Frontline Perspectives on Buprenorphine for the Management of Chronic Pain.

Due to the prevalence of chronic pain and high-impact chronic pain in the US, a significant percentage of the population is prescribed opioids for pain management. However, opioid use disorder is associated with reduced quality of life, along with fatal opioid overdoses, and is a significant burden on the US economy. Considering the clinical needs of patients with intractable chronic pain and the potential harms associated with prescribed and illicit opioids in our communities, having a deep understanding of current treatment options, supporting evidence, and clinical practice guidelines is essential for optimizing treatment selections. Buprenorphine is a Schedule III opioid with a unique mechanism of action, allowing effective and long-lasting analgesia at microgram doses with fewer negative side effects and adverse events, including respiratory depression, when compared with other immediate-release, long-acting, and extended-release prescription opioids. Due to its relatively lower risk for overdose and misuse, buprenorphine was recently added to the Clinical Practice Guideline for the Use of Opioids in the Management of Chronic Pain as a first-line treatment for chronic pain managed by opioids by the US Departments of Defense and Veterans Affairs, and the Department of Health and Human Services recommends that buprenorphine be made available for the treatment of chronic pain. In this narrative review, we discuss the different buprenorphine formulations, clinical efficacy, advantages for older adults and other special populations, clinical practice guideline recommendations, and payer considerations of buprenorphine and suggest that buprenorphine products approved for chronic pain should be considered as a first-line treatment for this indication.

Mobility and bioaccessibility of arsenic (As) bound to titanium dioxide (TiO2) water treatment residuals (WTRs).

This work systematically describes arsenic mobility and potential bioaccessibility of arsenic-enriched titanium dioxide water treatment residuals (TiO2 WTRs) by employing a suite of wet chemical experiments and spectroscopic measurements. Specifically, Environmental Protection Agency (EPA) digestion method 3051a indicated <3% of total arsenic in the solid phase was released, and arsenic assessed by EPA method 1340 for bioaccessibility was below detection limits. A novel finding is while the arsenic appeared to be stable under highly acidic digestion conditions, it is in fact highly mobile when exposed to simple phosphate solutions. On average, 55% of arsenic was extracted from all samples during a 50-day replenishment study. This was equivalent to 169 mg kg-1 arsenic released from the solid phase. Macroscopic desorption experiments indicated arsenic likely formed inner-sphere bonds with the TiO2 particles present in the samples. This was confirmed with X-ray absorption spectroscopy (XAS), where an interatomic distance of 3.32 Å and a coordination number (CN) of 1.79 titanium atoms were determined. This translates to a configuration of arsenic on TiO2 surfaces as a bidentate binuclear inner-sphere complex. Thus, both macroscopic and spectroscopic data are in agreement. During incubation experiments, arsenic(V) was actively reduced to arsenic(III); the amount of arsenic(III) in solution varied from 8 to 38% of total dissolved arsenic. Lastly, elevated concentrations and mobility of vanadium in these systems merit further investigation. The high mobility of arsenic and its potential for reduction when reintroduced into the environment, particularly in agriculturally important areas, presents an important risk when waste products are not properly managed.

The Evolving Need for Neuropsychology in Neurosurgical Settings: Challenges Facing Transformative Care.

Clinical neuropsychology has been a valuable asset to neurologic surgery, contributing to lateralization and localization of pathologic brain tissue, identification of eloquent cortex, and evaluation of postoperative neuropsychological functioning. Moreover, neuropsychologists provide empirically driven interventions aimed at supporting preparation and/or recovery of neurosurgery patients. Nonetheless, several challenges may limit the reliability, validity, and generalizability of the assessment data obtained and reduce the usefulness of other neuropsychological services provided. Specifically, linguistic, cultural, educational, and other biases associated with demographic characteristics can lead to a narrowed view of an individual's life experiences, which must be confronted to fulfill the mission of ensuring that all patients have access to care that is appropriate to their needs. Instead of perceiving these challenges as insurmountable barriers, such issues can be viewed as opportunities to catalyze change and foster innovation for the future of neuropsychological care in neurosurgical settings. In addition to reviewing the possible mechanisms of these obstacles, the current article offers tangible solutions at both a macro level (e.g., discipline-wide transformations) and micro level (e.g., individualized patient-centric approaches). Outlined are practical techniques to potentially improve consensus and standardization of methods, advance and globalize research, expand representativeness of measures and practices to serve diverse individuals, and increase treatment adherence through engagement of patients and their families.

Foundations of Neuropsychology: Collaborative Care in Neurosurgery.

