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1.
BMC Public Health ; 23(1): 1430, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37495970

RESUMEN

BACKGROUND: Research on the impacts of exposure to workplace harassment (WH) is largely cross-sectional, and existing prospective studies generally are between two and five years of follow-up, with the longest US study being 10 years. However, the effects of exposure to WH may persist longer, particularly if exposure has been chronic. This study fills this gap by examining effects of prior exposure to chronic sexual and generalized WH on psychological distress and alcohol misuse over an approximately 25 year study period. METHODS: Individuals originally recruited from a university-employed sample in the United States were surveyed at 8 time points from 1996-2007 and again in 2020-2021. A series of hybrid path analyses were tested on a sample of 2352 individuals, regressing recent outcomes on latent classes of harassment derived from earlier survey waves, controlling baseline outcomes and demographics. Model fit was assessed using a variety of fit statistics, and standardized regression coefficients were used to assess significance of individual pathways. RESULTS: Prior exposure to chronic sexual harassment had significant direct associations with psychological distress, alcohol misuse, and recent stressors at follow-up. Prior exposure to chronic generalized harassment had significant direct associations with lower income and alcohol misuse. Both forms of WH were significantly indirectly associated with psychological distress through recent stressors at follow-up. CONCLUSIONS: Exposure to chronic WH is associated with long-term effects on psychological distress and alcohol misuse in a sample representing a wide variety of job types and racial/ethnic identities. Enforcement of anti-sexual harassment law and policies and enactment of policies and laws to prevent generalized harassment/workplace bullying are imperative for the protection of worker health.


Asunto(s)
Alcoholismo , Salud Mental , Humanos , Estudios de Seguimiento , Alcoholismo/epidemiología , Estudios Prospectivos , Estudios Transversales , Lugar de Trabajo/psicología , Encuestas y Cuestionarios
2.
Cardiovasc Intervent Radiol ; 46(5): 600-609, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37012392

RESUMEN

PURPOSE: The OsteoCool Tumor Ablation Post-Market Study (OPuS One) was a prospective, multi-national, single-arm study to investigate safety and effectiveness of radiofrequency ablation (RFA) for palliation of painful lytic bone metastases with 12 months of follow-up. RFA has demonstrated effective palliation of osseous metastases in small clinical studies with short-term follow-up; however, a long-term assessment with robust subject numbers is lacking. MATERIALS AND METHODS: Prospective assessments were conducted at Baseline, 3 days, 1 week, and 1, 3, 6, and 12-months. Pain and quality of life were measured prior to RFA and postoperatively using the Brief Pain Inventory, European Quality of Life-5 Dimension, and European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire for palliative care. Radiation, chemotherapy and opioid usage, and related adverse events were collected. RESULTS: 206 subjects were treated with RFA at 15 institutions in OPuS One. Worst pain, average pain, pain interference and quality of life significantly improved at all visits starting 3 days post-RFA and sustained to 12 months (P < 0.0001). Post hoc analysis found neither systemic chemotherapy nor local radiation therapy at the index site of RFA influenced worst pain, average pain, or pain interference. Six subjects had device/procedure-related adverse events. CONCLUSION: RFA for lytic metastases provides rapid (within 3 days) and statistically significant pain and quality of life improvements with sustained long-term relief through 12 months and a high degree of safety, independent of radiation. LEVEL OF EVIDENCE: 2B, PROSPECTIVE, NON-RANDOMIZED, POST-MARKET STUDY: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Neoplasias Óseas , Ablación por Catéter , Ablación por Radiofrecuencia , Humanos , Cuidados Paliativos/métodos , Calidad de Vida , Estudios Prospectivos , Resultado del Tratamiento , Dolor/cirugía , Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Ablación por Radiofrecuencia/métodos , Ablación por Catéter/métodos
3.
Interv Pain Med ; 2(1): 100243, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39239603

