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1.
Nat Commun ; 15(1): 1800, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413603

RESUMO

Earth's radiation belts consist of high-energy charged particles trapped by Earth's magnetic field. Strong pitch angle diffusion of electrons caused by wave-particle interaction in Earth's radiation belts has primarily been considered as a loss process, as trapped electrons are rapidly diffused into the loss cone and lost to the atmosphere. However, the wave power necessary to produce strong diffusion should also produce rapid energy diffusion, and has not been considered in this context. Here we provide evidence of strong diffusion using satellite data. We use two-dimensional Fokker-Planck simulations of electron diffusion in pitch angle and energy to show that scaling up chorus wave power to the strong diffusion limit produces rapid acceleration of electrons, sufficient to outweigh the losses due to strong diffusion. The rate of losses saturates at the strong diffusion limit, whilst the rate of acceleration does not. This leads to the surprising result of an increase, not a decrease in the trapped electron population during strong diffusion due to chorus waves as expected when treating strong diffusion as a loss process. Our results suggest there is a tipping point in chorus wave power between net loss and net acceleration that global radiation belt models need to capture to better forecast hazardous radiation levels that damage satellites.

2.
J Obstet Gynaecol Can ; 46(3): 102276, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37944819

RESUMO

OBJECTIVES: The Omicron variant of the SARS-CoV-2 virus is described as more contagious than previous variants. We sought to assess risk to health care workers (HCWs) caring for patients with COVID-19 in surgical/obstetrical settings, and the perception of risk among this group. METHODS: From January to April 2022, reverse transcription polymerase chain reaction was used to detect the presence of SARS-CoV-2 viral ribonucleic acid in patient, environmental (floor, equipment, passive air) samples, and HCWs' masks (inside surface) during urgent surgery or obstetrical delivery for patients with SARS-CoV-2 infection. The primary outcome was the proportion of HCWs' masks testing positive. Results were compared with our previous cross-sectional study involving obstetrical/surgical patients with earlier variants (2020-2021). HCWs completed a risk perception electronic questionnaire. RESULTS: Eleven patients were included: 3 vaginal births and 8 surgeries. In total, 5/108 samples (5%) tested positive (SARS-CoV-2 Omicron) viral ribonucleic acid: 2/5 endotracheal tubes, 1/22 floor samples, 1/4 patient masks, and 1 nasal probe. No samples from the HCWs' masks (0/35), surgical equipment (0/10), and air (0/11) tested positive. No significant differences were found between the Omicron and 2020/21 patient groups' positivity rates (Mann-Whitney U test, P = 0.838) or the level of viral load from the nasopharyngeal swabs (P = 0.405). Nurses had a higher risk perception than physicians (P = 0.038). CONCLUSION: No significant difference in contamination rates was found between SARS-CoV-2 Omicron BA.1 and previous variants in surgical/obstetrical settings. This is reassuring as no HCW mask was positive and no HCW tested positive for COVID-19 post-exposure.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Gravidez , Humanos , SARS-CoV-2 , Pessoal de Saúde , RNA , Assistência ao Paciente
3.
Support Care Cancer ; 32(1): 18, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38091116

RESUMO

INTRODUCTION: Bones are frequent sites of metastatic disease, observed in 30-75% of advanced cancer patients. Quality of life (QoL) is an important endpoint in studies evaluating the treatments of bone metastases (BM), and many patient-reported outcome tools are available. The primary objective of this systematic review was to compile a list of QoL issues relevant to BM and its interventions. The secondary objective was to identify common tools used to assess QoL in patients with BM, and the QoL issues they fail to address. METHODS: A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases between 1946 and 27 January 2023 with the keywords "bone metastases", "quality of life", and "patient reported outcomes". Specific QoL issues in original research studies and the QoL tools used were extracted. RESULTS: The review identified the QoL issues most prevalent to BM in the literature. Physical and functional issues observed in patients included pain, interference with ambulation and daily activities, and fatigue. Psychological symptoms, such as helplessness, depression, and anxiety were also common. These issues interfered with patients' relationships and social activities. Items not mentioned in existing QoL tools were related to newer treatments of BM, such as pain flare, flu-like symptoms, and jaw pain due to osteonecrosis. CONCLUSIONS: This systematic review highlights that QoL issues for patients with BM have expanded over time due to advances in BM-directed treatments. If they are relevant, additional treatment-related QoL issues identified need to be validated prospectively by patients and added to current assessment tools.


