Barriers to neurosurgery for medical students: a national study focused on the intersectionality of gender and race.

OBJECTIVE: Despite 51.2% of medical school graduates being female, only 29.8% of neurosurgery residency applicants are female. Furthermore, only 12.6% of neurosurgery applicants identify as underrepresented in medicine (URM). Evaluating the entry barriers for female and URM students is crucial in promoting the equity and diversity of the neurosurgical workforce. The objective of this study was to evaluate barriers to neurosurgery for medical students while considering the interaction between gender and race. METHODS: A Qualtrics survey was distributed widely to US medical students, assessing 14 factors of hesitancy toward neurosurgery. Likert scale responses, representing statement agreeability, converted to numeric values on a 7-point scale were analyzed by Mann-Whitney U-test and ANOVA comparisons with Bonferroni correction. RESULTS: Of 540 respondents, 68.7% were female and 22.6% were URM. There were 22.6% male non-URM, 7.4% male URM, 53.5% female non-URM, and 15.2% female URM respondents. The predominant reasons for hesitancy toward neurosurgery included work/life integration, length of training, competitiveness of residency position, and perceived malignancy of the field. Females were more hesitant toward neurosurgery due to maternity/paternity needs (p = 0.005), the absence of seeing people like them in the field (p < 0.001), and opportunities to pursue health equity work (p < 0.001). Females were more likely to have difficulties finding a mentor in neurosurgery who represented their identities (p = 0.017). URM students were more hesitant toward neurosurgery due to not seeing people like them in the field (p < 0.001). Subanalysis revealed that when students were stratified by both gender and URM status, there were more reasons for hesitancy toward neurosurgery that had significant differences between groups (male URM, male non-URM, female URM, and female non-URM students), suggesting the importance of intersectionality in this analysis. CONCLUSIONS: The authors highlight the implications of gender and racial diversity in the neurosurgical workforce on medical student interest and recruitment. Their findings suggest the importance of actively working to address these barriers, including 1) maternity/paternity policy reevaluation, standardization, and dissemination; and 2) actively providing resources for the creation of mentorship relationships for both women and URM students in an effort to create a workforce that aligns with the changing demographics of medical graduates to continue to improve diversity in neurosurgery.

Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Posttraumatic cognition change trajectories in veterans with PTSD who completed an intensive Cognitive Processing Therapy treatment program.

Negative posttraumatic cognitions (NPCs) have been linked to symptoms of PTSD and are an important target of cognitive behavioral treatments for PTSD, including Cognitive Processing Therapy (CPT). Yet to be explored are the different change trajectories of NPCs during CPT. Knowledge of such change trajectories could elucidate common NPC change processes within CPT and their relationship to PTSD symptom severity. We examined NPC change trajectories in a group of 443 veterans who completed a 2-week intensive CPT program. We identified four NPC trajectory groups termed start high end high, start high end moderate, start moderate end low, and start low end low. Most of the groups showed an increase in NPCs at the midpoint of treatment before ultimately decreasing. As predicted, baseline PTSD symptom severity predicted change trajectory group membership. Also, NPC change trajectories were associated with PTSD severity at the end of treatment such that individuals in smaller NPC change groups had higher PTSD symptoms at the end of treatment, and vice versa. Clinicians can use this knowledge to make predictions of a particular client's NPC change trajectory and set expectations for what progress in treatment may look like, including normalizing increases in NPCs from the start of treatment.

A case of disseminated spinal astroblastoma harboring a MAMLD1::BEND2 fusion.

