Buprenorphine discontinuation in telehealth-only treatment for opioid use disorder: A longitudinal cohort analysis.

INTRODUCTION: At the beginning of the COVID-19 pandemic, federal agencies permitted telehealth initiation of buprenorphine treatment for opioid use disorder (OUD) without in-person assessment. It remains unclear how telehealth-only buprenorphine treatment impacts time to discontinuation and patient reported treatment outcomes. METHODS: A longitudinal observational cohort study conducted September 2021 through March, 2023 enrolled participants with OUD initiating buprenorphine (≤ 45 days) with internet and phone access in Oregon and Washington. The intervention was a fully telehealth-only (THO) app versus treatment as usual (TAU) in office-based settings with some telehealth. We assessed self-reported buprenorphine discontinuation at 4-,12-, and 24-weeks. Generalized estimating equations (GEE) calculated unadjusted and adjusted relative risk ratios (RR) for discontinuation averaged over the study period. Secondary outcomes included change in the Brief Addiction Monitor (BAM) and the visual analogue craving scale. Generalized linear models estimated average within-group and between-group differences over time. RESULTS: Participants (n = 103 THO; n = 56 TAU) had a mean age of 37 years (SD = 9.8 years) and included 52 % women, 83 % with Medicaid insurance, 80 % identified as White, 65 % unemployed/student, and 19 % unhoused. There were differences in gender (THO = 54 % women vs. TAU = 44 %, p = .04), unemployed status (60 % vs 75 %, p = .02), and stable housing (84 % vs 73 %, p = .02). Rates of buprenorphine discontinuation were low in the THO (4 %) and TAU (13 %) groups across 24 weeks. In the adjusted analysis, the risk of discontinuation was 61 % lower in the THO group (aRR = 0.39, 95 % CI [0.17, 0.89], p = .026). Decreases occurred over time on the harms subscale of the BAM (within-group difference - 0.85, p = .0004 [THO], and - 0.68, p = .04 [TAU]) and cravings (within-group difference - 13.47, p = .0001 [THO] vs -7.65, p = .01 [TAU]). CONCLUSIONS: A telehealth-only platform reduced the risk of buprenorphine discontinuation compared to office-based TAU. In-person evaluation to receive buprenorphine may not be necessary for treatment-seeking patients. CLINICAL TRIALS IDENTIFIER: NCT03224858.

AB088. Spinal cord diffuse midline glioma in adults: a case report and literature review.

BACKGROUND: Spinal cord diffuse midline gliomas are rare, infiltrative entities with an extremely grim prognosis. Standard of care is limited and extrapolated from those for intracranial gliomas, focusing on maximal safe resection, chemotherapy and radiation therapy. These do not prolong survival significantly and while advances in molecular profiling and targeted therapy have been promising, further research still needs to be performed. Here, we present a case of a young lady with a cervical cord diffuse midline glioma, along with a literature review of the disease and treatment options. CASE DESCRIPTION: A 35-year-old female presented with progressive neck pain and left sided weakness. MRI revealed an intramedullary cervical spinal cord lesion. The lesion progressed rapidly to the medulla, resulting in lower cranial nerve palsies and left hemiplegia. Investigations for autoimmune and infective causes were negative. Cervical laminectomy and debulking was performed. Histological analysis showed high grade diffuse glioma, IDH-wildtype, loss of H3K27me3 staining and H3K27M positivity. The patient was treated with fractionated radiation and temozolamide, followed by lomustine and bevacizumab. A literature review was performed to better understand the molecular features, natural history and treatment options for spinal cord high grade gliomas. Our case highlights the importance of maintaining broad differentials for patients exhibiting features of cervical myelopathy. Malignant spinal cord tumours could be a differential. Molecular testing can aid in achieving an accurate diagnosis to better understand prognosis and determine treatment options. Early, function-preserving debulking with neuromonitoring is feasible. Adjuvant therapy with chemotherapy and radiation can prolong survival. CONCLUSIONS: Spinal cord diffuse midline gliomas H3 K27-altered demonstrate rapid progression and a poor prognosis. They should be considered as a differential in patients with cervical myelopathy. Molecular testing for H3 K27 alterations facilitates an accurate diagnosis. Surgical debulking and adjuvant therapy are viable treatment options.

