Designing Multivalent and Multispecific Biologics.

In the era of precision medicine, multivalent and multispecific therapeutics present a promising approach for targeted disease intervention. These therapeutics are designed to interact with multiple targets simultaneously, promising enhanced efficacy, reduced side effects, and resilience against drug resistance. We dissect the principles guiding the design of multivalent biologics, highlighting challenges and strategies that must be considered to maximize therapeutic effect. Engineerable elements in multivalent and multispecific biologic design-domain affinities, valency, and spatial presentation-must be considered in the context of the molecular targets as well as the balance of important properties such as target avidity and specificity. We illuminate recent applications of these principles in designing protein and cell therapies and identify exciting future directions in this field, underscored by advances in biomolecular and cellular engineering and computational approaches. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering , Volume 15 is June 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Qualitative perspectives on COVID-19, interpersonal violence, and interventions to improve well-being from adolescent girls and young women in Kisumu, Kenya.

Introduction: Adolescent girls and young women (AGYW) face a high burden of gender-based violence (GBV) worldwide. The COVID-19 pandemic and associated policies led to global increases in GBV, decreased access to resources, and disruptions of pathways to care. We aimed to understand the effects of COVID-19 on AGYW affected by GBV in Kisumu, Kenya, as well as to identify possible interventions to mitigate those effects. Methods: Focus group discussions (FGDs) were conducted with AGYW aged 15-25 with a history of exposure to GBV. AGYW were split into age-matched groups; aged 15-19 for younger groups and 19-25 for older groups. Discussions focused on how COVID-19 affected experiences of GBV, access to care services, economic and social outcomes, and opportunities for interventions to mitigate negative impacts of COVID-19 and violence. Results: Five FGDs with 46 AGYW were completed in June-September 2021. AGYW described increases in all types of GBV, particularly sexual abuse and intimate partner violence. Early marriage and subsistence transactional sex also increased. AGYW described violence as both a cause and effect of poor economic, social and health consequences related to the pandemic. Notably, AGYW emphasized stress, lack of mental health support and increased substance use as risk factors for violence, and discussed the deleterious mental health effects of violence-particularly in the wake of disruption of mental health services. COVID-19 disrupted referrals to violence-related services, and reduced access to both medical services and psychosocial services. AGYW believed that interventions focused on improving mental health as well as economic empowerment would be the most feasible and acceptable in mitigating the negative effects of COVID-19 and related exacerbations in violence. Discussion: AGYW reported increases in almost all forms of GBV during the pandemic, with related exacerbation in mental health. Concurrently, AGYW endorsed decreased access to care services. As there is no evidence that violence and mental health challenges will quickly resolve, there is an urgent need to identify and implement interventions to mitigate these negative effects.

Understanding ART Adherence among Adolescent Girls and Young Women in Western Kenya: A Cross-Sectional Study of Barriers and Facilitators.

BACKGROUND: HIV remains a leading cause of death for adolescent girls and young women (AGYW) in sub-Saharan Africa. This population has a high incidence of HIV and other comorbidities, such as experiencing violence, and low antiretroviral therapy (ART) adherence. To reach global HIV goals, data are needed on the specific adherence barriers for AGYW living with HIV, so interventions can be targeted effectively. METHODS: Cross-sectional data were collected at urban and rural health facilities in and around Kisumu County, western Kenya, from January to June 2022, from AGYW 15-24 years of age who were living with HIV. Surveys included questions on intimate partner violence, mental health issues, food security, and orphanhood. Adherence was categorized using viral load testing where available and the Center for Adherence Support Evaluation (CASE) adherence index otherwise. Logistic regression was used to assess associations between potential explanatory variables and adherence. FINDINGS: In total, 309 AGYW participated. AGYW with experiences of emotional violence (Odds Ratio [OR] = 1.94, 95% Confidence Interval [CI] = 1.03-3.66), moderate or severe depression (OR = 3.19, 95% CI = 1.47-6.94), and/or substance use (OR = 2.71, 95% CI = 1.24-5.92) had significantly higher odds of poor adherence when compared to AGYW without these respective experiences. Physical and sexual violence, food insecurity, and orphanhood were not associated with poor adherence in this cohort. INTERPRETATION: Elucidating the risk factors associated with poor adherence among AGYW living with HIV allows us to identify potential targets for future interventions to improve ART adherence and HIV care outcomes. Mental health and violence prevention interventions, including combination interventions, may prove to be promising approaches.

