The unnecessary use of short tandem repeat testing on bone marrow samples in patients after 1 year following allogeneic hematopoietic stem cell transplant.

OBJECTIVES: To determine whether the information provided by short tandem repeat (STR) testing and bone marrow (BM) biopsy specimens following hematopoietic stem cell transplant (HSCT) provides redundant information, leading to test overutilization, without additional clinical benefit. METHODS: Cases with synchronous STR and flow cytometric immunophenotyping (FCI) testing, as part of the BM evaluation, were assessed for STR/FCI concordance. RESULTS: Of 1199 cases (410 patients), we found the overall concordance between STR and FCI was 93%, with most cases (1063) classified as STR-/FCI-. Of all discordant cases, 75 (6%) were STR+/FCI-, with only 5 (6.7%) cases best explained as identification of disease relapse. Eight cases were STR-/FCI+, representing relapsed/residual disease. Analysis of cases 1 year or more from transplant (54% of all cases) indicated only 9 (1.5%) were STR+/FCI-, and none uniquely identified relapse. CONCLUSIONS: These data suggest that STR analysis performed 1 year or more post-HSCT does not identify unknown cases of relapse. Furthermore, while STR testing is critical for identifying graft failure/rejection within the first year posttransplant, FCI appears superior to STR at detecting late relapses with low-level disease. Therefore, STR testing from patients 1 year or more post-HSCT may be unnecessary, as BM biopsy evaluation is sufficient to identify disease relapse.

Clinical Considerations and Outcomes of Robotic Urologic Surgery in Obese Patients.

Obesity is associated with many significant physiological changes. These considerations are important to surgery, especially in urological procedures. Obese patients often undergo surgical procedures and are at higher risk of complications. This investigation reviews physiological and anaesthesia considerations for obese and morbidly obese patients. In addition, urological surgeries and procedures should be considered for these higher risk patients. Clinical anaesthesiologists must use detailed assessment and, when appropriate, consultation in developing safe anaesthesia plans for these patients. Newer technologies have improved safety related to airway management, advanced airway devices, and regional anaesthesia with ultrasound-guided nerve blocks, which can reduce the need for opioids postoperatively. Recent developments in drug and monitoring technologies have also been developed and can be effective for obese and morbidly obese patients undergoing urological procedures and perioperative surgery, thus improving the likelihood of safety in this higher risk population.

Moving from development to implementation of digital innovations within the NHS: myHealthE, a remote monitoring system for tracking patient outcomes in child and adolescent mental health services.

Objective: This paper aims to report our experience of developing, implementing, and evaluating myHealthE (MHE), a digital innovation for Child and Adolescents Mental Health Services (CAMHS), which automates the remote collection and reporting of Patient-Reported Outcome Measures (PROMs) into National Health Services (NHS) electronic healthcare records. Methods: We describe the logistical and governance issues encountered in developing the MHE interface with patient-identifiable information, and the steps taken to overcome these development barriers. We describe the application's architecture and hosting environment to enable its operability within the NHS, as well as the capabilities needed within the technical team to bridge the gap between academic development and NHS operational teams. Results: We present evidence on the feasibility and acceptability of this system within clinical services and the process of iterative development, highlighting additional functions that were incorporated to increase system utility. Conclusion: This article provides a framework with which to plan, develop, and implement automated PROM collection from remote devices back to NHS infrastructure. The challenges and solutions described in this paper will be pertinent to other digital health innovation researchers aspiring to deploy interoperable systems within NHS clinical systems.

Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.

AIMS: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: A 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.

Examining the acceptability of actigraphic devices in children using qualitative and quantitative approaches: protocol for a systematic review and meta-analysis.

INTRODUCTION: Actigraphy is commonly used to record free living physical activity in both typically and atypically developing children. While the accuracy and reliability of actigraphy have been explored extensively, research regarding young people's opinion towards these devices is scarce. This review aims to identify and synthesise evidence relating to the acceptability of actigraphic devices in 5-11 year olds. METHODS AND ANALYSIS: Database searches will be applied to Embase, MEDLINE, PsychInfo and Social Policy and Practice through the OVID interface; and Education Resources Information Center (ERIC), British Education Index and CINAHL through the EBSCO interface from January 2018 until February 2023. Supplementary forward and backward citation and grey literature database searches, including Healthcare Management Information Consortium (HMIC) and PsycEXTRA will be conducted. Qualitative and quantitative studies, excluding review articles and meta-analyses, will be eligible, without date restrictions. Article screening and data extraction will be undertaken by two review authors and disagreements will be deferred to a third reviewer. The primary outcome, actigraphic acceptability, will derive from the narrative synthesis of the main themes identified from included qualitative literature and pooled descriptive statistics relating to acceptability identified from quantitative literature. Subgroup analyses will determine if acceptability changes as a function of the key participant and actigraphic device factors. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review as it uses data from previously published literature. The results will be presented in a manuscript and published in a peer review journal and will be considered alongside a separate stream of codesign research to inform the development of a novel child-worn actigraphic device. PROSPERO REGISTRATION NUMBER: CRD42021232466.

