Is the Child Opportunity Index a Factor in Surgical Outcomes for Adolescent Idiopathic Scoliosis?

BACKGROUND: Low socioeconomic status (SES) has been previously associated with delays in orthopaedic care. However, it is unclear how SES impacts patients with adolescent idiopathic scoliosis (AIS), particularly regarding preoperative major coronal curve angle or surgical outcomes. Utilizing the Child Opportunity Index (COI)-an address-driven measure of pediatric education, health/environment, and SES-we investigated whether COI is associated with differences in preoperative scoliosis magnitude, age at surgery, and AIS surgical outcomes. METHODS: Consecutive patients with AIS surgically treated at a single center from 2011 to 2017 were reviewed. COI was calculated by inserting a patient's home address into the nationally available COI database to derive a COI value. COI is scored from 0.0 to 100.0 (0.0 is lowest, 100.0 is highest). Specifically, COI is categorized as very low (<20.0), low (20 to 39.9), moderate (40 to 59.9), high (60 to 79.9), and very high (≥80). Those without addresses were excluded. Patients without proper radiographs to assess curve correction were also excluded. A COI threshold of 60.0 was used to separate patients into a low (<60.0) or high COI ( ) group based on published COI guidelines. Outcomes, including preoperative curve magnitude, age at surgery, percentage curve correction, operative time (OT), intraoperative estimated blood loss per level fused, length of stay, and complications, were compared across groups. Pearson correlation analysis was used to assess correlations between COI and preoperative curve magnitude, as well as age. RESULTS: Four hundred four patients were included in the study, and 263 had 2-year follow-up data. Patients were an average age of 14.9 years old (range: 11.2 to 19.8), had a median COI of 76 (range: 4 to 100), and had a mean preoperative major curve angle of 59 degrees (range: 36 to 93). COI was significantly higher for white patients compared with non-white (80.0 vs 40.0, P < 0.001), and higher for non-Hispanic individuals (79.0 vs 15.0, P < 0.001). Patients with Low COI were associated with a lower OT per level fused ( P = 0.003) and decreased postoperative complication risk ( P = 0.02). COI was not associated with preoperative major coronal curve angle, age at surgery, or any other surgical outcomes. CONCLUSION: COI was significantly lower for non-white patients and those of Hispanic ethnicity. Patients from low COI backgrounds achieved similar surgical results as those from high COI addresses and had a decreased OT per level fused and complication incidence, though the clinical significance of these differences is unknown. Future prospective studies are needed to determine whether these findings are reproducible across other states and health systems. LEVEL OF EVIDENCE: Level III-prognostic study.

Effects of dim light at night in C57BL/6 J mice on recovery after spinal cord injury.

Spinal cord injury (SCI) can cause long-lasting locomotor deficits, pain, and mood disorders. Anatomical and functional outcomes are exacerbated by inflammation after SCI, which causes secondary damage. One promising target after SCI is manipulating the circadian system, which optimizes biology and behavior for time of day - including neuroimmune responses and mood-related behaviors. Circadian disruption after SCI is likely worsened by a disruptive hospital environment, which typically includes dim light-at-night (dLAN). Here, we hypothesized that mice subjected to SCI, then placed in dLAN, would exhibit worsened locomotor deficits, pain-like behavior, and anxiety-depressive-like symptoms compared to mice maintained in light days with dark nights (LD). C57BL/6 J mice received sham surgery or moderate T9 contusion SCI, then were placed permanently in LD or dLAN. dLAN after SCI did not worsen locomotor deficits; rather, SCI-dLAN mice showed slight improvement in open-field locomotion at the final timepoint. Although dLAN did not alter SCI-induced heat hyperalgesia, SCI-dLAN mice exhibited an increase in mechanical allodynia at 13 days post-SCI compared to SCI-LD mice. SCI-LD and SCI-dLAN mice had similar outcomes using sucrose preference (depressive-like) and open-field (anxiety-like) tests. At 21 dpo, SCI-dLAN mice had reduced preference for a novel juvenile compared to SCI-LD, implying that dLAN combined with SCI may worsen this mood-related behavior. Finally, lesion size was similar between SCI-LD and SCI-dLAN mice. Therefore, newly placing C57BL/6 J mice in dLAN after SCI had modest effects on locomotor, pain-like, and mood-related behaviors. Future studies should consider whether clinically-relevant circadian disruptors, alone or in combination, could be ameliorated to enhance outcomes after SCI.