Astroblastoma, MN1-altered, is a rare neoplasm of the central nervous system (CNS). This malignancy shares similar histopathological features with other CNS tumors, including ependymomas, making it challenging to diagnose. DNA methylation profiling is a new and robust technique that may be used to overcome this diagnostic hurdle. We report the case of a now 25-year-old female diagnosed with what was initially called an ependymoma located in the cervical spine at the age of 2 years old. After initial resection, the tumor recurred multiple times and within 2 years of diagnosis had disseminated disease throughout the brain and spinal cord. She has now undergone over two decades of treatment, including multiple surgical resections, radiation therapy, and administration of numerous chemotherapeutic agents. In 2021, the patient presented to our institution with lumbosacral radicular symptoms due to enlarging lesions within the lumbosacral spine. Reexamination of formalin-fixed, paraffin-embedded material from the patient's tumor using genomic DNA methylation profiling resulted in a diagnostic change from grade III anaplastic ependymoma to astroblastoma, MN1-altered. This work describes another confirmed case of astroblastoma, MN1-altered, to the growing body of literature.

SOARinG to New Heights Through a Structured Medical Student Research Program.

Introduction: Since the US Medical Licensing Examination (USMLE) Step 1 became Pass/Fall in 2022, medical students competing for residency spots must distinguish themselves with alternative criteria. Research experiences and output offer valuable skill development and objective metrics to support competitive residency applications. Objective: We describe the methodological development of a structured program to support, enhance, and track medical student research efforts at the University of South Carolina School of Medicine Greenville, explain the implementation of the program, and summarize initial program outcomes. Methods: The Student Opportunities for Academic Achievement Through Research in Greenville (SOARinG) Program was established to serve as a centralized hub for rising second year medical student research. The program matched medical students with mentored research projects scheduled during the summer following first-year coursework. The program included a required weekly seminar series on research basics and current biomedical literature. SOARinG culminated with a student research symposium for which students submitted abstracts and presented a poster or a talk. Quantitative and qualitative program outcomes of student and mentor satisfaction with the program were measured through surveys. Results and Discussion: The program was successfully implemented in summers 2021 and 2022. Most students (80-95%) in each class engaged in mentored summer research projects. Students reported overall satisfaction with research projects and mentor support. Overall, 69% of students rated their overall research experience in the program as extremely good or very good. Each student submitted an abstract and presented at the program's symposium or alternate research venue. Overall, 97% of research mentors reported that students were adequately prepared for summer research and suggested that students would benefit from additional skills-specific research training. Conclusion: The SOARinG Program provided a formalized process for tracking and showcasing medical student research and allowed for increased student participation in research. Additionally, each participating student produced objective research output, thus enhancing future residency applications.

Patient-centred outcomes following non-operative treatment or appendicectomy for uncomplicated acute appendicitis in children.

While non-operative treatment has emerged as an alternative to surgery for the treatment of uncomplicated acute appendicitis in children, comparative patient-centred outcomes are not well documented. We investigated these in a feasibility randomised trial. Of 57 randomised participants, data were available for 26. Compared with appendicectomy, children allocated to non-operative treatment reported higher short-term quality of life scores, shorter duration of requiring analgesia, more rapid return to normal activities and shorter parental absence from work. These preliminary data suggest differences exist in recovery profile and quality of life between these treatments that are important to measure in a larger RCT. Trial registration number is ISRCTN15830435.

Glioblastoma may evade immune surveillance through primary cilia-dependent signaling in an IL-6 dependent manner.

Glioblastoma is the most common, malignant primary brain tumor in adults and remains universally fatal. While immunotherapy has vastly improved the treatment of several solid cancers, efficacy in glioblastoma is limited. These challenges are due in part to the propensity of glioblastoma to recruit tumor-suppressive immune cells, which act in conjunction with tumor cells to create a pro-tumor immune microenvironment through secretion of several soluble factors. Glioblastoma-derived EVs induce myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs) from myeloid precursors leading to systemic and local immunosuppression. This process is mediated by IL-6 which contributes to the recruitment of tumor-associated macrophages of the M2 immunosuppressive subtype, which in turn, upregulates anti-inflammatory cytokines including IL-10 and TGF-ß. Primary cilia are highly conserved organelles involved in signal transduction and play critical roles in glioblastoma proliferation, invasion, angiogenesis, and chemoradiation resistance. In this perspectives article, we provide preliminary evidence that primary cilia regulate intracellular release of IL-6. This ties primary cilia mechanistically to tumor-mediated immunosuppression in glioblastomas and potentially, in additional neoplasms which have a shared mechanism for cancer-mediated immunosuppression. We propose potentially testable hypotheses of the cellular mechanisms behind this finding.