Assuntos
Neoplasias Ósseas , Qualidade de Vida , Humanos , Neoplasias Ósseas/secundário , Emoções , Ansiedade/terapia , Dor/etiologia
4.
Int J Comput Assist Radiol Surg ; 18(12): 2339-2347, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37245180

RESUMO

PURPOSE: Bone-targeted radiofrequency ablation (RFA) is widely used in the treatment of vertebral metastases. While radiation therapy utilizes established treatment planning systems (TPS) based on multimodal imaging to optimize treatment volumes, current RFA of vertebral metastases has been limited to qualitative image-based assessment of tumour location to direct probe selection and access. This study aimed to design, develop and evaluate a computational patient-specific RFA TPS for vertebral metastases. METHODS: A TPS was developed on the open-source 3D slicer platform, including procedural setup, dose calculation (based on finite element modelling), and analysis/visualization modules. Usability testing was carried out by 7 clinicians involved in the treatment of vertebral metastases on retrospective clinical imaging data using a simplified dose calculation engine. In vivo evaluation was performed in a preclinical porcine model (n = 6 vertebrae). RESULTS: Dose analysis was successfully performed, with generation and display of thermal dose volumes, thermal damage, dose volume histograms and isodose contours. Usability testing showed an overall positive response to the TPS as beneficial to safe and effective RFA. The in vivo porcine study showed good agreement between the manually segmented thermally damaged volumes vs. the damage volumes identified from the TPS (Dice Similarity Coefficient = 0.71 ± 0.03, Hausdorff distance = 1.2 ± 0.1 mm). CONCLUSION: A TPS specifically dedicated to RFA in the bony spine could help account for tissue heterogeneities in both thermal and electrical properties. A TPS would enable visualization of damage volumes in 2D and 3D, assisting clinicians in decisions about potential safety and effectiveness prior to performing RFA in the metastatic spine.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Humanos , Suínos , Animais , Estudos Retrospectivos , Coluna Vertebral , Ablação por Radiofrequência/métodos , Ablação por Cateter/métodos
5.
CMAJ Open ; 10(2): E450-E459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35609928

RESUMO

BACKGROUND: The exposure risks to front-line health care workers caring for patients with SARS-CoV-2 infection undergoing surgery or obstetric delivery are unclear, and an understanding of sample types that may harbour virus is important for evaluating risk. We sought to determine whether SARS-CoV-2 viral RNA from patients with SARS-CoV-2 infection undergoing surgery or obstetric delivery was present in the peritoneal cavity of male and female patients, in the female reproductive tract, in the environment of the surgery or delivery suite (surgical instruments or equipment used, air or floors), and inside the masks of the attending health care workers. METHODS: We conducted a cross-sectional study from November 2020 to May 2021 at 2 tertiary academic Toronto hospitals, during urgent surgeries or obstetric deliveries for patients with SARS-CoV-2 infection. The presence of SARS-CoV-2 viral RNA in patient, environmental and air samples was identified by real-time reverse transcription polymerase chain reaction (RT-PCR). Air samples were collected using both active and passive sampling techniques. The primary outcome was the proportion of health care workers' masks positive for SARS-CoV-2 RNA. We included adult patients with positive RT-PCR nasal swab undergoing obstetric delivery or urgent surgery (from across all surgical specialties). RESULTS: A total of 32 patients (age 20-88 yr) were included. Nine patients had obstetric deliveries (6 cesarean deliveries), and 23 patients (14 male) required urgent surgery from the orthopedic or trauma, general surgery, burn, plastic surgery, cardiac surgery, neurosurgery, vascular surgery, gastroenterology and gynecologic oncology divisions. SARS-CoV-2 RNA was detected in 20 of 332 (6%) patient and environmental samples collected: 4 of 24 (17%) patient samples, 5 of 60 (8%) floor samples, 1 of 54 (2%) air samples, 10 of 23 (43%) surgical instrument or equipment samples, 0 of 24 cautery filter samples and 0 of 143 (95% confidence interval 0-0.026) inner surface of mask samples. INTERPRETATION: During the study period of November 2020 to May 2021, we found evidence of SARS-CoV-2 RNA in a small but important number of samples obtained in the surgical and obstetric operative environment. The finding of no detectable virus inside the masks worn by the health care teams would suggest a low risk of infection for health care workers using appropriate personal protective equipment.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Salas Cirúrgicas , RNA Viral/genética , SARS-CoV-2/genética , Adulto Jovem
6.
J Med Eng Technol ; 46(1): 46-58, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34678121