The significance of recurrent de novo amino acid substitutions that emerged during chronic SARS-CoV-2 infection: an observational study.

BACKGROUND: De novo amino acid substitutions (DNS) frequently emerge among immunocompromised patients with chronic SARS-CoV-2 infection. While previous studies have reported these DNS, their significance has not been systematically studied. METHODS: We performed a review of DNS that emerged during chronic SARS-CoV-2 infection. We searched PubMed until June 2023 using the keywords "(SARS-CoV-2 or COVID-19) and (mutation or sequencing) and ((prolonged infection) or (chronic infection) or (long term))". We included patients with chronic SARS-CoV-2 infection who had SARS-CoV-2 sequencing performed for at least 3 time points over at least 60 days. We also included 4 additional SARS-CoV-2 patients with chronic infection of our hospital not reported previously. We determined recurrent DNS that has appeared in multiple patients and determined the significance of these mutations among epidemiologically-significant variants. FINDINGS: A total of 34 cases were analyzed, including 30 that were published previously and 4 from our hospital. Twenty two DNS appeared in ≥3 patients, with 14 (64%) belonging to lineage-defining mutations (LDMs) of epidemiologically-significant variants and 10 (45%) emerging among chronically-infected patients before the appearance of the corresponding variant. Notably, nsp9-T35I substitution (Orf1a T4175I) emerged in all three patients with BA.2.2 infection in 2022 before the appearance of Variants of Interest that carry nsp9-T35I as LDM (EG.5 and BA.2.86/JN.1). Structural analysis suggests that nsp9-T35I substitution may affect nsp9-nsp12 interaction, which could be critical for the function of the replication and transcription complex. INTERPRETATION: DNS that emerges recurrently in different chronically-infected patients may be used as a marker for potential epidemiologically-significant variants. FUNDING: Theme-Based Research Scheme [T11/709/21-N] of the Research Grants Council (See acknowledgements for full list).

The impact of vaccine type and booster dose on the magnitude and breadth of SARS-CoV-2-specific systemic and mucosal antibodies among COVID-19 vaccine recipients.

The COVID-19 pandemic has had a major impact on global health and economy, which was significantly mitigated by the availability of COVID-19 vaccines. The levels of systemic and mucosal antibodies against SARS-CoV-2 correlated with protection. However, there is limited data on how vaccine type and booster doses affect mucosal antibody response, and how the breadth of mucosal and systemic antibodies compares. In this cross-sectional study, we compared the magnitude and breadth of mucosal and systemic antibodies in 108 individuals who received either the BNT162b2 (Pfizer) or CoronaVac (SinoVac) vaccine. We found that BNT162b2 (vs CoronaVac) or booster doses (vs two doses) were significantly associated with higher serum IgG levels, but were not significantly associated with salivary IgA levels, regardless of prior infection status. Among non-infected individuals, serum IgG, serum IgA and salivary IgG levels were significantly higher against the ancestral strain than the Omicron BA.2 sublineage, but salivary IgA levels did not differ between the strains. Salivary IgA had the weakest correlation with serum IgG (r = 0.34) compared with salivary IgG (r = 0.63) and serum IgA (r = 0.60). Our findings suggest that intramuscular COVID-19 vaccines elicit a distinct mucosal IgA response that differs from the systemic IgG response. As mucosal IgA independently correlates with protection, vaccine trials should include mucosal IgA as an outcome measure.

Traumatic Cervical Spinal Cord Injury and Income and Employment Status.