The disciplines of neuropsychology and neurosurgery have a history of partnership that has improved prognoses for patients with neurologic diagnoses that once had poor outcomes. This article outlines the evolution of this relationship and describes the current role that clinical neuropsychology has within a department of neurological surgery across the preoperative, intraoperative, and postoperative stages of treatment. Understanding the foundations of collaboration between neuropsychology and neurosurgery contextualizes present challenges and future innovations for advancing excellence along the continuum of care for all neurosurgical patients.

Innovations in Neuropsychology: Future Applications in Neurosurgical Patient Care.

Over the last century, collaboration between clinical neuropsychologists and neurosurgeons has advanced the state of the science in both disciplines. These advances have provided the field of neuropsychology with many opportunities for innovation in the care of patients prior to, during, and following neurosurgical intervention. Beyond giving a general overview of how present-day advances in technology are being applied in the practice of neuropsychology within a neurological surgery department, this article outlines new developments that are currently unfolding. Improvements in remote platform, computer interface, "real-time" analytics, mobile devices, and immersive virtual reality have the capacity to increase the customization, precision, and accessibility of neuropsychological services. In doing so, such innovations have the potential to improve outcomes and ameliorate health care disparities.

Rehabilitation of Neuropsychiatric Symptoms in Patients With Long COVID: Position Statement.

Long COVID, a term used to describe ongoing symptoms after COVID-19 infection, parallels the course of other postviral syndromes. Neuropsychiatric symptoms of long COVID can be persistent and interfere with quality of life and functioning. Within the biopsychosocial framework of chronic illness, rehabilitation professionals can address the neuropsychiatric sequelae of long COVID. However, current practice models are not designed to address concurrent psychiatric and cognitive symptoms in adults living with long COVID. Thus, we present a biopsychosocial framework for long COVID and provide treatment strategies based on evidence from current literature of postviral chronic illness. These recommendations will guide rehabilitation professionals in identifying common neuropsychiatric symptoms in long COVID that can be targeted for intervention and addressing these symptoms via integrative interventions taking into account the biopsychosocial presentation of long COVID symptoms.

A porous ceramic particle with or without a preservative blend did not impair apparent digestibility of macro- and micro-nutrients of postweaned pigs.

The objective of this study was to determine the effects of supplementing a commercial porous ceramic clay particle, with or without a blend of preservatives, on the performance and nutrient digestibility of weanling pigs. Fifteen weanling pigs of the Yorkshire, Landrace, and Duroc breeds were blocked by breed and randomly assigned to one of three treatments (n = 5): (1) Control, non-medicated diet with no additional feed additives (CON); (2) PowerGuard, basal diet with 0.25% of the DM consisting of a ceramic particle mixed into the pelleted feed (PG; MB Nutritional Sciences, Lubbock, TX, 79403); or (3) Power Guard + a blend of preservatives, basal diet with 0.3% of the DM consisting of the ceramic clay and preservatives mixed into the pelleted feed (PG-D). The facility was temperature controlled with an average temperature of 28.5 °C. Pigs were offered ad libitum access to feed and water and were housed individually in elevated crates. Body weights were collected upon enrollment on day 0 and at the end of the observation period on day 18. On day 15 , a 72-h total feed and fecal collection period began. Feed and fecal samples were analyzed for DM, CP, Ash, OM, ADF, NDF, zinc, copper, thiamin (vitamin B1), and retinol (vitamin A). Liver samples were collected immediately after harvest and frozen for later mineral analysis. Data were analyzed using Proc Mixed in SAS with dietary group as the main effect and block as the random effect (SAS 9.4, Cary, NC). There were no treatment differences in performance measures including final BW, ADG, or G:F (P ≥ 0.701). There were no treatment differences in diet nutrient digestibility for DM, CP, Ash, OM, ADF, or NDF (P ≥ 0.312). Additionally, there were no treatment effects on zinc, copper, or retinol digestibility (P ≥ .298); however, thiamin inclusion rate was increased for the PG-D treatment, thus leading to an increased digestibility for thiamin (P = 0.018) in the PG-D treatment. There were no treatment differences in hepatic mineral concentrations (P ≥ 0.532); however, there was a tendency for pigs fed PG-D to have increased hepatic concentrations of lead and mercury when compared with both PG and CON pigs (P ≤ 0.066). In summary, supplementation of a commercial ceramic particle with or without a blend of preservatives to weaned pigs did not affect performance or apparent nutrient digestibility.

Reverse Lymphatic Mapping and Immediate Microsurgical Lymphatic Reconstruction Reduces Early Risk of Breast Cancer-Related Lymphedema.

