Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 414
Filtrar
Mais filtros

Bases de dados
Tipo de documento
Intervalo de ano de publicação
1.
Headache ; 64(2): 179-187, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38017629

RESUMO

BACKGROUND: We evaluated galcanezumab for migraine prevention in patients who met International Classification of Headache Disorders, 3rd edition criteria for menstrually related migraine (MRM). METHODS: Patients were identified post hoc from three double-blind, randomized, phase 3 clinical trials in patients with episodic migraine. Patients completed a 1-month prospective baseline period and up to 6 months (EVOLVE-1 and -2, studies pooled) of double-blind treatment with galcanezumab (120 mg/month) or placebo. Menses and headache information were recorded by electronic daily diary. Patients with a migraine attack starting during the 5-day perimenstrual interval (first day of bleeding ± 2 days) for ≥2 of their first three diary-recorded menstrual cycles were categorized as having MRM. The primary efficacy measure was mean change in monthly migraine headache days from baseline, averaged over Months 4 through 6. Response rates, change in monthly perimenstrual migraine headache days, monthly non-perimenstrual migraine headache days, and quality of life were also assessed. RESULTS: Post hoc MRM analysis criteria were met by 462/1133 women (41%). Mean (standard deviation) baseline monthly migraine headache days were 9.7 (±3.1; n = 146) for galcanezumab-treated patients and 9.6 (±2.8; n = 316) for placebo-treated patients. The mean change (standard error [SE]) in migraine headache days over Months 4 through 6 was -5.1 days (±0.39) for galcanezumab versus -3.2 (±0.35) for placebo (p < 0.001). The mean change (SE) in perimenstrual migraine headache days over Months 4 through 6 was -0.75 days (±0.08) for galcanezumab versus -0.49 (±0.07) for placebo (p = 0.004). For migraine headache days outside the perimenstrual period, the mean change in migraine headache days was -4.6 (±0.38) for galcanezumab and -2.8 (±0.33) for placebo (p < 0.001). Improvements in response rates and the Migraine-Specific Quality of Life Questionnaire were also observed over Months 4 through 6. CONCLUSION: Galcanezumab was effective for migraine prevention in women with MRM.


Assuntos
Anticorpos Monoclonais Humanizados , Transtornos de Enxaqueca , Qualidade de Vida , Humanos , Feminino , Resultado do Tratamento , Estudos Prospectivos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Cefaleia , Método Duplo-Cego
2.
Phys Rev Lett ; 131(14): 145101, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37862644

RESUMO

We report the observation of a set of coherent high frequency electromagnetic fluctuations that leads to a turbulence induced self-regulating phenomenon in the DIII-D high bootstrap current fraction plasma. The fluctuations have frequency of 130-220 kHz, the poloidal wavelength and phase velocity are 16-30 m^{-1} and ∼30 km/s, respectively, in the outboard midplane with the estimated toroidal mode number n∼5-9. The fluctuations are located in the internal transport barrier (ITB) region at large radius and are experimentally validated to be kinetic ballooning modes (KBM). Quasilinear estimation predicts the KBM to be able to drive experimental particle flux and non-negligible thermal flux, suggesting its significant role in regulating the ITB saturation.