Importance: Spinal cord injury (SCI) causes drastic changes to an individual's physical health that may be associated with the ability to work. Objective: To estimate the association of SCI with individual earnings and employment status using national administrative health databases linked to income tax data. Design, Setting, and Participants: This was a retrospective, national, population-based cohort study of adults who were hospitalized with cervical SCI in Canada between January 2005 and December 2017. All acute care hospitalizations for SCI of adults ages 18 to 64 years were included. A comparison group was constructed by sampling from individuals in the injured cohort. Fiscal information from their preinjury years was used for comparison. The injured cohort was matched with the comparison group based on age, sex, marital status, province of residence, self-employment status, earnings, and employment status in the year prior to injury. Data were analyzed from August 2022 to January 2023. Main outcomes and Measures: The first outcome was the change in individual annual earnings up to 5 years after injury. The change in mean yearly earnings was assessed using a linear mixed-effects differences-in-differences regression. Income values are reported in 2022 Canadian dollars (CAD $1.00 = US $0.73). The second outcome was the change in employment status up to 5 years after injury. A multivariable probit regression model was used to compare proportions of individuals employed among those who had experienced SCI and the paired comparison group of participants. Results: A total of 1630 patients with SCI (mean [SD] age, 47 [13] years; 1304 male [80.0%]) were matched to patients in a preinjury comparison group (resampled from the same 1630 patients in the SCI group). The mean (SD) of preinjury wage earnings was CAD $46 000 ($48 252). The annual decline in individual earnings was CAD $20 275 (95% CI, -$24 455 to -$16 095) in the first year after injury and CAD $20 348 (95% CI, -$24 710 to -$15 985) in the fifth year after injury. At 5 years after injury, 52% of individuals who had an injury were working compared with 79% individuals in the preinjury comparison group. SCI survivors had a decrease in employment of 17.1 percentage points (95% CI, 14.5 to 19.7 percentage points) in the first year after injury and 17.8 percentage points (14.5 to 21.1 percentage points) in the fifth year after injury. Conclusions and Relevance: In this study, SCI was associated with a decline in earnings and employment up to 5 years after injury for adults aged 18 to 64 years in Canada.

Piloting a Hospital-Based Rapid Methadone Initiation Protocol for Fentanyl.

OBJECTIVES: Treating acute opioid withdrawal and offering medications for opioid use disorder (OUD) is critical. Hospitalization offers a unique opportunity to rapidly initiate methadone for OUD; however, little clinical guidance exists. This report describes our experience during the first 9 months following introduction of a hospital-based rapid methadone initiation protocol. METHODS: We conducted a retrospective chart review of hospitalized patients with OUD seen by our interprofessional addiction medicine consult service at an urban academic center between December 2022 and August 2023. We identified patients who initiated methadone using the rapid methadone initiation protocol, which includes dose recommendations (maximum 60 mg day 1, 70 mg day 2, 80 mg day 3, 100 mg days 4-7) and strict inclusion and exclusion criteria (end organ failure, arrhythmia, concurrent benzodiazepine or alcohol use, age >65). RESULTS: There were 171 patients that received methadone for OUD during the study period. Of those, 25 patients (15%) received rapid methadone initiation. The average total daily dose of methadone on days 1-7 was 53.0 mg, 69.2 mg, 75.4 mg, 79.5 mg, 87.1 mg, 92.2 mg, and 96.6 mg, respectively. There were no adverse events requiring holding a dose of scheduled methadone, naloxone administration, or transfer to higher level of care. CONCLUSIONS: A rapid methadone initiation protocol for OUD can be implemented in the inpatient setting. Patients up-titrated their methadone doses quicker than with traditional induction methods, and there were no serious adverse events. Appropriate patient selection may be important to avoid harms.

Cost Analysis of Bladder Catheterization After Pelvic Floor Surgery.