Comparison of neonatal outcomes in pregnant women undergoing medication-assisted treatment of opioid use disorder with methadone or buprenorphine/naloxone.

INTRODUCTION: The number of pregnant women with opioid use disorder (OUD) has quadrupled from 1999 to 2014. Current first line treatment for OUD in pregnancy is methadone with increasing support for buprenorphine. Limited data exist on use of buprenorphine/naloxone for OUD in pregnancy despite it being standard therapy in the non-pregnant individuals. The aim of this study was to compare neonatal opioid withdrawal syndrome (NOWS) prevalence and characteristics among neonates born to women prescribed methadone and buprenorphine/naloxone. METHODS: This is a retrospective cohort analysis of mother-neonate dyads treated with either methadone or buprenorphine/naloxone for OUD in pregnancy who received prenatal care in the substance abuse, treatment, education, and prevention program (STEPP) clinic and delivered at OSU. Primary neonatal outcomes included: neonates diagnosed and treated for NOWS, peak scores on Modified Finnegan Neonatal Abstinence Score (FNAS), number of scores ≥9 on FNAS, and duration of treatment for NOWS. Secondary outcomes included: fetal growth restriction, preterm birth (<37 weeks), neonatal head circumference, birth weight, NICU admission, five-minute Apgar score, and length of hospitalization. RESULTS: From 2013 to 2017, we identified 588 mother-neonate dyads: 149 treated with methadone and 439 treated with buprenorphine/naloxone. Ninety-eight neonates (65.8%) in the methadone group were diagnosed with NOWS requiring pharmacological interventions compared with 170 (38.7%) in the buprenorphine/naloxone group (aOR 3.46, 95% confidence interval (CI) 2.31-5.20, p < .01). Methadone-exposed neonates were six times more likely to be treated with >1 medication for NOWS (aOR 6.32, 95% CI 2.20-18.13, p < .01). Fetal growth restriction was diagnosed more often in the methadone group compared to the buprenorphine/naloxone group (aOR 1.73, 95% CI 1.02-2.93, p < .01). Significant maternal findings were that women using methadone for OUD started PNC earlier (15w vs. 17w, p = .04) and were less likely to be taking selective serotonin-reuptake inhibitors (SSRIs) (15% vs. 25%, p = .02) compared to the buprenorphine/naloxone group. CONCLUSIONS: Buprenorphine/naloxone treatment for OUD in pregnancy appears safe and has decreased NOWS and pharmacologic intervention for the neonate.

Establishing risk factors and outcomes for congenital hypothyroidism with gland in situ using population-based data linkage methods: study protocol.

INTRODUCTION: There has been an increase in the birth prevalence of congenital hypothyroidism (CH) since the introduction of newborn screening, both globally and in the UK. This increase can be accounted for by an increase in CH with gland in situ (CH-GIS). It is not known why CH-GIS is becoming more common, nor how it affects the health, development and learning of children over the long term. Our study will use linked administrative health, education and clinical data to determine risk factors for CH-GIS and describe long-term health and education outcomes for affected children. METHODS AND ANALYSIS: We will construct a birth cohort study based on linked, administrative data to determine what factors have contributed to the increase in the birth prevalence of CH-GIS in the UK. We will also set up a follow-up study of cases and controls to determine the health and education outcomes of children with and without CH-GIS. We will use logistic/multinomial regression models to establish risk factors for CH-GIS. Changes in the prevalence of risk factors over time will help to explain the increase in birth prevalence of CH-GIS. Multivariable generalised linear models or Cox proportional hazards regression models will be used to assess the association between type of CH and school performance or health outcomes. ETHICS AND DISSEMINATION: This study has been approved by the London Queen Square Research Ethics Committee and the Health Research Authority's Confidentiality Advisory Group CAG. Approvals are also being sought from each data provider. Obtaining approvals from CAG, data providers and information governance bodies have caused considerable delays to the project. Our methods and findings will be published in peer-reviewed journals and presented at academic conferences.

