Fentanyl Test Strips for Harm Reduction: A Scoping Review.

BACKGROUND: High potency synthetic opioids like fentanyl have continued to replace or contaminate the supply of illicit drugs in North America, with fentanyl test strips (FTSs) often used as a harm reduction tool for overdose prevention. The available evidence to support FTS for harm reduction has yet to be summarized. METHODS: A search of PubMed, Ovid Embase, and Web of Science was conducted in March 2023. A 2-stage review was conducted to screen by title and abstract and then by full text by 2 reviewers. Data were extracted from each study using a standardized template. RESULTS: A total of 91 articles were included, mostly from North America, predominantly reporting on FTS along with other harm reduction tools, and all conducted after 2016. No randomized controlled trials are reported. Robust evidence exists supporting the sensitivity and specificity of FTS, along with their acceptability and feasibility of use for people who use drugs and as a public health intervention. However, limited research is available on the efficacy of FTS as a harm reduction tool for behavior change, engagement in care, or overdose prevention. CONCLUSIONS: Though FTSs are highly sensitive and specific for point of care testing, further research is needed to assess the association of FTS use with overdose prevention. Differences in FTS efficacy likely exist between people who use opioids and nonopioid drugs, with additional investigation strongly needed. As drug testing with point-of-care immunoassays is embraced for nonfentanyl contaminants such as xylazine and benzodiazepines, increased investment in examining overdose prevention is necessary.

Sex differences in trajectories of cortical development in autistic children from 2-13 years of age.

Previous studies have reported alterations in cortical thickness in autism. However, few have included enough autistic females to determine if there are sex specific differences in cortical structure in autism. This longitudinal study aimed to investigate autistic sex differences in cortical thickness and trajectory of cortical thinning across childhood. Participants included 290 autistic (88 females) and 139 nonautistic (60 females) individuals assessed at up to 4 timepoints spanning ~2-13 years of age (918 total MRI timepoints). Estimates of cortical thickness in early and late childhood as well as the trajectory of cortical thinning were modeled using spatiotemporal linear mixed effects models of age-by-sex-by-diagnosis. Additionally, the spatial correspondence between cortical maps of sex-by-diagnosis differences and neurotypical sex differences were evaluated. Relative to their nonautistic peers, autistic females had more extensive cortical differences than autistic males. These differences involved multiple functional networks, and were mainly characterized by thicker cortex at ~3 years of age and faster cortical thinning in autistic females. Cortical regions in which autistic alterations were different between the sexes significantly overlapped with regions that differed by sex in neurotypical development. Autistic females and males demonstrated some shared differences in cortical thickness and rate of cortical thinning across childhood relative to their nonautistic peers, however these areas were relatively small compared to the widespread differences observed across the sexes. These results support evidence of sex-specific neurobiology in autism and suggest that processes that regulate sex differentiation in the neurotypical brain contribute to sex differences in the etiology of autism.

Acute sympathetic activation blunts the hyperemic and vasodilatory response to passive leg movement.

Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) has not been adequately addressed. This study sought to test the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 year). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) of maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after the cessation of exercise and central and peripheral hemodynamics were assessed. MSNA was directly recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+ 15 ± 5 burst/100 bpm) and ExPECO 40% (+ 22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Vasodilation, assessed by the change in leg vascular conductance during PLM, was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate that elevated MSNA attenuates the vasodilatory response to PLM and that the magnitude of reduction in vasodilation during PLM is graded in relation to the degree of sympathoexcitation.

Quality of Life for Patients with Sporadic Small Vestibular Schwannomas Following Middle Fossa Craniotomy.