BACKGROUND: Breast cancer-related lymphedema is a progressive disease that poses tremendous physical, psychosocial, and financial burden on patients. Immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection is emerging as a potential therapeutic paradigm to decrease the incidence of breast cancer-related lymphedema in high-risk patients. METHODS: Eighty-one consecutive patients underwent reverse lymphatic mapping and, when feasible, supermicrosurgical immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection at a tertiary care cancer center. Patients were followed prospectively in a multidisciplinary lymphedema clinic (plastic surgery, certified lymphatic therapy, dietary, case management) at 3-month intervals with clinical examination, circumferential limb girth measurements, and bioimpedance spectroscopy. An institutional control cohort was assessed for the presence of objectively diagnosed and treated breast cancer-related lymphedema. Data were analyzed by a university statistician. RESULTS: Seventy-eight patients met inclusion, and 66 underwent immediate lymphaticovenular anastomosis. Mean follow-up was 250 days. When compared to a retrospective control group, the rate of lymphedema in patients who underwent immediate lymphaticovenular anastomosis was significantly lower (6 percent versus 44 percent; p < 0.0001). Patients with 6-month follow-up treated with combined adjuvant radiation therapy and chemotherapy had significantly greater risk of developing breast cancer-related lymphedema (p = 0.04) compared to those without combined adjuvant therapy. Arborized anastomotic technique had a statistically shorter operative time than end-to-end anastomosis (p = 0.005). CONCLUSIONS: This series of consecutive patients demonstrate a 6 percent incidence of early-onset breast cancer-related lymphedema with immediate lymphaticovenular anastomosis and an increased risk in those undergoing combined adjuvant treatment. These early data represent an encouraging and substantial decrease of breast cancer-related lymphedema in high-risk patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Conversion of Schedule II Opioids to Buprenorphine Buccal Film: A Retrospective Analysis.

OBJECTIVE: To provide clinical data for the conversion of Schedule II opioids to buprenorphine buccal film and to demonstrate sustained analgesia and a reduction in morphine milligram equivalents after conversion. DESIGN: Retrospective review of electronic medical records. SETTING: Group clinical practice providing outpatient chronic pain management care in Winston-Salem, North Carolina. SUBJECTS: Patients who received opioids for chronic pain between January 1, 2016, and June 30, 2019, were selected for chart review if they were converted to buprenorphine buccal film from a Schedule II opioid. METHODS: Patients who met inclusion criteria were stratified into subgroups on the basis of preconversion morphine milligram equivalents, whether they remained on opioids for breakthrough pain postconversion, and pre- and postconversion numerical rating scale pain scores. Outcomes of interest included the differences between pre- and postconversion numerical rating scale pain scores and daily morphine milligram equivalents for each subgroup. RESULTS: Of 157 patients reviewed, 87.9% were successfully converted to buprenorphine buccal film. Overall, numerical rating scale pain scores were stable after conversion. Statistically significant reductions were demonstrated in the <90 daily morphine milligram equivalent subgroup. Postconversion daily morphine milligram equivalents decreased by 85.4% from baseline. Change in daily morphine milligram equivalents is representative of patients who remained on breakthrough pain medication. CONCLUSIONS: Results demonstrate continued analgesia after conversion to buprenorphine buccal film despite reductions in daily morphine milligram equivalents. Most patients were able to convert directly from their long-acting opioid to buprenorphine buccal film and stabilized without the use of concomitant opioids for breakthrough pain. Aggressive titration strategies were associated with greater success.

Experiences and Beliefs of Low-Income Patients With Hypertension in Louisiana and Mississippi During the COVID-19 Pandemic.

Background The coronavirus disease 2019 (COVID-19) pandemic disproportionately affects individuals with hypertension and health disparities. Methods and Results We assessed the experiences and beliefs of low-income and minority patients with hypertension during the COVID-19 pandemic. Participants (N=587) from the IMPACTS-BP (Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control) study completed a telephone survey in May and June of 2020. Participants were 65.1% Black and 59.7% female, and 57.7% reported an income below the federal poverty level. Overall, 2.7% tested positive and 15.3% had lost a family member or friend to COVID-19. These experiences were significantly more common in Black (3.9% and 19.4%, respectively) than in non-Black participants (0.5% and 7.8%, respectively). In addition, 14.5% lost a job and 15.9% reported food shortages during the pandemic. Most participants complied with stay-at-home orders (98.3%), social distancing (97.8%), and always wearing a mask outside their home (74.6%). Participants also reported high access to needed health care (94.7%) and prescription medications (97.6%). Furthermore, 95.7% of respondents reported that they continued to take their regular dosage of antihypertensive medications. Among the 44.5% of participants receiving a healthcare appointment by telehealth, 96.6% got the help they needed, and 80.8% reported that the appointment quality was as good as or better than in-person visits. Finally, 88.9% were willing to return to their primary care clinic. Conclusions These data suggest that low-income patients, especially Black patients, were negatively impacted by COVID-19. However, most patients were able to access needed healthcare services and were willing to return to their primary care clinic for hypertension management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03483662.

Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control (IMPACTS): Rationale and design of a cluster-randomized trial.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) reported that intensive blood pressure (BP) treatment reduced cardiovascular disease and mortality compared to standard BP treatment in hypertension patients. The next important question is how to implement more intensive BP treatment in real-world clinical practice. We designed an effectiveness-implementation hybrid trial to simultaneously test the effectiveness of a multifaceted intervention for intensive BP treatment and its feasibility, fidelity, and sustainability in underserved hypertension patients. METHODS: Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control (IMPACTS) is a cluster randomized trial conducted in 36 Federally Qualified Health Center clinics in Louisiana and Mississippi. Federally Qualified Health Center clinics were randomized to either a multifaceted intervention for intensive BP treatment, including protocol-based treatment using the SPRINT intensive BP management algorithm, dissemination of SPRINT findings, BP audit and feedback, home BP monitoring, and health coaching, or enhanced usual care. Difference in mean systolic BP change from baseline to 18 months is the primary clinical effectiveness outcome, and intervention fidelity, measured by treatment intensification and medication adherence, is the primary implementation outcome. The planned sample size of 1,260 participants (36 clinics with 35 participants each) has 90% power to detect a 5.0-mm Hg difference in systolic BP at a .05 significance level and 80% follow-up rate. CONCLUSIONS: IMPACTS will generate critical data on the effectiveness and implementation of a multifaceted intervention for intensive BP treatment in real-world clinical practice and could directly impact the BP-related disease burden in minority and low-income populations in the United States.

Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia.

Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding of the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate the passage of sensory information conveyed by low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate the polysynaptic relay of LTMR input to pain circuits by inhibiting lamina II excitatory interneurons whose axons project into lamina I. We show changes in the functional properties of these PV interneurons following peripheral nerve injury and that silencing these cells unmasks a circuit that allows innocuous touch inputs to activate pain circuits by increasing network activity in laminae I-IV. Such changes are likely to result in the development of tactile allodynia and could be targeted for more effective treatment of mechanical pain.

Distinct Modes of Presynaptic Inhibition of Cutaneous Afferents and Their Functions in Behavior.

Presynaptic inhibition (PSI) of primary sensory neurons is implicated in controlling gain and acuity in sensory systems. Here, we define circuit mechanisms and functions of PSI of cutaneous somatosensory neuron inputs to the spinal cord. We observed that PSI can be evoked by different sensory neuron populations and mediated through at least two distinct dorsal horn circuit mechanisms. Low-threshold cutaneous afferents evoke a GABAA-receptor-dependent form of PSI that inhibits similar afferent subtypes, whereas small-diameter afferents predominantly evoke an NMDA-receptor-dependent form of PSI that inhibits large-diameter fibers. Behaviorally, loss of either GABAA receptors (GABAARs) or NMDA receptors (NMDARs) in primary afferents leads to tactile hypersensitivity across skin types, and loss of GABAARs, but not NMDARs, leads to impaired texture discrimination. Post-weaning age loss of either GABAARs or NMDARs in somatosensory neurons causes systemic behavioral abnormalities, revealing critical roles of two distinct modes of PSI of somatosensory afferents in adolescence and throughout adulthood.

Patterns of Cyclist and Pedestrian Street Crossing Behavior and Safety on an Urban Greenway.

Greenways are linear open spaces, which are often used as trails for pedestrians and cyclists, but junctions with roads are a safety concern and act as a potential impediment to active transportation. This study evaluated crossing behavior patterns and safety at greenway⁻road junctions in New Orleans, LA. Crossing behaviors, safety and motor vehicle behavior were collected using direct observation methods. Intercept surveys were conducted to assess greenway use and safety perceptions. Logistic and negative binomial regression were used to assess the relationships between crossing signal (rectangular rapid flash beacon) activation and motor vehicle behavior. Fewer unsafe crossings occurred when the crossing signals were activated for cyclists and pedestrians (p-values of 0.001 and 0.01, respectively). There was no association between pedestrian use of crossing signals and motor vehicle stopping behavior but cyclists had significantly higher odds of motor vehicles failing to stop when the signal was activated (OR 5.12, 95% CI 2.86⁻9.16). The activation of rectangular rapid flash beacons at urban greenway junctions with roads did not influence motor vehicle behavior. Differences in crossing safety by signal use cannot be attributed to the signal's influence on motor vehicle stopping behavior.

