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1.
Artigo em Inglês | MEDLINE | ID: mdl-38958596

RESUMO

KEY POINTS: A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab. Revision sinus surgery immediately prior to dupilumab reduces long-term interleukin (IL)-4/IL-13 tissue mRNA. Pre-dupilumab revision surgery is associated with reduced tissue eosinophils and GATA-3+ cells.

2.
Laryngoscope ; 134(3): 1100-1106, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37589314

RESUMO

OBJECTIVES: Oxymetazoline relieves nasal obstructive symptoms via vasoconstriction, however, the changes in nasal structures and aerodynamics that impact symptoms the most remain unclear. METHODS: This prospective, longitudinal, and single blinded cohort study applied Computational Fluid Dynamic (CFD) modeling based on CT scans at baseline and post-oxymetazoline on 13 consecutive patients with chronic nasal obstruction secondary to inferior turbinate hypertrophy from a tertiary medical center. To account for placebo effect, a sham saline spray was administered with subject blindfolded prior to oxymetazoline, with 30 min rest in between. Nasal Obstruction Symptom Evaluation (NOSE) and unilateral Visual Analogue Scale (VAS) scores of nasal obstructions were collected at baseline, after sham, and 30 min after oxymetazoline. RESULTS: Both VAS and NOSE scores significantly improved from baseline to post-oxymetazoline (NOSE: 62.3 ± 12.4 to 31.5 ± 22.5, p < 0.01; VAS: 5.27 ± 2.63 to 3.85 ± 2.59, p < 0.05), but not significantly from baseline to post-sham. The anatomical effects of oxymetazoline were observed broadly throughout the entire length of the inferior and middle turbinates (p < 0.05). Among many variables that changed significantly post-oxymetazoline, only decreased nasal resistance (spearman r = 0.4, p < 0.05), increased regional flow rates (r = -0.3 to -0.5, p < 0.05) and mucosal cooling heat flux (r = -0.42, p < 0.01) in the inferior but not middle turbinate regions, and nasal valve Wall Shear Stress (WSS r = -0.43, p < 0.05) strongly correlated with symptom improvement. CONCLUSION: Oxymetazoline broadly affects the inferior and middle turbinates, however, symptomatic improvement appears to be driven more by global nasal resistance and regional increases in airflow rate, mucosal cooling, and WSS, especially near the head of the inferior turbinate. LEVEL OF EVIDENCE: 3: Well-designed, prospective, single blinded cohort trial. Laryngoscope, 134:1100-1106, 2024.


Assuntos
Obstrução Nasal , Doenças dos Seios Paranasais , Humanos , Oximetazolina , Conchas Nasais/diagnóstico por imagem , Obstrução Nasal/tratamento farmacológico , Obstrução Nasal/etiologia , Estudos Prospectivos , Estudos de Coortes , Hipertrofia , Doenças dos Seios Paranasais/tratamento farmacológico
3.
Microbiol Resour Announc ; 12(6): e0012223, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37133378

RESUMO

We report a complete genome sequence of bovine coronavirus (BCoV) isolated from a goat in the state of Pennsylvania in 2022. BCoV often causes calf scours and winter dysentery in cattle.

4.
Oper Neurosurg (Hagerstown) ; 25(1): e55-e59, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37039583

RESUMO

BACKGROUND AND IMPORTANCE: Unilateral inferior hypophyseal artery (IHA) sacrifice is routinely performed during endoscopic endonasal transcavernous interdural posterior clinoidectomy. However, unilateral IHA sacrifice presents the risk of temporary postoperative diabetes insipidus. We present a case demonstrating the feasibility of endoscopic endonasal transcavernous posterior clinoidectomy without IHA sacrifice. CLINICAL PRESENTATION: A 62-year-old man presented with progressive weakness of his left oculomotor and abducens nerves. MRI of the brain revealed a small lesion suspicious for hemangioma in the posterior compartment of the left cavernous sinus. Following an endoscopic endonasal transcavernous approach using the interdural peeling technique, an IHA-sparing posterior clinoidectomy was performed to provide access to the tumor in the posterior cavernous sinus. After complete resection, the patient's symptoms improved and a diagnosis of cavernous sinus hemangioma was confirmed by histopathology. CONCLUSION: Unilateral IHA preservation may be performed safely when performing a transcavernous interdural posterior clinoidectomy. IHA preservation can be readily achieved if the artery is redundant, the lesion is small and located in the posterior cavernous sinus, and there is a short posterior clinoid, ultimately avoiding the risk of transient postoperative diabetes insipidus.