Clinical recommendations for posttransplant assessment of anti-HLA (Human Leukocyte Antigen) donor-specific antibodies: A Sensitization in Transplantation: Assessment of Risk consensus document.

Although anti-HLA (Human Leukocyte Antigen) donor-specific antibodies (DSAs) are commonly measured in clinical practice and their relationship with transplant outcome is well established, clinical recommendations for anti-HLA antibody assessment are sparse. Supported by a careful and critical review of the current literature performed by the Sensitization in Transplantation: Assessment of Risk 2022 working group, this consensus report provides clinical practice recommendations in kidney, heart, lung, and liver transplantation based on expert assessment of quality and strength of evidence. The recommendations address 3 major clinical problems in transplantation and include guidance regarding posttransplant DSA assessment and application to diagnostics, prognostics, and therapeutics: (1) the clinical implications of positive posttransplant DSA detection according to DSA status (ie, preformed or de novo), (2) the relevance of posttransplant DSA assessment for precision diagnosis of antibody-mediated rejection and for treatment management, and (3) the relevance of posttransplant DSA for allograft prognosis and risk stratification. This consensus report also highlights gaps in current knowledge and provides directions for clinical investigations and trials in the future that will further refine the clinical utility of posttransplant DSA assessment, leading to improved transplant management and patient care.

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report.

The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical testing, highlights gaps in current knowledge, and proposes areas for further research to enhance histocompatibility testing in support of solid organ transplantation. This report provides updates on topics discussed by the previous Sensitization in Transplantation: Assessment of Risk working groups and introduces 2 areas of exploration: non-human leukocyte antigen antibodies and utilization of human leukocyte antigen antibody testing measurement to evaluate the efficacy of antibody-removal therapies.

Assessing the feasibility of a web-based outcome measurement system in child and adolescent mental health services - myHealthE a randomised controlled feasibility pilot study.

BACKGROUND: Interest in internet-based patient reported outcome measure (PROM) collection is increasing. The NHS myHealthE (MHE) web-based monitoring system was developed to address the limitations of paper-based PROM completion. MHE provides a simple and secure way for families accessing Child and Adolescent Mental Health Services to report clinical information and track their child's progress. This study aimed to assess whether MHE improves the completion of the Strengths and Difficulties Questionnaire (SDQ) compared with paper collection. Secondary objectives were to explore caregiver satisfaction and application acceptability. METHODS: A 12-week single-blinded randomised controlled feasibility pilot trial of MHE was conducted with 196 families accessing neurodevelopmental services in south London to examine whether electronic questionnaires are completed more readily than paper-based questionnaires over a 3-month period. Follow up process evaluation phone calls with a subset (n = 8) of caregivers explored system satisfaction and usability. RESULTS: MHE group assignment was significantly associated with an increased probability of completing an SDQ-P in the study period (adjusted hazard ratio (HR) 12.1, 95% CI 4.7-31.0; p = <.001). Of those caregivers' who received the MHE invitation (n = 68) 69.1% completed an SDQ using the platform compared to 8.8% in the control group (n = 68). The system was well received by caregivers, who cited numerous benefits of using MHE, for example, real-time feedback and ease of completion. CONCLUSIONS: MHE holds promise for improving PROM completion rates. Research is needed to refine MHE, evaluate large-scale MHE implementation, cost effectiveness and explore factors associated with differences in electronic questionnaire uptake.

A Primer on Chimerism Analysis: A Straightforward, Thorough Review.

Short tandem repeat (STR) analysis to assess chimerism is a critical aspect of routine care particularly in patients facing stem cell transplants but is also relevant in other clinical scenarios. STR analysis provides a means to assess donor and recipient cellular origins in a patient, and, as such, can inform engraftment, rejection, and relapse status in stem cell transplant recipients. In this review of STR testing, the most commonly used method to assess chimerism, its background, procedural details, and clinical utility are discussed.

