DNA triplet repeat expansion and mismatch repair.

DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSß and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway.

Sustained molecular response following a failed attempt of tyrosine kinase inhibitor discontinuation & the effects on growth in a child with chronic myeloid leukemia: not always a short story.

We report a patient who developed chronic myelogenous leukemia (CML) at 12 months of age. She was treated aggressively with stem cell transplant (SCT), interferon, donor lymphocytes and imatinib, with subsequent molecular progression. She received dasatinib, achieving a complete molecular response. Dasatinib was discontinued at 3 years but she had a molecular recurrence. Dasatinib was restarted and continued for 5 additional years with a second major molecular remission (MMR). While on dasatinib therapy she suffered growth failure and was treated with concurrent growth hormone (GH). After discontinuing dasatinib and GH, catch-up growth continues and she remains in MMR. Discontinuation of TKI therapy and the toxicity of long-term TKI therapy is discussed.

Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with Down syndrome: A case report and retrospective review of Children's Oncology Group acute myeloid leukemia trials.

Children with Down syndrome have a 150-fold increased risk of developing acute myeloid leukemia (AML) and 20-fold increased risk of developing acute lymphoblastic leukemia (ALL). Although the risk of developing AML and ALL is significantly increased in children with Down syndrome, the development of both malignancies in the same patient is very rare. We describe a patient with Down syndrome who developed ALL 6 years after being diagnosed with AML. We performed a literature review and Children's Oncology Group query and discovered eight published cases and five cases of ALL following AML in pediatric patients with Down syndrome, as well as six cases of ALL following AML in non-Down syndrome patients. There was a similar cumulative incidence of ALL after treatment for AML in the Down syndrome and non-Down syndrome populations. Overall survival in patients with Down syndrome who developed ALL after treatment for AML was comparable to overall survival for patients with Down syndrome with de novo ALL with an average follow-up of 7 years after ALL diagnosis. Clinical data collected were used to discuss whether this phenomenon represents a secondary leukemia, second primary cancer, or mixed-lineage leukemia.

Contrast Extravasation as a Complication of Emergency Nurse-Performed Ultrasound-Guided Peripheral Intravenous Catheter Placement.

INTRODUCTION: Vascular access procedures are among the most commonly performed procedures in the emergency department. The objective of the current study was to compare the contrast extravasation rate for ultrasound-guided peripheral intravenous (USGPIV) catheter placement by emergency nurses with peripheral intravenous catheters placed by standard landmark techniques. METHODS: A retrospective chart review of all ED patients at our urban tertiary-care institution who underwent contrasted computed tomography examination and suffered contrast extravasation events was performed. A logbook of all ED patients who underwent USGPIV placement and an institution-wide electronic patient safety incident-reporting system was reviewed for all contrast extravasation events between May 2014, and February 2017. Data were analyzed using descriptive statistics, Student t-tests for continuous data, and χ2 or Fisher's exact test for categorical data. RESULTS: One thousand five hundred USGPIV catheters were placed by 27 emergency nurses. Contrast material was administered 29,508 times, and, of these, 291 were administered via USGPIV placement. There were 74 peripheral IV lines with documented contrast extravasations (0.25%) as reported in the safety-event database; 12 (4.1%) were from the USGPIV population, and 62 (0.21%) occurred in the standard landmark technique population. Relative risk of contrast extravasation events with USGPIV placement was 19.4 (95% confidence interval [CI], 10.6-35.6), and the absolute risk difference was 3.9% (95% CI 1.6%-6.2%). DISCUSSION: USGPIV placement by trained emergency nurses has higher rates of contrast extravasation than with standard landmark technique placement.

Modifying bone mineral density, physical function, and quality of life in children with acute lymphoblastic leukemia.