RESUMEN

Background: Chronic low back pain (CLBP) is often associated with clinical evidence of central nervous system sensitization and finding a clear source of nociceptive input can be challenging. Conventional therapies targeting peripheral spinal pain structures can fail to address centrally-mediated, underlying causes of pain. Sixty-day percutaneous peripheral nerve stimulation (PNS) applied to the lumbar medial branch nerves is a non-surgical, non-opioid treatment that may restore the balance of peripheral inputs to the central nervous system and reverse maladaptive changes in central pain processing. As a minimally invasive, non-destructive treatment, percutaneous PNS was designed to be used earlier in the treatment continuum than radiofrequency ablation or permanently-implanted neurostimulation systems. Objective: The objective of this clinical trial was to characterize the durability of responses to medial branch PNS in a prospective multicenter case series study of CLBP patients recalcitrant to multiple non-surgical treatments. Design: Prospective, multicenter clinical trial. Population: Adults with CLBP without radicular leg pain who had previously failed multiple types of conventional treatments. Intervention: Sixty-day percutaneous PNS applied to the lumbar medial branch nerves. Methods: Percutaneous PNS leads were implanted under image guidance (ultrasound and/or fluoroscopy) and treatment was applied for up to 60 days, after which the leads were removed. Participants were followed through 14 months (12 months after the 2-month PNS treatment). Prospectively-defined endpoints included assessments of pain intensity, disability, pain interference, health-related quality of life, depression, and patient global impression of change. Results: Treatment of CLBP with 60-day percutaneous PNS treatment produced clinically meaningful improvements in average pain intensity, disability, and/or pain interference for a majority of participants through the entire 14 month follow up period without requiring permanent system implantation. The proportion of participants experiencing clinically meaningful improvement in at least one outcome (pain intensiy, disability, pain interference) with PNS was 91% after 2 months, 79% at 5 months, 73% at 8 months, 75% at 11 months, and 77% at 14 months. There were no serious or unanticipated study-related adverse events. Conclusion: This prospective multicenter clinical trial demonstrates the clinical utility of percutaneous PNS when applied to the medial branch nerves for the treatment of chronic low back pain recalcitrant to non-surgical treatments. Given the minimally invasive nature of percutaneous PNS and the significant benefits experienced by participants, percutaneous PNS provides a safe and effective first-line neuromodulation treatment for patients with CLBP that may obviate the need for neuroablative procedures or permanent neurostimulation system implantation.

4.
Spine J ; 22(12): 2072-2081, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35753638

RESUMEN

BACKGROUND CONTEXT: The treatment of vertebral compression fractures using percutaneous augmentation is an effective method to reduce pain and decrease mortality rates. Surgical methods include vertebroplasty, kyphoplasty, and vertebral augmentation with implants. A previous study suggested that a titanium implantable vertebral augmentation device (TIVAD) produced superior height restoration compared to balloon kyphoplasty (BKP) but was based on a less clinically relevant biomechanical model. Moreover, the introduction of high pressure balloons and directional instruments may further aid in restoring height. PURPOSE: The objective was to evaluate three procedures (BKP, BKP w/ Kyphon Assist (KA; directional instruments), and TIVAD) used for percutaneous augmentation of vertebral fractures with respect to height restoration and sustainability post-operatively. STUDY DESIGN/SETTING: This is an in vitro cadaver study performed in a laboratory setting. METHODS: Five osteoporotic female human cadaver thoracolumbar spines (age: 63-77 years, T-score: -2.5 to -3.5, levels: T7-S1) were scanned using computed tomography and dissected into 30 two-functional spine units (2FSUs). Vertebral wedge compression fractures were created by reducing the anterior height of the vertebrae by 25% and holding the maximum displacement for 15 minutes. Post-fracture, surgery was performed on each 2FSU with a constant 100 N load. Surgeries included BKP, BKP w/ KA, or TIVAD (n=10 per treatment group). Post-surgery, cyclic loading was performed on each 2FSU for 10,000 cycles at 600 N (walking), followed by 5,000 cycles at 850 N (standing up/sitting down), and 5,000 cycles at 1250 N (lifting a 5-10kg weight from the floor). Fluoroscopic images were taken and analyzed at the initial, post-fracture, post-surgery, and post-loading timepoints. Anterior, central, and posterior heights, Beck Index, and angle between endplates were assessed. RESULTS: No difference in height restoration was observed among treatment groups (p=.72). Compared to the initial height, post-surgery anterior height was 96.3±8.7% for BKP, 94.0±10.0% for BKP w/ KA, and 95.3±5.8% for TIVAD. No difference in height sustainability in response to 600 N (p=.76) and 850 N (p=.20) load levels was observed among treatment groups. However, after 1250 N loading, anterior height decreased to 93.8±6.8% of the post-surgery height for BKP, 95.9±6.4% for BKP w/ KA, and 86.0±6.6% for TIVAD (p=.02). Specifically, the mean anterior height reduction between post-surgery and post-1250 N loading timepoints was lower for BKP w/ KA compared to TIVAD (p=.02), but not when comparing BKP to TIVAD (p=.07). No difference in Beck Index or angle between endplates was observed at any timepoint among the treatment groups. CONCLUSIONS: The present study, utilizing a clinically relevant biomechanical model, demonstrated equivalent height restoration post-surgery and at relatively lower-level cyclic loading using BKP, BKP w/ KA, and TIVAD, contrary to results from a previous study. Less anterior height reduction in response to high-level cyclic loading was observed in the BKP w/ KA group compared to TIVAD. CLINICAL SIGNIFICANCE: All three treatments can restore height similarly after a vertebral compression fracture, which may lead to pain reduction and decreased mortality. BKP w/ KA may exhibit less height loss in higher-demand patients who engage in physical activities that involve increased weight resistance.