OBJECTIVE: To evaluate quality-of-life outcomes for patients with vestibular schwannomas (VS) undergoing a middle cranial fossa (MCF) approach. STUDY DESIGN: Prospective study from 2018 to 2023. SETTING: Tertiary academic institution. PATIENTS: Adults with sporadic VS. INTERVENTIONS: MCF. MAIN OUTCOME MEASURES: The primary outcome measure was the change in preoperative and 1-year postoperative Penn Acoustic Neuroma Quality-of-life (PANQOL) scores. Secondary outcome measures included hearing preservation and facial nerve function. RESULTS: Of the 164 patients who underwent MCF for sporadic VS, 78 patients elected to voluntarily complete preoperative PANQOL assessments prior to surgery. Seventy-one (91%) of those 78 patients completed postoperative PANQOL surveys. Fifty (70%) of the respondents were female and the median age was 48 years (range, 27-71 years). Overall, at 1-year postsurgery, a minimal clinically important difference (MCID) was obtained in the hearing (mean difference, 10.5; 95% confidence interval [CI], 4.3-16.7) and anxiety (mean difference, 18.8; 95% CI, 11.7-25.9) domains. For patients with hearing preservation (n = 48, 68%), MCIDs were reached in the hearing (mean difference, 13.4; 95% CI, 6.3-20.6), anxiety (mean difference, 20.8; 95% CI, 11.8-29.9), energy (mean difference, 13.7; 95% CI, 3.6-23.8), pain (mean difference, 13.7; 95% CI, 3.6-23.8) domains, and overall PANQOL scores (mean difference, 12.7; 95% CI, 7.1-18.3). Postoperatively, 64 (90%) patients maintained a House-Brackmann I. CONCLUSIONS: To our knowledge, this is the largest study examining disease-specific QOL for VS patients undergoing MCF. Based on our institution's experience, MCF approach for small VS is associated with clinically meaningful improvements in QOL, hearing preservation, and excellent facial nerve outcomes.

Diffusional and Biochemical Limitations to Photosynthesis Under Water Deficit for Field-Grown Cotton.

Water deficit stress limits net photosynthetic rate (AN), but the relative sensitivities of underlying processes such as thylakoid reactions, ATP production, carbon fixation reactions, and carbon loss processes to water deficit stress in field-grown upland cotton require further exploration. Therefore, the objective of the present study was to assess (1) the diffusional and biochemical mechanisms associated with water deficit-induced declines in AN and (2) associations between water deficit-induced variation in oxidative stress and energy dissipation for field-grown cotton. Water deficit stress was imposed for three weeks during the peak bloom stage of cotton development, causing significant reductions in leaf water potential and AN. Among diffusional limitations, mesophyll conductance was the major contributor to the AN decline. Several biochemical processes were adversely impacted by water deficit. Among these, electron transport rate and RuBP regeneration were most sensitive to AN-limiting water deficit. Carbon loss processes (photorespiration and dark respiration) were less sensitive than carbon assimilation, contributing to the water deficit-induced declines in AN. Increased energy dissipation via non-photochemical quenching or maintenance of electron flux to photorespiration prevented oxidative stress. Declines in AN were not associated with water deficit-induced variation in ATP production. It was concluded that diffusional limitations followed by biochemical limitations (ETR and RuBP regeneration) contributed to declines in AN, carbon loss processes partially contributed to the decline in AN, and increased energy dissipation prevented oxidative stress under water deficit in field-grown cotton.

Impact of jail-based methadone or buprenorphine treatment on non-fatal opioid overdose after incarceration.

BACKGROUND: Non-fatal overdose is a leading predictor of subsequent fatal overdose. For individuals who are incarcerated, the risk of experiencing an overdose is highest when transitioning from a correctional setting to the community. We assessed if enrollment in jail-based medications for opioid use disorder (MOUD) is associated with lower risk of non-fatal opioid overdoses after jail release among individuals with opioid use disorder (OUD). METHODS: This was a retrospective, observational cohort study of adults with OUD who were incarcerated in New York City jails and received MOUD or did not receive any MOUD (out-of-treatment) within the last three days before release to the community in 2011-2017. The outcome was the first non-fatal opioid overdose emergency department (ED) visit within 1 year of jail release during 2011-2017. Covariates included demographic, clinical, incarceration-related, and other characteristics. We performed multivariable cause-specific Cox proportional hazards regression analysis to compare the risk of non-fatal opioid overdose ED visits within 1 year after jail release between groups. RESULTS: MOUD group included 8660 individuals with 17,119 incarcerations; out-of-treatment group included 10,163 individuals with 14,263 incarcerations. Controlling for covariates and accounting for competing risks, in-jail MOUD was associated with lower non-fatal opioid overdose risk within 14 days after jail release (adjusted HR=0.49, 95% confidence interval=0.33-0.74). We found no significant differences 15-28, 29-56, or 57-365 days post-release. CONCLUSION: MOUD group had lower risk of non-fatal opioid overdose immediately after jail release. Wider implementation of MOUD in US jails could potentially reduce post-release overdoses, ED utilization, and associated healthcare costs.