BACKGROUND: The early effects of childhood acute lymphoblastic leukemia (ALL) include decreased physical function, bone mineral density (BMD/g/cm2 ), and health-related quality of life (HRQL). We assessed the capacity of a physical therapy and motivation-based intervention, beginning after diagnosis and continuing through the end of treatment, to positively modify these factors. PROCEDURE: A 2.5-year randomized controlled trial of 73 patients aged 4-18.99 years within 10 days of ALL diagnosis assessed BMD at baseline (T0 ) and end of therapy (T3 ), strength, range of motion, endurance, motor skills, and HRQL at baseline (T0 ), 8 (T1 ), 15 (T2 ), and 135 (T3 ) weeks. RESULTS: There were no significant changes between groups (intervention, n = 33; usual care, n = 40) in BMD (P = 0.059) at T3 or physical function and HRQL at T0 -T3 . While BMD declined in both the intervention (T0  = -0.21, T3  = -0.55) and usual care (T0  = -0.62, T3  = -0.78) groups, rates of decline did not differ between groups (P = 0.56). Univariate analysis (n = 73) showed associations of higher T3 bone density with body mass index T1 (P = 0.01), T2 (P = <0.0001), T3 (P = 0.01), T3 ankle flexibility/strength (P = 0.001), and T2 parent (P = 0.02)/T0 child (P = 0.03) perceptions of less bodily pain. CONCLUSIONS: The intervention delivered during treatment was not successful in modifying BMD, physical function, or HRQL. Physical activity, at the level and intensity required to modify these factors, may not be feasible during early treatment owing to the child's responses to the disease and treatment. Future studies will consider intervention implementation during late maintenance therapy, extending into survivorship.

Outcomes of children, adolescents, and young adults following allogeneic stem cell transplantation for secondary acute myeloid leukemia and myelodysplastic syndromes-The MD Anderson Cancer Center experience.

We conducted a retrospective analysis of outcomes for children and young adults with sAML/sMDS who underwent HSCT at our institution. Thirty-two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/sMDS diagnosis to HSCT was 4.1 months (range: 1.2-27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow-up of 62.3 months (range: 0.4-250.9 months), 14 patients had disease recurrence. Acute GVHD, grade III/IV, occurred in three patients. Causes of death were as follows: disease relapse (n=12), infection (n=2), pneumonia (n=1), pulmonary hemorrhage (n=1), acute GVHD (n=1), and graft failure (n=1). A PS of ≥90% at the time of HSCT had a significant impact on PFS (P=.02). Patients achieving pretransplant primary CR (n=8) and those with sMDS and RA (n=6) had prolonged PFS (P=.04). On multivariate analysis, shorter time to transplantation (≤6 months from diagnosis of sAML/sMDS) was associated with superior OS (P=.0018) and PFS (P=.0005).

Symptom profiles in children with advanced cancer: Patient, family caregiver, and oncologist ratings.

BACKGROUND: Systematic symptom assessment is not routinely performed in pediatric oncology. The objectives of the current study were to characterize the symptoms of pediatric oncology outpatients and evaluate agreement between patient and proxy reports and the association between children's ratings and oncologists' treatment recommendations. METHODS: Two versions of the pediatric Memorial Symptom Assessment Scale (pMSAS) were translated into Spanish. An age-appropriate and language-appropriate pMSAS was administered independently before visits to the oncologist to patients and family caregivers (caregivers) and after visits to consenting oncologists. Statistical analysis included Spearman correlation coefficients and weighted kappa values. RESULTS: English and Spanish results were similar and were combined. A total of 60 children and their caregivers completed the pMSAS. The children had a median age of 10 years (range, 7-18 years); approximately 62% were male and 33% were Spanish-speaking. Fourteen oncologists completed the pMSAS for 25 patients. Nine patients (15%) had no symptoms and 38 patients (63%) reported ≥2 symptoms. The most common symptoms were fatigue (12 patients; 40%) and itch (9 patients; 30%) for the younger children and pain (15 patients; 50%) and lack of energy (13 patients; 45%) among the older children. Total and subscale score agreement varied by proxy type and subscale, ranging from fair to good for most comparisons. Agreement for individual symptoms between the patient and proxy ranged from a kappa of -0.30 (95% confidence interval, -0.43 to -0.01) to 0.91 (95% confidence interval, 0.75 to 1.00). Three of 51 symptomatic patients (6%) had treatment recommendations documented in the electronic health record. CONCLUSIONS: Symptoms are common and cross several functional domains. Proxy and child reports are often not congruent, possibly explaining apparent undertreatment among this group of patients.