Asunto(s)
Fracturas por Compresión , Cifoplastia , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Femenino , Persona de Mediana Edad , Anciano , Fracturas por Compresión/cirugía , Fracturas de la Columna Vertebral/cirugía , Fracturas Osteoporóticas/cirugía , Cementos para Huesos/uso terapéutico , Cifoplastia/métodos , Columna Vertebral , Dolor/cirugía , Cadáver , Resultado del Tratamiento
5.
JPEN J Parenter Enteral Nutr ; 46(7): 1650-1659, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35289416

RESUMEN

BACKGROUND: Patients with short-bowel syndrome and intestinal failure (SBS-IF) require parenteral support (PS) and experience various symptoms and comorbidities. This survey assessed the impact of SBS-IF and PS on patients and their health-related quality of life (HRQoL). METHODS: An online survey of adult patients who had a self-reported clinician diagnosis of SBS-IF and were receiving PS was conducted in France, Germany, Italy, the UK, and the USA. Patients reported symptoms, comorbidities, and treatment satisfaction; the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) and the Home Parenteral Nutrition-Quality of Life (HPN-QoL) questionnaire assessed impact on work and HRQoL, respectively. RESULTS: Patients (N = 181; aged 52.0 ± 15.1 years; 56.9% women) experienced fatigue (75.1%), anemia (49.7%), and difficulty spending time with family (36.5%) and friends (30.4%). A total work productivity loss of 37.5% was calculated in patients reporting employment (29.3%). Patients typically (64.0%) reported some degree of satisfaction with their PS treatment. Almost two-thirds (59.7%) reported that their PS was either "not," "a little," or "moderately" convenient. The mean HPN-QoL scores were higher for patients who were satisfied with treatment (n = 116; 17.1 ± 21.0 [median, 16.7; interquartile range, 0.0-31.7]) than for patients who were dissatisfied/neither (n = 65; 1.7 ± 19.7 [median, 0.0; interquartile range, -13.3-13.3]). CONCLUSIONS: Patients with SBS-IF who are receiving PS experience burdensome symptoms and comorbidities and report impacts on work productivity and time spent with friends and family. This study can increase awareness of the impacts of SBS-IF and PS and how treatment satisfaction may influence patients' health and HRQoL.


Asunto(s)
Insuficiencia Intestinal , Nutrición Parenteral en el Domicilio , Síndrome del Intestino Corto , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Calidad de Vida , Síndrome del Intestino Corto/terapia
6.
Global Spine J ; 12(3): 373-380, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32975442

RESUMEN

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The purpose of this study was to compare outcomes between different treatment modalities for metastatic disease with indeterminate instability (Spinal Instability Neoplastic Score [SINS] 7-12). METHODS: We retrospectively reviewed neurologically intact patients treated for spinal metastatic disease with a SINS of 7 to 12. The cohort was stratified by treatment approach: external beam radiation therapy alone (EBRT), surgery + EBRT (S+E), and cement augmentation + EBRT (K+E). Kaplan-Meier analysis was used to assess differences in length of survival (LOS) and ability to ambulate at time of death. Multivariate analysis was performed to assess adjusted LOS and ability to ambulate at time of death. RESULTS: The cohort included 211 patients, S+E (n = 57), EBRT (n = 128), and K+E (n = 27). In the S+E group, the median LOS was 430 days, which was statistically longer than the median LOS for the EBRT group (121 days) and the K+E group (169 days). In the S+E group, 52 patients (91.2%) and in the K+E group 24 patients (92.3%) retained the ability to ambulate at their time of death compared to 99 patients (77.3%) of the EBRT patients (P = .01). The overall rate of revision treatment at the spinal level initially treated was 17.5%, S+E (15.8%), EBRT (20.3%), and K+E (7.7%). CONCLUSIONS: The length of survival, ability to maintain ambulatory ability, and revision treatment rates were all improved following surgical management and radiation therapy compared to radiation therapy alone. The authors' conclusion from these results are that patients with indeterminate spinal instability should be discussed in a multidisciplinary setting for the need of spinal stabilization in addition to radiation therapy.

7.
Biomaterials ; 277: 121099, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34537501

RESUMEN

Follicle development in the ovary must be tightly regulated to ensure cyclical release of oocytes (ovulation). Disruption of this process is a common cause of infertility, for example via polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Recent ex vivo studies suggest that follicle growth is mechanically regulated, however, crucially, the actual mechanical properties of the follicle microenvironment have remained unknown. Here we use atomic force microscopy (AFM) spherical probe indentation to map and quantify the mechanical microenvironment in the mouse ovary, at high resolution and across the entire width of the intact (bisected) ovarian interior. Averaging over the entire organ, we find the ovary to be a fairly soft tissue comparable to fat or kidney (mean Young's Modulus 3.3±2.5 kPa). This average, however, conceals substantial spatial variations, with the overall range of tissue stiffnesses from c. 0.5-10 kPa, challenging the concept that a single Young's Modulus can effectively summarize this complex organ. Considering the internal architecture of the ovary, we find that stiffness is low at the edge and centre which are dominated by stromal tissue, and highest in an intermediate zone that is dominated by large developmentally-advanced follicles, confirmed by comparison with immunohistology images. These results suggest that large follicles are mechanically dominant structures in the ovary, contrasting with previous expectations that collagen-rich stroma would dominate. Extending our study to the highest resolutions (c. 5 µm) showed substantial mechanical variations within the larger zones, even over very short (sub-100 µm) lengths, and especially within the stiffer regions of the ovary. Taken together, our results provide a new, physiologically accurate, framework for ovarian biomechanics and follicle tissue engineering.


