Rethinking the Body in the Brain after Spinal Cord Injury

Spinal cord injuries (SCI) are disruptive neurological events that severly affect the body leading to the interruption of sensorimotor and autonomic pathways. Recent research highlighted SCI-related alterations extend beyond than the expected network, involving most of the central nervous system and goes far beyond primary sensorimotor cortices. The present perspective offers an alternative, useful way to interpret conflicting findings by focusing on the deafferented and deefferented body as the central object of interest. After an introduction to the main processes involved in reorganization according to SCI, we will focus separately on the body regions of the head, upper limbs, and lower limbs in complete, incomplete, and deafferent SCI participants. On one hand, the imprinting of the body’s spatial organization is entrenched in the brain such that its representation likely lasts for the entire lifetime of patients, independent of the severity of the SCI. However, neural activity is extremely adaptable, even over short time scales, and is modulated by changing conditions or different compensative strategies. Therefore, a better understanding of both aspects is an invaluable clinical resource for rehabilitation and the successful use of modern robotic technologies.

INNV-26. NCI-CONNECT PROGRAM PROVIDES RESOURCES TO IMPROVE CARE FOR PEOPLE WITH RARE CENTRAL NERVOUS SYSTEM (CNS) TUMORS

The National Cancer Institute Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) program focuses on improving approaches to care and treatment for 12 rare CNS tumors, each with < 2,000 diagnoses per year. To reach this rare population, the primary objective was to develop a website to share educational resources that provide patients direct access to clinical care and trials. METHODS: The NCI-CONNECT website uses the Drupal platform within NCI’s framework and the content is free to syndicate. A multidisciplinary team developed tumor-specific content in English and Spanish, clinical trial information, and survivorship resources using evidence-based sources. The Central Brain Tumor Registry of the United States provided statistics on incidence and prevalence of rare tumors. Population reach was calculated using Adobe Experience Cloud website analytics. NCI-CONNECT referrals and study participation data were collected prospectively. RESULTS: The English website launched in September 2018 and visits have increased 2,384%. The Spanish website launched in March 2020 and visits have increased 1,137%. From April 2020 to March 2021, top website page views by English page views / Spanish page views / people living with this disease include oligodendroglioma (43,859 / 8,241 / 11,757), ependymoma (31,579 / 12,684 / 13,294), meningioma (30,261 / 19,507 / 2,692), medulloblastoma (28,487 / 9,999 / 3,840), diffuse midline gliomas (23,064 / 3,851 / 6,033), and pineal region tumors (19,939 / 9,973 / 1,297). Referral rates and participation have accelerated – 45% of patients visiting the Neuro-Oncology Clinic at NIH have a rare CNS tumor and 409 patients enrolled in an NCI-CONNECT study. CONCLUSION: Patient-focused websites can provide guidance to those affected by rare cancers outside of in-person health care visits. The NCI-CONNECT website is an educational and clinical resource for patients and families affected by rare CNS tumors and was created to raise awareness and improve patient outcomes.

144. Antifungal Use Trends in Hospitalized Adults in the United States, 2016-2020

Background Surveillance of antimicrobial use is a cornerstone of antimicrobial stewardship, though antifungal (AF) use is less frequently characterized. AFs are a major driver of inpatient costs and their use both reflects and drives changes in fungal susceptibility patterns. We report on trends in AF use in a large sample of United States hospitals over time including predictors of AF use. Methods We performed a retrospective analysis of adult inpatient visits between 2016 and 2020 at hospitals contributing data to the Vizient Clinical Database/Clinical Resource Manager (www.vizientinc.com). Inpatient use of systemically administered AFs was investigated as a function of study quarter, diagnosis code, and underlying immunosuppressive condition. Changes in AF use were modeled using logistic and negative binomial regression. Results We examined over 23 million admissions across 470 hospitals, 43% of which were classified as teaching hospitals and 54% of which performed solid organ transplants. During the study period, 4.03% (951,284/23,565,493) of admissions were billed for one or more of the study AFs. Among admissions receiving AFs, 86% received an azole, with the most frequently used agent being fluconazole, which accounted for for 46% of total AF days. Likelihood of AF receipt during admission increased by quarter (OR 1.012, p< 0.001), controlling for length of stay, presence of fungal infection, hematologic malignancy (HM), or solid organ transplant (SOT). Odds of any receipt and days of therapy (DOT) of fluconazole, isavuconazole, posaconazole, and echinocandins increased over the study period while those of voriconazole, itraconazole, and flucytosine decreased; odds of receipt of amphotericin products increased while DOT decreased; flucytosine receipt odds increased while DOT did not change. Only 30% of admissions with AF use were associated with a documented fungal infection, with 93% of these episodes documented as candidiasis. Admissions associated with SOT or HM represented 2% and 3% of all patient-days, but 11% and 25% of total AF days, respectively. Antifungal Utilization Conclusion AF use increased significantly over the study period, with changes across agents and classes. Most AF use occurred in the absence of administratively documented infection and was more common among SOT and HM patients. Disclosures All Authors: No reported disclosures