Clinical correlates of early onset antipsychotic treatment resistance.

BACKGROUND: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. AIM: This study investigates sociodemographic and clinical correlates of early onset of TRS. METHOD: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. RESULTS: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). CONCLUSION: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

A predictor model of treatment resistance in schizophrenia using data from electronic health records.

OBJECTIVES: To develop a prognostic tool of treatment resistant schizophrenia (TRS) in a large and diverse clinical cohort, with comprehensive coverage of patients using mental health services in four London boroughs. METHODS: We used the Least Absolute Shrinkage and Selection Operator (LASSO) for time-to-event data, to develop a risk prediction model from the first antipsychotic prescription to the development of TRS, using data from electronic health records. RESULTS: We reviewed the clinical records of 1,515 patients with a schizophrenia spectrum disorder and observed that 253 (17%) developed TRS. The Cox LASSO survival model produced an internally validated Harrel's C index of 0.60. A Kaplan-Meier curve indicated that the hazard of developing TRS remained constant over the observation period. Predictors of TRS were: having more inpatient days in the three months before and after the first antipsychotic, more community face-to-face clinical contact in the three months before the first antipsychotic, minor cognitive problems, and younger age at the time of the first antipsychotic. CONCLUSIONS: Routinely collected information, readily available at the start of treatment, gives some indication of TRS but is unlikely to be adequate alone. These results provide further evidence that earlier onset is a risk factor for TRS.

The patient with obesity and super-super obesity: Perioperative anesthetic considerations.

Obesity is associated with increased morbidity and mortality related to many complex physiologic changes and the rise worldwide has had far ranging implications in healthcare. According to the World Health Organization, over 2.8 million people die each year from being overweight or obese. Patients who are obese often need surgical procedures or interventional pain procedures and are at higher risk of complications. Patients with super-super obesity are those with body mass index greater than 60 kg/m2 and are at even greater risk for complications. The present investigation reviews epidemiology, pathophysiology, and anesthesia considerations for best practice strategies in managing these higher risk patients. Clinical anesthesiologists must utilize careful assessment and consultation in developing safe anesthesia plans. Improvements in technology have advanced safety with regard to airway management with advanced airway devices and in regional anesthesia with ultrasound-guided nerve blocks that can provide increased flexibility in formulating a safe anesthetic plan. As well, newer drugs and monitors have been developed for perioperative use to enhance safety in patients with obesity.

Atypical action updating in a dynamic environment associated with adolescent obsessive-compulsive disorder.

BACKGROUND: Computational research had determined that adults with obsessive-compulsive disorder (OCD) display heightened action updating in response to noise in the environment and neglect metacognitive information (such as confidence) when making decisions. These features are proposed to underlie patients' compulsions despite the knowledge they are irrational. Nonetheless, it is unclear whether this extends to adolescents with OCD as research in this population is lacking. Thus, this study aimed to investigate the interplay between action and confidence in adolescents with OCD. METHODS: Twenty-seven adolescents with OCD and 46 controls completed a predictive-inference task, designed to probe how subjects' actions and confidence ratings fluctuate in response to unexpected outcomes. We investigated how subjects update actions in response to prediction errors (indexing mismatches between expectations and outcomes) and used parameters from a Bayesian model to predict how confidence and action evolve over time. Confidence-action association strength was assessed using a regression model. We also investigated the effects of serotonergic medication. RESULTS: Adolescents with OCD showed significantly increased learning rates, particularly following small prediction errors. Results were driven primarily by unmedicated patients. Confidence ratings appeared equivalent between groups, although model-based analysis revealed that patients' confidence was less affected by prediction errors compared to controls. Patients and controls did not differ in the extent to which they updated actions and confidence in tandem. CONCLUSIONS: Adolescents with OCD showed enhanced action adjustments, especially in the face of small prediction errors, consistent with previous research establishing 'just-right' compulsions, enhanced error-related negativity, and greater decision uncertainty in paediatric-OCD. These tendencies were ameliorated in patients receiving serotonergic medication, emphasising the importance of early intervention in preventing disorder-related cognitive deficits. Confidence ratings were equivalent between young patients and controls, mirroring findings in adult OCD research.

Intravenous vitamin C administration to patients with septic shock: a pilot randomised controlled trial.