RESUMO

Intramedullary (IM) nailing is the standard of care for adult lower extremity long bone fracture stabilisation. Key to this procedure is obtaining the correct entry point and trajectory for initial guide pin insertion. This work presents the Femoral Antegrade Starting Tool (FAST), a surgical tool that addresses the lack of connectivity in utilising sequential 2D fluoroscopic images to achieve 3D alignment of femoral guide pin placement. The user centred design and development of FAST is introduced and the performance of this device evaluated during guide pin insertion for femoral IM nailing in a series of sawbones and cadaveric models leading to a first in human clinical cohort study. The results demonstrated the potential of FAST to improve time and consistency of the guide pin insertion for femoral IM nailing for less experienced surgeons and trainees. Overall, FAST was found to be easy to use with a high degree of clinical interest (particularly for use in large patients) and acceptance motivating continued development of this new technology.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Adulto , Pinos Ortopédicos , Estudos de Coortes , Fraturas do Fêmur/cirurgia , Humanos , Extremidade Inferior , Resultado do Tratamento
7.
Spine (Phila Pa 1976) ; 47(2): E73-E85, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474449

RESUMO

STUDY DESIGN: Systematic review. OBJECTIVE: The aim of this study was to review the current spine surgery literature to establish a definition for adequate spine decompression using intraoperative ultrasound (IOUS) imaging. SUMMARY OF BACKGROUND DATA: IOUS remains one of the few imaging modalities that allows spine surgeons to continuously monitor the spinal cord in real-time, while also allowing visualization of surrounding soft tissue anatomy during an operation. Although this has valuable applications for decompression surgery in spinal canal stenosis, it remains unclear how to best characterize adequacy of spinal decompression using IOUS. METHODS: We conducted a systematic search of multiple databases including: Medline, Embase, and Cochrane Central Register of Controlled Trials Strategy. Our search terms were spine, spinal cord diseases, decompression surgery, ultrasonogra-phy, and intraoperative period. We were interested in studies that used intraoperative use of ultrasound imaging in spinal decompression surgery for the cervical, thoracic, and lumbar spine. Study quality was evaluated using the Methodological Index for Non-Randomized Studies (MINORS). RESULTS: Our search strategy yielded 985 of potentially relevant publications, 776 underwent title and abstract screening, and 31 full-text articles were reviewed. We found IOUS to be useful in spine surgery for decompression of degenerative cases in all regions of the spine. The thoracic spine was unique for IOUS-guided decompression of fractures, and the lumbar spine for decompressing nerve roots. Although we did not identify a universal definition for adequate decompression, there was common description of decompression that qualitatively described the ventral aspect of the spinal cord being "free floating" within the cerebrospinal fluid. Other measurable definitions, such as spinal cord diameter or spinal cord pulsatility, were not good definitions given there was insufficient evidence and/or poor reliability. CONCLUSION: The systematic review examines the current literature on IOUS and spinal decompression surgery. We identified a common qualitative definition for adequate decompression involving a "free floating" spinal cord within the cerebrospinal fluid which indicates that the spinal cord is free from contact of the anterior elements.Level of Evidence: 1.


Assuntos
Descompressão Cirúrgica , Estenose Espinal , Humanos , Reprodutibilidade dos Testes , Estenose Espinal/cirurgia , Ultrassonografia
8.
J Pain ; 22(11): 1385-1395, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33964414