Risk factors for preterm birth among gravid individuals receiving buprenorphine for opioid use disorder.

BACKGROUND: Opioid use disorder (OUD) has dramatically increased over the last few decades, with 11.5 million American misusing opioids in 2016. Untreated OUD in pregnancy is associated with unique adverse obstetric and perinatal outcomes including insufficient prenatal care, preterm birth (PTB), fetal growth restriction, fetal demise, and placental abruption . The mainstay treatment for OUD management in pregnancy is medication for opioid use disorder (MOUD) including methadone or buprenorphine. The association of PTB and opioid use in pregnancy has been described for over 50 years, and efforts to significantly eliminate this risk are challenged by the many confounding risks described above. When comparing rates of PTB in individuals with OUD on methadone vs buprenorphine. Buprenorphine has been associated with overall lower PTB than Methadone by almost 50 %. OBJECTIVE: Pregnancies complicated by opioid use disorder are at an increased risk for preterm birth, defined as delivery <37 weeks' gestation. Limited literature is available on the prevalence and risk factors for preterm birth in pregnancies complicated by opioid use disorder maintained on buprenorphine. Therefore, we sought to determine the rate of preterm birth and risk factors for preterm birth in this population. STUDY DESIGN: We performed a retrospective cohort study of pregnant individuals with singleton gestations receiving buprenorphine for opioid use disorder, who delivered at a tertiary academic medical center between July 1, 2013 and June 30, 2018. Individuals who had at least 3 visits to our colocated clinic were included in the analysis. Patients were divided into 2 groups: the preterm group for patients who delivered at <37 weeks of gestation and the term group for those who delivered at ≥37 weeks of gestation. We defined "supplements to buprenorphine" to include any illicit drugs found on antepartum urine toxicology. Variables evaluated as potential risk factors for preterm birth included medical and infectious comorbidities and illicit polysubstance use. RESULTS: The overall preterm birth rate in this cohort was 22.7% (115/507). There was a nonsignificant trend toward decrease in overall preterm birth and provider-initiated preterm birth rate over the study period. No differences were found between the groups in spontaneous preterm birth rate at <34 weeks of gestation. There were no differences between the groups in the use of tobacco or alcohol, number of prenatal visits, or gestational age when prenatal care started. Individuals with preterm birth in the index pregnancy were more likely to have a history of preterm birth than individuals with term delivery (73% vs 16%; P<.01). No medical or infectious comorbidity or any specific supplement increased the risk of preterm birth. Among individuals using 0, 1, 2, or 3 or more illicit supplements in addition to confirmed buprenorphine for opioid use disorder, the preterm birth rate was 27.4% (reference), 18.0% (P=.09), 18.1% (P=.44), and 15.8% (P=.77), respectively. CONCLUSION: The preterm birth rate among individuals using buprenorphine for opioid use disorder (22.7%) is higher than the national average but lower than the reported preterm birth rate in individuals using methadone for the treatment of opioid use disorder. No medical or infectious comorbidity or use of additional illicit substances increased the risk of preterm birth.

A Reading Comprehension Intervention for Dual Language Learners With Weak Language and Reading Skills.

