-Volume Infusions into the Brain: A Comparative Study of Catheter Designs.

BACKGROUND/AIMS: "Whole-brain" infusions have emerged as a potential need with the promise of disease-modifying therapies for neurodegenerative diseases. In addition, several current clinical trials in brain cancer utilize direct delivery of drugs that are required to fill large volumes. Such requirements may not be well served by conventional single port catheters with their "point source" of delivery. Our aim is to examine infusions into large volumes of heterogeneous tissue, aiming for uniformity of distribution. METHODS: A porous catheter (porous brain infusion catheter, PBIC), designed by Twin Star TDS LLC, for brain infusions was developed for this study and compared with another convection-enhanced delivery catheter (SmartFlowTM NGS-NC-03 from MRI Interventions, a step end-port catheter, SEPC) in current use in clinical trials. The studies were in vivo in porcine brain. A total of 8 pigs were used: the size of the pig brain limited the porous length to 15 mm. The placements of the tips of the two catheters were chosen to be the same (at the respective brain hemispheres). RESULTS: The PBIC and SEPC both performed comparably and well, with the PBIC having some advantage in effecting larger distributions: p ∼ 0.045, with 5 infusions from each. CONCLUSIONS: Given the performance of the PBIC, it would be highly appropriate to use the device for therapeutic infusions in human clinical trials to assess its capability for large-volume infusions.

A pilot study in intraparenchymal therapy delivery in the prostate: a comparison of delivery with a porous needle vs standard needle.

BACKGROUND: New biologic therapies directly injected into the prostate are in clinical trials for prostatic diseases. There is a need to understand distribution of injected therapies as a function of prostatic anatomy, physiology, and device design. METHODS: A needle with a porous length of customizable-length was tested and its performance compared with a standard needle. Injections of magnetic resonance contrast reagent were placed into ex-vivo human prostates after surgical excision in standard of care therapy for invasive bladder cancer patients. Magnetic resonance images were acquired using sequences to quantify volume delivered, distributed, and backflow. RESULTS: Magnetic resonance images analysis revealed heterogeneity distribution with injection into the specimens. There was low resistance to flow along ductal pathways and high resistance to flow into glandular nodules and smooth muscle/fibrous parenchyma. Data confirm previous studies showing injection loss via urethra backflow, urethra, and prostatic ducts. Tissue fraction of dose was significantly higher with porous needle compared with standard needle (p = .03). We found that a greater volume of distribution divided by the amount infused (Vd/Vi) increased by 80% with the porous needle, though no statistically significant association due to small sample size. CONCLUSIONS: This study demonstrated that prostatic tissue is anatomically heterogenic and limits distribution of needle injection. There is greater distribution in the ex-vivo prostate using a porous needle. The complexity of intra prostatic flow pathways suggests preoperative imaging and pre-treatment planning will enhance therapy.

Calm child programme: Parental programme for anxiety in children and young people with autism spectrum disorder and intellectual disabilities.

Children with autism spectrum disorder (ASD) and intellectual disabilities (IDs) are more vulnerable to experiencing anxiety disorders. Parental involvement in intervention is crucial for successful management of the interventions in the population of people with ASDs. This article describes the design and evaluation of parenting programme for anxiety disorders in children and young people with ASD and ID. In phase 1 semi-structured interviews were conducted to explore management strategies for anxiety at home and in school settings. A total of 34 participants (14 parents, 20 teachers) participated in the interviews. A Delphi process was conducted with health professionals to develop consensus on appropriate anxiety interventions. In phase 2 the intervention programme was implemented by seven parents who also participated in focus group to evaluate the developed programme. A parental programme, calm child programme (CCP), was developed, implemented and evaluated. The evaluations show significant decrease in children's anxiety as a result of implementing the programme. This study contributes further evidence to parental involvement in interventions for children and young people with ASD and IDs. The CCP is a useful and cost-effective approach in enabling parents to provide anxiety interventions in a home setting.

A model for optimizing delivery of targeted radionuclide therapies into resection cavity margins for the treatment of primary brain cancers.

Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67Ga, 77Br, 111In, 125I, 123I, 193mPt, 195mPt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.

Theory of porous catheters and their applications in intraparenchymal infusions.