RESUMO

Skeletal diseases and their surgical treatment induce severe pain. The innervation density of bone potentially explains the severe pain reported. Animal studies concluded that sensory myelinated A∂-fibers and unmyelinated C-fibers are mainly responsible for conducting bone pain, and that the innervation density of these nerve fibers was highest in periosteum. However, literature regarding sensory innervation of human bone is scarce. This observational study aimed to quantify sensory nerve fiber density in periosteum, cortical bone, and bone marrow of axial and appendicular human bones using immunohistochemistry and confocal microscopy. Multivariate Poisson regression analysis demonstrated that the total number of sensory and sympathetic nerve fibers was highest in periosteum, followed by bone marrow, and cortical bone for all bones studied. Bone from thoracic vertebral bodies contained most sensory nerve fibers, followed by the upper extremity, lower extremity, and parietal neurocranium. The number of nerve fibers declined with age and did not differ between male and female specimens. Sensory nerve fibers were organized as a branched network throughout the periosteum. The current results provide an explanation for the severe pain accompanying skeletal disease, fracture, or surgery. Further, the results could provide more insight into mechanisms that generate and maintain skeletal pain and might aid in developing new treatment strategies. PERSPECTIVE: This article presents the innervation of human bone and assesses the effect of age, gender, bone compartment and type of bone on innervation density. The presented data provide an explanation for the severity of bone pain arising from skeletal diseases and their surgical treatment.


Assuntos
Doenças Ósseas , Medula Óssea/inervação , Osso Cortical/inervação , Dor Musculoesquelética , Periósteo/inervação , Fatores Etários , Humanos , Imuno-Histoquímica
9.
Pain Pract ; 21(6): 703-707, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33522082

RESUMO

Pudendal neuralgia (PN) is an impairing neuropathic disorder, affecting both men and women, involving a severe burning and sharp pain along the course of the pudendal nerve. Treatment is often insufficient, and options are limited. Pulsed radiofrequency (PRF) is a technique which might be useful in therapy. This case series aims to determine the effectiveness of PRF in patients with PN in the context of evaluation of care. Between 2010 and 2016, all female patients of University Medical Center Utrecht diagnosed with PN who experience insufficient pain relief after common treatment were offered PRF. Patient Global Impression of Improvement (PGI-I) scores were assessed at 3-month follow-up and at long-term follow-up (median 4 years). PGI-I scores were recorded to evaluate our quality of care. Twenty patients with PN consented to undergo PRF. We lost one patient in follow-up. Seventy-nine percent of the patients described their condition as "(very) much better" at 3-month follow-up. At long-term follow-up, 89% of the patients described their condition as "(very) much better." No serious side effects were observed. In conclusion, PRF is a successful treatment option in patients not responding to standard treatment options, including pudendal nerve blocks. PRF of the pudendal nerve can be used for PN to provide relief in patients' chronic pelvic pain.


Assuntos
Nervo Pudendo , Neuralgia do Pudendo , Tratamento por Radiofrequência Pulsada , Feminino , Seguimentos , Humanos , Masculino , Dor Pélvica/terapia , Neuralgia do Pudendo/terapia
10.
Bone ; 134: 115272, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32062002

RESUMO

Skeletal pathologies are often accompanied by bone pain, which has negative effects on the quality of life and functional status of patients. Bone pain can be caused by a wide variety of injuries and diseases including (poorly healed) fractures, bone cancer, osteoarthritis and also iatrogenic by skeletal interventions. Orthopedic interventions are considered to be the most painful surgical procedures overall. Two major groups of medication currently used to attenuate bone pain are NSAIDs and opioids. However, these systemic drugs frequently introduce adverse events, emphasizing the need for alternative therapies that are directed at the pathophysiological mechanisms underlying bone pain. The periosteum, cortical bone and bone marrow are mainly innervated by sensory A-delta fibers and C-fibers. These fibers are mostly present in the periosteum rendering this structure most sensitive to nociceptive stimuli. A-delta fibers and C-fibers can be activated upon mechanical distortion, acidic environment and increased intramedullary pressure. After activation, these fibers can be sensitized by inflammatory mediators, phosphorylation of acid-sensing ion channels and cytokine receptors, or by upregulation of transcription factors. This can result in a change of pain perception such that normally non-noxious stimuli are now perceived as noxious. Pathological conditions in the bone can produce neurotrophic factors that bind to receptors on A-delta fibers and C-fibers. These fibers then start to sprout and increase the innervation density of the bone, making it more sensitive to nociceptive stimuli. In addition, repetitive painful stimuli cause neurochemical and electrophysiological alterations in afferent sensory neurons in the spinal cord, which leads to central sensitization, and can contribute to chronic bone pain. Understanding the pathophysiological mechanisms underlying bone pain in different skeletal injuries and diseases is important for the development of alternative, targeted pain treatments. These pain mechanism-based alternatives have the potential to improve the quality of life of patients suffering from bone pain without introducing undesirable systemic effects.