3.
Headache ; 63(5): 683-691, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36797223

RESUMO

OBJECTIVE: To evaluate changes in interictal burden with galcanezumab versus placebo in patients with episodic (EM) or chronic migraine (CM). BACKGROUND: The disruptive effects of migraine occur both during attacks (ictal period) and between attacks (interictal period), affecting work, school, family, and social life. Migraine clinical trials typically assess ictal burden endpoints, neglecting interictal burden. METHODS: CONQUER was a 3-month, double-blind study that randomized adult patients with EM or CM who had experienced failure of two to four standard-of-care migraine preventive medication categories to receive monthly galcanezumab (n = 232) or placebo (n = 230), followed by 3 months of open-label galcanezumab. The mean change in interictal burden, a secondary objective, was measured using the four-item Migraine Interictal Burden Scale (MIBS-4). The total score for MIBS-4 can range from zero to 12, with scores ≥5 indicating severe interictal burden. Post hoc analyses evaluated shifts in MIBS-4 severity categories and item-level improvement. RESULTS: The MIBS-4 total score indicated severe interictal burden at baseline (mean [SD]: all patients, 5.5 [3.5]; EM, 5.0 [3.4]; CM, 6.2 [3.5]). Reductions in the MIBS-4 score were significantly greater with galcanezumab versus placebo at Month 3 (mean [SE]: all patients -1.9 [0.2] vs. -0.8 [0.2], p < 0.0001; EM, -1.8 [0.3] vs. -1.1 [0.3], p = 0.033; CM, -1.8 [0.4] vs. -0.3 [0.4], p < 0.001), with further improvement at Month 6 after all patients had received galcanezumab (mean [SE]: all patients, -2.4 [0.2] vs. -2.0 [0.2]; EM, -2.3 [0.3] vs. -2.2 [0.3]; CM, -2.1 [0.4] vs. -1.5 [0.4]). The percentage of patients with severe interictal burden decreased substantially for the galcanezumab-treated patients, from 59% (137/232) at baseline to 27% (58/217) at Month 6 (EM from 51% [70/137] to 23% [30/131]; CM from 71% [67/95] to 33% [28/86]). CONCLUSION: In addition to the known efficacy of galcanezumab in the ictal period, these findings suggest treatment with galcanezumab results in a significant reduction in interictal burden.


Assuntos
Anticorpos Monoclonais Humanizados , Transtornos de Enxaqueca , Adulto , Humanos , Resultado do Tratamento , Método Duplo-Cego , Anticorpos Monoclonais Humanizados/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico
4.
Nature ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922491
5.
Gynecol Oncol ; 167(1): 3-10, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36085090

RESUMO

OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.


Assuntos
Carcinoma de Células Escamosas , Linfadenopatia , Linfonodo Sentinela , Neoplasias Vulvares , Carcinoma de Células Escamosas/patologia , Feminino , Virilha , Humanos , Excisão de Linfonodo/efeitos adversos , Linfonodos/patologia , Linfonodos/cirurgia , Linfadenopatia/patologia , Metástase Linfática/patologia , Recidiva Local de Neoplasia/patologia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias Vulvares/patologia
6.
Nature ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497408
7.
Parasitology ; : 1-9, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33612124

RESUMO

Ascaris lumbricoides and Ascaris suum are helminth parasites of humans and pigs, respectively. The life cycle of Ascaris sets it apart from the other soil-transmitted helminths because of its hepato-tracheal migration. Larval migration contributes to underestimated morbidity in humans and pigs. This migration, coupled with a lack of a murine model in which the Ascaris parasite might complete its life cycle, has undoubtedly contributed to the neglected status of the ascarid. Our knowledge of the epidemiology of adult worm infections had led us to an enhanced understanding of patterns of infection such as aggregation and predisposition; however, the mechanisms underlying these complex phenomena remain elusive. Carefully controlled experiments in defined inbred strains of mice ­ with enhanced recovery of larvae in tandem with measurements of cellular, histopathological and molecular processes ­ have greatly enhanced our knowledge of the early phase of infection, a phase crucial to the success or failure of adult worm establishment. Furthermore, the recent development of a mouse model of susceptibility and resistance, with highly consistent and diverging Ascaris larval burdens in the murine lungs, represents the extremes of the host phenotype displayed in the aggregated distribution of worms and provides an opportunity to explore the mechanistic basis that confers predisposition to light and heavy Ascaris infection. Certainly, detailed knowledge of the cellular hepatic and pulmonary responses at the molecular level can be accrued from murine models of infection and, once available, may enhance our ability to develop immunomodulatory therapies to elicit resistance to infection.