Multiport catheters and catheters with a porous surface have been proposed for intraparenchymal infusions of therapeutics in fluid suspensions. Target diseases include brain cancer and serious neurodegenerative diseases, as well as peripheral tumors, for example in the prostate and the liver. We set up the theory for infusions from such devices, in particular the fluid flow equations which demand a coupling between the flow within the catheter and that in tissue. (Such a coupling is not necessary in the theory of infusion from single port catheters.) The new feature of such catheters, treated by our model, is revealed by infusions into inhomogeneous media. Multiport designs have the potential to overcome the limitation of single port catheters, for which the path of the fluid leaving the port is dominated by the inhomogeneities. We solve these equations for some simple cases to illustrate the key design features of porous catheters that show such advantages. The mathematics required for numerical solution with more realistic assumptions is also developed. We confirm the robustness of such catheters, when the ports are sufficiently resistive, against leakage paths that would compromise the infusions from catheters with one or a few large ports. The methods of this paper can be incorporated into a larger planning system for intraparenchymal infusions involving such devices.

Delivering therapy to target: improving the odds for successful drug development.

The direct delivery of drugs and other agents into tissue (in contrast to systemic administration) has been used in clinical trials for brain cancer, neurodegenerative diseases and peripheral tumors. However, continuing evidence suggests that clinical efficacy depends on adequate delivery to a target. Inadequate delivery may have doomed otherwise effective drugs, through failure to distinguish drug inefficacy from poor distribution at the target. Conventional pretreatment clinical images of the patient fail to reveal the complexity and diversity of drug transport pathways in tissue. We discuss the richness of these pathways and argue that development and patient treatment can be sped up and improved by: using quantitative as well as 'real-time' imaging; customized simulations using data from that imaging; and device designs that optimize the drug-device combination.

The Relation between Catheter Occlusion and Backflow during Intraparenchymal Cerebral Infusions.

Background/Aims: The distribution of infusate into the brain by convection-enhanced delivery can be affected by backflow along the catheter shaft. This work assesses the following: (1) whether tissue coring and occlusion of the catheter lumen occurs when an open end-port catheter is inserted, (2) whether there is a relationship between intracatheter pressure and backflow, and (3) whether catheter occlusion increases backflow. Methods: Freshly excised monkey brains were used to assess tissue coring and its correlation with the behavior of the line pressure. In vivo infusions of gadolinium solution into monkey putamen at 1 µl/min were conducted with and without a stylet during insertion. The effect of flow during insertion was evaluated in vivo in the pig thalamus. MRI and line pressure were continuously monitored during in vivo infusions. Results: Ex vivo testing showed that open end-port insertions always cored tissue (which temporarily plugs the catheter tip) and increased pressure followed by a rapid fall after its expulsion. Catheter insertion with a stylet in place prevented coring but not flow insertion; neither affected backflow. Conclusion: Open end-port catheters occlude during insertion, which can be prevented by temporarily closing the port with a stylet but not by infusing while inserting. Backflow was not completely prevented by any insertion method. © 2015 S. Karger AG, Basel.

In vivo performance of a microfabricated catheter for intraparenchymal delivery.

BACKGROUND: Convection-enhanced delivery (CED) is currently the only effective clinical technique to deliver biological therapeutic agents that would otherwise not cross the blood-brain barrier. Despite the promise of CED, several technical problems have limited its effectiveness. NEW METHOD: Brain infusions into a large mammal (pig) were performed with a catheter that was fabricated using micro-electro-mechanical systems (MEMS) technology (Olbricht et al., 2010). The performance of the catheter was evaluated for infusions at increasing infusion rates. Magnetic resonance (MR) images were acquired in real time to examine the distribution of infused tracers in the parenchyma. RESULTS: Both backflow and the distribution of CED of infusates into a variety of cytoarchitectures in porcine brain were quantified. Concentration profiles were determined for several MR contrast reagents as well as a fluorescent dye that are the sizes of small molecules, therapeutic proteins and an adeno-associated virus (AAV). The reagents can serve as surrogates for assessing the convective distribution of active molecules. Infusion rates up to 20µL/min were attained without evidence of backflow along the catheter. COMPARISON WITH EXISTING METHODS: The device performed well in terms of both backflow and infusion, superior to that of many studies reported in the literature on other catheters. All infused molecules had comparable ratios of distribution to infusion volumes. CONCLUSIONS: The catheter described in this report appears able to target tissue structures with precision, deliver therapeutics at high infusion rates, and resist backflow that can compromise the efficacy of CED therapy. The technology allows development of "smart" catheters for future applications.