Effects of dim light at night in C57BL/6J mice on recovery after spinal cord injury.

Spinal cord injury (SCI) can cause long-lasting locomotor deficits, pain, and mood disorders. Anatomical and functional outcomes are exacerbated by inflammation after SCI, which causes secondary damage. One promising target after SCI is manipulating the circadian system, which optimizes biology and behavior for time of day - including neuroimmune responses and mood-related behaviors. Circadian disruption after SCI is likely worsened by a disruptive hospital environment, which typically includes dim light-at-night (dLAN). Here, we hypothesized that mice subjected to SCI, then placed in dLAN, would exhibit worsened locomotor deficits, pain-like behavior, and anxiety-depressive-like symptoms compared to mice maintained in light days with dark nights (LD). C57BL/6J mice received sham surgery or moderate T9 contusion SCI, then were placed permanently in LD or dLAN. dLAN after SCI did not worsen locomotor deficits; rather, SCI-dLAN mice showed slight improvement in open-field locomotion at the final timepoint. Although dLAN did not alter SCI-induced heat hyperalgesia, SCI-dLAN mice exhibited an increase in mechanical allodynia at 13 days post-SCI compared to SCI-LD mice. SCI-LD and SCI-dLAN mice had similar outcomes using sucrose preference (depressive-like) and open-field (anxiety-like) tests. At 21 dpo, SCI-dLAN mice had reduced preference for a novel juvenile compared to SCI-LD, implying that dLAN combined with SCI may worsen this mood-related behavior. Finally, lesion size was similar between SCI-LD and SCI-dLAN mice. Therefore, newly placing C57BL/6J mice in dLAN after SCI had modest effects on locomotor, pain-like, and mood-related behaviors. Future studies should consider whether clinically-relevant circadian disruptors, alone or in combination, could be ameliorated to enhance outcomes after SCI.

"The library is so much more than books": considerations for the design and implementation of teen digital mental health services in public libraries.

Background: Adolescence is a vulnerable developmental period, characterized by high rates of mental health concerns, yet few adolescents receive treatment. Public libraries support adolescents by providing them with access to teen programming, technological resources, and have recently been providing mental health services. Digital mental health (DMH) services may help libraries provide scalable mental health solutions for their adolescent patrons and could be well positioned to address the mental health needs of historically underrepresented racial and ethnic (HURE) adolescents; however, little research has been conducted on the compatibility of DMH services with adolescent patron mental health needs or resource needs of library workers supporting them. Methods: The research team formed a partnership with a public library, which serves a large HURE adolescent population. We conducted needs assessment and implementation readiness interviews with 17 library workers, including leadership, librarians, and workers with specialized areas of practice. Interview questions focused on library infrastructure, as well as library needs and preferences around the design and implementation of DMH services for adolescents. We used the Consolidated Framework for Implementation Research as guiding implementation determinant framework to code and analyze the interview transcripts. Results: Our findings revealed library workers play an important role in guiding patrons to desired resources and share a goal of implementing adolescent DMH resources into the library and elevating marginalized adolescents' voices. Existing library resources, such as the library's role as a safe space for adolescents in the community, close relationships with external and community organizations, and availability of no-cost technological resources, could help facilitate the implementation of DMH services. Barriers related to community buy-in, mental health stigma, and library worker confidence in supporting adolescent mental health could affect service implementation. Conclusions: Our findings suggest public libraries are highly promising settings to deploy DMH services for adolescents. We identified important determinants that may impact the implementation of DMH services in public library settings. Special considerations are needed to design services to meet the mental health needs of HURE adolescent populations and those adolescents' most experiencing health inequities.

Spinal cord injury in mice amplifies anxiety: A novel light-heat conflict test exposes increased salience of anxiety over heat.