Vector-based feedback of continuous wave radiofrequency compression cavity for ultrafast electron diffraction.

The temporal resolution of ultrafast electron diffraction at weakly relativistic beam energies (≲100 keV) suffers from space-charge induced electron pulse broadening. We describe the implementation of a radio frequency (RF) cavity operating in the continuous wave regime to compress high repetition rate electron bunches from a 40.4 kV DC photoinjector for ultrafast electron diffraction applications. Active stabilization of the RF amplitude and phase through a feedback loop based on the demodulated in-phase and quadrature components of the RF signal is demonstrated. This scheme yields 144 ± 19 fs RMS temporal resolution in pump-probe studies.

Targeting aryl hydrocarbon receptor to prevent cancer in barrier organs.

The skin, lung, and gut are important barrier organs that control how the body reacts to environmental stressors such as ultraviolet (UV) radiation, air pollutants, dietary components, and microorganisms. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that plays an important role in maintaining homeostasis of barrier organs. AhR was initially discovered as a receptor for environmental chemical carcinogens such as polycyclic aromatic hydrocarbons (PAHs). Activation of AhR pathways by PAHs leads to increased DNA damage and mutations which ultimately lead to carcinogenesis. Ongoing evidence reveals an ever-expanding role of AhR. Recently, AhR has been linked to immune systems by the interaction with the development of natural killer (NK) cells, regulatory T (Treg) cells, and T helper 17 (Th17) cells, as well as the production of immunosuppressive cytokines. However, the role of AhR in carcinogenesis is not as straightforward as we initially thought. Although AhR activation has been shown to promote carcinogenesis in some studies, others suggest that it may act as a tumor suppressor. In this review, we aim to explore the role of AhR in the development of cancer that originates from barrier organs. We also examined the preclinical efficacy data of AhR agonists and antagonists on carcinogenesis to determine whether AhR modulation can be a viable option for cancer chemoprevention.

Measuring and improving quality in esophageal care and swallowing disorders.

Evaluating clinical care through quality-related metrics is increasingly common. There are now numerous quality statements and indicators related to the medical management of benign and pre-malignant esophageal diseases. Expert consensus leveraging evidence-based recommendations from published society guidelines has been the most frequently used basis for developing esophageal quality statements. While surgical care of patients with esophageal malignancies, including squamous cell carcinoma, has also been developed, those related to benign esophageal disease now include domains of diagnosis, treatment, and monitoring for gastroesophageal reflux disease, eosinophilic esophagitis (EoE), achalasia, and Barrett's esophagus (BE). Several recent studies evaluating adherence to quality metrics affirm substantial variation in practice patterns with opportunities for improvement in care across esophageal diseases. In particular, patient education regarding treatment options in achalasia, frequency of esophageal biopsies among patients with dysphagia to evaluate for EoE, and endoscopic evaluation within a BE segment are areas identified to have need for improvement. As the management of esophageal diseases becomes more complex and interdisciplinary, adherence to quality metrics may be a source of standardization and improvement in delivery and ultimately patient outcomes. Indeed, the development of national quality databases has resulted in a significant growth in the use of these metrics for quality improvement activities and may form the basis for future inclusion in quality reporting and payment programs.

A Comparison of Short-Term Outcomes after Surgical Treatment of Multilevel Degenerative Cervical Myelopathy in the Geriatric Patient Population: An Analysis of the National Surgical Quality Improvement Program Database 2010-2020.