Effect of graphene-based nanomaterials on corneal wound healing in vitro.

Graphene-based nanomaterials (GBNs) are widely used due to their chemical and physical properties for multiple commercial and environmental applications. From an occupational health perspective, there is concern regarding the effects of inhalation on the respiratory system, and many studies have been conducted to study inhalation impacts on lung. Similar to the respiratory system, the eyes may also be exposed to GBNs and thus impacted. In this study, immortalized human corneal epithelial (hTCEpi) cells and rabbit corneal fibroblasts (RCFs) were used to investigate the toxicity of eight types of GBN: graphene oxide (GO; 400 nm), GO (1 µm), partially reduced graphene oxide (PRGO; 400 nm), reduced graphene oxide (RGO; 400 nm), RGO (2 µm), graphene (110 nm), graphene (140 nm), and graphene (1 µm). We next examined the effects of these GBNs on hTCEpi cell migration. We also determined whether the expression of α-smooth muscle actin (αSMA), a myofibroblast marker, is altered by the GBNs using RCFs. We found that RGO (400 nm) and RGO (2 µm) were highly toxic to hTCEPi cells and RCFs meanwhile, PRGO (400 nm) was toxic only to hTCEpi cells. In addition, PRGO (400 nm), RGO (400 nm), and RGO (2 µm) inhibited hTCEpi cell migration and significantly increased αSMA mRNA expression. Further study in vivo is required to determine if RGO nanomaterials delay corneal epithelial healing and induce scar formation.

Prevalence of Osteoporosis in Cirrhosis: A Systematic Review and Meta-Analysis.

The prevalence of osteoporosis in individuals with cirrhosis varies based on the diagnostic approach and etiology of the underlying liver disease. This systematic review aims to evaluate the prevalence of osteoporosis in individuals with cirrhosis. Electronic databases were searched for studies reporting the prevalence of osteoporosis among patients with cirrhosis. The primary outcome was the presence of osteoporosis, as determined by a dual-energy x-ray absorptiometry (DEXA) scan. Secondary outcomes were levels of biochemical markers of bone metabolism, including calcium, vitamin D, phosphorus, and parathormone (PTH) levels. A cohort of 836 patients from 10 studies was included in the final analysis. The pooled rate of osteoporosis was 14.80% (95% CI: 14.19-15.49). Pooled levels of biochemical markers of bone metabolism were as follows: calcium 9.09 mg/dL (95% CI: 8.73-9.45), 25-hydroxyvitamin D (25-OH vitamin D) 15.41 ng/mL (95% CI: 14.79-16.03), phosphorus 15.41 mg/dL (95% CI: 2.99-3.51), and PTH 26.58 pg/mL (95% CI: 25.45-27.71). Pooled levels of liver biochemistries were: bilirubin 3.04 mg/dL (95% CI: 2.84-3.25), aspartate aminotransferase (AST) 65.35 U/L (95% CI: 61.39-69.31), alanine aminotransferase (ALT) 50.17 U/L (95% CI: 46.18-54.10), alkaline phosphatase 133.31 U/L (95% CI: 124.89-141.73), and albumin 3.25 g/dL (95% CI: 3.05-3.45). Cirrhosis appears to be associated with an increased risk for osteoporosis, with a pooled prevalence of 15%. This can include men and individuals younger than 50 years of age, a cohort not typically considered to be at an increased risk of osteoporosis. Levels of 25-hydroxyvitamin D and insulin-like growth factor-1 (IGF-1) were also significantly low. Further studies are required to evaluate the risk of osteoporosis based on the etiology and stage of cirrhosis, especially in younger males, to incorporate this into future prediction models for fragility fractures.

Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation In Vitro.

Corneal opacification due to fibrosis is a leading cause of blindness worldwide. Fibrosis occurs from many causes including trauma, photorefractive surgery, microbial keratitis (infection of the cornea), and chemical burns, yet there is a paucity of therapeutics to prevent or treat corneal fibrosis. This study aimed to determine if andrographolide, a labdane diterpenoid found in Andrographis paniculate, has anti-fibrotic properties. Furthermore, we evaluated if andrographolide could prevent the differentiation of fibroblasts to myofibroblasts in vitro, given that the transforming growth factor beta-1(TGF-ß1) stimulated persistence of myofibroblasts in the cornea is a primary component of fibrosis. We demonstrated that andrographolide inhibited the upregulation of alpha smooth muscle actin (αSMA) mRNA and protein in rabbit corneal fibroblasts (RCFs), thus, demonstrating a reduction in the transdifferentiation of myofibroblasts. Immunofluorescent staining of TGF-ß1-stimulated RCFs confirmed a dose-dependent decrease in αSMA expression when treated with andrographolide. Additionally, andrographolide was well tolerated in vivo and had no impact on corneal epithelialization in a rat debridement model. These data support future studies investigating the use of andrographolide as an anti-fibrotic in corneal wound healing.

Ultra-Early Cranioplasty versus Conventional Cranioplasty: A Retrospective Cohort Study at an Academic Level 1 Trauma Center.

The goal of this study was to ascertain the efficacy, safety, and comparability of ultra-early cranioplasty (CP; defined here as <30 days from the original craniectomy) to conventional cranioplasty (defined here as >30 days from the original craniectomy). A retrospective review of CPs performed at our institution between January 2016 and July 2020 was performed. Craniectomies initially performed at other institutions were excluded. Seventy-seven CPs were included in our study. Ultra-early CP was defined as CP performed within 30 days of craniectomy whereas conventional CP occurred after 30 days. Post-operative wound infection rates, rate of return to the operating room (OR) with or without bone flap removal, operative length, and rate of post-CP hydrocephalus were compared between the two groups. Thirty-nine and 38 patients were included in the ultra-early and conventional CP groups, respectively. The average number of days to CP in the ultra-early group was 17.70 ± 7.75 days compared to 95.70 ± 65.60 days in the conventional group. The mean Glasgow Coma Scale upon arrival to the emergency room was 7.28 ± 3.90 and 6.92 ± 4.14 for the ultra-early and conventional groups, respectively. The operative time was shorter in the ultra-early cohort than that in the conventional cohort (ultra-early, 2.40 ± 0.71 h; conventional, 3.00 ± 1.63 h; p = 0.0336). The incidence of post-CP hydrocephalus was also lower in the ultra-early cohort (ultra-early, 10.3%; conventional, 31.6%; p = 0.026). No statistically significant differences were observed regarding post-operative infection, return to the OR, or bone flap removal. Our study shows that ultra-early CP can significantly reduce the rate of post-CP hydrocephalus, as well as operative time in comparison to conventional CP. However, the timing of CP post-DC should remain a patient-centered consideration.

Development of the Bleeding and Pelvic Discomfort Scale for Use in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids.

OBJECTIVES: This study aimed to define a cardinal symptom burden measure based on items from the Uterine Fibroid Symptom and Quality of Life questionnaire for use as a clinical trial endpoint. METHODS: Exploratory factor analysis was computed to assess the Uterine Fibroid Symptom and Quality of Life symptom severity scale factor structure, using phase 2 data. Pooled blinded data from phase 3 studies were used for the confirmatory factor analysis and the psychometric evaluation of the new measure. Exit interviews in 30 patients from phase 3 studies provided additional qualitative evidence. A meaningful change threshold was determined using anchor-based analyses supported by patient feedback in the exit interviews. RESULTS: Three factors emerged from the exploratory factor analysis. Factor 1, called the bleeding and pelvic discomfort (BPD) scale, consists of cardinal symptoms, measuring menstrual distress owing to heavy bleeding, passing blood clots, and feeling tightness or pressure in pelvic area. Patients generally understood the items in the scale and the recall period as intended. The BPD scale had good item performance and internal consistency reliability, strong item-to-total correlations, good item discrimination, known-groups validity, and ability to detect change. A 20-point change on the BPD scale was determined as the clinically meaningful change threshold. CONCLUSIONS: The BPD scale assesses symptom burden owing to bleeding, passing blood clots, and pelvic pressure. The subscale is based on a subset of items selected to measure the cardinal symptoms of uterine fibroids in a clinical trial setting. The responder threshold evaluates whether patients experience a meaningful treatment benefit over the on-treatment period.