BACKGROUND: Intravenous vitamin C administration in septic shock may have a sparing effect on vasopressor requirements, and vitamin C's enzyme cofactor functions provide a mechanistic rationale. Our study aimed to determine the effect of intravenous vitamin C administration on vasopressor requirements and other outcomes in patients with septic shock. METHODS: This was a double-blind, randomised placebo-controlled trial in 40 patients with septic shock who were randomised (1:1) to receive intravenous vitamin C (at a dose of 25 mg/kg of body weight every 6 h) or placebo (intravenous 5% dextrose) for up to 96 h, or until death or discharge. The primary outcome was intravenous vasopressor requirements (dose and duration), and secondary outcomes included Sequential Organ Failure Assessment (SOFA) scores, intensive care unit (ICU) and hospital length of stay, and mortality. In addition, blood samples were collected to determine vitamin C kinetics and inflammatory marker concentrations. RESULTS: Median plasma vitamin C concentrations were deficient at baseline (9.2 [4.4, 12] µmol/L) and increased to 408 (227, 560) µmol/L following 72 h of intervention. The mean duration of intravenous vasopressor infusion in the vitamin C group was 48 (95% CI 35-62) hours and in the placebo group was 54 (95% CI 41-62) hours (p = 0.52). The dose of vasopressor delivered over time was comparable between the two groups, as were SOFA scores (p > 0.05). The median ICU length of stay in the intervention group was 3.8 (2.2, 9.8) days versus 7.1 (3.1, 20) days in the placebo group (p = 0.12). The median hospital length of stay for the vitamin C group was 18 (11, 35) days versus 22 (10, 52) days for the placebo group (p = 0.65). Mortality was comparable between the two groups (p > 0.05). Of the inflammatory markers, neutrophil counts were elevated in the vitamin C group relative to placebo by 72 h (p = 0.01). C-reactive protein and myeloperoxidase concentrations were elevated at baseline, however, the two groups were comparable over time (p > 0.05). CONCLUSIONS: Our pilot study indicated that intravenous vitamin C did not provide significant decreases in the mean dose or duration of vasopressor infusion. Further research that takes into account the potential impact of intervention timing, dose and duration, and location of trial, may provide more definitive evidence. TRIAL REGISTRATION: ACTRN12617001184369 (11/8/2017).

Ageing well with diabetes: A workshop to co-design research recommendations for improving the diabetes care of older people.

AIMS: To identify key research questions where answers could improve care for older people living with diabetes (PLWD), and provide detailed recommendations for researchers and research funders on how best to address them. METHODS: A series of online research workshops were conducted, bringing together a range of PLWD and an acknowledged group of academic and clinical experts in their diabetes care to identify areas for future research. Throughout the pre-workshop phase, during each workshop, and in manuscript preparation and editing, PLWD played an active and dynamic role in discussions as part of both an iterative and narrative process. RESULTS: The following key questions in this field were identified, and research recommendations for each were developed: How can we improve our understanding of the characteristics of older people living with diabetes (PLWD) and their outcomes, and can this deliver better person-centred care? How are services to care for older PLWD currently delivered, both for their diabetes and other conditions? How can we optimise and streamline the process and ensure everyone gets the best care, tailored to their individual needs? What tools might be used to evaluate the level of understanding of diabetes in the older population amongst non-specialist Healthcare Professionals (HCPs)? How can virtual experts or centres most effectively provide access to specialist multi-disciplinary team (MDT) expertise for older PLWD and the HCPs caring for them? Is a combination of exercise and a nutrition-dense, high protein diet effective in the prevention of the adverse effects of type 2 diabetes and deterioration in frailty, and how might this be delivered in a way which is acceptable to people with type 2 diabetes? How might we best use continuous glucose monitoring (CGM) in older people and, for those who require support, how should the data be shared? How can older PLWD be better empowered to manage their diabetes in their own home, particularly when living with additional long-term conditions? What are the benefits of models of peer support for older PLWD, both when living independently and when in care? CONCLUSIONS: This paper outlines recommendations supported by PLWD through which new research could improve their diabetes care and calls on the research community and funders to address them in future research programmes and strategies.

The feasibility of a strategy for the remote recruitment, consenting and assessment of recent referrals: a protocol for phase 1 of the On-Line Parent Training for the Initial Management of ADHD referrals (OPTIMA).