Assuntos
Doenças Ósseas , Dor Crônica , Qualidade de Vida , Humanos , Manejo da Dor , Periósteo , Células Receptoras Sensoriais
11.
Eur Spine J ; 28(11): 2437-2443, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407164

RESUMO

PURPOSE: The purpose of this article is to review the importance of contemporary spine surgery fellowships and educational strategies to assist with fellowship design and delivery. METHODS: Spine surgery fellowship includes trainees from orthopaedic and neurosurgical backgrounds and is increasingly indicated for individuals wishing to pursue spine surgery as a career, recognizing how spinal surgery evolved significantly in scope and complexity. We combine expert opinion with a review of the literature and international experience to expound spine fellowship training. RESULTS: Contemporary learning techniques include boot camps at the start of fellowship which may reinforce previous clinical learning and help prepare fellows for their new clinical roles. There is good evidence that surgical specialty training boot camps improve clinical skills, knowledge and trainee confidence prior to embarking upon new clinical roles with increasing levels of responsibility. Furthermore, as simulation techniques and technologies take on an increasing role in medical and surgical training, we found evidence that trainees' operative skills and knowledge can improve with simulated operations, even if just carried out briefly. Finally, we found evidence to suggest a role for establishing competence-based objectives for training in specific operative and technical procedures. Competence-based objectives are helpful for trainees and trainers to highlight gaps in a trainee's skill set that may then be addressed during training. CONCLUSIONS: Spinal fellowships may benefit from certain contemporary strategies that assist design and delivery of training in a safe environment. Interpersonal factors that promote healthy teamwork may contribute to an environment conducive to learning. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Bolsas de Estudo , Procedimentos Neurocirúrgicos/educação , Ortopedia/educação , Coluna Vertebral/cirurgia , Competência Clínica , Humanos , Internacionalidade , Treinamento por Simulação
12.
JDR Clin Trans Res ; 4(4): 323-332, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30931720

RESUMO

INTRODUCTION: School screening and the note home (pinned to a backpack) informing parents/caregivers that their child needs to see a dentist have not been effective. OBJECTIVES: The Family Access to a Dentist Study (FADS) evaluated the effectiveness of school interventions based on the common-sense model of self-regulation (CSM) among K-4 children needing restorative treatment. METHODS: FADS was a multisite double-blind randomized controlled trial with 5 arms. FADS tested a CSM-driven referral letter and dental information guide (DIG) to move caregivers from inaccurate to accurate perceptions of dental caries. Six school districts from Ohio and Washington (14 schools) participated in school years 2015 to 2016 and 2016 to 2017. A total of 611 caregivers were randomized, and 86% (n = 597 children) completed the exit examination. The primary outcome was receipt of care based on a change in oral health status determined clinically within 1 school year. RESULTS: In accordance with our primary aims, 5 arms were collapsed into 3: CSM letter and reduced CSM letter (combined), CSM letter + DIG and reduced CSM letter + reduced DIG (combined), and standard letter. Among all sites, 39.7% received restorative care (237 of 597). Combined analysis of sites revealed that the CSM referral letter (with and without the DIG) did not increase dental visits when compared with the standard letter. However, for combined sites (East Cleveland, Ohio; Washington), the CSM + DIG increased dental visits when compared with standard letter in univariate analysis (51.3% vs. 40.9%), indicating 1.6-times increased odds of a dental visit (95% CI, 0.97 to 2.58) after imputation and adjustment for covariates. The CSM + DIG group had 1.9-times increased odds (95% CI, 1.21 to 3.08) of care when compared the CSM letter alone. CONCLUSION: A CSM-driven approach to informing caregivers of the chronic nature of caries with resources in an illustrative manner can increase the benefit of school oral health screening (ClinicalTrials.gov NCT02395120). KNOWLEDGE TRANSFER STATEMENT: A school dental referral (note home) that tells a parent that the child has cavities has not been effective. In this trial, a referral based on the common-sense model of self-regulation increased follow-up care for children with restorative needs.