Spinal cord injury (SCI) predisposes individuals to anxiety and chronic pain. Anxiety- and pain-like behavior after SCI can be tested in rodents, yet commonly used tests assess one variable and may not replicate effects of SCI or sex differences seen in humans. Thus, novel preclinical tests should be optimized to better evaluate behaviors relating to anxiety and pain. Here, we use our newly developed conflict test - the Thermal Increments Dark-Light (TIDAL) test - to explore how SCI affects anxiety- vs. pain-like behavior, and whether sex affects post-SCI behavior. The TIDAL conflict test consists of two plates connected by a walkway; one plate remains illuminated and at an isothermic temperature, whereas the other plate is dark but is heated incrementally to aversive temperatures. A control mice thermal place preference test was also performed in which both plates are illuminated. Female and male mice received moderate T9 contusion SCI or remained uninjured. At 7 days post-operative (dpo), mice with SCI increased dark plate preference throughout the TIDAL conflict test compared to uninjured mice. SCI increased dark plate preference for both sexes, although female (vs. male) mice remained on the heated-dark plate to higher temperatures. Mice with SCI that repeated TIDAL at 7 and 21 dpo showed reduced preference for the dark-heated plate at 21 dpo. Overall, in female and male mice, SCI enhances the salience of anxiety (vs. heat sensitivity). The TIDAL conflict test meets a need for preclinical anxiety- and pain-related tests that recapitulate the human condition; thus, future rodent behavioral studies should incorporate TIDAL or other conflict tests to help understand and treat neurologic disorders.

Acute central nervous system inflammation following COVID-19 vaccination: An observational cohort study.

BACKGROUND: Reports suggest a potential association between coronavirus disease 2019 (COVID-19) vaccines and acute central nervous system (CNS) inflammation. OBJECTIVE: The main objective of this study is to describe features of acute CNS inflammation following COVID-19 vaccination. METHODS: A retrospective observational cohort study was performed at the BARLO MS Centre in Toronto, Canada. Clinicians reported acute CNS inflammatory events within 60 days after a COVID-19 vaccine from March 2021 to August 2022. Clinical characteristics were evaluated. RESULTS: Thirty-eight patients (median age 39 (range: 20-82) years; 60.5% female) presented within 0-55 (median 15) days of a receiving a COVID-19 vaccine and were diagnosed with relapsing remitting multiple sclerosis (MS) (n = 16), post-vaccine transverse myelitis (n = 7), clinically isolated syndrome (n = 5), MS relapse (n = 4), tumefactive demyelination (n = 2), myelin oligodendrocyte glycoprotein antibody disease (n = 1), neuromyelitis optica spectrum disorder (n = 1), chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (n = 1) and primary autoimmune cerebellar ataxia (n = 1). Twenty-two received acute treatment and 21 started disease-modifying therapy. Sixteen received subsequent COVID-19 vaccination, of which 87.5% had no new or worsening neurological symptoms. CONCLUSION: To our knowledge, this is the largest study describing acute CNS inflammation after COVID-19 vaccination. We could not determine whether the number of inflammatory events was higher than expected.

Sex Differences in Pain: Spinal Cord Injury in Female and Male Mice Elicits Behaviors Related to Neuropathic Pain.

Spinal cord injury (SCI) in humans frequently causes intractable chronic pain. Females are susceptible to worse pain than males, and females may show higher pain prevalence after SCI. Despite this difference in the clinical prevalence of SCI pain, few pre-clinical studies have systematically studied sex differences in SCI-elicited pain-related behaviors in rodents. Here, we leverage data from a large cohort of mice to test whether contusion SCI consistently causes pain symptoms in mice, and to establish whether female (vs. male) mice display heightened hypersensitivity after SCI. Mechanical and heat sensory thresholds were assessed using the von Frey and Hargreaves tests, respectively. In an initial experiment, female mice receiving moderate 60 kDyn SCI or moderate-to-severe 75 kDyn SCI at T9 both exhibited mechanical and heat pain symptoms compared with sham controls. A 75 kDyn SCI caused excess motor deficits that confounded defining pain sensitivity at acute times; therefore, the moderate SCI force was used for subsequent experiments. Next, adult female and male C57BL6/J mice received sham surgery or T9 moderate contusion SCI. Comparing female to male mice after SCI, we reveal that mice of both sexes displayed mechanical and heat hypersensitivity compared with sham controls, from acute-to-chronic post-injury times. Females had amplified SCI-elicited hypersensitivity compared with males. Our data suggest that thoracic contusion SCI elicits consistent and persistent pain-associated symptoms, which are more intense in female than in male mice. These results have important implications for uncovering sex-specific mechanisms and therapeutic targets to ameliorate neuropathic pain after SCI.

Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas.