Youth voices from an informal settlement of Nairobi, Kenya: Engaging adolescent perspectives on violence to inform prevention.

We examined the experiences of violence and self-reported behavioural and community changes as a result of participation in a sexual assault prevention intervention in an informal settlement in Nairobi, Kenya. We conducted longitudinal qualitative in-depth interviews with 20 adolescent girls and 11 adolescent boys at baseline, 12, and 24 months. Analysis was thematic with two investigators coding and reaching consensus about the themes. Participants' ages ranged from 10 to 13 at baseline; girls' mean age was 11.9, boys' mean age was 11.6. Participants reported experiencing high levels of violence at all stages of the study. Most reported feeling more empowered to protect themselves and others from sexual assault because of the intervention. While participants had mixed responses about change in sexual assault incidence, most perceived an improvement in inter-gender relationships after the intervention. Participants at midline and endline cited acquaintances and friends as potential perpetrators of sexual violence more often than at baseline and were more open to reporting violent incidents. The very young adolescents in this setting perceived that this sexual assault prevention intervention led to improvements in gender relations, adolescent girls' empowerment and, recognition of harmful rape myths.Trial registration: ClinicalTrials.gov identifier: NCT02771132.

Differences of the Nasal Microbiome and Mycobiome by Clinical Characteristics of COPD Patients.

Rationale: While studies suggest that the lung microbiome may influence risk of chronic obstructive pulmonary disease (COPD) exacerbations, little is known about the relationship between the nasal biome and clinical characteristics of COPD patients. Methods: We sampled the nasal lining fluid by nasosorption of both nares of 20 people with moderate-to-severe COPD. All 40 samples, plus 4 negative controls, underwent DNA extraction, and 16SV4 ribosomal RNA (rRNA) (bacterial) and ribosomal internal transcribed spacer 2 (ITS2) (fungal) sequencing. We measured the proportion of variance (R2) in beta diversity explained by clinical factors, including age, sex, body mass index (BMI), COPD treatment, disease severity (forced expiratory volume in 1 second [FEV1], symptom/exacerbation frequency), peripheral eosinophil level (≥150 versus <150 cells/µL) and season of sampling, with the PERMANOVA test on the Bray-Curtis dissimilarities, accounting for within-person correlation of samples. We assessed the relative abundance of microbial features in the nasal community and their associations with clinical characteristics using the Microbiome Multivariable Association with Linear Models (MaAsLin2) package. Results: The most abundant nasal fluid bacterial taxa were Corynebacterium, Staphylococcus, Streptococcus, Moraxella, and Dolosigranulum, and fungal taxa were Malassezia, Candida, Malasseziales, Cladosporium and Aspergillus. Bacterial microbiome composition was associated with short-acting muscarinic antagonist use (R2 11.8%, p=0.002), sex (R2 8.3%, p=0.044), nasal steroid use (R2 7.7%, p=0.064), and higher eosinophil level (R2 7.6%, p=0.084). Mycobiome composition was associated with higher eosinophil level (R2 14.4%, p=0.004) and low FEV1 (R2 7.5%, p=0.071). No specific bacterium or fungus differed significantly in relative abundance by clinical characteristics in the multivariate per-feature analysis. Conclusion: The taxonomical composition of the nasal biome is heterogeneous in COPD patients and may be explained in part by clinical characteristics.