8.
Parasitology ; : 1-5, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34376259

RESUMO

Ascaris lumbricoides, the roundworm, and Trichuris trichiura, the whipworm, are human intestinal nematode parasites; both are soil-transmitted helminths, are often placed together in an epidemiological context and both remain neglected despite high prevalence. Our understanding of parasitic disease continues to be enhanced through animal models. Despite the similarities between whipworm and roundworm, there are key differences between the two species and these have influenced the application of their respective animal models. In the case of T. trichiura, the fact that a murine equivalent, T. muris completes its life cycle in a mouse model has greatly enhanced our knowledge of whipworm biology, pathogenicity and immunology. In contrast, A. lumbricoides and its porcine equivalent, Ascaris suum, lack a rodent model in which the life cycle is completed. However, evidence continues to accumulate demonstrating that mice represent useful models of early Ascaris infection, a key stage of the life cycle. The use of mouse models for both Ascaris and Trichuris has a long history with early pioneers discovering fundamental aspects of each parasite's biology. Novel technologies and perspectives, as outlined in this special issue, demonstrate how through the prism of mouse models, we can continue to explore the similarities and differences between roundworms and whipworms.

9.
Headache ; 60(2): 348-359, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31710104

RESUMO

OBJECTIVE: To evaluate onset of effect of galcanezumab in patients with episodic migraine. BACKGROUND: Galcanezumab is a monoclonal antibody that binds to calcitonin gene-related peptide and is indicated for preventive treatment of migraine. DESIGN/METHODS: Data on the primary outcome measure were analyzed from 2 previously published double-blind, Phase 3 studies (EVOLVE-1 [N = 858] and EVOLVE-2 [N = 915]) wherein adult patients with episodic migraine were randomized to receive monthly subcutaneous injections of galcanezumab 120 mg (with 240-mg loading dose) or 240 mg or placebo for up to 6 months. Monthly onset of effect was defined as the earliest month at which galcanezumab achieved and subsequently maintained statistical superiority to placebo on the mean change from baseline in the number of monthly migraine headache days (MHDs). If onset occurred in Month 1, weekly onset was evaluated and defined as the earliest week at which galcanezumab statistically separated from placebo and maintained statistical separation for remaining weeks in that month. Day of onset of effect was also analyzed, as were monthly and weekly onset, for occurrence of ≥50% reduction from baseline in number of MHDs. RESULTS: For both studies, change from baseline in monthly MHDs showed a statistically significant separation of galcanezumab from placebo at Month 1 and each subsequent month (each P < .001). Analysis of the first month for both studies indicated onset of effect in the first week, with galcanezumab-treated patients having significantly higher odds of having fewer MHDs in the first week (odds ratio [95% confidence interval] for EVOLVE-1, 2.71 [2.00, 3.66], and for EVOLVE-2, 2.88 [2.16, 3.86]; both P < .001) and each subsequent week compared with placebo-treated patients (P ≤ .004). Daily analysis showed onset of effect at Day 1 (first day after injection day). Galcanezumab also demonstrated superiority to placebo on occurrence of ≥50% reduction in MHDs starting at Week 1 (percentage of patients with 50% response in galcanezumab group vs placebo group for EVOLVE-1, 54.3% vs 32.4% [P < .001], and for EVOLVE-2, 59.4% vs 38.0% [P < .001]). CONCLUSION: Rapid onset of preventive effect on the first day after injection of galcanezumab was confirmed in both studies of episodic migraine.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade
10.
J Helminthol ; 94: e128, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32100653

RESUMO

Ascariasis is a neglected tropical disease, caused by Ascaris lumbricoides, affecting 800 million people worldwide. Studies focused on the early stage of parasite infection, occurring in the gut, liver and lungs, require the use of a mouse model. In these models, the porcine ascarid, Ascaris suum, is often used. The results obtained from these studies are then used to draw conclusions about A. lumbricoides infections in humans. In the present study, we sought to compare larval migration of A. suum and A. lumbricoides in mouse models. We used a previously developed mouse model of ascariasis, which consists of two mouse strains, where one mouse strain - C57BL/6J - is a model for relative susceptibility and the other - CBA/Ca - for relative resistance. Mice of both strains were infected with either A. suum or A. lumbricoides. The larval burden was assessed in two key organs, the liver and lungs, starting at 6 h post infection (p.i.) and ending on day 8 p.i. Additionally, we measured the larval size of each species (µm) at days 6, 7 and 8 p.i. in the lungs. We found that larval burden in the liver is significantly higher for A. lumbricoides than for A. suum. However, the inverse is true in the lungs. Additionally, our results showed a reduced larval size for A. lumbricoides compared to A. suum.