PURPOSE: We evaluated the efficacy of a reading comprehension intervention with dual language learners (DLLs) with documented English reading comprehension difficulties, half of whom had a developmental language disorder. The intervention EMBRACE (Enhanced Moved by Reading to Accelerate Comprehension in English) required children to move images on an iPad to both improve and demonstrate understanding of multichapter stories. Additionally, we determined the characteristics of students who most benefit from the intervention. METHOD: Fifty-six participants in second to fifth grades were randomly assigned to one of two groups: (a) Spanish support intervention or (b) Spanish support control. Outcome measures included performance on comprehension questions related to the intervention texts, two transfer texts with no strategy instruction, and the Gates-MacGinitie Reading Tests-Fourth Edition Reading Comprehension subtest administered pre- and post-intervention. RESULTS: Multilevel hierarchical linear models were used to account for nesting of question within child within classroom. For this group of DLLs, the overall intervention effect was not statistically significant. However, the intervention was most effective with narrative (vs. expository) texts and easy (vs. more difficult) texts. DLLs with lower initial English reading abilities (decoding and comprehension) benefited more from the intervention than those with stronger reading skills. CONCLUSIONS: The EMBRACE intervention has promise for use with DLLs with low baseline decoding and comprehension skills, particularly in early elementary grades. Future research should aim to match text difficulty with child skills when introducing new comprehension strategies to maximize benefit from the intervention.

RIPK1 Is Cleaved by 3C Protease of Rhinovirus A and B Strains and Minor and Major Groups.

Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we have shown that RVA-16 3C protease cleaves Receptor-interacting protein kinase-1 (RIPK1), a key host factor that modulates various cell death and cell survival pathways. In the current study, we have investigated whether this cleavage is conserved across selected RV strains. RIPK1 was cleaved in cells infected with strains representing diversity across phylogenetic groups (A and B) and receptor usage (major and minor groups). The cleavage was abrogated in the presence of the specific 3C protease inhibitor, Rupintrivir. Interestingly, there appears to be involvement of another protease (maybe 2A protease) in RIPK1 cleavage in strains belonging to genotype B. Our data show that 3C protease from diverse RV strains cleaves RIPK1, highlighting the importance of the cleavage to the RV lifecycle.

A naturopathic treatment approach for mild and moderate COVID-19: A retrospective chart review.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has led to significant morbidity and mortality. Although COVID-19 vaccination is available, therapeutic options are still needed. The goal of the present manuscript is to report on a treatment strategy used in a naturopathic medical practice for mild and moderate COVID-19. DESIGN: A retrospective chart review was conducted of 30 consecutive patients diagnosed with mild and moderate COVID-19 who were provided multi-nutrient, herbal, and probiotic treatment in a rural, out-patient, naturopathic primary care setting. MAIN OUTCOMES MEASURES: The primary outcome was treatment safety; secondary outcomes included changes in symptoms, progression to severe COVID-19, incidence of long COVID, and recovery time. RESULTS: No side effects or adverse events were reported from treatment and all patients experienced resolution of symptoms presumed to be associated with COVID-19 infection. One patient who had been ill for 28 days prior to presentation was hospitalized. Five patients had an illness duration of more than one month. Time to treatment was correlated with duration of illness post-treatment (r = 0.63, p < 0.001) and more symptoms at presentation was correlated with a longer duration of illness (r = 0.52, p < 0.01). CONCLUSIONS: In this retrospective chart review, a multi-nutrient, herbal, and probiotic therapeutic approach for mild and moderate COVID-19 appeared to be well-tolerated. Delay in seeking treatment after symptom onset, as well as more symptoms at presentation, were correlated with a longer duration of illness. This treatment strategy may have clinical benefit, warranting prospective clinical trials with confirmed COVID-19 cases.

Protocol for developing core outcome sets for evaluation of psychosocial interventions for children and families with experience or at risk of child maltreatment or domestic abuse.

INTRODUCTION: Recognition that child maltreatment (CM) and domestic violence and abuse (DVA) are common and have serious and long-term adverse health consequences has resulted in policies and programmes to ensure that services respond to and safeguard children and their families. However, high-quality evidence about how services can effectively intervene is scant. The value of the current evidence base is limited partly because of the variety of outcomes and measures used in evaluative studies. One way of addressing this limitation is to develop a core outcome set (COS) which is measured and reported as a minimum standard in the context of trials and other types of evaluative research. The study described in this protocol aims to develop two discrete COSs for use in future evaluation of psychosocial interventions aimed at improving outcomes for children and families at risk or with experience of (1) CM or (2) DVA. METHODS AND ANALYSIS: A two-phase mixed methods design: (1) rapid reviews of evidence, stakeholder workshops and semistructured interviews with adult survivors of CM/DVA and parents of children who have experienced CM/DVA and (2) a three panel adapted E-Delphi Study and consensus meeting. This study protocol adheres to reporting guidance for COS protocols and has been registered on the Core Outcome Measures for Effectiveness Trials (COMET) database. ETHICS AND DISSEMINATION: We will disseminate our findings through peer-reviewed and open access publications, the COMET website and presentations at international conferences. We will engage with research networks, journal editors and funding agencies to promote awareness of the CM-COS and DVA-COS. We will work with advisory and survivor and public involvement groups to coproduce a range of survivor, policy and practice facing outputs.Approval for this study has been granted by the Research Ethics Committee at University College London.