Assuntos
Seio Cavernoso , Hemangioma Cavernoso , Hemangioma , Masculino , Humanos , Pessoa de Meia-Idade , Seio Cavernoso/diagnóstico por imagem , Seio Cavernoso/cirurgia , Nariz , Hemangioma Cavernoso/cirurgia , Hemangioma/cirurgia , Artéria Carótida Interna
5.
Ann Otol Rhinol Laryngol ; 132(11): 1306-1313, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36704822

RESUMO

BACKGROUND: Topical sinus irrigation plays a critical role in the management of sinonasal diseases. Yet, the penetration of irrigant to targeted sinuses may be highly variable and difficult to predict. Here, we investigate the use of 3D printing as a planning tool to optimize outcomes. METHODS: Eight post-operative models were 3D printed with a FormLabs Form3 printer based on individual CT scans. Irrigations were performed and video recorded with a squeeze bottle attached via silicon water-tight seal, in 4 head positions: 45° to-the-side, 90° to-the-side, 45° forward and 45° to-the-side, and 90° forward, with irrigation fluid entering the upper (conventional) or lower (backfill) nostrils. RESULTS: Significant individual variations were observed in sinus penetration as a function of head position. In general, the maxillary sinus was the easiest to irrigate in most head positions (P < .05), followed by frontal and ethmoid, with sphenoid being the most difficult. Both the 90°-to-the-side and the 90°-forward positions were significantly more effective than the others (P < .05), with 90°-forward better for frontal sinuses and 90°-to-the-side superior for all other sinuses. The backfill was significantly superior to conventional technique in head positions involving a side tilt (P < .05). CONCLUSION: Variations in technique and position significantly impacted irrigation outcome. Backfill irrigation that pushes fluid against gravity to pool around the ostium, seems to provide overall better outcomes. This study demonstrates the advantage of 3D printing as a rapid planning tool to guide irrigation strategies.


Assuntos
Seio Frontal , Cavidade Nasal , Humanos , Cavidade Nasal/cirurgia , Seio Frontal/cirurgia , Seio Maxilar , Osso Esfenoide , Impressão Tridimensional , Irrigação Terapêutica
6.
FASEB J ; 36(5): e22328, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35471732

RESUMO

Interleukin-4 (IL-4) is a signature cytokine pivotal in Type 2 helper T cell (Th2) immune response, particularly in allergy and hypersensitivity. Interestingly, IL-4 increases endogenous levels of prostaglandin D2 (PGD2 ) and its metabolites, Δ12 -prostaglandin J2 (Δ12 -PGJ2 ) and 15-deoxy-Δ12,14 -prostaglandin J2 (15d-PGJ2 ), collectively called cyclopentenone PGs (CyPGs). However, the therapeutic role of IL-4 in hematologic malignancies remains unclear. Here, we employed a murine model of acute myeloid leukemia (AML), where human MLL-AF9 fusion oncoprotein was expressed in hematopoietic progenitor cells, to test the effect of IL-4 treatment in vivo. Daily intraperitoneal treatment with IL-4 at 60 µg/kg/d significantly alleviated the severity of AML, as seen by decreased leukemia-initiating cells (LICs). The effect of IL-4 was mediated, in part, by the enhanced expression of hematopoietic- PGD2  synthase (H-PGDS) to effect endogenous production of CyPGs, through autocrine and paracrine signaling mechanisms. Similar results were seen with patient-derived AML cells cultured ex vivo with IL-4. Use of GW9662, a peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, suggested endogenous CyPGs-PPARγ axis mediated p53-dependent apoptosis of LICs by IL-4. Taken together, our results reveal a beneficial role of IL-4 treatment in AML suggesting a potential therapeutic regimen worthy of clinical trials in patients with AML.