Asunto(s)
Folículo Ovárico , Ovario , Animales , Colágeno , Módulo de Elasticidad , Femenino , Ratones , Microscopía de Fuerza Atómica
8.
Pain Pract ; 21(8): 877-889, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34216103

RESUMEN

BACKGROUND: The objective of this prospective, multicenter study is to characterize responses to percutaneous medial branch peripheral nerve stimulation (PNS) to determine if results from earlier, smaller single-center studies and reports were generalizable when performed at a larger number and wider variety of centers in patients recalcitrant to nonsurgical treatments. MATERIALS & METHODS: Participants with chronic axial low back pain (LBP) were implanted with percutaneous PNS leads targeting the lumbar medial branch nerves for up to 60 days, after which the leads were removed. Participants were followed long-term for 12 months after the 2-month PNS treatment. Data collection is complete for visits through end of treatment with PNS (primary end point) and 6 months after lead removal (8 months after start of treatment), with some participant follow-up visits thereafter in progress. RESULTS: Clinically and statistically significant reductions in pain intensity, disability, and pain interference were reported by a majority of participants. Seventy-three percent of participants were successes for the primary end point, reporting clinically significant (≥30%) reductions in back pain intensity after the 2-month percutaneous PNS treatment (n = 54/74). Whereas prospective follow-up is ongoing, among those who had already completed the long-term follow-up visits (n = 51), reductions in pain intensity, disability, and pain interference were sustained in a majority of participants through 14 months after the start of treatment. CONCLUSION: Given the minimally invasive, nondestructive nature of percutaneous PNS and the significant benefits experienced by participants who were recalcitrant to nonsurgical treatments, percutaneous PNS may provide a promising first-line neurostimulation treatment option for patients with chronic axial back pain.


Asunto(s)
Dolor de la Región Lumbar , Estimulación Eléctrica Transcutánea del Nervio , Dolor de Espalda/tratamiento farmacológico , Humanos , Dolor de la Región Lumbar/terapia , Estudios Prospectivos , Resultado del Tratamiento
10.
Pain Med ; 22(3): 548-560, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33616178

RESUMEN

OBJECTIVE: Lumbar radiofrequency ablation is a commonly used intervention for chronic back pain. However, the pain typically returns, and though retreatment may be successful, the procedure involves destruction of the medial branch nerves, which denervates the multifidus. Repeated procedures typically have diminishing returns, which can lead to opioid use, surgery, or implantation of permanent neuromodulation systems. The objective of this report is to demonstrate the potential use of percutaneous peripheral nerve stimulation (PNS) as a minimally invasive, nondestructive, motor-sparing alternative to repeat radiofrequency ablation and more invasive surgical procedures. DESIGN: Prospective, multicenter trial. METHODS: Individuals with a return of chronic axial pain after radiofrequency ablation underwent implantation of percutaneous PNS leads targeting the medial branch nerves. Stimulation was delivered for up to 60 days, after which the leads were removed. Participants were followed up to 5 months after the start of PNS. Outcomes included pain intensity, disability, and pain interference. RESULTS: Highly clinically significant (≥50%) reductions in average pain intensity were reported by a majority of participants (67%, n = 10/15) after 2 months with PNS, and a majority experienced clinically significant improvements in functional outcomes, as measured by disability (87%, n = 13/15) and pain interference (80%, n = 12/15). Five months after PNS, 93% (n = 14/15) reported clinically meaningful improvement in one or more outcome measures, and a majority experienced clinically meaningful improvements in all three outcomes (i.e., pain intensity, disability, and pain interference). CONCLUSIONS: Percutaneous PNS has the potential to shift the pain management paradigm by providing an effective, nondestructive, motor-sparing neuromodulation treatment.