A novel trial of topotecan, ifosfamide, and carboplatin (TIC) in children with recurrent solid tumors.

BACKGROUND: Ifosfamide, carboplatin, and etoposide (ICE) in children with refractory or recurrent solid tumors and lymphomas has resulted in good overall response rates (ORR). Etoposide, a topoisomerase-II inhibitor, however, has been associated with a significant increase in secondary leukemia. The rationale for substituting topotecan, a topoisomerase-I inhibitor, for etoposide in this regimen, a topoisomerase-II inhibitor, includes its limited toxicity profile and decreased leukemogenicity. Furthermore, topotecan in combination with both alkylators and platinating agents are additive and/or synergistic against a variety of solid tumors. PROCEDURE: Patients with relapsed/refractory solid tumors received ifosfamide (9 g/m2 ) and carboplatin (area under the curve: 3 mg/ml/min). Topotecan was also administered at 0.5 mg/m2 /day × 3 days (N = 12) and in a small cohort (N = 3) at 0.75 mg/m2 /day. RESULTS: Fifteen patients were entered onto study. Two patients developed seizures/encephalitis secondary to ifosfamide. One patient had dose-limiting thrombocytopenia secondary to TIC that resolved with supportive care. Patients received a median of three cycles (1-3) of TIC. Of the 14 evaluable patients for response, 4/14 had a complete response (CR), 2/14 had a partial response (PR), and 1/14 patients had stable disease (SD). The ORR (CR + PR) was 43%. CONCLUSION: TIC chemotherapy is feasible and tolerable in children and adolescents with refractory/recurrent solid tumors and lymphomas and results in a 43% excellent ORR in this poor-risk group of patients. A larger cohort of patients, especially in Wilms tumor and central nervous system (CNS) tumors, should be studied in the future to attempt to confirm these preliminary findings. Pediatr Blood Cancer 2015;62:274-278. © 2014 Wiley Periodicals, Inc.

An improved procedure to prepare 3-methyl-4-nitroalkylenethylisoxazoles and their reaction under catalytic enantioselective Michael addition with nitromethane.

Herein, we describe a short synthesis of 3-methyl-4-nitro-5-alkylethenyl isoxazoles and their reactivity as Michael acceptors. The title compounds reacted with nitromethane under phase-transfer catalysis to provide highly enantioenriched adducts (up to 93% ee) which were then converted to the corresponding γ-nitroacids.

Spatial characterization of riparian buffer effects on sediment loads from watershed systems.

Understanding all watershed systems and their interactions is a complex, but critical, undertaking when developing practices designed to reduce topsoil loss and chemical/nutrient transport from agricultural fields. The presence of riparian buffer vegetation in agricultural landscapes can modify the characteristics of overland flow, promoting sediment deposition and nutrient filtering. Watershed simulation tools, such as the USDA-Annualized Agricultural Non-Point Source (AnnAGNPS) pollution model, typically require detailed information for each riparian buffer zone throughout the watershed describing the location, width, vegetation type, topography, and possible presence of concentrated flow paths through the riparian buffer zone. Research was conducted to develop GIS-based technology designed to spatially characterize riparian buffers and to estimate buffer efficiency in reducing sediment loads in a semiautomated fashion at watershed scale. The methodology combines modeling technology at different scales, at individual concentrated flow paths passing through the riparian zone, and at watershed scales. At the concentrated flow path scale, vegetative filter strip models are applied to estimate the sediment-trapping efficiency for each individual flow path, which are aggregated based on the watershed subdivision and used in the determination of the overall impact of the riparian vegetation at the watershed scale. This GIS-based technology is combined with AnnAGNPS to demonstrate the effect of riparian vegetation on sediment loadings from sheet and rill and ephemeral gully sources. The effects of variability in basic input parameters used to characterize riparian buffers, onto generated outputs at field scale (sediment trapping efficiency) and at watershed scale (sediment loadings from different sources) were evaluated and quantified. The AnnAGNPS riparian buffer component represents an important step in understanding and accounting for the effect of riparian vegetation, existing and/or managed, in reducing sediment loads at the watershed scale.