Assuntos
Interleucina-4 , Leucemia Mieloide Aguda , Prostaglandina D2 , Animais , Citocinas , Humanos , Interleucina-4/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Camundongos , PPAR gama/metabolismo , Prostaglandina D2/metabolismo
7.
J Sch Psychol ; 89: 72-90, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34836577

RESUMO

Students often hear their peers use biased language regarding race, religion, sexual orientation, or disability status in the school setting. Prior research has indicated that biased language is related to school climate, and specifically to school-based relationships between peers and between students and their teachers. This study investigated the longitudinal associations among student-student relationships, teacher-student relationships, and being the target of or hearing biased language in middle school students. Students (N = 501; 46.5% White, 21.8% Hispanic, 13% African American, and 15% Multi-Racial; 48.7% female) reported on how much they were targeted or heard biased language related to race/religion, sexual orientation, and disability status. Students also reported on their relationships with their peers and teachers. Using a cross-lagged panel model with the overall sample, a negative unidirectional association from being the target of or hearing biased language and student-student relationships and teacher-student relationships was identified. Separate models for boys and girls identified unique patterns. For boys, biased-language exposure predicted more negative student-student relationships and teacher-student relationships, whereas for girls, biased-language exposure was not associated with school-based relationships. Implications include addressing language use and building positive student-student and teacher-student relationships.


Assuntos
Relações Interpessoais , Idioma , Feminino , Humanos , Masculino , Grupo Associado , Professores Escolares , Instituições Acadêmicas , Estudantes
8.
Curr Allergy Asthma Rep ; 21(8): 42, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499234

RESUMO

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a highly prevalent disease with large social and financial burdens. The pathophysiology is multifactorial. Environmental pollutants have been suggested to play a role in the inflammatory component of the disease process. RECENT FINDINGS: Recent work has focused on exposure to various pollutants, primarily particulate matter (PM). Exposure to environmental pollutants leads to upregulation of inflammatory markers and ciliary dysfunction at the cellular level. Mouse models suggest a role for epithelial barrier dysfunction contributing to inflammatory changes after pollutant exposure. Clinical studies support the role of pollutants contributing to disease severity in certain populations, but the role in CRS incidence or prevalence is less clear. Research is limited by the retrospective nature of most studies. This review focuses on recent advancements in our understanding of the impact of environmental pollutants in CRS, limitations of the available data, and potential opportunities for future studies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Animais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Camundongos , Material Particulado/efeitos adversos , Estudos Retrospectivos
9.
J Sch Psychol ; 86: 49-63, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34051917

RESUMO

Although some research has evidenced a negative association between involvement in bullying and academic performance, more work is needed to understand the associations between academic performance and involvement in a more comprehensive range of bully role behaviors. The goals of the current study were to determine (a) the associations among a broader range of bully role behaviors (i.e., bullying, assisting, victimization, defending, and outsider behavior) and academic performance (i.e., grade point average; GPA), and (b) gender differences within these associations. The current study investigated these issues over the course of an academic year with 7794 students in middle through high school. Bullying behaviors were assessed in the fall and GPA data were gathered from school records from the spring of the same academic year. The results identified significant negative associations between bullying (b = -0.07, p = .001), assisting (b = -0.16, p < .001), victimization (b = -0.06, p < .001), and defending (b = -0.04, p < .001) with student GPA, whereas no significant association emerged for outsider behavior and GPA (b = -0.02, p = .13). In addition, several gender differences were found in these associations, including a stronger negative association between assisting and GPA for girls (b = -0.23, p = .001) than for boys (b = -0.08, p = .014) and a significant negative association between victimization and GPA for girls (b = -0.09, p < .001), but not boys (b = -0.02, p = .117). Differences in results across schools were also examined in an exploratory manner. The educational impact associated with bullying behaviors, limitations of the current study, and suggestions for future research are discussed.