Improvement in Existing Chest Wall Irregularities During Breast Reconstruction.

Mastectomies for both cancer resection and risk reduction are becoming more common. Existing chest wall irregularities are found in these women presenting for breast reconstruction after mastectomy and can pose reconstructive challenges. Women who desired breast reconstruction after mastectomy were evaluated preoperatively for existing chest wall irregularities. Case reports were selected to highlight common irregularities and methods for improving cosmetic outcome concurrently with breast reconstruction procedures. Muscular anomalies, pectus excavatum, scoliosis, polythelia case reports are discussed. Relevant data from the literature are presented. Chest wall irregularities are occasionally encountered in women who request breast reconstruction. Correction of these deformities is possible and safe during breast reconstruction and can lead to improved cosmetic outcome and patient satisfaction.

In the Age of Breast Augmentation, Breast Reconstruction Provides an Opportunity to Augment the Breast.

BACKGROUND: Augmentation mammoplasty remains the most common cosmetic surgery procedure performed. The objective of this article is to evaluate the impact of augmented volume of the reconstructed breast in patients that undergo nipple-sparing mastectomy and patients previously augmented who undergo mastectomy with tissue expander/implant-based reconstruction. METHODS: Patients undergoing skin-sparing mastectomy, nipple-sparing mastectomy, and mastectomy after previous augmentation followed by tissue expander/implant-based reconstruction between June 2011 and April 2015 by 2 surgeons at the same institution were included. Retrospective chart review of the patients identified using these criteria was performed to record patient characteristics, complications, breast volume, implant volume, and percentage change in volume at the time of reconstruction. Percentage change of breast volume was calculated using the formula (implant breast weight)/(breast weight) for skin-sparing and nipple-sparing mastectomy patients and (final breast implant weight - [breast weight + augmentation breast implant weight])/([breast weight + augmentation breast implant]) for patients undergoing mastectomy following previous augmentation. RESULTS: A total of 293 patients were included in the study with 63 patients who underwent nipple-sparing mastectomy, 166 patients who underwent skin-sparing mastectomy, and 64 patients who underwent previous augmentation with subsequent mastectomy. Mean percentage change in breast volume was 66% in the nipple-sparing mastectomy group, 15% for the right breast and 18% for the left breast in the skin-sparing mastectomy group, and 81% for the right breast and 72% for the left breast in the mastectomy following previous augmentation group. Complication rate for nipple-sparing mastectomy was 27%, mastectomy following previous augmentation was 20.3%, and skin-sparing mastectomy group was 18.7%. CONCLUSION: Patients who undergo nipple-sparing mastectomy or mastectomy following previous augmentation have the ability to achieve greater volume in their reconstructed breast via tissue expander/implant-based reconstruction.

The Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn.

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception.

Tyrosine Hydroxylase Expression in Type II Cochlear Afferents in Mice.

Acoustic information propagates from the ear to the brain via spiral ganglion neurons that innervate hair cells in the cochlea. These afferents include unmyelinated type II fibers that constitute 5 % of the total, the majority being myelinated type I neurons. Lack of specific genetic markers of type II afferents in the cochlea has been a roadblock in studying their functional role. Unexpectedly, type II afferents were visualized by reporter proteins induced by tyrosine hydroxylase (TH)-driven Cre recombinase. The present study was designed to determine whether TH-driven Cre recombinase (TH-2A-CreER) provides a selective and reliable tool for identification and genetic manipulation of type II rather than type I cochlear afferents. The "TH-2A-CreER neurons" radiated from the spiral lamina, crossed the tunnel of Corti, turned towards the base of the cochlea, and traveled beneath the rows of outer hair cells. Neither the processes nor the somata of TH-2A-CreER neurons were labeled by antibodies that specifically labeled type I afferents and medial efferents. TH-2A-CreER-positive processes partially co-labeled with antibodies to peripherin, a known marker of type II afferents. Individual TH-2A-CreER neurons gave off short branches contacting 7-25 outer hair cells (OHCs). Only a fraction of TH-2A-CreER boutons were associated with CtBP2-immunopositive ribbons. These results show that TH-2A-CreER provides a selective marker for type II versus type I afferents and can be used to describe the morphology and arborization pattern of type II cochlear afferents in the mouse cochlea.