Influence of placement stability on developmental outcomes of children and young people in out-of-home care: Findings from the Pathways of Care Longitudinal Study.

BACKGROUND: Placement stability is an important indicator of the functioning of an out-of-home care system. Previous research suggests that frequent placement changes have a negative impact on the outcomes for children and young people in out-of-home care. OBJECTIVE: This paper examines the association between placement stability in out-of-home care and children's socio-emotional, cognitive and physical health outcomes. PARTICIPANT AND SETTING: The Pathways of Care Longitudinal Study (POCLS) is the first large-scale prospective longitudinal study of children in out-of-home care in Australia. The sample consists of any study child who participated in any of the first three waves of the POCLS interview. METHODS: Unweighted data from the first three waves of the POCLS interview and administrative data was used. A measure of placement stability was developed that accounted for both number of placements and length of time in care. Mixed effect modelling was used to examine the link between placement stability and children's developmental outcomes. RESULTS: Placement stability was found to have a significant association with socio-emotional, cognitive (non-verbal) and physical health (gross and fine motor skill) development. A number of other factors were also found to be associated with positive development. CONCLUSIONS: The findings support the existing evidence that placement stability is an important factor for children's development. Other factors including placement type, carer wellbeing and carer support are also important for positive development. Appropriate policy and practice intervention to support children and families to improve placement stability is fundamental to achieving positive developmental outcomes for children in out-of-home care.

The model of access to speech-language pathology services.

PURPOSE: Within Australia, some families face challenges in accessing paediatric speech-language pathology services. This research sought to investigate the factors that impact access to paediatric speech-language pathology services within Western Australia. METHOD: Researchers used constructivist grounded theory to investigate the construct of access, as experienced and perceived by service decision-makers, namely caregivers of children with communication needs and speech-language pathologists who provide communication services. Eleven speech-language pathologists and 16 caregivers took part in 32 semi-structured in-depth interviews. Researchers used layers of coding of interviews transcripts and the constant comparative method to investigate data. RESULT: Findings outline the factors that impact access to speech-language pathology services, as organised into the seven categories of the Model of Access to Speech-Language Pathology Services (MASPS). The categories and properties of this model are grounded within experiences and perspectives that participants contributed to the dataset. CONCLUSION: MASPS provides a theoretical structure that has been constructed using inductive and abductive reasoning. This model can be used by service designers and decision-makers to reflect upon and improve experiences of service for a range of consumers. MASPS can also be used as a basis for further investigation into aspects of service access.

Non-pharmacological interventions to support coronary artery bypass graft (CABG) patient recovery following discharge: protocol for a scoping review.

BACKGROUND: In Canada, approximately 15 000 people undergo coronary artery bypass grafting (CABG) each year. However, 9.5% of these patients are urgently readmitted to hospital within 30 days of surgery. Postoperative interventions following discharge play an important role in reducing readmissions and improving CABG patient outcomes. Therefore, it is important to determine effective interventions available to enhance CABG patient recovery following postoperative discharge. OBJECTIVES: Our scoping review aims to identify non-pharmacological interventions available to support recovery of patients who are discharged after CABG in the community setting. METHODS: The methodological framework described by Arksey and O'Malley will be applied to this review. Our search strategy will include electronic databases (Medline, Embase, Cochrane Library and CINAHL), and studies will be screened and reviewed by two independent reviewers. Studies looking at non-pharmacological interventions targeting patients who are discharged after CABG will be included. Preliminary searches were conducted March 2022 and following abstract screening, full-text screening was completed May 2023. Data extraction is planned to begin September 2023 with an expected finish date of October 2023. The study is expected to be completed by January 2024. ETHICS AND DISSEMINATION: This scoping review will retrieve and analyse previously published studies in which informed consent was obtained by primary investigators. Therefore, no ethical review or approval will be required. This scoping review aims to enumerate available non-pharmacological interventions to support recovery of patients who are discharged after CABG and identify gaps in postoperative recovery after discharge to support the development of innovative and targeted interventions. On completion of this review, we will ensure broad dissemination of our findings through peer-reviewed, open-access journals, conference presentations and hold meetings to engage stakeholders, including clinicians, policy makers and others.

