Mixed Protocol Research Articles

Could bipolar depressed patients respond better to rTMS than unipolar depressed patients? A naturalistic, observational study

Previous studies of rTMS for bipolar depressed (BD) patients have yielded mixed results. In this retrospective, naturalistic, observational study, we reviewed charts of 317 patients undergoing rTMS treatment between 1/2015–2/2018, yielding 283 unipolar depressed (UD) and 34 BD patients. All were treated with a figure-of-8 coil, with either high-frequency (HF) left-sided, sequential bilateral (HF left-sided and low-frequency right-sided), or mixed protocols (switched from unilateral to bilateral mid-course). Outcomes were the Generalized Anxiety Disorder scale (GAD-7) and Patient Health Questionnaire (PHQ-9). Total number of treatments and initial PHQ-9 scores did not differ between groups. BD patients had greater PHQ-9 change by treatment conclusion than UD patients. GAD-7 changes showed no between-group differences overall. PHQ-9 changes differences between groups were only seen with unilateral treatment, not with bilateral or mixed protocols. Unilateral treatment resulted in 45% remission (9/20) for BD patients vs. 15% (24/160) for UD patients by treatment end. Response was seen in 80% (16/20) of the unilaterally-treated BD patients vs. 39% (62/160) in UD patients. Regression analyses within BD patients found that unilateral treatment, use of non-lithium mood stabilizers, male sex, and number of treatments predicted PHQ-9 improvement.

An assessment of three methods for extracting bacterial DNA from beach sand

Beach water quality is regulated by faecal indicator bacteria levels, sand is not, despite known human health risk from exposure to beach sand. We compared the performance of three methods to extract bacterial DNA from beach sand as a step toward a standard method. The analytical sensitivity of quantitative polymerase chain reaction (qPCR) for Enterococcus was compared for the slurry (suspension, agitation, membrane filtration of supernatant), versus direct extraction using PowerSoil™ or PowerMax Soil™ kits. The slurry method had the lowest limit of detection at 20-80gene copiesg-1 , recovered significantly more DNA, and the only method that detected Enterococcus by qPCR in all samples; therefore, the only method used in subsequent experiments. The slurry method reflected the spatial variability of Enterococcus in individual transect samples. Mean recovery efficiency of the microbial source tracking marker HF183 from wastewater spiked marine and freshwater beach sand was 100.8% and 64.1%, respectively, but varied, indicating that the mixing protocol needs improvement. Among the three methods, the slurry method had the best analytical sensitivity and produced extracts that were useful for culture or molecular analysis. Standardization of methods for extraction of bacterial DNA from sand facilitates comparisons among studies, and ultimately contributes to the safety of recreational beaches.

Online synchronous chat counselling for young people aged 12–25: a mixed methods systematic review protocol

IntroductionYouth mental health is a global issue, with 75% of many serious mental health difficulties emerging before the age of 25. An increase in the popularity of online counselling for...

Successful Use of Anti-IL-6R Therapy to Achieve Cardiac Allograft Tolerance in Non-Human Primates

<h3>Purpose</h3> In contrast to kidney allografts, attempts to achieve tolerance of isolated cardiac allografts in non-human primates (NHPs) using a mixed chimerism strategy have been unsuccessful. IL-6 is a pro-inflammatory cytokine known to play an important role in allograft rejection. We investigated whether adding anti-IL-6R therapy to our mixed chimerism protocol would enable the induction of tolerance in NHP recipients of MHC mismatched heart allografts. <h3>Methods</h3> Ten cynomolgous NHPs underwent heart and bone marrow transplantation (BMTx) with non-myeloablative conditioning including total body and thymic irradiation, ATGAM, anti-CD154 mAb, and cyclosporine until post-operative day (POD) 28, with or without anti-IL-6R therapy (tocilizumab, 10 mg/kg IV on POD 0, 7, 14, 21, 28, 56, 84). Group A (n=2) received allogeneic BMTx without anti-IL-6R therapy, Group B (n=6) received allogeneic BMTx with anti-IL-6R therapy, and Group C (n=2) received autologous BMTx with anti-IL-6R therapy. <h3>Results</h3> In Group A, both recipients experienced allograft failure due to rejection on POD 104 and 132 [Table]. In Group B, 3 recipients achieved long-term cardiac allograft survival of >400 days off immunosuppression; one recipient is ongoing at POD 360. Two rejected on POD 169 and 383. For Groups A and B, peak lymphocyte chimerism was 10.1% and 18.1%, respectively and duration of lymphocyte chimerism was 57 and 178 days, respectively. In Group C, one recipient rejected on POD 131 and one is ongoing at POD 120. There was no significant difference in magnitude of peripheral T_reg expansion between groups (p=0.77). Compared to Group A, Groups B and C had lower CRP levels (mean 12.3 vs 54.3 μg/mL) and higher free serum IL-6 (mean 23.0 vs <7.7 pg/mL) while receiving anti-IL-6R therapy. <h3>Conclusion</h3> Tolerance of cardiac allografts has been achieved for the first time in NHPs using a combination of IL-6 signaling blockade and mixed chimerism. This approach represents significant progress towards clinical cardiac allograft tolerance.