Asunto(s)
Ablación por Radiofrecuencia , Estimulación Eléctrica Transcutánea del Nervio , Dolor de Espalda , Humanos , Nervios Periféricos , Estudios Prospectivos , Resultado del Tratamiento
11.
Behav Brain Res ; 403: 113139, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33497748

RESUMEN

Serotonin signaling influences satiety and motivation through known actions in the hindbrain and hypothalamus. Recently, we reported that some classes of serotonin receptors also modulate food intake through actions in the ventral tegmentum and the nucleus accumbens. In the current experiments, we examined whether activation or blockade of individual serotonin receptor subtypes in the ventral tegmentum might also affect appetitive motivation for sugar pellets as assessed in a progressive ratio (PR) task. Separate groups of rats were tested following stimulation or blockade of ventral tegmental serotonin 1A, 1B, 2A, 2B, 2C, or 3 receptors. Rats within each group received multiple doses of a single drug across days; each test was separated by 72 h. Progressive ratio break point was significantly affected by stimulation of ventral tegmental serotonin 1A receptors with 8-OH-DPAT (0, 2, 4, 8 µg/side) or stimulation of serotonin 3 receptors with mCPBG (0, 10, & 20 µg/side). High doses of both agents tended to decrease break point. Additionally, stimulation of serotonin 2C receptors with RO60-0175 (at 0, 2, and 5 µg/side) reduced total lever presses and demonstrated a trend towards reducing break point. There were no effects of stimulating ventral tegmental serotonin 1B, 2A, or 2B receptors on break point; neither did antagonism of any of the serotonin receptor subtypes significantly affect performance. These data provide additional evidence that serotonergic signaling in the mesolimbic pathway affects motivated behavior, and demonstrate that a subset of serotonin receptors impact not only food consumption, but appetitive food-seeking as well.


Asunto(s)
Conducta Animal/fisiología , Conducta Alimentaria/fisiología , Motivación/fisiología , Receptores de Serotonina/metabolismo , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , Serotonina/fisiología , Área Tegmental Ventral/metabolismo , Animales , Conducta Apetitiva/efectos de los fármacos , Conducta Apetitiva/fisiología , Conducta Animal/efectos de los fármacos , Azúcares de la Dieta , Conducta Alimentaria/efectos de los fármacos , Motivación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Serotonina/efectos de los fármacos , Recompensa , Área Tegmental Ventral/efectos de los fármacos
12.
Int J Clin Pharm ; 43(2): 394-403, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33459948

RESUMEN

Background Duloxetine is currently approved for chronic pain management; however, despite some evidence, its utility in acute, postoperative pain remains unclear Aim of the review This systematic review and meta-analysis is to determine if duloxetine 60 mg given perioperatively, is safe and effective at reducing postoperative opioid consumption and reported pain following elective orthopedic surgery. Method CINAHL, Medline, Cochrane Central Registry for Clinical Trials, Google Scholar, and Clinicaltrials.gov were searched using a predetermined search strategy from inception to January 15, 2019. Covidence.org was used to screen, select, and extract data by two independent reviewers. Individual study bias was assessed using the Cochrane Risk of Bias tool. Opioid consumption data were converted to oral morphine milligram equivalents (MME) and exported to RevMan where meta-analysis was conducted using a DerSimonian and Laird random effects model. Results Six randomized-controlled trials were included in the literature review of postoperative pain and adverse effects. Five studies were utilized for the meta-analysis of postoperative opioid consumption; totaling 314 patients. Postoperative pain analysis showed variable statistical significance with overall lower pain scores with duloxetine. Adverse effects included an increase in insomnia with duloxetine but lower rates of nausea and vomiting. Meta-analysis revealed statistically significant [mean difference (95% CI)] lower total opioid use with duloxetine postoperatively at 24 h [- 31.9 MME (- 54.22 to - 9.6), p = 0.005], 48 h [- 30.90 MME (- 59.66 to - 2.15), p = 0.04] and overall [- 31.68 MME (- 46.62 to - 16.74), p < 0.0001]. Conclusion These results suggest that adding perioperative administration duloxetine 60 mg to a multimodal analgesia regimen within the orthopedic surgery setting significantly lowers total postoperative opioid consumption and reduces pain without significant adverse effects.


Asunto(s)
Analgesia , Procedimientos Ortopédicos , Analgésicos Opioides/efectos adversos , Clorhidrato de Duloxetina , Humanos , Procedimientos Ortopédicos/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico
13.
Clin Pharmacol Ther ; 109(5): 1293-1303, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33113155