Assuntos
Desempenho Acadêmico , Bullying , Vítimas de Crime , Feminino , Humanos , Masculino , Instituições Acadêmicas , Inquéritos e Questionários
10.
J Tissue Eng Regen Med ; 14(11): 1673-1684, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32893492

RESUMO

Small-diameter vascular grafts perform poorly as arterial bypasses. We developed a cell-free, resorbable graft intended to remodel in situ into a living vessel. The graft consisted of a soft electrospun poly(glycerol sebacate) (PGS) core, a PGS prepolymer (pPGS) coating, and a reinforcing electrospun poly(ε-caprolactone) (PCL) sheath. The core contained 4.37 ± 1.95 µm fibers and had a porosity of 66.4 ± 3.2%, giving it large pores to encourage cellular infiltration and pro-healing macrophages. The sheath contained 6.63 ± 0.89 µm fibers and had a porosity of 80.5 ± 2.1%. in vitro testing suggested that the stress achieved at arterial pressure would be 13-fold lower than the yield stress of the graft. Grafts were implanted as 7 cm carotid interpositions in two sheep. Sheep were maintained on dual antiplatelet therapy and followed with duplex ultrasound. One graft ruptured at 13 days. The second animal was euthanized with a dilated graft at 15 days. Histology showed near-total degradation of the core and a robust inflammatory response within the sheath. Little neotissue had formed within the graft wall or lumen, but the graft had become surrounded by fibroblast-rich and vascularized connective tissue. Because PCL is commonly used in resorbable grafts, this mechanical destabilization was unexpected. We speculate that the inflammatory response instigated by the rapidly degrading PGS intensified degradation of the PCL and that the large pores enabled a prolonged acute host-graft reaction which attacked the entire bulk of the material, speeding weakening. Future work will focus on how to moderate inflammation and improve remodeling of grafts in large animals.


Assuntos
Implantes Absorvíveis , Prótese Vascular , Artérias Carótidas/fisiologia , Animais , Artérias Carótidas/diagnóstico por imagem , Ovinos , Engenharia Tecidual , Tomografia Computadorizada por Raios X
11.
J Vet Diagn Invest ; 32(5): 722-726, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32715936

RESUMO

Twenty-eight lactating dairy cattle in New York State were exposed to botulism toxin; 12 died and 16 recovered but never returned to full productivity. Pieces of a raccoon carcass were found in the total mixed ration on the first day of the outbreak. Clinical signs included anorexia, decreased milk production, decreased tongue tone, profound weakness, and recumbency. Clostridium botulinum type A (BoNT/A) was detected in rumen contents from 2 deceased cows via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In addition, C. botulinum type C was cultured from the liver of a third cow, and C. botulinum neurotoxin-producing type C gene (bont/C) was detected via real-time PCR. On postmortem examination, 4 cows had findings suggestive of toxic myopathy, but the cause and significance of these lesions is unknown given that botulism is typically not associated with gross or histologic lesions. This outbreak of BoNT/A in cattle in North America was diagnosed via MALDI-TOF MS, a rapid and sensitive modality for detection of botulinum preformed neurotoxin.


Assuntos
Botulismo/veterinária , Doenças dos Bovinos/diagnóstico , Surtos de Doenças/veterinária , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/veterinária , Animais , Toxinas Botulínicas/análise , Botulismo/diagnóstico , Botulismo/epidemiologia , Bovinos , Doenças dos Bovinos/epidemiologia , Clostridium botulinum/isolamento & purificação , Feminino , New York/epidemiologia
12.
Immunol Allergy Clin North Am ; 40(2): 371-383, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32278458

RESUMO

Chronic rhinosinusitis (CRS) is present in up to 100% of patients with cystic fibrosis (CF). CF-associated CRS is particularly recalcitrant, and sinus disease can have important implications in the health of the lower airways and overall quality of life in these patients. Both medical and surgical management play important roles in treating CF-associated CRS, but guidelines are lacking. This review summarizes the current literature on both medical and surgical management of this disease to provide an up-to-date analysis and recommendations on the treatment of CF-associated CRS.