Using mTOR Inhibitor Nanoimmunotherapy to Induce Cardiac Allograft Tolerance in Non-Human Primates

<h3>Purpose</h3> Though tolerance to kidney allografts has been consistently achieved using a mixed chimerism model, cardiac allografts remain resistant to tolerance induction. Lipoprotein-based nanobiologics loaded with a mammalian target of rapamycin inhibiting prodrug (mTOR inhibiting nanobiologics, mTORi-NBs) inhibit trained immunity and promote graft infiltrating M2-macrophages that provide a favorable local immunologic milieu for tolerance induction. In this study, we evaluate the ability of mTORi-NBs to induce tolerance in a cardiac allograft model in NHPs. <h3>Methods</h3> Six NHPs underwent simultaneous heterotopic heart and bone marrow transplantation for mixed chimerism induction. Group A (n=3) was conditioned with 3 Gy total body irradiation (TBI), 7 Gy thymic irradiation (TI), ATGAM, anti-CD40L monoclonal antibody on days 0, 2, 5,7, 9, and 12 post-bone marrow transplant (pBMTx), and cyclosporine until day 28 pBMTx. Group B recipients (n=3) underwent the same conditioning regimen with the addition of mTORi-NBs at a dose of 0.15 mg/kg on days 2, 5, 12, 19, and 26 pBMTx. Group B donors were also treated with a single dose of mTORi-NBs two days before transplant. <h3>Results</h3> In group A, all allografts had end stage rejection by day 175 pBMTx with a mean duration of lymphocyte chimerism of 74 days. The first recipient in group B developed durable full chimerism and mild graft versus host disease (GVHD) which resolved after a course of steroids and cyclosporine. After resolution of his GVHD, his graft continued beating strongly with no evidence of rejection through day 239 pBMTx. The second and third recipients received half dose (1.5 Gy) TBI and both allografts are contracting strongly at days 271 and 26 pBMTx, though the second recipient had some evidence of rejection at day 212 pBMTx. Currently, the mean duration of lymphocyte chimerism in Group B is 149 days. <h3>Conclusion</h3> Preliminary studies suggest that adding mTORi-NB nanoimmunotherapy to a mixed chimerism protocol prolongs both donor lymphocyte chimerism and heart graft survival in NHPs even when reducing pre-operative TBI.

Side Effects of Mixing Vaccines against COVID-19 Infection among Saudi Population.

Background: Mixing two different vaccines has been utilized to minimize the impact of any supply chain interruptions and to combat the COVID-19 pandemic in Saudi Arabia. We conducted this study to evaluate the side effects, if any, associated with the mixed vaccination approach. Methods: An online survey study was administered among COVID-19 vaccine recipients in Saudi Arabia. Symptoms post vaccination were assessed in 311 vaccinated participants with two matched doses of either Oxford–AstraZeneca or Pfizer–BioNTech vaccines, or two mixed doses, respectively. Results: After the second dose, around 31% of the matched vaccine group reported no symptoms, while only 6% of the mixed vaccine group reported no symptoms. Most of the side effects after the second dose associated with matched vaccines were injection site pain (46%), while the mixed vaccines group reported significantly more symptoms compared with the matched vaccine group, which included fever (41%), fatigue (66%), muscle pain (44%), chills (17%) and injection site pain (60%). Conclusion: The data suggest the overall safety of the mixed vaccination protocol; however, it might be associated with side effects such as fever, fatigue, muscle pain, chills, and injection site pain. Further studies with a larger cohort size could shed more light on this aspect, which would be imperative for deciding to utilize a mixed vaccination approach.