Collaborative Goal Setting: A Clinical Approach for Adults With Mild Traumatic Brain Injury

Purpose Speech-language pathologists (SLPs) have many available procedural options when setting treatment goals. Extant literature supports goal setting protocols that include and value the perspectives of the client; however, in practice, rehabilitation professionals may lean toward expert models of care when planning treatment. Our purpose is to describe a newly developed approach for SLPs and individuals with mild traumatic brain injury (mTBI) to work together to build meaningful, relevant goals. Method We utilized a multiple case study format to exemplify goal setting procedures. Specifically, we describe procedures and outcomes for a 29-year-old female 28 days postinjury and a 70-year-old male 9 months postinjury. Results Clients who engaged in this protocol worked collaboratively with a clinician to identify strengths and challenges postinjury, select and prioritize goal areas, and discuss and develop meaningful, personalized treatment activities. For both participants, use of the proposed protocol resulted in meaningful goals that addressed their self-reported deficits as well as their respective cognitive–linguistic deficits noted on objective, standardized measures. Conclusions Clinician and client collaboration during treatment goal development can facilitate increased client motivation and functional outcomes. The described approach is feasible from a clinical resource standpoint and promotes a systematic approach to placing the client at the forefront of clinical decision making to enhance therapeutic gains. Such client-centered approaches may be particularly valuable for individuals with mTBI who experience substantial cognitive and communicative challenges but may maintain high levels of self-awareness postinjury.

Patient and health provider costs of integrated HIV, diabetes and hypertension ambulatory health services in low-income settings — an empirical socio-economic cohort study in Tanzania and Uganda

Background Integration of health services might be an efficient strategy for managing multiple chronic conditions in sub-Saharan Africa, considering the scope of treatments and synergies in service delivery. Proven to promote compliance, integration may lead to increased economies-of-scale. However, evidence on the socio-economic consequences of integration for providers and patients is lacking. We assessed the clinical resource use, staff time, relative service efficiency and overall societal costs associated with integrating HIV, diabetes and hypertension services in single one-stop clinics where persons with one or more of these conditions were managed. Methods 2273 participants living with HIV infection, diabetes, or hypertension or combinations of these conditions were enrolled in 10 primary health facilities in Tanzania and Uganda and followed-up for up to 12 months. We collected data on resources used from all participants and on out-of-pocket costs in a sub-sample of 1531 participants, while a facility-level costing study was conducted at each facility. Health worker time per participant was assessed in a time-motion morbidity-stratified study among 228 participants. The mean health service cost per month and out-of-pocket costs per participant visit were calculated in 2020 US$ prices. Nested bootstrapping from these samples accounted for uncertainties. A data envelopment approach was used to benchmark the efficiency of the integrated services. Last, we estimated the budgetary consequences of integration, based on prevalence-based projections until 2025, for both country populations. Results Their average retention after 1 year service follow-up was 1911/2273 (84.1%). Five hundred and eighty-two of 2273 (25.6%) participants had two or all three chronic conditions and 1691/2273 (74.4%) had a single condition. During the study, 84/2239 (3.8%) participants acquired a second or third condition. The mean service costs per month of managing two conditions in a single participant were $39.11 (95% CI 33.99, 44.33), $32.18 (95% CI 30.35, 34.07) and $22.65 (95% CI 21.86, 23.43) for the combinations of HIV and diabetes and of HIV and hypertension, diabetes and hypertension, respectively. These costs were 34.4% (95% CI 17.9%, 41.9%) lower as compared to managing any two conditions separately in two different participants. The cost of managing an individual with all three conditions was 48.8% (95% CI 42.1%, 55.3%) lower as compared to managing these conditions separately. Out-of-pocket healthcare expenditure per participant per visit was $7.33 (95% CI 3.70, 15.86). This constituted 23.4% (95% CI 9.9, 54.3) of the total monthly service expenditure per patient and 11.7% (95% CI 7.3, 22.1) of their individual total household income. The integrated clinics’ mean efficiency benchmark score was 0.86 (range 0.30–1.00) suggesting undercapacity that could serve more participants without compromising quality of care. The estimated budgetary consequences of managing multi-morbidity in these types of integrated clinics is likely to increase by 21.5% (range 19.2–23.4%) in the next 5 years, including substantial savings of 21.6% on the provision of integrated care for vulnerable patients with multi-morbidities. Conclusion Integration of HIV services with diabetes and hypertension control reduces both health service and household costs, substantially. It is likely an efficient and equitable way to address the increasing burden of financially vulnerable households among Africa’s ageing populations. Additional economic evidence is needed from longer-term larger-scale implementation studies to compare extended integrated care packages directly simultaneously with evidence on sustained clinical outcomes.