Assuntos
Cárie Dentária , Criança , Método Duplo-Cego , Família , Humanos , Ohio , Washington
13.
Global Spine J ; 9(1): 18-24, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30775204

RESUMO

STUDY DESIGN: Longitudinal survey. OBJECTIVE: It remains important to align competence-based objectives for training as deemed important by clinical fellows to those of their fellowship supervisors and program educators. The primary aim of this study was to determine trainee views on the relative importance of specific procedural training competencies. Secondarily, we aimed to evaluate self-perceived confidence in procedural performance at the commencement and completion of fellowship. METHODS: Questionnaires were administered to 68 clinical fellows enrolled in the AOSNA fellowship program during the 2015-2016 academic year. A Likert-type scale was used to quantify trainee perspectives on the relative importance of specific procedural competencies to their training base on an established curriculum including 53 general and 22 focused/advanced procedural competencies. We measured trainee self-perceived confidence in performing procedures at the commencement and completion of their program. Statistical analysis was performed on fellow demographic data and procedural responses. RESULTS: Our initial survey response rate was 82% (56/68) and 69% (47/68) for the follow-up survey. Although most procedural competencies were regarded of high importance, we did identify several procedures of high importance yet low confidence among fellows (ie, upper cervical, thoracic discectomy surgery), which highlights an educational opportunity. Overall procedural confidence increased from an average Likert score of 4.2 (SD = 1.3) on the initial survey to 5.4 (SD = 0.8) by follow-up survey (P < .0001). CONCLUSIONS: Understanding trainee goals for clinical fellowship remains important. Identification of areas of low procedural confidence and high importance to training experience will better guide fellowship programs and supervisors in the strategic delivery of the educational experience.

14.
BMC Med ; 16(1): 228, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30518427

RESUMO

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.


Assuntos
Adjuvantes Imunológicos/economia , Análise Custo-Benefício/métodos , Vacina contra Herpes Zoster/economia , Herpes Zoster/tratamento farmacológico , Vacinas Atenuadas/economia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Vacina contra Herpes Zoster/farmacologia , Vacina contra Herpes Zoster/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Qualidade de Vida , Vacinas Atenuadas/farmacologia , Vacinas Atenuadas/uso terapêutico
15.
Scand J Pain ; 16: 1-9, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28850381

RESUMO

BACKGROUND AND AIMS: Despite widespread use, the efficacy of neuraxial glucocorticoids for neuropathic pain is subject to debate. Since most glucocorticoid actions are mediated through its receptor, we explored the effects of intrathecal methylprednisolone acetate (MPA) on total glucocorticoid receptor (tGR) levels and activation of the glucocorticoid receptor (phosphorylated state=pGR) within the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) in a spinal nerve ligation (SNL) model in rats. METHODS: Rats received unilateral ligation of the L5/L6 spinal nerves and were treated with two intrathecal doses of either 400µg MPA or 0.9% saline with a 72-h interval. Plantar tactile thresholds were measured over time. Seven days after drug treatment, DRG and SDH were harvested to assess tGR and pGR levels using immunohistochemistry and qPCR. RESULTS: Allodynia, defined by lowered tactile withdrawal thresholds after SNL, was unaltered by intrathecal MPA. In saline controls, mRNA levels of tGR did not change after SNL in the DRGs or SDH. tGR and pGR protein levels in the SDH however, significantly increased on the ipsilateral side of SNL compared to the contralateral side and to naïve tissue. When treating rats with MPA, tGR mRNA levels were significantly reduced in the SDH compared to saline controls. tGR and pGR protein levels, however were not significantly lower compared to saline controls. CONCLUSIONS: In intrathecal MPA treated rats, tGR mRNA levels decreased after SNL. However this did not result in lower tGR and pGR protein levels compared to saline controls, and did not decrease ligation-induced mechanical hypersensitivity. IMPLICATIONS: Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.


Assuntos
Glucocorticoides/farmacologia , Injeções Espinhais , Acetato de Metilprednisolona/farmacologia , Receptores de Glucocorticoides , Nervos Espinhais/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Hiperalgesia , Ligadura , Masculino , Neuralgia/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
16.
Gastrointest Endosc ; 86(4): 655-663, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28188723