The LTAR cropland common experiment in the Lower Mississippi River Basin.

The Lower Mississippi River Basin-Long-Term Agroecosystem Research Site (LMRB-LTAR) encompasses six states from Missouri to the Gulf of Mexico and is coordinated by the USDA-ARS National Sedimentation Laboratory, Oxford, MS. The overarching goal of LTAR is to assess regionally diverse and geographically scalable farming practices for enhanced sustainability of agroecosystem goods and services under changing environment and resource-use conditions. The LMRB-LTAR overall goal is to assess sustainable row crop agricultural production systems that integrate regional environmental and socioeconomic needs. Primary row crops in the region include soybeans, corn, cotton, rice, and sugarcane with crop rotations influenced by commodity crop price and other factors. The field-scale common experiment (CE) includes four row crop farms (26-101 ha) established in 2021 and 2023. Three fields are managed with alternative practices, including reduced tillage, cover crops, and automated prescription irrigation, and three fields are managed with prevailing farming practices, consisting of conventional tillage, no cover crop, and nonprescription irrigation. Treatment effects on crop productivity, soil quality, water use efficiency, water quality, and carbon storage are assessed. Research from the LMRB CE will deliver outcomes linked to overarching LTAR network goals, including innovative agricultural systems, strengthened partnerships, data management technologies, and precision environmental tools.

From coordinated care trials to medicare locals: what difference does changing the policy driver from efficiency to quality make for coordinating care?

The terms coordination and integration refer to a wide range of interventions, from strategies aimed at coordinating clinical care for individuals to organizational and system interventions such as managed care, which contract medical and support services. Ongoing debate about whether financial and organizational integration are needed to achieve clinical integration is evident in policy debates over several decades, from a focus through the 1990s on improving coordination through structural reform and the use of market mechanisms to achieve allocative efficiencies (better overall service mix) to more recent attention on system performance to improve coordination and quality. We examine this shift in Australia and ask how has changing the policy driver affected efforts to achieve coordination? Care planning, fund pooling and purchasing are still important planks in coordination. Evidence suggests that financial strategies can be used to drive improvements for particular patient groups, but these are unlikely to improve outcomes without being linked to clinical strategies that support coordination through multidisciplinary teamwork, IT, disease management guidelines and audit and feedback. Meso level organizational strategies might align the various elements to improve coordination. Changing the policy driver has refocused research and policy over the last two decades from a focus on achieving allocative efficiencies to achieving quality and value for money. Research is yet to develop theoretical approaches that can deal with the implications for assessing effectiveness. Efforts need to identify intervention mechanisms, plausible relationships between these and their measurable outcomes and the components of contexts that support the emergence of intervention attributes.

Unlocking information for coordination of care in Australia: a qualitative study of information continuity in four primary health care models.

BACKGROUND: Coordination of care is considered a key component of patient-centered health care systems, but is rarely defined or operationalised in health care policy. Continuity, an aspect of coordination, is the patient's experience of care over time, and is often described in terms of three dimensions: information, relational and management continuity. With the current health policy focus on both the use of information technology and care coordination, this study aimed to 1) explore how information continuity supports coordination and 2) investigate conditions required to support information continuity. METHODS: Four diverse Australian primary health care initiatives were purposively selected for inclusion in the study. Each has improved coordination as an aim or fundamental principle. Each organization was asked to identify practitioners, managers and decision makers who could provide insight into the use of information for care coordination to participate in the study. Using in-depth semi-structured interviews, we explored four questions covering the scope and use of information, the influence of governance, data ownership and confidentiality and the influence of financial incentives and quality improvement on information continuity and coordination. Data were thematically analyzed using NVivo 8. RESULTS: The overall picture that emerged across all four cases was that whilst accessibility and continuity of information underpin effective care, they are not sufficient for coordination of care for complex conditions. Shared information reduced unnecessary repetition and provided health professionals with the opportunity to access records of care from other providers, but participants described their role in coordination in terms of the active involvement of a person in care rather than the passive availability of information. Complex issues regarding data ownership and confidentiality often hampered information sharing. Successful coordination in each case was associated with responsiveness to local rather than system level factors. CONCLUSIONS: The availability of information is not sufficient to ensure continuity for the patient or coordination from the systems perspective. Policy directed at information continuity must give consideration to the broader 'fit' with management and relational continuity and provide a broad base that allows for local responsiveness in order for coordination of care to be achieved.