Assuntos
Fibrose Cística/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Doença Crônica , Fibrose Cística/complicações , Fibrose Cística/terapia , Endoscopia , Humanos , Guias de Prática Clínica como Assunto , Qualidade de Vida , Rinite/complicações , Rinite/terapia , Sinusite/complicações , Sinusite/terapia
13.
Curr Med Res Opin ; 35(12): 2117-2127, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31387410

RESUMO

Objective: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients with knee or hip pain related to moderate-to-severe osteoarthritis.Methods: Osteoarthritic patients (aged ≥18 years) from four phase 3 randomized, double-blind (DB), placebo-controlled studies were randomized to receive placebo, fulranumab 1 mg every 4 weeks (Q4wk), or 3 mg Q4wk in 16-week DB phase, followed by a 52-week post-treatment follow-up phase. Safety assessments included treatment-emergent adverse events (TEAEs), and neurological, sympathetic, and joint-related events of interest. Efficacy assessments included pain and physical function sub-scales of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores.Results: Of 245 patients from the ITT set (median age = 64 years; 62% women), 84 (34%) completed the DB phase; the majority of discontinuations (57%) were due to early study termination. In the DB phase, the incidence of TEAEs in fulranumab 3 mg (57.8%) and 1 mg (56.8%) was similar to placebo (56.8%). Two events adjudicated as joint-related events of interest include rapidly progressive osteoarthritis and fracture of unknown etiology. There were no new neurological TEAEs. Fulranumab showed evidence of efficacy in improving pain and physical function based on WOMAC sub-scale scores. Due to premature study termination, the number of patients enrolled were too small to make any definitive efficacy claims.Conclusions: Treatment with fulranumab was generally tolerated with no new safety signals. Within the limited sample analyzed, fulranumab showed evidence of improvement of pain and function in patients with moderate-to-severe osteoarthritis who had failed prior therapy and were candidates for joint replacement surgery.Clinical trial registration numbers: NCT02336685; NCT02336698; NCT02289716; NCT02301234KEY POINTSFulranumab as adjuvant or monotherapy was well tolerated with no new safety signalsFulranumab demonstrated evidence suggestive of efficacy in osteoarthritic pain of hip and kneeFulranumab demonstrated evidence suggestive of improvement of pain and physical function in osteoarthritis.


Assuntos
Artralgia/tratamento farmacológico , Osteoartrite do Quadril , Osteoartrite do Joelho , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Artralgia/diagnóstico , Artralgia/etiologia , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/fisiopatologia , Medição da Dor/métodos , Desempenho Físico Funcional , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Neurosurgery ; 85(4): E662-E669, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30937451

RESUMO

BACKGROUND: Though it is well known that normal pressure hydrocephalus (NPH) patients can cognitively improve after ventriculoperitoneal shunting (VPS), one of the major dilemmas in NPH is the ability to prospectively predict which patients will improve. OBJECTIVE: To prospectively assess preoperative predictors of postshunt cognitive improvement. METHODS: This was a prospective observational cohort including 52 consecutive patients with approximately 1-yr follow-up. Patients underwent neuropsychological testing at baseline, postlumbar drainage, and postshunt. Cerebrospinal fluid (CSF) biomarkers and cortical biopsies were also collected to examine their relationship with postshunt cognitive improvement. RESULTS: Rey Auditory Verbal Learning Test-L (RAVLT-L) was the only neuropsychological test to demonstrate statistically significant improvement both postlumbar drain and postshunt. Improvement on the RAVLT-L postlumbar drain predicted improvement on the RAVLT-L postshunt. Patients with biopsies demonstrating Aß+ Tau+ had lower ventricular CSF Aß42 and higher lumbar CSF pTau compared to Aß- Tau- patients. A receiver operating curve analysis using lumbar pTau predicted Aß+ Tau+ biopsy status but was not related to neuropsychological test outcome. CONCLUSION: The RAVLT can be a useful preoperative predictor of postoperative cognitive improvement, and thus, we recommend using the RAVLT to evaluate NPH patients. CSF biomarkers could not be related to neuropsychological test outcome. Future research in a larger patient sample will help determine the prospective utility of CSF biomarkers in the evaluation of NPH patients.