The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dose-adjusted [DA]-EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) typically used for the highest risk histologies. This was a single-center, open-label, prospective clinical trial of 6 cycles of Pola-DA-EPCH-R (vincristine omitted) in aggressive large B-cell lymphomas. The primary end point was to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with prespecified suspension rules. Secondary and exploratory end points included efficacy and correlation with circulating tumor DNA (ctDNA) levels. We enrolled 18 patients on study, and with only 3 DLTs observed, the study met its primary end point for safety. There were 5 serious adverse events, including grade 3 febrile neutropenia (3, 17%), grade 3 colonic perforation in the setting of diverticulitis, and grade 5 sepsis/typhlitis. Among 17 evaluable patients, the best overall response rate was 100%, and the complete response rate was 76%. With a median follow-up of 12.9 months, 12-month event-free survival was 72%, and 12-month overall survival was 94%. No patient with undetectable ctDNA at the end of treatment has relapsed to date. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety end point. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. This trial was registered at www.clinicaltrials.gov as #NCT04231877.

Ovarian resection in anti-N-methyl-D-aspartate receptor encephalitis: A comparison of surgical approaches.

Background: For patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) and ovarian teratoma, "conservative" surgical approaches (complete or partial unilateral oophorectomy or bilateral partial oophorectomies) are associated with clinical improvement. "Aggressive" ovarian resections (complete bilateral oophorectomy or "blind" ovarian resections without pre-operative evidence of teratoma) are also reported, although the evidence supporting these approaches is unclear. Objective: To compare the one-year functional outcomes of patients with NMDARE who underwent conservative vs. aggressive ovarian resections. Methods: Patients with NMDARE undergoing ovarian resection between January 1st, 2012 and December 31st, 2021 were retrospectively identified from three North American tertiary care centers. Primary outcome was a modified Rankin Scale score of 0-2 one year after ovarian resection. Fisher exact and Wilcoxon rank sum tests were used to compare demographic features, disease characteristics, and functional outcomes between the two surgical groups. A fixed-effects meta-analysis of studies reporting functional outcomes based on surgical approach was also performed. Results: Twenty-three patients were included. Eight underwent aggressive surgical management. There was a non-significant trend toward an association between aggressive surgical management and younger age-at-onset, higher baseline disease severity, and longer delays to treatment. There was no difference between "aggressive" (3/8, 38%) and "conservative" (11/15, 73%) management groups in achieving the primary outcome (OR95% = <0.1-1.9; p = 0.18). Findings were similar when considering data from 52 patients in two published studies (RR = 0.74; CI95% = 0.48-1.13; p = 0.16). Conclusions: Aggressive ovarian resection was not associated with improved outcomes in patients with NMDARE in this series. Group differences may have contributed, recognizing that patients who underwent aggressive resection tended to be sicker, with procedures performed later in the disease course. Based on available evidence, we advocate for function-sparing resection in patients with imaging-confirmed/suspected teratoma, and repeated multi-modal imaging in at-risk patients with NMDARE refractory to conventional treatment.

The impact of B-cell-directed therapy on SARS-CoV-2 vaccine efficacy in chronic lymphocytic leukaemia.

Prior reports evaluating SARS-CoV-2 vaccine efficacy in chronic lymphocytic leukaemia (CLL) used semiquantitative measurements of anti-S to evaluate immunity; however, neutralization assays were used to assess functional immunity in the trials leading to vaccine approval. Here, we identified decreased rates of seroconversion in vaccinated CLL patients and lower anti-S levels compared to healthy controls. Notably, we demonstrated similar results with the Roche anti-S assay and neutralization activity. Durable responses were seen at six months; augmentation with boosters was possible in responding patients. Absence of normal B cells, frequently seen in patients receiving Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors, was a strong predictor of lack of seroconversion.

Successful Fidaxomicin Hospital Discharges of Adult Patients With Clostridioides difficile Infections Post-2021 Guidelines: Are Economic Barriers Finally Coming Down?

We reviewed Clostridioides difficile-positive patients discharged on fidaxomicin after local adoption of 2021 C. difficile infection (CDI) guidelines. From 14 June to 3 October 2021, 80% (12/15) had copayments of $0-$35 and 27% (4/15) required prior authorization. The 30-day CDI recurrence was 7%.

Factors Associated with Having a Will, Power of Attorney, and Advanced Healthcare Directive in Patients Presenting to a Rural and Remote Memory Clinic.