R loops stimulate genetic instability of CTG.CAG repeats.

Transcription stimulates the genetic instability of trinucleotide repeat sequences. However, the mechanisms leading to transcription-dependent repeat length variation are unclear. We demonstrate, using biochemical and genetic approaches, that the formation of stable RNA.DNA hybrids enhances the instability of CTG.CAG repeat tracts. In vitro transcribed CG-rich repeating sequences, unlike AT-rich repeats and nonrepeating sequences, form stable, ribonuclease A-resistant structures. These RNA.DNA hybrids are eliminated by ribonuclease H treatment. Mutation in the rnhA1 gene that decreases the activity of ribonuclease HI stimulates the instability of CTG.CAG repeats in E. coli. Importantly, the effect of ribonuclease HI depletion on repeat instability requires active transcription. We also showed that transcription-dependent CTG.CAG repeat instability in human cells is stimulated by siRNA knockdown of RNase H1 and H2. In addition, we used bisulfite modification, which detects single-stranded DNA, to demonstrate that the nontemplate DNA strand at transcribed CTG.CAG repeats remains partially single-stranded in human genomic DNA, thus indicating that it is displaced by an RNA.DNA hybrid. These studies demonstrate that persistent hybrids between the nascent RNA transcript and the template DNA strand at CTG.CAG tracts promote instability of DNA trinucleotide repeats.

Outcomes of Ultrasound Guided Peripheral Intravenous Catheters Placed in the Emergency Department and Factors Associated with Survival.

Background: Patients with difficult peripheral intravenous (IV) access are common in emergency departments (EDs). Ultrasound-guided peripheral intravenous catheters (USIVs) are frequently used in this population; however, information regarding the effect of patient and IV characteristics on the dwell time (DT) and survival probability (SP) of USIVs is limited. Objective: Our study aimed to evaluate for associations between patient or IV characteristics and the DT and SP of USIVs. Methods: Retrospective analysis was performed on a database from an ED nurse (RN) USIV training program at an urban, academic hospital. Patients over 18 years with an USIV placed during the study period were included. Subject demographics, history, IV characteristics, insertion, and removal times were collected. Data were analyzed using descriptive statistics and univariable and multivariable Cox regression. USIV survival times for variates of interest were estimated using Kaplan-Meier curves for three censoring points. Results: The final analysis cohort was 388 patients. Mean age was 56.6 years, 66.5% were female, mean BMI was 29.9 kg/m2, and 42.5% were obese (BMI ≥30). Median DT was 40.3 hours in admitted patients (N=340). SP for USIVs at 96 hours was 87.8%. A total of 21 of 340 (6.2%) USIVs failed. USIV location conferred a difference on DT in obese patients when dichotomized into upper arm versus antecubital fossa and forearm together (38.6 hours vs 44.6 hours, p=0.03). No factors were associated with a difference in USIV SP. Conclusion: Median USIV DT of 40.3 hours for admitted patients was higher than in previous studies. Only 7% of USIVs in our study failed. Overall, catheters survived longer than expected.

Guided self-help for anxiety among Huntington's disease gene expansion carriers (GUIDE-HD) compared to treatment as usual: a randomised controlled feasibility trial.