STUDY DESIGN: Retrospective review of the American College of Surgeons-National Surgical Quality Improvement Program database from 2010 to 2020. PURPOSE: To compare the short-term complication rates of anterior cervical decompression and fusion (ACDF), posterior cervical laminoplasty (LP), and posterior cervical laminectomy and fusion (PCF) in a geriatric population. OVERVIEW OF LITERATURE: The geriatric population in the United States has increased significantly. Degenerative cervical myelopathy (DCM) is caused by cervical spinal stenosis, and its prevalence increases with age. Therefore, the incidence of multilevel DCM requiring surgical intervention is likely to increase. ACDF, LP, and PCF are the most commonly used surgical techniques for treating multilevel DCM. However, there is uncertainty regarding the optimal surgical technique for the decompression of DCM in geriatric patients. METHODS: Patients aged 65 years who had undergone either multilevel ACDF, LP, or PCF for the treatment of DCM were analyzed. Additional analysis was performed by standardizing the data for the American Society of Anesthesiologists classification scores and preoperative functional status. RESULTS: A total of 23,129 patients were identified. Patients with ACDF were younger, more often female, and preoperatively healthier than those in the other two groups. The estimated postoperative mortality and morbidity, mean operation time, and length of hospital stay were the lowest for ACDF, second lowest for LP, and highest for PCF. The readmission and reoperation rates were comparable between ACDF and LP; however, both were significantly lower than PCF. CONCLUSIONS: PCF is associated with the highest risk of mortality, morbidity, unplanned reoperation, and unplanned readmission in the short-term postoperative period in patients aged 65 years. In contrast, ACDF carries the lowest risk. However, some disease-specific factors may require posterior treatment. For these cases, LP should be included in the preoperative discussion when determining the ideal surgical approach for geriatric patients.

Target trial emulation for comparative effectiveness research with observational data: Promise and challenges for studying medications for opioid use disorder.

Medications for opioid use disorder (MOUD) increase retention in care and decrease mortality during active treatment; however, information about the comparative effectiveness of different forms of MOUD is sparse. Observational comparative effectiveness studies are subject to many types of bias; a robust framework to minimize bias would improve the quality of comparative effectiveness evidence. This paper discusses the use of target trial emulation as a framework to conduct comparative effectiveness studies of MOUD with administrative data. Using examples from our planned research project comparing buprenorphine-naloxone and extended-release naltrexone with respect to the rates of MOUD discontinuation, we provide a primer on the challenges and approaches to employing target trial emulation in the study of MOUD.

Cavity-agnostic acoustofluidic manipulations enabled by guided flexural waves on a membrane acoustic waveguide actuator.

This article presents an in-depth exploration of the acoustofluidic capabilities of guided flexural waves (GFWs) generated by a membrane acoustic waveguide actuator (MAWA). By harnessing the potential of GFWs, cavity-agnostic advanced particle manipulation functions are achieved, unlocking new avenues for microfluidic systems and lab-on-a-chip development. The localized acoustofluidic effects of GFWs arising from the evanescent nature of the acoustic fields they induce inside a liquid medium are numerically investigated to highlight their unique and promising characteristics. Unlike traditional acoustofluidic technologies, the GFWs propagating on the MAWA's membrane waveguide allow for cavity-agnostic particle manipulation, irrespective of the resonant properties of the fluidic chamber. Moreover, the acoustofluidic functions enabled by the device depend on the flexural mode populating the active region of the membrane waveguide. Experimental demonstrations using two types of particles include in-sessile-droplet particle transport, mixing, and spatial separation based on particle diameter, along with streaming-induced counter-flow virtual channel generation in microfluidic PDMS channels. These experiments emphasize the versatility and potential applications of the MAWA as a microfluidic platform targeted at lab-on-a-chip development and showcase the MAWA's compatibility with existing microfluidic systems.

Parakinesia Brachialis Oscitans and Excessive yawning From Tumefactive Demyelination.