Exploring the barriers and enablers experienced by people with Cystic Fibrosis and their healthcare professionals in accessing, utilising and delivering maternity and Cystic Fibrosis care during the pre-conception to post-partum period: A mixed methods systematic review protocol.

Background Cystic Fibrosis (CF) is an autosomal recessive inherited multi-system disease that primarily affects the lungs and digestive system. New drug therapies and treatments are improving the lives of many people with CF. With improved life expectancy and increased quality of life, many people with CF are now contemplating parenthood and becoming pregnant, an aspiration that decades ago was almost unheard of. Given this quickly evolving and more positive health landscape, it is vital to understand how people with CF experience the care they receive whilst accessing and utilising fertility and maternity services. It is also important to explore the experiences of healthcare professionals involved in providing care during this period. The overall aim of the mixed-methods systematic review will be to explore the barriers and enablers experienced by people with CF and the healthcare professionals involved in their care in the pre-conception to post-partum period. Methods The proposed review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for convergent integrated mixed methods systematic reviews. A systematic search of Medline (Ebsco), Cinahl, Embase, APA PsychINFO and Cochrane Library from inception to February 2022 will be conducted. Quantitative, qualitative and mixed methods studies pertaining to the experience of pre-conception to post-partum care for people with CF and their healthcare professionals will be included. Two independent reviewers will screen titles, abstracts and full texts with disagreements being resolved by a third reviewer. Conclusion This review will help to determine the potential barriers and facilitators experienced by people with Cystic Fibrosis and the health care professionals involved in their care during the pre-conception to post-partum period. The results will be of benefit specifically to the CF population and their healthcare providers when planning further studies in the area of fertility and pregnancy for this population and when delivering care.

Healthcare system resilience in Bangladesh\xa0and Haiti in times of global changes (climate-related events, migration and Covid-19): an interdisciplinary mixed method research protocol

BackgroundSince climate change, pandemics and population mobility are challenging healthcare systems, an empirical and integrative research to studying and help improving the health systems resilience is needed. We present an interdisciplinary and mixed-methods research protocol, ClimHB, focusing on vulnerable localities in Bangladesh and Haiti, two countries highly sensitive to global changes. We develop a protocol studying the resilience of the healthcare system at multiple levels in the context of climate change and variability, population mobility and the Covid-19 pandemic, both from an institutional and community perspective.MethodsThe conceptual framework designed is based on a combination of Levesque’s Health Access Framework and the Foreign, Commonwealth and Development Office’s Resilience Framework to address both outputs and the processes of resilience of healthcare systems. It uses a mixed-method sequential exploratory research design combining multi-sites and longitudinal approaches. Forty clusters spread over four sites will be studied to understand the importance of context, involving more than 40 healthcare service providers and 2000 households to be surveyed. We will collect primary data through questionnaires, in-depth and semi-structured interviews, focus groups and participatory filming. We will also use secondary data on environmental events sensitive to climate change and potential health risks, healthcare providers’ functioning and organisation. Statistical analyses will include event-history analyses, development of composite indices, multilevel modelling and spatial analyses.DiscussionThis research will generate inter-disciplinary evidence and thus, through knowledge transfer activities, contribute to research on low and middle-income countries (LMIC) health systems and global changes and will better inform decision-makers and populations.

Assessing Determinants of Programmatic Performance of Community Management of Malaria, Pneumonia, and Diarrhea in Children in Africa: Protocol and Data Collection for a Mixed Methods Evaluation of Integrated Community Case Management.