BACKGROUND: Huntington's disease (HD) is an adult-onset genetic neurodegenerative condition associated with cognitive decline, motor impairments, and emotional difficulties. Anxiety affects up to 71% of HD gene expansion carriers (i.e., those with the version of the gene that causes HD) and can negatively impact quality of life, worsen other HD symptoms, and increase suicide risk. Therefore, helping people with their anxiety should be a clinical priority. A significant evidence base now exists for low-cost talking therapies for anxiety, such as guided self-help, and with people with other neurodegenerative conditions (e.g., Parkinson's disease). However, this type of intervention has not been specifically assessed with HD gene expansion carriers. METHODS: This protocol describes an exploratory randomised controlled feasibility study of a psychological intervention for anxiety for HD gene expansion carriers. The 10 session guided self-help intervention ('GUIDE-HD') is based on a blend of second and third wave cognitive behavioural models of anxiety (cognitive behaviour therapy [CBT] and acceptance and commitment therapy [ACT]) and is adapted to meet the specific needs of an HD population. This study will compare guided self-help with treatment as usual (TAU), with 15 HD gene expansion carriers randomly allocated to each group. Participants will be recruited across the UK. Quantitative data will be collected pre-intervention, immediately post-intervention, 3-month post-intervention and 6-month post-intervention. Qualitative data will be collected at one month post-intervention from participants, including HD carers. The data will be analysed to assess whether the current intervention and study design are feasible to progress to a larger randomised controlled trial. Feasibility has been defined in terms of recruitment rate, retention rate to both trial arms, intervention adherence, and acceptability of the intervention and measurement tools. DISCUSSION: Given the lack of evidenced interventions to date to support the wellbeing of people with the expanded Huntington's gene, this study will assess the feasibility of progressing this particular intervention to a full trial. To try and increase the acceptability of the intervention, a number of stakeholders, including those affected by HD and in caring roles, have been fundamental to the creation of the intervention (e.g., therapy manual, planned therapy process) to date. TRIAL REGISTRATION: Trial ID: ISRCTN47330596 . Date registered: 28/09/2022. Protocol version and date: Version 2, 09/06/22. Trial sponsor organisation and contact: Leicestershire Partnership NHS Trust (Dave Clarke). Role of sponsor: Overall responsibility for the conduct and governance of the trial. Role of funder: Review of initial research proposal.

E-prescribing and medication safety in community settings: A rapid scoping review.

Background: Medication prescribing is essential for the treatment, curing, maintenance, and/or prevention of an illness and disease, however, medication errors remain common. Common errors including prescribing and administration, pose significant risk to patients. Electronic prescribing (e-prescribing) is one intervention used to enhance the safety and quality of prescribing by decreasing medication errors and reducing harm. E-prescribing in community-based settings has not been extensively examined. Objective: To map and characterize the current evidence on e-prescribing and medication safety in community pharmacy settings. Methods: We conducted a rapid scoping review of quantitative, qualitative, and mixed methods studies reporting on e-prescribing and medication safety. MEDLINE All (OVID), Embase (Elsevier), CINAHL Full Text (EBSCOHost), and Scopus (Elsevier) databases were searched December 2022 using keywords and MeSH terms related to e-prescribing, medication safety, efficiency, and uptake. Articles were imported to Covidence and screened by two reviewers. Data were extracted by a single reviewer and verified by a second reviewer using a standardized data extraction form. Findings are reported in accordance with JBI Manual for Evidence Synthesis following thematic analysis to narratively describe results. Results: Thirty-five studies were included in this review. Most studies were quantitative (n = 22), non-experimental study designs (n = 16) and were conducted in the United States (n = 18). Half of included studies reported physicians as the prescriber (n = 18), while the remaining reported a mix of nurse practitioners, pharmacists, and physician assistants (n = 6). Studies reported on types of errors, including prescription errors (n = 20), medication safety errors (n = 9), dispensing errors (n = 2), and administration errors (n = 1). Few studies examined patient health outcomes, such as adverse drug events (n = 5). Conclusions: Findings indicate that most research is descriptive in nature and focused primarily on rates of prescription errors. Further research, such as experimental, implementation, and evaluation mixed-methods research, is needed to investigate the effects of e-prescribing on reducing error rates and improving patient and health system outcomes.