Convection-enhanced delivery for high-grade glioma.

Glioblastoma (GBM) is the most common adult primary malignant brain tumor and is associated with a dire prognosis. Despite multi-modality therapies of surgery, radiation, and chemotherapy, its 5-year survival rate is 6.8%. The presence of the blood-brain barrier (BBB) is one factor that has made GBM difficult to treat. Convection-enhanced delivery (CED) is a modality that bypasses the BBB, which allows the intracranial delivery of therapies that would not otherwise cross the BBB and avoids systemic toxicities. This review will summarize prior and ongoing studies and highlights practical considerations related to clinical care to aid providers caring for a high-grade glioma patient being treated with CED. Although not the main scope of this paper, this review also touches upon relevant technical considerations of using CED, an area still under much development.

Electrographic Seizure Detection by Neuroscience Intensive Care Unit Nurses via Bedside Real-Time Quantitative EEG.

OBJECTIVE: Our primary objective was to determine the performance of real-time neuroscience intensive care unit (neuro-ICU) nurse interpretation of quantitative EEG (qEEG) at the bedside for seizure detection. Secondary objectives included determining nurse time to seizure detection and assessing factors that influenced nurse accuracy. METHODS: Nurses caring for neuro-ICU patients undergoing continuous EEG (cEEG) were trained using a 1-hour qEEG panel (rhythmicity spectrogram and amplitude-integrated EEG) bedside display. Nurses' hourly interpretations were compared with post hoc cEEG review by 2 neurophysiologists as the gold standard. Diagnostic performance, time to seizure detection compared with standard of care (SOC), and effects of other factors on nurse accuracy were calculated. RESULTS: A total of 109 patients and 65 nurses were studied. Eight patients had seizures during the study period (7%). Nurse sensitivity and specificity for the detection of seizures were 74% and 92%, respectively. Mean nurse time to seizure detection was significantly shorter than SOC by 132 minutes (Cox proportional hazard ratio 6.96). Inaccurate nurse interpretation was associated with increased hours monitored and presence of brief rhythmic discharges. CONCLUSIONS: This prospective study of real-time nurse interpretation of qEEG for seizure detection in neuro-ICU patients showed clinically adequate sensitivity and specificity. Time to seizure detection was less than that of SOC. TRIAL REGISTRATION INFORMATION: Clinical trial registration number NCT02082873. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that neuro-ICU nurse interpretation of qEEG detects seizures in adults with a sensitivity of 74% and a specificity of 92% compared with traditional cEEG review.

Metal Oxide Engineered Nanomaterials Modulate Rabbit Corneal Fibroblast to Myofibroblast Transformation.

Purpose: Corneal keratocyte-fibroblast-myofibroblast (KFM) transformation plays a critical role in corneal stromal wound healing. However, the impact of engineered nanomaterials (ENMs), found in an increasing number of commercial products, on this process is poorly studied. This study investigates the effects of metal oxide ENMs on KFM transformation in vitro and in vivo. Methods: Cell viability of rabbit corneal fibroblasts (RCFs) was tested following treatment with 11 metal oxide ENMs at concentrations of 0.5 to 250 µg/ml for 24 hours. Messenger RNA (mRNA) and protein expression of αSMA, a marker of myofibroblast transformation, were measured using RCFs after exposure to 11 metal oxide ENMs at a concentration that did not affect cell viability, in media containing either 0 or 10 ng/ml of TGF-ß1. Additionally, the effect of topical Fe2O3 nanoparticles (NPs) (50 ng/ml) on corneal stromal wound healing following phototherapeutic keratectomy (PTK) was determined. Results: V2O5, Fe2O3, CuO, and ZnO ENMs were found to significantly reduce cell viability as compared to vehicle control and the other seven metal oxide ENMs tested. V2O5 nanoflakes significantly reduced mRNA and protein αSMA concentrations in the presence of TGF-ß1. Fe2O3 NPs significantly increased αSMA mRNA expression in the presence of TGF-ß1 but did not alter αSMA protein expression. Topically applied Fe2O3 NPs in an in vivo rabbit corneal stromal wound healing model did not delay healing. Conclusions: Fe2O3 NPs promote corneal myofibroblast induction in vitro but do not impair corneal stromal wound healing in vivo. Translational Relevance: These experimental results can apply to human nanomedical research.