BACKGROUND: In the UK, children with high levels of hyperactivity, impulsivity and inattention referred to clinical services with possible attention-deficit/hyperactivity disorder (ADHD) often wait a long time for specialist diagnostic assessment. Parent training (PT) has the potential to support parents during this difficult period, especially regarding the management of challenging and disruptive behaviours that often accompany ADHD. However, traditional face-to-face PT is costly and difficult to organise in a timely way. We have created a low-cost, easily accessible PT programme delivered via a phone app, Structured E-Parenting Support (STEPS), to address this problem. The overall OPTIMA programme will evaluate the efficacy and cost-effectiveness of STEPS as a way of helping parents manage their children behaviour while on the waitlist. To ensure the timely and efficient evaluation of STEPS in OPTIMA, we have worked with children's health services to implement a remote strategy for recruitment, screening and assessment of recently referred families. Part of this strategy is incorporated into routine clinical practice and part is OPTIMA specific. Here, we present the protocol for Phase 1 of OPTIMA-a study of the feasibility of this remote strategy, as a basis for a large-scale STEPS randomised controlled trial (RCT). METHODS: This is a single arm observational feasibility study. Participants will be parents of up to 100 children aged 5-11 years with high levels of hyperactivity/impulsivity, inattention and challenging behaviour who are waiting for assessment in one of five UK child and adolescent mental health or behavioural services. Recruitment, consenting and data collection will occur remotely. The primary outcome will be the rate at which the families, who meet inclusion criteria, agree in principle to take part in a full STEPS RCT. Secondary outcomes include acceptability of remote consenting and online data collection procedures; the feasibility of collecting teacher data remotely within the required timeframe, and technical difficulties with completing online questionnaires. All parents in the study will receive access to STEPS. DISCUSSION: Establishing the feasibility of our remote recruitment, consenting and assessment strategy is a pre-requisite for the full trial of OPTIMA. It can also provide a model for future trials conducted remotely.

Systematic review of tendon transfers in the foot and ankle using interference screw fixation: Outcomes and safety of early versus standard postoperative rehabilitation.

AIMS: To compare the outcomes of early and standard rehabilitation protocols following tendon transfers in the foot and ankle using interference screw fixation (ISF). METHODS: A systematic review was performed for relevant articles (1998 to 2020) reporting foot tendon transfer using ISF in adults. The primary outcome was early tendon failure. Secondary outcomes included function and complications. RESULTS: In total, 21 studies met the inclusion criteria, totalling 494 patients. Seven studies reported early rehabilitation protocols. The rate of early tendon failure was zero for each protocol and studies consistently reported a significant improvement in function. No differences were found comparing different rehabilitation protocols for tendon transfer for Achilles tendon pathology and foot drop. CONCLUSION: Both early and standard rehabilitation protocols are associated with high patient satisfaction and low complication rates, but currently there is a lack of evidence to support early loaded activities or motion. LEVEL OF EVIDENCE: IV Systematic review including case series.

Novel metrics for evaluating decision making in a 'Treat and Extend' regimen for neovascular age related macular degeneration.

BACKGROUND: The primary aim was to investigate outcome of the decision making on duration of injection intervals between injection visits over the first 2 years of a treat and extend regimen. METHOD: Consecutive patients receiving Aflibercept for treatment naïve neovascular age-related macular degeneration between 01.01.2016 and 15.07.2017 were identified from our departmental register. Retrospective data collected on all visits over 24 months were classified into three groups: (A) Without Interval Decision Events (IDE)" Injection only" (B) IDE resulting in injection intervals of <5 weeks and (C) IDE resulting in intervals of >5 weeks. The primary outcome was number of successful IDE relative to the total visits in Group C. Successful decision making was defined as absence of worsening of visual acuity (>5 L) or central retinal thickness (>50 microns) at the subsequent visit. Secondary visual and anatomical outcomes at 24 months were also evaluated. RESULTS: Data from 56 eyes of 50 patients were included in the study. Visual acuity improved by +7.11 L at 24 months. Forty one patients with unilateral therapy made 721 visits: 280 visits (38.8%) were group A; 164 visits (22.8%) were group B and 277 visits (38.4%) were group C. Average interval in Group C was 8.9 weeks (range 5-15). The success rate of extension was 95.31% (264/277 visits). CONCLUSION: These metrics for evaluating the decision making aspect of disease activity monitoring may be useful for monitoring performance and have given us a more realistic view and expectations of what can be achieved using this regime to optimise the timing of injections.