We present a case and video of a 31-year-old man with biopsy-confirmed tumefactive demyelination affecting the right internal capsule causing left hemiplegia, excessive yawning, and the curious but well-described phenomenon of parakinesia brachialis oscitans (PBO) with transient tonic elevation of his paralyzed arm while yawning. PBO is most commonly reported in ischemic stroke with internal capsule or pontomedullary brainstem lesions. Our case uniquely demonstrates this phenomenon in the case of tumefactive demyelination. We also highlight excessive yawning which has also been described in multiple sclerosis.

Management of Tracheobronchial Stenosis in Chondrodysplasia Punctata.

Chondrodysplasia punctata (CDP) is a rare congenital syndrome characterized by aberrant, punctate deposition of calcium during endochondral bone formation, resulting in the characteristic finding of epiphyseal stippling on radiographs. While otolaryngologic manifestations such as nasomaxillary hypoplasia and mixed hearing loss are common, tracheobronchial calcification occurs rarely in neonates with CDP. The management of CDP-related airway stenosis is complex and there is limited literature pertaining to outcomes of airway interventions. Herein, we describe the clinical course and outcome of tracheal dilation for a newborn patient with CDP. Laryngoscope, 134:1464-1468, 2024.

Cohort study on immune checkpoint inhibitor-associated acute kidney injury: Incidence, risk factors, and management strategies.

INTRODUCTION: Case studies and retrospective chart reviews of health system data have demonstrated an increased risk of nephrotoxicity in patients receiving immune checkpoint inhibitors compared to clinical trials. This study investigated the frequency, causes, and risk factors for acute kidney injury in a real-world, rural setting. METHODS: This was a retrospective cohort study of patients who received at least one dose of a checkpoint inhibitor at a rural health system from May 2013 to February 2020 and who received at least one dose of a checkpoint inhibitor. Electronic and manual chart review helped to determine the incidence of, risk factors for, and renal outcomes and management strategies of checkpoint inhibitor-related acute kidney injury. Multivariable Fine and Gray subdistribution hazard models were used to assess the impact of patient characteristics on the incidence of sustained acute kidney injury and checkpoint inhibitor-induced acute kidney injury. RESULTS: After exclusion criteria, 906 patients who received at least one dose of a checkpoint inhibitor at Marshfield Clinic Health System during the study period were included. The incidence of acute kidney injury of any duration and due to any cause was 36.1%, while sustained acute kidney injury occurred in 28.7% of patients. Checkpoint inhibitor-related acute kidney injury was thought to have occurred in 2.7% of patients. Baseline estimated glomerular filtration rate < 60 was the sole predictor of checkpoint inhibitors-related acute kidney injury. Most patients with suspected checkpoint inhibitor-related acute kidney injury were managed with corticosteroids, and 62.5% experienced complete renal recovery. CONCLUSIONS: Ours is the first retrospective cohort study to test whether baseline Eastern Cooperative Oncology Group score and checkpoint inhibitor place in therapy were associated with checkpoint inhibitor-related acute kidney injury, and neither of these data points were found to be predictive. Even after expanding the parameters and methodologies of our study as compared to other retrospective cohort studies, we found only three baseline characteristics to be predictive of sustained acute kidney injury: Baseline eGFR, loop diuretic, and spironolactone use. For checkpoint inhibitor-related baseline, eGFR alone was predictive.

Jail-based medication for opioid use disorder and patterns of reincarceration and acute care use after release: A sequence analysis.