The New National Headache Management System is an easy solution to provide more efficient and evidence-based headache services

Headaches make up 30% of all Neurology outpatient consultations.1 There is distinct variability in the management of headaches by Neurologists, leading to unnecessary disparities in the standard of care and likelihood of response between patients. A significant proportion of patients with headache diagnoses do not receive the evidence-based treatments recommended in national or international guidelines,2 and substantial numbers of patients are not receiving preventive therapies.3 Ziegeler et al. found that a third of patients reporting to a tertiary headache centre had not received preventive therapy in line with guidelines, and half had never been prescribed a preventive treatment.2 Considering that 46% of the global adult population are estimated to have a headache disorder,4 this lack of a consistent, evidence-based approach is somewhat incongruent with the patient socio-economic impact. It is probable that lack of adherence to current headache guidelines is a multi-faceted issue. This variation in treatment (and therefore patient outcome), although unexplored,2 is not likely to be a simple educational issue. To add to this, an educational approach, in the form of seminars and workshops, does not have entirely positive evidence to support its use in implementing changes to patient care.5 It seems more probable that there are also structural issues within the health service that in some way preclude patients with headache disorders from gaining appropriate care. For example, using only doctors to care for patients with such a common condition may cause bottle-necking in access, and may not be an appropriate use of clinical resource. The current context of a global pandemic has shown us the importance of using the skillsets of all NHS staff working together for patient care. For headache care this could involve greater use of nursing colleagues or allied health professionals such as Pharmacists. To facilitate such an aim, an easily used and standardised approach is essential. We believe that the guidelines from the British Association for the Study of Headache (BASH),6 could facilitate such an approach.

P–552 Delayed blastocyst development is associated with a higher risk of aneuploidy in patients of advanced maternal age

Study question Is delayed blastocyst development, assessed by the day of trophectoderm (TE) biopsy, associated with higher rates of aneuploidy? Summary answer Our findings show an association between delayed blastocyst development and poorer prognosis, in terms of euploidy rates, in patients of advanced maternal age. What is known already Extended culture of embryos past day 5 of development has become routine practice in all freeze-all cycles, including those applying preimplantation genetic testing for aneuploidies (PGT-A). As healthy live births have been obtained from day 6 and day 7 blastocysts, increasing the pool of embryos available for PGT-A is beneficial, particularly for patients of advanced maternal age who face higher cancellation rates. Nevertheless, the association between delayed blastocyst development and aneuploidy rates remains unclear. As current studies have reported opposing findings, detailed analysis of the chromosomal constitution of slowly developing embryos remains paramount. Study design, size, duration Retrospective, international, multicentre cohort study of 4211 patients undergoing preimplantation genetic testing for aneuploidy (PGT-A) from January 2016 to July 2020. We evaluated the chromosomal status of 14757 blastocysts tested using TE biopsy and next generation sequencing (NGS). Both autologous and donation cycles were included in the analysis. Cycles were excluded if they utilised preimplantation genetic testing for monogenic disorders (PGT-M) or preimplantation genetic testing for structural rearrangements (PGT-SR). Participants/materials, setting, methods We evaluated euploidy, aneuploidy and mosaicism rates reported in day 5 (n = 9560), day 6 (n = 4753) and day 7 (n = 262) blastocysts, stratified by SART-defined maternal age categories (<35, 35–37, 38–40, 41–42, >42). We further assessed the type and frequency of abnormalities reported in all blastocysts classified as clinically unsuitable, according to the day of biopsy. Finally, we examined the specific chromosomes affected in embryos diagnosed with a single uniform (n = 3882) or single mosaic (n = 518) abnormality. Main results and the role of chance The mean maternal age within our patient cohort was 39.9±3.7. Overall, slowly developing blastocysts were significantly more likely to be classified as clinically unsuitable (60.6%) compared to day 5 embryos (55.2%; p < 0.0001). This correlation was also observed when stratified by age, with the exception of the <35 age group (p = 0.25). Markedly, the risk of aneuploidy in slowly developing blastocysts became progressively higher with advancing maternal age (p < 0.0001). We did not observe any significant differences in the types of abnormalities diagnosed in slowly developing embryos compared to day 5 blastocysts. Nevertheless, abnormalities affecting all chromosomes were present at the blastocyst stage. Single trisomies and monosomies were the most frequent across all age groups, and were equally prevalent in day 5, 6 and 7 blastocysts. These most commonly affected chromosomes 16, 22, 21 and 15. We observed no significant differences in the incidence of segmental aneuploidies in relation to the day of biopsy, across all age groups. When considered separately, day 7 blastocysts presented with higher rates of structural aberrations, however low numbers limited statistical power. Finally, delayed blastocyst development was not associated with higher mosaicism rates (p = 0.79). Interestingly, single mosaic trisomies and monosomies were most frequently associated with chromosome 19. Limitations, reasons for caution Due to the retrospective nature of the study, full elucidation of all potential confounders may not be possible in all instances. The low number of day 7 blastocysts limited statistical power. As such, the results from day 6 and day 7 embryos were evaluated together. Wider implications of the findings: Our findings offer an important clinical resource for counselling patients of advanced maternal age. Maternal aging may be associated with a higher incidence of aneuploidy in slowly developing blastocysts. Nevertheless, extended culture increases the pool of biopsiable blastocysts, ultimately improving the chance of having a euploid embryo for transfer. Trial registration number NA