BACKGROUND: A Will, Power of Attorney, and Advanced Healthcare Directive are critical to guide decision-making in patients with dementia. We identified characteristics that are associated with the existence of these documents in patients who presented to a rural and remote memory clinic (RRMC). METHODS: Ninety-five consecutive patients were included in this study. Patients and caregivers completed questionnaires on initial presentation to the RRMC and patients were asked if they had legal documents. Patients also completed neuropsychological testing. Statistical analysis (t-test and χ2 test) was performed to identify significant variables. RESULTS: Seventy (73.7%) patients had a Will, 62 (65.3%) had a Power of Attorney, and 21 (22.1%) had an Advanced Healthcare Directive. Having a Will was associated with good quality of life (p = 0.001), living alone or with a spouse or partner only (p = 0.034), poor verbal fluency (p = 0.055), and European ethnicity (p = 0.028). Factors associated with having a Power of Attorney included good quality of life (p = 0.031), living alone or with a spouse or partner only (p = 0.053), and poor verbal fluency (p = 0.015). Old age (p = 0.015), poor verbal fluency (p = 0.023), and greater severity of cognitive and functional impairment (p = 0.023) were associated with having an Advanced Healthcare Directive. CONCLUSIONS: Our results indicate that poor quality of life, good performance on verbal fluency, Indigenous ethnicity, and living with others are associated with a lower likelihood of legal documents in patients with dementia. These factors can help physicians identify patients at risk of leaving their legal affairs unattended to. Physicians should discuss the creation of legal documents early on in patients with signs of dementia.

Forced normalization after turning off vagus nerve stimulation in Lennox-Gastaut syndrome.

Forced normalization is the development of psychiatric symptoms in a patient experiencing remission of seizures. We present a case of Lennox Gastaut syndrome in which forced normalization developed after vagus nerve stimulation was stopped. The patient had drug resistant epilepsy and failed anti-seizure drugs, vagus nerve stimulation, and a partial callosotomy. The patient had multiple types of seizures including drop attacks, absences, and tonic-clonic seizures. He tried vagus nerve stimulation for two years without success. Forced normalization developed after the vagus nerve stimulator was turned off. This is the first case to our knowledge to describe forced normalization after turning off the vagus nerve stimulator.

Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system.

Mitochondria are considered autonomous organelles, physically separated from endocytic and biosynthetic pathways. However, recent work uncovered a PINK1/parkin-dependent vesicle transport pathway wherein oxidized or damaged mitochondrial content are selectively delivered to the late endosome/lysosome for degradation, providing evidence that mitochondria are indeed integrated within the endomembrane system. Given that mitochondria have not been shown to use canonical soluble NSF attachment protein receptor (SNARE) machinery for fusion, the mechanism by which mitochondrial-derived vesicles (MDVs) are targeted to the endosomal compartment has remained unclear. In this study, we identify syntaxin-17 as a core mitochondrial SNARE required for the delivery of stress-induced PINK1/parkin-dependent MDVs to the late endosome/lysosome. Syntaxin-17 remains associated with mature MDVs and forms a ternary SNARE complex with SNAP29 and VAMP7 to mediate MDV-endolysosome fusion in a manner dependent on the homotypic fusion and vacuole protein sorting (HOPS) tethering complex. Syntaxin-17 can be traced to the last eukaryotic common ancestor, hinting that the removal of damaged mitochondrial content may represent one of the earliest vesicle transport routes in the cell.

Validating the use of ICD-9-CM codes to evaluate gestational age and birth weight.

BACKGROUND: Efforts to reduce preterm and low-weight births are among the leading public health objectives in the United States and the world. A necessary component of any public health endeavor is surveillance. The Department of Defense (DoD) Birth and Infant Health Registry (Registry) uses electronic healthcare utilization data to assess reproductive health outcomes among military families. Infant health outcomes are coded using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). The objective of this study was to determine the accuracy of using electronically derived ICD-9-CM codes for assessing gestational age and birth weight among Registry infants compared to medical records. METHODS: The authors assessed birth outcome agreement by comparing electronic Registry data for infants born at military treatment facilities (MTFs) from 1999-2002 and 1,858 randomly selected birth medical records from 17 MTFs, with descriptive statistics and measures of agreement, including the kappa statistic. RESULTS: Of the 1,858 reviewed infant records, 1,669 were successfully matched to the Registry analytic dataset for analyses. Despite small differences in parental demographics, this investigation established "near perfect" agreement for the primary outcomes: kappa of 0.83 for preterm and 0.87 for low birth weight. Subgroup analyses revealed no significant differences in gestational age and birth-weight agreement based on the presence of a birth defect, military parent rank, branch of military service, or specific hospital characteristics. CONCLUSIONS: Electronically derived ICD-9-CM codes provide an accurate assessment of the gestational age and low birth weight reflected in the birth medical records of infants in a large birth and infant health registry. These findings support the integrity of Registry data for investigations assessing preterm and low-weight births among U.S. service member families.