Primary brain tumor patients admitted to a US intensive care unit: a descriptive analysis.

Purpose: To describe our population of primary brain tumor (PBT) patients, a subgroup of cancer patients whose intensive care unit (ICU) outcomes are understudied. Methods: Retrospective analysis of PBT patients admitted to an ICU between 2013 to 2018 for an unplanned need. Using descriptive analyses, we characterized our population and their outcomes. Results: Fifty-nine PBT patients were analyzed. ICU mortality was 19% (11/59). The most common indication for admission was seizures (n = 16, 27%). Conclusion: Our ICU mortality of PBT patients was comparable to other solid tumor patients and the general ICU population and better than patients with hematological malignancies. Further study of a larger population would inform guidelines for triaging PBT patients who would most benefit from ICU-level care.

Lay abstract Purpose: Data are lacking regarding outcomes of patients with primary brain tumors (PBTs) admitted to an intensive care unit (ICU), which may it difficult for ICU providers to know who of these patients will best benefit from ICU-level care. We aimed to describe our patient population to contribute to the limited data. Methods: We performed a retrospective analysis of critically ill PBT patients in our ICU. Results: Of 59 patients analyzed, ICU mortality was 19% (11/59), and the most common indication for admission was seizures (n = 16, 27%). Conclusion: Our ICU mortality of PBT patients was comparable to other solid tumor patients and the general ICU population and better than patients with hematological malignancies.

Progression of vertebral bone disease in mucopolysaccharidosis VII dogs from birth to skeletal maturity.

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient ß-glucuronidase activity, leading to accumulation of incompletely degraded heparan, dermatan and chondroitin sulfate glycosaminoglycans. Patients with MPS VII exhibit progressive spinal deformity, which decreases quality of life. Previously, we demonstrated that MPS VII dogs exhibit impaired initiation of secondary ossification in the vertebrae and long bones. The objective of this study was to build on these findings and comprehensively characterize how vertebral bone disease manifests progressively in MPS VII dogs throughout postnatal growth. Vertebrae were collected postmortem from MPS VII and healthy control dogs at seven ages ranging from 9 to 365 days. Microcomputed tomography and histology were used to characterize bone properties in primary and secondary ossification centers. Serum was analyzed for bone turnover biomarkers. Results demonstrated that not only was secondary ossification delayed in MPS VII vertebrae, but that it progressed aberrantly and was markedly diminished even at 365 days-of-age. Within primary ossification centers, bone volume fraction and bone mineral density were significantly lower in MPS VII at 180 and 365 days-of-age. MPS VII growth plates exhibited significantly lower proliferative and hypertrophic zone cellularity at 90 days-of-age, while serum bone-specific alkaline phosphatase (BAP) was significantly lower in MPS VII dogs at 180 days-of-age. Overall, these findings establish that vertebral bone formation is significantly diminished in MPS VII dogs in both primary and secondary ossification centers during postnatal growth.

Palliative Care Use for Critically Ill Patients With Brain Metastases.

CONTEXT: Critically ill patients with brain metastases (BM) face significant uncertainty regarding prognosis and survival and can benefit from Palliative care (PC). However, research regarding the role of PC in this population is lacking. OBJECTIVES: We sought to compare BM patients admitted to an intensive care unit who received an inpatient PC consult (PC cohort) to those who did not (Usual Care, UC cohort). METHODS: We performed a single-institution retrospective cohort analysis. Our outcome variables were mortality, time from intensive care unit admission to death, disposition, and change in code status. We also evaluated PC's role in complex medical decision making, symptom management and hospice education. RESULTS: PC consult was placed in 31 of 118 (28%) of patients. The overall mortality rates were not statistically different (78.8% vs. 90.3%, P= 0.15, UC vs. PC cohort). Patients in the PC cohort had a shorter time to death, higher rate of death within 30 days of admission, increased rate of discharge to hospice, and increase percentage of code status change to "do not attempt resuscitation" during the admission. The primary services provided by PC were symptom management (n = 21, 67.7%) and assistance in complex medical decision making (n = 20, 64.5%). CONCLUSION: In our patient cohort, PC is an underutilized service that can assist in complex medical decision making and symptom management of critically ill BM patients. Further prospective studies surveying patient, family and provider experiences could better inform the qualitative impact of PC in this unique patient population.