RESUMEN

Activated T cells drive a range of immune-mediated inflammatory diseases. LAG-3 is transiently expressed on recently activated CD4+ and CD8+ T cells. We describe the engineering and first-in-human clinical study (NCT02195349) of GSK2831781 (an afucosylated humanized IgG1 monoclonal antibody enhanced with high affinity for Fc receptors and LAG-3 and antibody-dependent cellular cytotoxicity capabilities), which depletes LAG-3 expressing cells. GSK2831781 was tested in a phase I/Ib, double-blind, placebo-controlled clinical study, which randomized 40 healthy participants (part A) and 27 patients with psoriasis (part B) to single doses of GSK2831781 (up to 0.15 and 5 mg/kg, respectively) or placebo. Adverse events were generally balanced across groups, with no safety or tolerability concern identified. LAG-3+ cell depletion in peripheral blood was observed at doses ≥ 0.15 mg/kg and was dose-dependent. In biopsies of psoriasis plaques, a reduction in mean group LAG-3+ and CD3+ T-cell counts was observed following treatment. Downregulation of proinflammatory genes (IL-17A, IL-17F, IFNγ, and S100A12) and upregulation of the epithelial barrier integrity gene, CDHR1, was observed with the 5 mg/kg dose of GSK2831781. Psoriasis disease activity improved up to day 43 at all GSK2831781 doses (0.5, 1.5, and 5 mg/kg) compared with placebo. Depletion of LAG-3-expressing activated T cells is a novel approach, and this first clinical study shows that GSK2831781 is pharmacologically active and provides encouraging early evidence of clinical effects in psoriasis, which warrants further investigation in T-cell-mediated inflammatory diseases.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Antígenos CD/inmunología , Psoriasis/tratamiento farmacológico , Linfocitos T/inmunología , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacocinética , Antígenos CD/sangre , Complejo CD3/metabolismo , Relación Dosis-Respuesta Inmunológica , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/genética , Psoriasis/patología , Resultado del Tratamiento , Proteína del Gen 3 de Activación de Linfocitos
14.
Can J Anaesth ; 68(1): 30-41, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33058058

RESUMEN

PURPOSE: We estimated the rate of unplanned hospital and intensive care unit (ICU) admissions following ambulatory surgery centre (ASC) procedures, and identified factors associated with their occurrence. METHODS: This retrospective cohort included adult patients who underwent ASC procedures within a large community practice from January 2010 to December 2014. Patients were categorized into two groups: unplanned postoperative hospital/ICU admission within 24 hr of procedure or uneventful discharge. Demographics, comorbidities, anesthesia type, procedure type, procedure group, and ASC facility were assessed. RESULTS: Of the 211,389 patients included, there were 211,147 uneventful discharges (99.89%) and 242 unplanned hospital admissions (0.11%), of which 75 were ICU admissions (0.04%). The multivariable logistic regression model for hospital admission showed an increased risk associated with age > 50 yr (odds ratio [OR], 1.53); American Society of Anesthesiologists (ASA) physical status (III vs II: OR, 1.45; IV vs II: OR, 1.88), comorbidity (chronic obstructive pulmonary disease: OR, 2.63; diabetes mellitus: OR, 1.62; transient ischemic attack: OR, 2.48) procedure (respiratory: OR, 2.92; digestive: OR, 2.66; musculoskeletal system: OR, 2.53), anesthetic management (general anesthesia [GA] and peripheral nerve block vs GA: OR, 1.79), and ASC facility (189BB: OR, 2.29; 30E9A: OR, 7.41; and BD21F: OR, 1.69). The multivariable logistic regression model for ICU admission showed increased risk of unplanned ICU admission associated with ASA physical status (ASA III vs II: OR, 3.0; ASA IV vs II: OR, 8.52), procedure (musculoskeletal system: OR, 2.45), and ASC facility (00E6C: OR, 3.14; 189BB: OR, 2.77; 30E9A: OR, 2.59; and BD21F: OR, 3.71). CONCLUSION: While a small percentage of adult patients who underwent ASC procedures required unplanned hospital admission (0.07%), approximately one-third of these admissions were to the ICU (0.04%). Facility was at least as strong a predictor of hospital admission as the patient- and/or procedure-specific variables.


RéSUMé: OBJECTIF: Nous avons estimé le taux d'admissions non planifiées à l'hôpital et à l'unité de soins intensifs (USI) après des interventions dans des centres de chirurgie ambulatoire (CCA), et identifié les facteurs associés à leur survenue. MéTHODE: Cette étude de cohorte rétrospective a porté sur des patients adultes ayant subi une intervention dans un CCA appartenant à une grande pratique communautaire entre janvier 2010 et décembre 2014. Les patients ont été catégorisés en deux groupes : admission postopératoire non planifiée à l'hôpital/USI dans les 24 h suivant l'intervention ou congé sans incident. Les données démographiques, les comorbidités, le type d'anesthésie, le type d'intervention, le groupe d'intervention et l'établissement de CCA ont été évalués. RéSULTATS: Parmi les 211 389 patients inclus, il y a eu 211 147 congés sans incident (99,89 %) et 242 admissions non planifiées à l'hôpital (0,11 %), 75 desquelles étaient des admissions à l'USI (0,04 %). Le modèle de régression logistique multivariée des admissions hospitalières a montré un risque accru associé à un âge > 50 ans (rapport de cotes [RC], 1,53); au statut physique ASA (American Society of Anesthesiologists) (III vs II : RC, 1,45; IV vs II : RC, 1,88), aux comorbidités (maladie pulmonaire obstructive chronique : RC, 2,63; diabète: RC, 1,62; accident ischémique transitoire : RC, 2,48); à l'intervention (respiratoire : RC, 2,92; digestive : RC, 2,66; appareil locomoteur : RC, 2,53); à la prise en charge anesthésique (anesthésie générale [AG] et bloc nerveux périphérique vs AG : RC, 1,79) et établissement de CCA (189BB : RC, 2,29; 30E9A : RC, 7,41; et BD21F : RC, 1,69). Le modèle de régression logistique multivariée des admissions à l'USI a montré un risque accru d'admission non planifiée à l'USI associé au statut physique ASA (ASA III vs II: RC, 3,0; ASA IV vs II: RC, 8,52), à l'intervention (appareil locomoteur : RC, 2,45), et à l'établissement de CCA (00E6C: RC, 3,14; 189BB: RC, 2,77; 30E9A: RC, 2,59; et BD21F: RC, 3,71). CONCLUSION: Alors qu'un faible pourcentage de patients adultes ayant subi des interventions en CCA ont nécessité une admission non planifiée à l'hôpital (0,11 %), environ un tiers de ces admissions étaient à l'USI (0,04 %). L'établissement était un prédicteur au moins aussi puissant d'admission à l'hôpital que les variables spécifiques au patient et/ou à l'intervention.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Hospitalización , Adulto , Estudios de Cohortes , Hospitales , Humanos , Admisión del Paciente , Complicaciones Posoperatorias , Estudios Retrospectivos
15.
J Vasc Interv Radiol ; 31(11): 1745-1752, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33129427