Assuntos
Cognição/fisiologia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/psicologia , Testes Neuropsicológicos , Cuidados Pré-Operatórios/tendências , Derivação Ventriculoperitoneal/tendências , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Drenagem/métodos , Drenagem/tendências , Feminino , Humanos , Hidrocefalia de Pressão Normal/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Derivação Ventriculoperitoneal/métodos
15.
Vet Pathol ; 56(4): 604-608, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30917745

RESUMO

Neurologic manifestations other than cerebellar hypoplasia are rarely associated with feline panleukopenia virus (FPV) infection in cats. Here the authors describe lymphoplasmacytic meningoencephalitis and neuronal necrosis in 2 cats autopsied after exhibiting ataxia and nystagmus. Gross changes consisted of cerebellar herniation through the foramen magnum, with flattening of cerebrocortical gyri and narrowing of sulci. Histologically, lymphoplasmacytic meningoencephalitis, extensive neuronal necrosis, and neuroaxonal degeneration with digestion chambers were present in the telencephalon and brain stem in both cats. Frozen brain tissue of both cats was positive for parvoviral antigen via fluorescent antibody testing, and formalin-fixed, paraffin-embedded tissue sections of brain were immunoreactive for parvovirus antigen and positive for parvoviral DNA on in situ hybridization. Frozen brain tissue from 1 case was positive for parvovirus NS1 and VP2 genes using conventional polymerase chain reaction, and subsequent DNA sequencing and phylogenetic analysis revealed that the viral strain was a FPV. Reverse transcription quantitative polymerase chain reaction on formalin-fixed, paraffin-embedded brain tissue revealed high levels of parvovirus in both cases, supporting an acute and active viral infection. Although rare, FPV infection should be considered in cases of lymphoplasmacytic meningoencephalitis and neuronal necrosis in cats.


Assuntos
Vírus da Panleucopenia Felina/isolamento & purificação , Panleucopenia Felina/patologia , Meningoencefalite/veterinária , Animais , Encéfalo/patologia , Gatos , Panleucopenia Felina/diagnóstico , Panleucopenia Felina/virologia , Vírus da Panleucopenia Felina/genética , Hibridização In Situ/veterinária , Meningoencefalite/diagnóstico , Meningoencefalite/virologia , Necrose/veterinária , Neurônios/patologia , Reação em Cadeia da Polimerase/veterinária
16.
J Pain ; 20(4): 440-452, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30368018

RESUMO

This randomized, double-blind (DB), placebo-controlled, phase 2 study assessed the efficacy and safety of fulranumab as a pain therapy adjunctive to opioids in terminally ill cancer patients. Ninety-eight patients were randomized (2:1) to receive one subcutaneous injection of fulranumab (9 mg) or placebo in the 4-week DB phase. Seventy-one (72%) patients entered the 48-week open-label extension phase and were administered 9 mg of fulranumab every 4 weeks. The study failed to demonstrated efficacy at the end of the DB phase (primary endpoint, mean [SD] change in average cancer-related pain intensity was -.8 (1.26) for fulranumab and -.7 (1.56) for placebo; P = .592). However, potential benefit is suggested based on secondary endpoints (30% responder rate [P = .020], Brief Pain Inventory-Short Form [BPI-SF] pain intensity subscale [P = .003], and pain interference subscale [P = .006]). The most commonly reported treatment-emergent adverse events were (fulranumab vs placebo): asthenia (16% vs 10%), decreased appetite (12% vs 6%), fatigue (10% vs 0%), and malignant neoplasm progression (10% vs 0%). Although no differences were seen between fulranumab and placebo groups on the primary endpoint, improvements in BPI-SF pain subscale scores and responder rates support further research of anti-nerve growth factor therapy in cancer-related pain. PERSPECTIVE: Efficacy and safety of fulranumab as adjunctive pain therapy in terminally ill cancer patients were assessed. Results suggest that anti-NGF agents may prove to be novel additions in helping to optimize pain relief in cancer patients who fail to respond adequately to opioids and other common co-analgesics.