BackgroundIntegrated community case management (iCCM) is a child health program designed to provide integrated community-based care for children with pneumonia, malaria, or diarrhea in hard-to-reach areas of low- and middle-income countries. The foundation of the intervention is service delivery by community health workers (CHWs) who depend on reliable provision of drugs and supplies, consistent supervision, comprehensive training, and community acceptance and participation to perform optimally. The effectiveness of the program may also depend on a number of other elements, including an enabling policy environment, financing mechanisms from the national to the local level, data transmission systems, and appropriate monitoring and evaluation. The extent to which these factors act upon each other to influence the effectiveness and viability of iCCM is both variable and challenging to assess, especially across different implementation contexts.ObjectiveIn this paper, we describe a mixed methods systems-based study protocol to assess the programmatic components of iCCM that are associated with intervention effectiveness and report preliminary results of data collection.MethodsThis protocol uses a mixed qualitative and quantitative study design based on a systems thinking approach within four iCCM programs in Malawi, Democratic Republic of the Congo, and Niger State and Abia State in Nigeria. Routine monitoring data are collected to determine intervention effectiveness, namely testing, treatment, and referral outcomes. Surveys with CHWs, supervisors, and caregivers are performed to collect quantitative data on their demographics, activities, and experiences within the program and how these relate to the areas of intervention effectiveness. Focus group discussions are conducted with these stakeholders as well as local traditional leaders to contextualize these data. Key informant interviews are undertaken with national- and district-level program stakeholders and officers knowledgeable in critical program processes.ResultsWe performed 3836 surveys and 45 focus group discussions of 379 participants with CHWs, supervisors, caregivers, and traditional leaders, as well as 120 key informant interviews with district- and national-level program managers, health officers, and ministry officials. Policy and program documents were additionally collected for review.ConclusionsWe expect that evidence from this study will inform child health programs and practice in low- and middle-income settings as well as future policy development within the iCCM intervention.International Registered Report Identifier (IRRID)DERR1-10.2196/33076

Improvement of spatial resolution of elemental imaging using laser ablation-ICP-mass spectrometry.

Laser ablation-ICP-mass spectrometer (LA-ICPMS) now becomes one of the most principal analytical technique for mapping analysis for major to trace elements in rocks, minerals, functional materials, or biological tissue samples. In this study, imaging analysis was conducted with coupling of small volume cell and off-set laser ablation protocol to improve the spatial resolution. Combination of newly designed small volume cell and in-torch gas mixing protocols provides faster washout time of the signals (about 0.8s for reducing 238U being one part in a hundred, 1% level). This is very important to improve the spatial resolution in a direction of laser scanning. Moreover, combination of small distances between the laser-line scan (laser pitch distance) and preferential and total ablation of only biological tissue samples placed on glass substrate results in laser ablation of smaller areas than the size of laser ablation pit (shaving ablation). With the shaving ablation, laser-line scanning with narrower-band width (e.g., 2µm) can be achieved even by the laser beam of 8µm diameter. To demonstrate the practical usage of the present technique, imaging analysis of Gd-ethylenediamine tetra-methylene phosphonic acid-doped mouse bone was conducted. Preferential distribution of Gd at the edge of the apatite cell was more clearly identified by the present technique. Combination of the shorter washout system setup and the shaving ablation protocol enables us to improve the spatial resolution of the elemental imaging obtained with the LA-ICPMS technique.

5G-IPAKA: An Improved Primary Authentication and Key Agreement Protocol for 5G Networks

The 3rd generation partnership project (3GPP) has been enhancing the security of the 5G AKA (authentication and key agreement) protocol. However, there may still be some shortcomings in the latest version of the 5G AKA protocol. According to the analysis of the latest version of the 5G AKA protocol, this paper points out seven of its shortcomings. To overcome these shortcomings, an improved primary authentication and key agreement protocol for 5G networks is proposed, which is named 5G-IPAKA. Compared with the latest version of the 5G AKA protocol, the main improvements include that the pre-shared key between the user equipment (UE) and the home network (HN) is replaced with a derivation key as the pre-shared key, the challenge-–response mechanism for the serving network (SN) is added, the mutual authentication and key confirmation occurs between the UE and the SN, and the message authentication code (MAC) failure procedure is replaced with a timeout mechanism on the HN. Then, the 5G-IPAKA protocol is proven secure in the mixed strand space model for mixed protocols. Further discussion and comparative analysis show that the 5G-IPAKA protocol can overcome the above shortcomings of the latest version of the 5G AKA protocol, and is better than the recently improved 5G AKA protocols. Additionally, the 5G-IPAKA protocol is efficient and backward-compatible.

Perceptions, representations and logics of action of urinary incontinence in institutionalised elderly people: a concurrent mixed study protocol

IntroductionUrinary incontinence (UI) is a major public health problem. It affects many institutionalised elderly people. In the literature, the phenomenon is well defined. Its frequency, risk factors, individual and social...