RESUMEN

PURPOSE: To evaluate the effectiveness of radiofrequency (RF) ablation as measured by change in worst pain score from baseline to 3 mo after RF ablation for the palliative treatment of painful bone metastases. MATERIALS AND METHODS: One hundred patients (mean age, 64.6 y) underwent RF ablation for metastatic bone disease and were followed up to 6 mo. Subjects' pain and quality of life were measured before RF ablation and postoperatively by using the Brief Pain Index and European Quality of Life questionnaires. Opioid agent use and device-, procedure-, and/or therapy-related adverse events (AEs) were collected. RESULTS: Eighty-seven patients were treated for tumors involving the thoracolumbar spine and 13 for tumors located in the pelvis and/or sacrum. All ablations were technically successful, and 97% were followed by cementoplasty. Mean worst pain score decreased from 8.2 ± 1.7 at baseline to 3.5 ± 3.2 at 6 mo (n = 22; P < 0.0001 for all visits). Subjects experienced significant improvement for all visits in average pain (P < .0001), pain interference (P < .0001), and quality of life (P < .003). Four AEs were reported, of which 2 resulted in hospitalization for pneumonia and respiratory failure. All 30 deaths reported during the study were attributed to the underlying malignancy and not related to the study procedure. CONCLUSIONS: Results from this study show rapid (within 3 d) and statistically significant pain improvement with sustained long-term relief through 6 mo in patients treated with RF ablation for metastatic bone disease.


Asunto(s)
Neoplasias Óseas/cirugía , Dolor/prevención & control , Cuidados Paliativos , Ablación por Radiofrecuencia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/complicaciones , Neoplasias Óseas/mortalidad , Neoplasias Óseas/secundario , Cementoplastia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Dolor/etiología , Dolor/mortalidad , Dimensión del Dolor , Estudios Prospectivos , Calidad de Vida , Ablación por Radiofrecuencia/efectos adversos , Ablación por Radiofrecuencia/mortalidad , Factores de Tiempo , Resultado del Tratamiento
16.
J Palliat Med ; 23(10): 1386-1391, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32865443

RESUMEN

Pain is a common symptom for patients with advanced illness. Palliative care (PC) clinicians are experts in pharmacologic and nonpharmacologic treatment of pain and other symptoms for these patients. True multimodal pain control should include consideration of interventional procedures and pumps to improve difficult-to-manage pain. This article, written by clinicians with expertise in interventional pain and PC, outlines and explains many of the adjunctive and interventional therapies that can be considered for patients with pain in the setting of serious illness. Only by understanding and considering all available options can we ensure that our patients are receiving optimal care.


Asunto(s)
Enfermería de Cuidados Paliativos al Final de la Vida , Cuidados Paliativos , Humanos , Dolor , Manejo del Dolor , Investigación
17.
AANA J ; 88(4): 325-332, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32718432

RESUMEN

Anesthetic modalities to mitigate the development of phantom limb pain have not been standardized into an evidence-based, multimodal anesthesia protocol to promote improved patient outcomes. This quality improvement project involved the implementation of a lower extremity, amputation-specific anesthesia protocol. In the postimplementation group, 94 patients were anesthetized for their amputation using an Amputation Improved Recovery Enhanced Recovery After Surgery (ERAS) protocol. Patient outcomes before and after protocol implementation were compared. The rate of continuous peripheral nerve block placement was higher in the postimplementation group (37.2%) than the preimplementation group (29.6%, P = .337). The 2 groups did not differ on average pain scores and morphine equivalent consumption rates per patient during hospitalization. The postimplementation group had significantly lower mean pain scores during the first 24 hours after amputation (P = .046); fewer postoperative complications (P = .001), amputation revisions (P = .003), 30-day hospital readmissions (P = .049), and readmissions related to amputation surgery (P = .019); and higher rates of early phantom limb pain that resolved during hospitalization (P = .012). Use of a standardized anesthetic protocol designed for patients undergoing amputation improved patient outcomes. Trials of this protocol elsewhere may contribute to improved recovery for patients undergoing amputations.