DOSE CONVERSION COEFFICIENTS FROM MONOENERGETIC NEUTRONS COMPUTED WITH THE MCNP6.2 CODE IN THE VIP-MAN PHANTOM.

Computational estimates of dosimetric quantities from external exposures to neutron fields are valuable to ongoing radiation protection studies that are of interest to US defense-focused organizations. Conversion coefficients for fluence-to-absorbed dose and fluence-to-effective dose were computed using version 6.2 of the Monte Carlo N-Particle® code (MCNP6.2) in the visible photographic man (VIP-Man) numerical model for 45 monoenergetic neutron fields between 10-9 and 20 MeV under six irradiation geometries. Comparisons to the formative VIP-Man study by Bozkurt et al. revealed excellent agreement. The mean relative difference between our VIP-Man/MCNP6.2-computed and the International Commission on Radiological Protection (ICRP) 116-published absorbed dose conversion coefficients in 14 organs and remainder tissues under all geometries was 4.7%, which is within ICRP-reported variations. The effective dose coefficients computed with VIP-Man/MCNP6.2 were strongly similar to ICRP 116 values in all geometries except for posterior-anterior, where the difference was attributed to shielding of anterior organs by the relatively fatty composition of the VIP-Man phantom.

Conservative treatment for uncomplicated appendicitis in children: the CONTRACT feasibility study, including feasibility RCT.

BACKGROUND: Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking. OBJECTIVES: The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children. DESIGN: This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set. SETTING: This study was set in three specialist NHS paediatric surgical units in England. PARTICIPANTS: Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set. INTERVENTIONS: Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial. DATA SOURCES: Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews. RESULTS: Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol. LIMITATIONS: Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time. CONCLUSIONS: A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres. FUTURE WORK: Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.

Appendicitis is usually treated with an operation to remove the appendix. But we have learned, from other research, that some children with appendicitis may not need an operation, and could be treated with antibiotics instead. To find out how these two different treatments compare with one another, we need to do a big study. First, though, we need to see if doing that kind of study would even be possible (or 'feasible'). We carried out a feasibility study that had several parts. First, we did a small study with children who had appendicitis, whereby children were randomly allocated to have either antibiotics or an operation, with an equal chance of having either treatment. Second, we asked parents and health-care staff about why they wanted, or did not want, to take part in that small study. This helped us to understand how to make a bigger future study as acceptable as possible to children, families and surgeons. Third, we asked parents, patients and surgeons what they think are the most important things ­ or 'outcomes' ­ we should look at in future research on children who have appendicitis. From that, we developed a list of outcomes that should be included in our future big study, so we can be certain that the research we do is likely to help parents and surgeons. Overall, we established that a future big study is feasible and we have plenty of information to help us with how to plan it best, so that it has the greatest possible chance of success. We were also guided in all of these steps of the research by a group of parents, children and young people, some of whom had appendicitis and some of whom did not.

CONservative TReatment of Appendicitis in Children: a randomised controlled feasibility Trial (CONTRACT).

OBJECTIVE: To establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis. DESIGN: Feasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial. SETTING: Three specialist paediatric surgery centres in the UK. PATIENTS: Children (aged 4-15 years) with a clinical diagnosis of uncomplicated acute appendicitis. INTERVENTIONS: Appendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation). MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course. RESULTS: Fifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable. CONCLUSION: Recruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible. TRIAL REGISTRATION NUMBER: ISRCTN15830435.