Does dual task merged in a mixed physical exercise protocol impact the mobility under dual task conditions in mild impaired stroke survivors? A feasibility, safety, randomized, and controlled pilot trial

Purpose To investigate the feasibility, safety, and effects of dual task (DT) in a mixed physical exercise protocol on mobility under DT in stroke survivors. Materials and methods Twenty-six chronic mild-impaired stroke survivors (age 51.57 ± 12.55; men= 13, women= 13) were randomly assigned into Experimental Group participating in a 15-week mixed (aerobic and resistance exercises performing a cognitive DT condition simultaneously) physical exercise protocol (30 sessions, 2x/week, duration of 60–90 min), and Control Group engaged in the same protocol without DT. Feasibility and outcome measures were assessed before and after the intervention and in a 5-week follow-up. Results DT physical exercise protocol was viable and safe. This protocol also improved mobility and gait when performed under DT, which was not found in the control group. DT does not influence aerobic resistance, strength, and balance responsiveness. It does not present any improvement in cognition, self-efficacy for falls, and quality of life. Conclusion The results indicate that mixed physical exercise under DT is feasible and safe for mild-impaired stroke survivors. Stroke survivors demonstrate more significant improvement in the mobility performance under DT when submitted to a DT mixed physical exercise protocol than the standard physical exercise intervention. Trial registration Brazilian clinical trials registry (RBR-4mvzz6); WHO trial record (U1111-1198-7173) IMPLICATIONS FOR REHABILITATION DT training can be prescribed by using clear and precise parameters for stroke survivors. Physical Exercise without DT requirements did not improve mobility performing and cognitive tasks simultaneously in stroke survivors. Clinicians are encouraged to incorporate DT requirements into the exercise routines to enhance mobility under DT to mild-moderate stroke survivors.

Development of strategies to promote healthy sexuality based on Iranian girls perspective about the role of virginity in the construction of their sexuality: an explanatory sequential mixed method study protocol

BackgroundThe modern Iran is a blend of tradition and modernity, but its dominant culture is still traditional and takes pride in female virginity. On the other hand, the influential factors such as modernity, education, social networks, global communication, influence from advanced Western societies, have obviously led to the emergence of a freer sexual attitude associated with less significance of virginity. Since the traditional, cultural and religious significance of virginity among Iranian girls can shape their sexual behaviors, therefore, the aim of the present study is development of strategies to promote healthy sexuality based on Iranian girls perspective about the role of virginity in the construction of their sexuality.Methods/designThis is a two-stage study; an explanatory sequential mixed-methods follow-up design will be employed in the first stage, which consists of two quantitative and qualitative phases. The first phase is the cross-sectional survey that will be conducted on 700 single girls born in the 1970s, 1980s and 1990s. The sample will be selected using the cluster sampling method in the health centers of Tabriz-Iran. The determined sample size will be divided among the selected health centers based on the quota criterion, and eligible households will be selected randomly from the said centers using the SIB website (sib.tbzmed.ac.ir). To collect the required data in the quantitative phase, we will use a researcher-made questionnaire to evaluate the girls’ views about virginity and its influential factors, designed based on the theory of “social construction of sexuality”. After quantitative data collection and analysis, the findings inform qualitative data collection and analysis. The qualitative phase of the study will be conducted on girls living in Tabriz using in-depth and semi-structured individual interviews and purposive sampling method to collect the required qualitative data. The collected data will be analyzed using the conventional content analysis approach. The findings of two phase will be integrated for further explanation and interpretation to be used in the second stage. In the second phase of this study, a nominal group meeting will be held with the participation of reproductive and sexual health experts. The strategies extracted from the results of the first phase and review the texts in this meeting will be provided to experts and after receiving the opinions and ideas of the relevant group of experts and prioritizing them, appropriate strategies to improve and promote the healthy sexuality of Iranian girls will be presented.DiscussionThis study is one of the few studies conducted in the field of sexual health and culture in Iran, that using a “mixed-methods” approach to determine and explain the role of virginity in the construction of the sexuality from the Iranian girls perspective. We hope that this study can present evidence-based documents from the latest physical, psychological and social developments in young Iranian girls’ sexuality and that the presented healthy sexuality promotion strategies, which will be based on Iranian socio-cultural developments, can provide the basic information required for policy-making and planning for young girls’ sexual health. It is also hoped that the findings of this study will be useful in culture-based sexuality education and support for reproductive and sexual health care for the young Iranian generation.

Architecture- and Composition-Controlled Self-Assembly of Block Copolymers and Binary Mixtures With Crosslinkable Components: Chain Exchange Between Block Copolymer Nanoparticles.