RESUMO

BACKGROUND AND AIMS: There is little evidence that structures targeted during EUS-guided celiac ganglia neurolysis (EUS-CGN) are celiac ganglia and that selective ethanol injection into ganglia is feasible. We aimed to visualize celiac ganglia, confirm that these structures are ganglia, and visualize ethanol spread after EUS-CGN and EUS-guided celiac plexus neurolysis (EUS-CPN). METHODS: First, celiac ganglia were sought during 97 consecutive EUS procedures. Second, ganglia were identified in a prosected human cadaver by placing a linear echoendoscope next to the celiac trunk and removing the underlying tissue for histology. Finally, various EUS-CGN and EUS-CPN techniques were performed in human cadavers; EUS-CGN was performed with 1 mL ethanol in 1 ganglion, 1 mL per ganglion (both low volume), and 4 mL per ganglion (high volume). EUS-CPN was performed with a central (20 mL) and a bilateral (2*10 mL) approach. Transverse sections (75 µm) were obtained and photographed to allow visualization of the spread of ethanol. RESULTS: A total of 204 ganglia were detected in 83 patients. Mean (± standard deviation) size of the long axis was 8.1 mm (± 7.4 mm). Histology of the removed region in the cadaver showed only nerve cell bodies. After low-volume EUS-CGN in cadavers, ethanol spread well beyond the targeted ganglion. After high-volume EUS-CGN in cadavers, a larger ethanol spread was seen, which also reached unidentified ganglia; the spread was comparable to the spread after EUS-CPN. CONCLUSIONS: Specific EUS-CGN is not feasible because ethanol spreads well beyond the targeted ganglion. Unidentified celiac ganglia are better reached with high-volume EUS-CGN, and this would likely result in a more thorough neurolysis. High-volume EUS-CGN should be preferred to low-volume EUS-CGN.


Assuntos
Dor Abdominal/terapia , Etanol/uso terapêutico , Gânglios Simpáticos/diagnóstico por imagem , Bloqueio Nervoso/métodos , Solventes/uso terapêutico , Adulto , Idoso , Cadáver , Endossonografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Orthop Translat ; 10: 18-27, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29662757

RESUMO

Spinal pain and associated disability is a leading cause of morbidity worldwide that has a strong association with degenerative disc disease (DDD). DDD can begin in early-late adolescence and has a variable course. Biologically based therapies to treat DDD face significant challenges posed by the unique milieu of the environment within the intervertebral discs. Many potential promising therapies are still in the early stages of development with a hostile microenvironment within the disc presenting unique challenges. The translational potential of this article: Patient selection, reasonable therapeutic goals, approach, and timing will need to be discerned in order to successfully translate potential therapeutics.

18.
Pain Pract ; 17(6): 738-746, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27611885

RESUMO

BACKGROUND: Herpes zoster (HZ) and postherpetic neuralgia are known to have a profound effect on the patient's quality of life, but the incidence and severity of itch and its relation with pain and quality of life in the long term are still relatively unknown. OBJECTIVE: The aim of this study was to measure the presence and severity of pain and itch and impact on quality of life in patients over 50 years old with HZ. METHODS: We enrolled 661 patients with HZ in this 12-month observational study. Patient data were collected via a web-based questionnaire. Outcomes were pain, itch, burden of illness, impact on patient's daily life, impact on quality of life, and healthcare costs. RESULTS: At inclusion, 94% of patients reported any pain, 74.3% significant pain, and 26% severe pain. After 3 months, 18.8% of patients suffered from postherpetic neuralgia. At inclusion, 70.8% of patients had any itch, 39.2% significant itch, and 7.3% severe itch. The occurrence of pain increases costs and has a high impact on the quality of life, lowering EQ-5D scores by an average of 18%. In contrast, itch has little effect on the quality of life. CONCLUSIONS: Pain and itch are highly prevalent months after HZ. Pain caused by HZ has a large impact on quality of life, burden of illness, impact on daily life, and health care costs for these patients. The impact of itch on quality of life is relatively small.


Assuntos
Custos de Cuidados de Saúde , Herpes Zoster/epidemiologia , Neuralgia Pós-Herpética/epidemiologia , Prurido/epidemiologia , Qualidade de Vida , Idoso , Feminino , Seguimentos , Herpes Zoster/diagnóstico , Herpes Zoster/economia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Neuralgia Pós-Herpética/diagnóstico , Neuralgia Pós-Herpética/economia , Prurido/diagnóstico , Prurido/economia , Inquéritos e Questionários
19.
Int J Radiat Oncol Biol Phys ; 97(1): 75-81, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27843032