Assuntos
Analgésicos Opioides/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Dor do Câncer/tratamento farmacológico , Fatores Imunológicos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Manejo da Dor , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Medição da Dor , Falha de Tratamento
17.
Curr Atheroscler Rep ; 19(12): 64, 2017 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-29147858

RESUMO

PURPOSE OF REVIEW: Acute stroke treatments reduce the risk of post-stroke disability. These treatments, tissue plasminogen activator (tPA) and intra-arterial treatment, are highly time-dependent; thus, one of the main barriers to treatment is pre-hospital delay. Stroke preparedness is defined as the ability to recognize stroke symptoms and the intent to activate emergency medical services (EMS). This review describes types of acute stroke treatment and preparedness interventions, including recent mass media interventions to increase acute stroke treatment rates, and adult and youth community interventions to increase stroke preparedness. RECENT FINDINGS: The mass media campaigns show mixed results regarding acute stroke treatment rates, possibly attributed to the various media platforms utilized and resources available. The adult and youth community interventions reveal an overall increase in stroke symptom recognition and behavioral intent to call EMS. However, most of these community interventions were not grounded in health behavior theory, and they were tested in single group, pre-post test study designs that assessed behavioral rather than clinical outcomes. The delivery of stroke preparedness information by youth to adults, for example via home assignments, is a promising and innovative approach to stroke preparedness. Mass media and community interventions show promise to increase stroke preparedness and acute stroke treatment rates. The development of health behavior theory-based interventions that are tested via scientifically rigorous study designs are needed to prioritize which interventions should be disseminated to culturally and socially similar communities.


Assuntos
Serviços de Saúde Comunitária , Promoção da Saúde , Acidente Vascular Cerebral/terapia , Fatores Etários , Informação de Saúde ao Consumidor , Serviços Médicos de Emergência , Comportamentos Relacionados com a Saúde , Humanos , Meios de Comunicação de Massa , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo
18.
BMC Urol ; 17(1): 2, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056917

RESUMO

BACKGROUND: This study was designed to evaluate the efficacy and safety of fulranumab, a fully human monoclonal antibody directed against nerve growth factor (NGF), for pain relief in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: In this multicenter, double-blind study, adults with IC/BPS (i.e., interstitial cystitis symptom index [ICSI] total score ≥8) accompanied by chronic, moderate-to-severe pain were randomized to fulranumab 9 mg or matching placebo, administered subcutaneously at weeks 1, 5, and 9. The primary efficacy endpoint was change from baseline to study endpoint (week 12 or at withdrawal) in average daily pain intensity score. Key secondary endpoints included change from baseline to study endpoint in worst pain intensity score, ICSI total score, Pelvic Pain and Urgency/Frequency total score, Patient Perception of Bladder Condition score, and global response assessment. RESULTS: This study was terminated prematurely based on concern that this class may be associated with rapidly progressing osteoarthritis or osteonecrosis. Thirty-one patients (of the targeted 70 patients) were randomized, 17 to placebo and 14 to fulranumab, with 15 and 10 patients, respectively, receiving all 3 doses of double-blind treatment. In ANOVA analyses, there was no statistically significant difference between treatment groups for the primary endpoint (LS mean difference [95% CI] vs. placebo, -0.2 [-1.52, 1.10]) or any of the secondary endpoints. Fulranumab was well tolerated, with no patient discontinuing due to an adverse event or experiencing a joint-related serious adverse event over a 26-week follow-up period. No events related to the neurologic or motor systems were reported. CONCLUSIONS: Efficacy was not demonstrated in the present study with the single dose tested and a limited sample size, leading to lack of statistical power. These findings do not exclude the possibility that fulranumab would provide clinical benefit in a larger study and/or specific populations (phenotypes) in this difficult to treat pain condition. TRIAL REGISTRATION: NCT01060254 , registered January 29, 2010.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Cistite Intersticial/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Arthritis Rheumatol ; 69(4): 763-773, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27748055