Chain exchange behaviors in self-assembled block copolymer (BCP) nanoparticles (NPs) at room temperature are investigated through observations of structural differences between parent and binary systems of BCP NPs with and without crosslinked domains. Pairs of linear diblock or triblock, and branched star-like polystyrene-poly(2-vinylpyridine) (PS-PVP) copolymers that self-assemble in a PVP-selective mixed solvent into BCP NPs with definite differences in size and self-assembled morphology are combined by diverse mixing protocols and at different crosslinking densities to reveal the impact of chain exchange between BCP NPs. Clear structural evolution is observed by dynamic light scattering and AFM and TEM imaging, especially in a blend of triblock + star copolymer BCP NPs. The changes are ascribed to the chain motion inherent in the dynamic equilibrium, which drives the system to a new structure, even at room temperature. Chemical crosslinking of PVP corona blocks suppresses chain exchange between the BCP NPs and freezes the nanostructures at a copolymer crosslinking density (CLD) of ∼9%. This investigation of chain exchange behaviors in BCP NPs having architectural and compositional complexity and the ability to moderate chain motion through tailoring the CLD is expected to be valuable for understanding the dynamic nature of BCP self-assemblies and diversifying the self-assembled structures adopted by these systems. These efforts may guide the rational construction of novel polymer NPs for potential use, for example, as drug delivery platforms and nanoreactors.

HALO: Study protocol for a single-case experimental design study evaluating the moderating impact of a befriending intervention on the association between loneliness and health in older adults.

Background: Loneliness in later life is often addressed with befriending interventions, yet evidence for their effectiveness is limited. Meanwhile it is known that loneliness has a deleterious impact on health. The aim of the study is to evaluate whether a befriending service for older adults mitigates the impact of loneliness on health outcomes, and to identify mechanisms through which befriending interventions might impact upon health. Methods: A mixed methods design is used. The quantitative component utilises an AB single-case experimental design, to gather intensive longitudinal data. These data will be analysed using a generalised additive modelling approach. The qualitative component of the study uses semi-structured dyadic interviews, structured and analysed according to the principles of constructivist grounded theory. Findings will then be triangulated according to an existing mixed methods integration protocol. Discussion: This mixed methods design has the potential to inform national and international policy in relation to befriending interventions for older adults. In addition, there is the potential for study results to inform our theoretical understanding of the nature of the relationship between loneliness and health. Trial registration: ClinicalTrials.gov identifier NCT04301167 (10 th March 2020). Protocol version 1.1, 26 th June 2020.

HALO: Study protocol for a single-case experimental design study evaluating the moderating impact of a befriending intervention on the association between loneliness and health in older adults

Background: Loneliness in later life is often addressed with befriending interventions, yet evidence for their effectiveness is limited. Meanwhile it is known that loneliness has a deleterious impact on health. The aim of the study is to evaluate whether a befriending service for older adults mitigates the impact of loneliness on health outcomes, and to identify mechanisms through which befriending interventions might impact upon health. Methods: A mixed methods design is used. The quantitative component utilises an AB single-case experimental design, to gather intensive longitudinal data. These data will be analysed using a generalised additive modelling approach. The qualitative component of the study uses semi-structured dyadic interviews, structured and analysed according to the principles of constructivist grounded theory. Findings will then be triangulated according to an existing mixed methods integration protocol. Discussion: This mixed methods design has the potential to inform national and international policy in relation to befriending interventions for older adults. In addition, there is the potential for study results to inform our theoretical understanding of the nature of the relationship between loneliness and health. Trial registration: ClinicalTrials.gov identifier NCT04301167 (10 th March 2020). Protocol version 1.1, 26 th June 2020.

A Nurse Practitioner service designed to address the health needs of children living in housing instability: A non-randomised, concurrent mixed methods study protocol.