IMPORTANCE: Approximately 15-45% of female patients develop transient postoperative urinary retention (POUR) following pelvic reconstructive surgery. Catheter options for bladder drainage include transurethral indwelling catheter (TIC), intermittent self-catheterization (ISC), and suprapubic tube (SPT). Each strategy has risks and benefits; none have been shown to be clinically superior, and to date, no comprehensive comparative economic analysis has been published. OBJECTIVE: The objective of this study was to evaluate the cost of these different bladder catheterization strategies after transvaginal pelvic surgery. STUDY DESIGN: A Canadian universal single-payer (government funded) health system perspective was taken, and a decision tree model was constructed to evaluate the costs associated with each catheterization strategy over a 6-week horizon. Base-cases were set based on recently published clinical data of our institutions, 2 academic tertiary care centers, and based on systematic reviews and meta-analyses. Costs were established in consultation with process stakeholders, in addition to published values. RESULTS: The average cost calculated for management of transient POUR after outpatient pelvic reconstructive surgery was 150.69 CAD (median 154.86; interquartile range [IQR] 131.30-176.33) for TIC, 162.28 CAD (median 164.72; IQR 144.36-189.39) for ISC and 255.67 CAD (median 270.63; IQR 234.32-276.82) for SPT. In costing inpatient surgical data, the average cost calculated was 134.22 CAD (median 123.61; IQR 108.87-151.85) for TIC and 224.61 CAD (median 216.07; IQR 203.86-231.23) for SPT. CONCLUSION: TIC and ISC were found to be significantly less costly than SPT in managing transient POUR following transvaginal pelvic reconstructive surgery.

Activity-driven chromatin organization during interphase: Compaction, segregation, and entanglement suppression.

In mammalian cells, the cohesin protein complex is believed to translocate along chromatin during interphase to form dynamic loops through a process called active loop extrusion. Chromosome conformation capture and imaging experiments have suggested that chromatin adopts a compact structure with limited interpenetration between chromosomes and between chromosomal sections. We developed a theory demonstrating that active loop extrusion causes the apparent fractal dimension of chromatin to cross-over between two and four at contour lengths on the order of 30 kilo-base pairs. The anomalously high fractal dimension [Formula: see text] is due to the inability of extruded loops to fully relax during active extrusion. Compaction on longer contour length scales extends within topologically associated domains (TADs), facilitating gene regulation by distal elements. Extrusion-induced compaction segregates TADs such that overlaps between TADs are reduced to less than 35% and increases the entanglement strand of chromatin by up to a factor of 50 to several Mega-base pairs. Furthermore, active loop extrusion couples cohesin motion to chromatin conformations formed by previously extruding cohesins and causes the mean square displacement of chromatin loci during lag times ([Formula: see text]) longer than tens of minutes to be proportional to [Formula: see text]. We validate our results with hybrid molecular dynamics-Monte Carlo simulations and show that our theory is consistent with experimental data. This work provides a theoretical basis for the compact organization of interphase chromatin, explaining the physical reason for TAD segregation and suppression of chromatin entanglements which contribute to efficient gene regulation.

Characterizing fitness and immune escape of SARS-CoV-2 EG.5 sublineage using elderly serum and nasal organoid.

SARS-CoV-2 Omicron variant has evolved into sublineages. Here, we compared the neutralization susceptibility and viral fitness of EG.5.1 and XBB.1.9.1. Serum neutralization antibody titer against EG.5.1 was 1.71-fold lower than that for XBB.1.9.1. However, there was no significant difference in virus replication between EG.5.1 and XBB.1.9.1 in human nasal organoids and TMPRSS2/ACE2 over-expressing A549 cells. No significant difference was observed in competitive fitness and cytokine/chemokine response between EG.5.1 and XBB.1.9.1. Both EG.5.1 and XBB.1.9.1 replicated more robustly in the nasal organoid from a younger adult than that from an older adult. Our findings suggest that enhanced immune escape contributes to the dominance of EG.5.1 over earlier sublineages. The combination of population serum susceptibility testing and viral fitness evaluation with nasal organoids may hold promise in risk assessment of upcoming variants. Utilization of serum specimens and nasal organoid derived from older adults provides a targeted risk assessment for this vulnerable population.