Asunto(s)
Amputación Quirúrgica , Anestesia General , Extremidad Inferior , Miembro Fantasma/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermeras Anestesistas , Periodo Perioperatorio , Miembro Fantasma/enfermería , Complicaciones Posoperatorias/enfermería , Complicaciones Posoperatorias/prevención & control , Mejoramiento de la Calidad
18.
Plast Reconstr Surg ; 145(3): 606-616, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32097291

RESUMEN

BACKGROUND: Enhanced recovery after surgery (ERAS) initiatives improve postoperative function and expedite recovery, leading to a decrease in length of stay. The authors noted a high rate of postoperative symptomatic hypotension in patients undergoing abdominal free flap breast reconstruction and wished to explore this observation. METHODS: Subjects undergoing abdominal free flap breast reconstruction at the authors' institution from 2013 to 2017 were identified. The ERAS protocol was initiated in 2015 at the authors' hospital; thus, 99 patients underwent traditional management and 138 patients underwent ERAS management. Demographics and perioperative data were collected and analyzed. Postoperative symptomatic hypotension was defined as mean arterial pressure below 80 percent of baseline with symptoms requiring evaluation. RESULTS: A significantly higher rate of postoperative symptomatic hypotension was observed in the ERAS cohort compared with the traditional management cohort (4 percent versus 22 percent; p < 0.0001). Patients in the ERAS cohort received significantly less intraoperative intravenous fluid (4467 ml versus 3505 ml; p < 0.0001) and had a significantly increased amount of intraoperative time spent with low blood pressure (22 percent versus 32 percent; p =0.002). Postoperatively, the ERAS cohort had significantly lower heart rate (77 beats per minute versus 88 beats per minute; p < 0.0001) and mean arterial pressure (71 mmHg versus 78 mmHg; p < 0.0001), with no difference in urine output or adverse events. CONCLUSIONS: The authors report that ERAS implementation in abdominal free flap breast reconstruction may result in a unique physiologic state with low mean arterial pressure, low heart rate, and normal urine output, resulting in postoperative symptomatic hypotension. Awareness of this early postoperative finding can help better direct fluid resuscitation and prevent episodes of symptomatic hypotension. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Asunto(s)
Recuperación Mejorada Después de la Cirugía , Colgajos Tisulares Libres/trasplante , Hipotensión/epidemiología , Mamoplastia/efectos adversos , Complicaciones Posoperatorias/epidemiología , Adulto , Presión Arterial/fisiología , Mama/cirugía , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Hipotensión/etiología , Hipotensión/fisiopatología , Tiempo de Internación/estadística & datos numéricos , Mamoplastia/métodos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
20.
Semin Cardiothorac Vasc Anesth ; 24(1): 96-103, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31617443

RESUMEN

Chronic pain after lung transplantation is a significant concern, in particular given the heterogeneity of the patient population and the challenges of achieving adequate pain control amid concerns related to complex immunosuppressant regimens and the possibility of respiratory depression. We undertook a patient-reported outcomes (PRO) survey administered via our electronic health care portal to examine the postoperative incisional pain prevalence in a cohort of lung transplant recipients at a single, high-volume center where bilateral thoracosternotomy is the preferred surgical approach. The Patient Reported Outcomes Measurement Information System (PROMIS) Global Health and Pain Intensity short forms were sent to a total of 173 lung transplant recipients who were more than 2 months postsurgery at the time of the study. A total of 64 patients responded to both PROMIS surveys (response rate 38%). In the cohort of survey respondents, we observed a chronic pain incidence of 58% after lung transplantation (median pain score 1/10) and an overall good quality of life score (median score 4/5); however, only 9.4% reported moderate-severe pain (pain score ≥5/10). Survey nonrespondents had higher rates of pretransplant opioid and psychiatric medication use compared with respondents. In this study, we demonstrated the feasibility of using an electronic PRO survey for assessing postoperative pain outcomes after lung transplantation. However, measuring pain outcomes using this type of tool highlights issues of response rate and potential selection bias. Larger studies are needed to adequately assess the risk and predictors of chronic pain after lung transplantation and its impact on quality of life.


Asunto(s)
Dolor Crónico/epidemiología , Trasplante de Pulmón/métodos , Dolor Postoperatorio/epidemiología , Calidad de Vida , Adulto , Anciano , Analgésicos Opioides/administración & dosificación , Dolor Crónico/etiología , Femenino , Humanos , Inmunosupresores/administración & dosificación , Incidencia , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Prevalencia , Estudios Retrospectivos , Sesgo de Selección , Encuestas y Cuestionarios
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