No evidence synthesis about me without me: Involving young people in the conduct and dissemination of a complex evidence synthesis.

OBJECTIVES: To describe and reflect on the methods and influence of involvement of young people with lived experience within a complex evidence synthesis. STUDY DESIGN AND SETTING: Linked syntheses of quantitative and qualitative systematic reviews of evidence about interventions to improve the mental health of children and young people (CYP) with long-term physical conditions (LTCs). METHODS: Involvement was led by an experienced patient and public involvement in research lead. Young people with long-term physical conditions and mental health issues were invited to join a study-specific Children and Young People's Advisory Group (CYPAG). The CYPAG met face to face on four occasions during the project with individuals continuing to contribute to dissemination following report submission. RESULTS: Eight young people joined the CYPAG. Their views and experiences informed (a) a systematic review evaluating the effectiveness of interventions intended to improve the mental health of CYP with LTCs, (b) a systematic review exploring the experiences of interventions intended to improve the mental well-being of CYP with LTCs and (c) an overarching synthesis. The CYPAG greatly contributed to the team's understanding and appreciation of the wider context of the research. The young people found the experience of involvement empowering and felt they would use the knowledge they had gained about the research process in the future. CONCLUSION: Creating an environment that enabled meaningful engagement between the research team and the CYPAG had a beneficial influence on the young people themselves, as well as on the review process and the interpretation, presentation and dissemination of findings.

The rectal route of medicine administration for children: Let's get to the bottom of it!

AIMS: Research around paediatric rectal drug delivery has previously been based on views of parents and healthcare workers. The aim of this exploratory study was to gauge whether children and young adults in the UK were comfortable with the idea of rectal drug delivery. METHODS: Eleven children from a pre-existing patient and public advisory group were involved in the session. Rectal drug delivery was explained and group participants were asked a series of questions. Responses were discussed in a group and recorded individually. RESULTS: Of the group, 27% would consider the rectal route, while 64% said it depended on other options available. The primary concern focused on potential for abusive misuse by others. Participants thought this would be overcome if the child could self-administer, although there was also concern about the process of self-administration. CONCLUSIONS: Not all children in the UK are against rectal drug delivery, but education is needed to teach children to self-administer medication in this way.

Experiences of interventions aiming to improve the mental health and well-being of children and young people with a long-term physical condition: A systematic review and meta-ethnography.

BACKGROUND: Children and young people with long-term physical health conditions are at increased risk of experiencing mental health and well-being difficulties. However, there is a lack of research that explores the experiences of and attitudes towards interventions aiming to improve their mental health and well-being. This systematic review seeks to address this gap in the literature by exploring what children and young people with long-term conditions, their caregivers, and health practitioners perceive to be important aspects of interventions aiming to improve their mental health and well-being. METHODS: An information specialist searched five academic databases using predefined criteria for qualitative evaluations of interventions aiming to improve the mental health or well-being of children with long-term physical conditions. Reviewers also performed supplementary citation and grey literature searches. Two reviewers independently screened titles, abstracts, and full texts that met the inclusion criteria and conducted data extraction and quality assessment. Meta-ethnography was used to synthesize the findings. RESULTS: Screening identified 60 relevant articles. We identified five overarching constructs through the synthesis: (a) Getting In and Staying In, (b) Therapeutic Foundation, (c) Social Support, (d) A Hopeful Alternative, and (e) Empowerment. The line of argument that links these constructs together indicates that when interventions can provide an environment that allows young people to share their experiences and build empathetic relationships, it can enable participants to access social support and increase feelings of hope and empowerment. CONCLUSION: These findings may provide a framework to inform the development of mental health interventions for this population and evaluate existing interventions that already include some of the components or processes identified by this research. Further research is needed to establish which of the constructs identified by the line of argument are most effective in improving the mental well-being of young people living with long-term conditions.