RESUMO

PURPOSE: To determine a threshold of vertebral body (VB) osteolytic or osteoblastic tumor involvement that would predict vertebral compression fracture (VCF) risk after stereotactic body radiation therapy (SBRT), using volumetric image-segmentation software. METHODS AND MATERIALS: A computational semiautomated skeletal metastasis segmentation process refined in our laboratory was applied to the pretreatment planning CT scan of 100 vertebral segments in 55 patients treated with spine SBRT. Each VB was segmented and the percentage of lytic and/or blastic disease by volume determined. RESULTS: The cumulative incidence of VCF at 3 and 12 months was 14.1% and 17.3%, respectively. The median follow-up was 7.3 months (range, 0.6-67.6 months). In all, 56% of segments were determined lytic, 23% blastic, and 21% mixed, according to clinical radiologic determination. Within these 3 clinical cohorts, the segmentation-determined mean percentages of lytic and blastic tumor were 8.9% and 6.0%, 0.2% and 26.9%, and 3.4% and 15.8% by volume, respectively. On the basis of the entire cohort (n=100), a significant association was observed for the osteolytic percentage measures and the occurrence of VCF (P<.001) but not for the osteoblastic measures. The most significant lytic disease threshold was observed at ≥11.6% (odds ratio 37.4, 95% confidence interval 9.4-148.9). On multivariable analysis, ≥11.6% lytic disease (P<.001), baseline VCF (P<.001), and SBRT with ≥20 Gy per fraction (P=.014) were predictive. CONCLUSIONS: Pretreatment lytic VB disease volumetric measures, independent of the blastic component, predict for SBRT-induced VCF. Larger-scale trials evaluating our software are planned to validate the results.


Assuntos
Fraturas por Compressão/etiologia , Osteólise/diagnóstico por imagem , Radiocirurgia/efeitos adversos , Software , Fraturas da Coluna Vertebral/etiologia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/secundário , Tomografia Computadorizada por Raios X , Vértebras Cervicais/diagnóstico por imagem , Feminino , Seguimentos , Fraturas por Compressão/epidemiologia , Humanos , Incidência , Vértebras Lombares/diagnóstico por imagem , Masculino , Osteólise/complicações , Dosagem Radioterapêutica , Medição de Risco/métodos , Fraturas da Coluna Vertebral/epidemiologia , Neoplasias da Coluna Vertebral/radioterapia , Vértebras Torácicas/diagnóstico por imagem , Fatores de Tempo
20.
Spine J ; 16(7): 889-95, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26972621

RESUMO

BACKGROUND CONTEXT: Defects in the annulus fibrosus (AF) remain a challenge in the surgical treatment of lumbar disc herniations with persistent defects, allowing potential re herniation of nucleus pulposus (NP) tissue. A cervical porcine model was chosen to simulate human lumbar intervertebral disc (IVD). PURPOSE: The aim of this study was to determine the technical feasibility of closure of the AF of the IVD using a novel minimally invasive Kerrison-shaped suture application device. STUDY DESIGN: Ex vivo biomechanical and in vivo porcine device evaluations were performed. METHODS: Ex vivo biomechanical evaluation: 15 porcine spinal units were explanted and subjected to mock discectomy. The annular defect was closed using 2-0 non-absorbable (ultra-high molecular-weight polyethylene, UHMWPE) suture and Dines knot. The knot was backed up with two, three, or four throws. The spinal unit was subject to 4000 cycles of flexion/extension with 1500 N of axial load, and assessed for knot slippage. In vivo porcine device evaluation: three pigs (53-57 kg) were anesthetized and underwent a ventral surgical approach to the cervical spine. The AF of two discs was incised, and simulated partial NP discectomy was performed. The defect was closed at one level using the AnchorKnot device to apply the suture with a Dines knot and four throws. The pigs were observed for 4 weeks before euthanasia, allowing 7T magnetic resonance imaging (MRI) and histological evaluation. RESULTS: A Dines knot with four throws experienced no slippage after 4000 cycles. This configuration was tested in vivo. Clinically, the neurological examination in treated pigs was normal following surgery. Histological and MRI assessment confirmed sustained defect closure at 4 weeks. There was no reaction to the suture material and no NP extrusion at any of the sutured levels. CONCLUSIONS: This study demonstrates that it is technically feasible to perform AF defect closure in a porcine model. This novel device achieved AF defect closure that was maintained through 4 weeks in vivo.


Assuntos
Anel Fibroso/cirurgia , Discotomia/métodos , Instrumentos Cirúrgicos/efeitos adversos , Suturas/efeitos adversos , Animais , Fenômenos Biomecânicos , Discotomia/instrumentação , Suínos
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