The study uses a concurrent mixed- method design where both qualitative and quantitative data are collected during the same period (between January 2021 and March 2022 as per the funding timeline). The concurrent mixed-method design will collect data from: A comprehensive assessment tool used by the Nurse Practitioner to evaluate the child accessing specialist homeless services, which assess their mental, physical and social health needs. Documentation about the child's referral needs and uptake by disadvantage families. Interviews with housing insecure families, and staff/managers of the specialist homeless service. A review of Nurse Practitioner case notes. Surveys of families with children accessing the Nurse Practitioner service. Addressing the childhood impacts of family homelessness is of global importance. Structural equation modelling, from the surveys and in-depth health assessments along with the thematic analysis of the interviews with parents and staff/managers provide an understanding of the relationships between referral uptake and variables such as education, homelessness and transport accessibility. Investigating the enablers and barriers to the usual health access and our extended referral uptake impacted by family homelessness enables a better understanding of the current health gaps. Just over one fifth of Australian children live with their families in some form of housing instability including homelessness. These children, aged from birth to 18years, are often disconnected from health and similar social institutions, making them an underserviced population. Our research investigates a Nurse Practitioner services that helps reconnect children with services to help avoid poor long-term health outcomes.

Planning implementation and scale-up of physical activity interventions for people with walking difficulties: study protocol for the process evaluation of the ComeBACK trial

BackgroundThere is currently little evidence of planning for real-world implementation of physical activity interventions. We are undertaking the ComeBACK (Coaching and Exercise for Better Walking) study, a 3-arm hybrid Type 1 randomised controlled trial evaluating a health coaching intervention and a text messaging intervention. We used an implementation planning framework, the PRACTical planning for Implementation and Scale-up (PRACTIS), to guide the process evaluation for the trial. The aim of this paper is to describe the protocol for the process evaluation of the ComeBACK trial using the framework of the PRACTIS guide.MethodsA mixed methods process evaluation protocol was developed informed by the Medical Research Council (MRC) guidance on process evaluations for complex interventions and the PRACTIS guide. Quantitative data, including participant questionnaires, health coach and administrative logbooks, and website and text message usage data, is being collected over the trial period. Semi-structured interviews and focus groups with trial participants, health coaches and health service stakeholders will explore expectations, factors influencing the delivery of the ComeBACK interventions and potential scalability within existing health services. These data will be mapped against the steps of the PRACTIS guide, with reporting at the level of the individual, provider, organisational and community/systems. Quantitative and qualitative data will elicit potential contextual barriers and facilitators to implementation and scale-up. Quantitative data will be reported descriptively, and qualitative data analysed thematically.DiscussionThis process evaluation integrates an evaluation of prospective implementation and scale-up. It is envisaged this will inform barriers and enablers to future delivery, implementation and scale-up of physical activity interventions. To our knowledge, this is the first paper to describe the application of PRACTIS to guide the process evaluation of physical activity interventions.Trial registrationAustralian and New Zealand Clinical Trials Registry (ANZCTR) Registration date: 10/12/2018.

Chimerism-Based Tolerance to Kidney Allografts in Humans: Novel Insights and Future Perspectives

Chronic rejection and immunosuppression-related toxicity severely affect long-term outcomes of kidney transplantation. The induction of transplantation tolerance – the lack of destructive immune responses to a transplanted organ in the absence of immunosuppression – could potentially overcome these limitations. Immune tolerance to kidney allografts from living donors has been successfully achieved in humans through clinical protocols based on chimerism induction with hematopoietic cell transplantation after non-myeloablative conditioning. Notably, two of these protocols have led to immune tolerance in a significant fraction of HLA-mismatched donor-recipient combinations, which represent the large majority of cases in clinical practice. Studies in mice and large animals have been critical in dissecting tolerance mechanisms and in selecting the most promising approaches for human translation. However, there are several key differences in tolerance induction between these models and humans, including the rate of success and stability of donor chimerism, as well as the relative contribution of different mechanisms in inducing donor-specific unresponsiveness. Kidney allograft tolerance achieved through durable full-donor chimerism may be due to central deletion of graft-reactive donor T cells, even though mechanistic data from patient series are lacking. On the other hand, immune tolerance attained with transient mixed chimerism-based protocols initially relies on Treg-mediated suppression, followed by peripheral deletion of donor-reactive recipient T-cell clones under antigenic pressure from the graft. These conclusions were supported by data deriving from novel high-throughput T-cell receptor sequencing approaches that allowed tracking of alloreactive repertoires over time. In this review, we summarize the most important mechanistic studies on tolerance induction with combined kidney-bone marrow transplantation in humans, discussing open issues that still need to be addressed and focusing on techniques developed in recent years to efficiently monitor the alloresponse in tolerance trials. These cutting-edge methods will be instrumental for the development of immune tolerance protocols with improved efficacy and to identify patients amenable to safe immunosuppression withdrawal.