BACKGROUND: Treatment with methadone and buprenorphine medications for opioid use disorder (MOUD) during incarceration may lead to better community re-entry, but evidence on these relationships have been mixed. We aimed to identify community re-entry patterns and examine the association between in-jail MOUD and a pattern of successful reentry defined by rare occurrence of reincarceration and preventable healthcare utilization. METHODS: Data came from a retrospective, observational cohort study of 6066 adults with opioid use disorder who were incarcerated in New York City jails and released to the community during 2011-14. An outcome was community re-entry patterns identified by sequence analysis of 3-year post-release reincarceration, emergency department visits, and hospitalizations. An exposure was receipt of in-jail MOUD versus out-of-treatment (42 % vs. 58 %) for the last 3 days before discharge. The study accounted for differences in baseline demographic, clinical, behavioral, housing, and criminal legal characteristics between in-jail MOUD and out-of-treatment groups via propensity score matching. RESULTS: This study identified five re-entry patterns: stability (64 %), hospitalization (23 %), delayed reincarceration (7 %), immediate reincarceration (4 %), and continuous incarceration (2 %). After addressing confounding, 64 % and 57 % followed the stability pattern among MOUD and out-of-treatment groups who were released from jail in 2011, respectively. In 2012-14, the prevalence of following the stability pattern increased year-by-year while a consistently higher prevalence was observed among those with in-jail MOUD. CONCLUSIONS: Sequence analysis helped define post-release stability based on health and criminal legal system involvement. Receipt of in-jail MOUD was associated with a marker of successful community re-entry.

Hypophosphatemia as a Predictor of Clinical Outcomes in Acute Pancreatitis: A Retrospective Study.

OBJECTIVE: Phosphate is crucial for cellular repair after injury and may be important in recovery following acute pancreatitis (AP). This study aimed to evaluate the association between hypophosphatemia and severity of AP. METHODS: Patients admitted with AP between 2014-2018 were identified and their records were retrospectively reviewed. Pancreatitis severity was defined using the modified Atlanta Criteria. Hypophosphatemia was defined as phosphate <2 mg/dL and was assessed at three time points: within one day, within two days, at any time during admission. The proportion of patients who developed severe AP was compared between patients with and without hypophosphatemia. RESULTS: Of 312 patients, 30.1% (n = 94) developed severe AP. Hypophosphatemia occurred in 25.0% overall, within one day in 19.7%, and within two days in 20.0%. A higher proportion of patients with hypophosphatemia developed severe AP (overall: 47.4% vs. 24.4%, P < 0.001; one day: 47.4% vs. 23.9%, P = 0.004; two days: 42.9% vs. 24.5%, P = 0.01). Patients with hypophosphatemia within one day were also more likely to have ICU admission ( P < 0.001) and longer length of stay ( P < 0.001). CONCLUSIONS: Early hypophosphatemia during an admission for AP was associated with increased AP severity, ICU admission, and longer length of stay.

Comparison of Postoperative Outcomes in Cystic Versus Solid Vestibular Schwannoma in a Multi-institutional Cohort.

OBJECTIVE: Cystic vestibular schwannomas (cVSs) have more variable and less favorable clinical outcomes after microsurgical resection compared with solid VS (sVS). This study compares the preoperative presentation and postoperative outcomes between cVS and sVS. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary skull base referral centers. METHODS: Consecutive adult patients who underwent VS resection from 2016 to 2021 were included. Univariate and multivariate analyses compared differences in baseline symptoms and postoperative outcomes between cVS and sVS. RESULTS: There were a total of 315 patients (64% female; mean age, 54 yrs) and 46 (15%) were cystic. cVS were significantly larger than sVS (maximum diameter, 28 vs. 18 mm, p < 0.001) and had higher rates of dysphagia and dysphonia preoperatively (p < 0.02). cVSs were more likely to undergo translabyrinthine resection (76 vs. 50%, p = 0.001) and have a higher rate of subtotal resection (STR) compared with sVS (30 vs. 13%, p = 0.003). At latest follow-up, fewer cVS achieved good facial nerve (FN) outcome (House-Brackmann [HB] I/II) (80 vs. 90%, p = 0.048). Subanalysis of cVS and sVS matched in tumor size, and surgical approach did not show differences in the rate of STR or FN outcomes (HB I/II, 82 vs. 78%, p = 0.79). CONCLUSION: In this large multi-institutional series, cVSs represent a distinct entity and are characterized by larger tumor size and higher incidence of atypical symptoms. Although cVSs were more likely to undergo STR and portend worse FN outcomes than sVSs, this may be due to their larger tumor size rather than the presence of the cystic component.