RESUMO

OBJECTIVE: To evaluate the long-term safety and efficacy of fulranumab in patients with knee or hip pain caused by moderate-to-severe chronic osteoarthritis (OA). METHODS: In this phase II double-blind, placebo-controlled extension study, patients who were randomized in equal proportions to receive subcutaneous doses of either placebo or fulranumab (1 mg every 4 weeks, 3 mg every 8 weeks, 3 mg every 4 weeks, 6 mg every 8 weeks, or 10 mg every 8 weeks) in the 12-week double-blind efficacy phase and who completed this double-blind efficacy phase were eligible to continue the dosage throughout a 92-week double-blind extension phase, followed by a 24-week posttreatment follow-up period. Safety assessments included evaluation of treatment-emergent adverse events (TEAEs), pre-identified AEs of interest, and joint replacements. Efficacy assessments included changes from baseline to the end of the double-blind extension phase in scores on the patient's global assessment and the pain and physical function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index. RESULTS: Overall, 401 of the 423 patients who completed the 12-week double-blind efficacy phase entered the extension study. Long-term sustained improvements were observed in all efficacy parameters following fulranumab treatment (1 mg every 4 weeks, 3 mg every 4 weeks, and 10 mg every 8 weeks) as compared with placebo. Similar percentages of patients in both groups experienced TEAEs (88% taking placebo and 91% taking fulranumab; all phases). Across all fulranumab groups, arthralgia (21%) and OA (18%) (e.g., exacerbation of OA pain) were the most common TEAEs. The most common serious TEAEs were the requirement for knee (10%) and hip (7%) arthroplasty, with 80% occurring during the posttreatment follow-up period. Neurologic-related TEAEs (28%; all phases) were generally mild-to-moderate. Overall, 81 joint replacements were performed in 71 patients (8 [11%] receiving placebo and 63 [89%] receiving fulranumab); 15 patients (21%) had rapid progression of OA (RPOA). All cases of RPOA occurred in fulranumab-treated patients who were concurrently receiving nonsteroidal antiinflammatory drugs and occurred in joints with preexisting OA. CONCLUSION: Long-term treatment with fulranumab was generally well-tolerated and efficacious. RPOA was observed as a safety signal. Future studies are warranted to demonstrate whether the risk of RPOA can be reduced in patients taking fulranumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/complicações , Osteoartrite do Joelho/complicações , Dor/etiologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
20.
Clin J Pain ; 33(2): 99-108, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27153360

RESUMO

OBJECTIVE: Fulranumab is an antibody that specifically neutralizes the biological activity of human nerve growth factor. This multicenter, phase-2, randomized, double-blind (DB), placebo-controlled study evaluated the analgesic efficacy and safety of fulranumab in postherpetic neuralgia (PHN) and posttraumatic neuropathy (PTN) patients. METHODS: Patients (18 to 80 y) with inadequately controlled moderate-to-severe pain received study medication (subcutaneous injection) every 4 weeks. PHN patients were randomized (3:2:2:3) to receive either placebo or one of 3 doses of fulranumab: 1 mg (1 mgQ4 wk), 3 mg (3 mgQ4 wk), or 10 mg (10 mgQ4 wk). PTN patients were randomized (1:1) to receive either placebo or fulranumab 10 mgQ4 wk. RESULTS: The US Food and Drug Administration placed a clinical hold (December 23, 2010) on all trials of antinerve growth factor drugs, including fulranumab, due to identified risks of osteonecrosis or rapidly progressing osteoarthritis; therefore, only 49 (of 150 planned) PHN patients and 34 (of 50 planned) PTN patients completed the DB efficacy evaluation. There was no significant difference (P>0.05, fulranumab vs. placebo) for change in 7-day average of daily pain intensity scores from DB baseline to end of 12-week DB efficacy phase in PHN or PTN patients (primary endpoint). No significant difference was found with fulranumab versus placebo (P>0.05) in other efficacy measures in either PHN or PTN patients. The most common treatment-emergent adverse events (>10% incidence) in PTN patients were sinusitis, carpal tunnel syndrome, and headache, whereas in PHN patients it was arthralgia. DISCUSSION: Fulranumab did not demonstrate efficacy in either PHN or PTN patients, but was generally well-tolerated in this small underpowered and abbreviated study.


Assuntos
Analgésicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neuralgia Pós-Herpética/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/efeitos adversos , Analgésicos/sangue , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Absorção Subcutânea , Falha de Tratamento , Adulto Jovem
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