Targeted housestaff intervention reduces opioid use without worsening patient-reported pain scores and improves outcomes among patients with IBD: the "IBD pain ladder".

BACKGROUND AND AIMS: Opioid analgesic use is associated with increased mortality, higher readmission rates, and reduced quality of life among patients with inflammatory bowel disease (IBD). With the goal of reducing inpatient opioid use among patients with IBD admitted to our inpatient gastroenterology (GI) service, we designed and implemented a standardized, educational intervention providing analgesic decision support to internal medicine and emergency medicine housestaff at our institution. METHODS: Pre-intervention data was collected from patients admitted during a 9-month period prior to intervention. Post-intervention patients were identified prospectively. The primary outcome was reduction in aggregate inpatient opioid use in oral morphine equivalents per patient. RESULTS: A total of 68 patients with 81 hospitalizations were analyzed. There was no statistically significant difference in baseline admission characteristics between the two groups. Our primary outcome was achieved with a statistically significant reduction in opioid use during hospitalization (43.4 mg vs 7.7 mg; p < 0.01). Secondary outcomes achieved included reduction in new opioid prescriptions upon discharge, reduced hospital length of stay, and reduced 90-day readmission rates. There was no significant difference between patients' pain scores between the two groups. CONCLUSION: We believe this intervention, aimed at housestaff education, provides a roadmap for pain management decision-making in this patient population. It is a readily reproducible strategy that can be widely applied to improve inpatient IBD patient care. Importantly, patient experience and pain scores were unchanged despite lower use of inpatient opioid analgesia, highlighting successful opioid-sparing analgesics in most inpatients with IBD.

A Triage Model for Interhospital Transfers of Low Risk Intracerebral Hemorrhage Patients.

OBJECTIVES: Intracerebral hemorrhage comprises a large proportion of inter-hospital transfers to comprehensive stroke centers from centers without comprehensive stroke center resources despite lack of mortality benefit and low comprehensive stroke center resource utilization. The subset of patients who derive the most benefit from inter-hospital transfers is unclear. Here, we create a triage model to identify patients who can safely avoid transfer to a comprehensive stroke center. MATERIALS AND METHODS: A retrospective cohort of spontaneous intracerebral hemorrhage patients transferred to our comprehensive stroke center from surrounding centers was used. Patients with early discharge from the Neuroscience Intensive Care Unit without use of comprehensive stroke center resources were identified as low risk, non-utilizers. Variables associated with this designation were used to develop and validate a triage model. RESULTS: The development and replication cohorts comprised 358 and 99 patients respectively, of whom 78 (22%) and 26 (26%) were low risk, non-utilizers. Initial Glasgow Coma Scale and baseline hemorrhage volume were associated with low risk, non-utilizers in multivariate analysis. Initial Glasgow Coma Scale >13, intracerebral hemorrhage volume <15ml, absence of intraventricular hemorrhage, and supratentorial location had an area under curve, specificity, and sensitivity of 0.72, 91.4%, 52.6%, respectively, for identifying low risk, non-utilizers, and 0.75, 84.9%, 65.4%, respectively, in the replication cohort. CONCLUSIONS: Spontaneous intracerebral hemorrhage patients with Glasgow Coma Scale >13, intracerebral hemorrhage volume <15 ml, absence of intraventricular hemorrhage, and supratentorial location might safely avoid inter-hospital transfer to a comprehensive stroke center. Validation in a prospective, multicenter cohort is warranted.