Assuntos
Ascaríase/parasitologia , Ascaris lumbricoides/fisiologia , Ascaris suum/fisiologia , Fígado/parasitologia , Pulmão/parasitologia , Carga Parasitária/estatística & dados numéricos , Animais , Modelos Animais de Doenças , Larva , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA
11.
J Helminthol ; 94: e191, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924909

RESUMO

Invasive species lose parasites in the process of invasion and tend to be less parasitized than conspecifics in the native range and sympatric native species in the invasive range (enemy release). We evaluated enemy release in an invasive freshwater fish in Ireland, common dace Leuciscus leuciscus, using helminth parasite community surveys at the core and front of the invasive range of common dace. Furthermore, we undertook a systematic literature review of helminth infection in common dace across its native range in Great Britain and Europe and invasive range in Ireland. The helminth parasite community survey revealed that invasive common dace were infected with fewer helminth species at the invasion front than at the core. Four helminth taxa - Acanthocephala, Monogenea, Digenea and Nematoda - were present in dace at the invasion core compared to only a single helminth species (Pomphorhynchus tereticollis) at the front. The systematic review revealed that invasive common dace in Ireland hosted fewer species of helminths than common dace in the native range. We report a total of three helminth species in common dace in Ireland compared to 24 in Great Britain and 84 in Continental Europe. Our results support the hypotheses that invasive populations are less parasitized than native populations and that more recently established populations host fewer parasites. However, we demonstrate that invasive species may continue to experience release from parasites long after initial invasion.


Assuntos
Cyprinidae/parasitologia , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/parasitologia , Helmintíase Animal/epidemiologia , Helmintos/isolamento & purificação , Espécies Introduzidas , Animais , Água Doce/parasitologia , Helmintos/classificação , Interações Hospedeiro-Parasita , Irlanda/epidemiologia , Inquéritos e Questionários
12.
Phys Rev Lett ; 123(22): 225002, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31868395

RESUMO

We report on the first direct comparisons of microtearing turbulence simulations to experimental measurements in a representative high bootstrap current fraction (f_{BS}) plasma. Previous studies of high f_{BS} plasmas carried out in DIII-D with large radius internal transport barriers (ITBs) have found that, while the ion energy transport is accurately reproduced by neoclassical theory, the electron transport remains anomalous and not well described by existing quasilinear transport models. A key feature of these plasmas is the large value of the normalized pressure gradient, which is shown to completely stabilize conventional drift-wave and kinetic ballooning mode instabilities in the ITB, but destabilizes the microtearing mode. Nonlinear gyrokinetic simulations of the ITB region performed with the cgyro code demonstrate that the microtearing modes are robustly unstable and capable of driving electron energy transport levels comparable to experimental levels for input parameters consistent with the experimental measurements. These simulations uniformly predict that the microtearing mode fluctuation and flux spectra extend to significantly shorter wavelengths than the range of linear instability, representing significantly different nonlinear dynamics and saturation mechanisms than conventional drift-wave turbulence, which is also consistent with the fundamental tearing nature of the instability. The predicted transport levels are found to be most sensitive to the magnetic shear, rather than the temperature gradients more typically identified as driving turbulent plasma transport.

13.
J Helminthol ; 94: e37, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30767800

RESUMO

The European badger (Meles meles) is Ireland's largest terrestrial carnivore. Since first being identified as a wildlife reservoir of bovine tuberculosis in 1974 there has been an increased research focus into the behaviour of these ecologically important mammals in the Republic of Ireland (ROI). However, to date there has never been an assessment of the helminth parasite community of Irish badgers. This study of 289 badgers found helminth infection to be endemic within the sample population and we report for the first time the prevalence, abundance, intensity and aggregation of helminth infection in ROI. Eight distinct helminth taxa were recorded: Aelurostrongylus falciformis, Crenosoma melesi, Eucoleus aerophilus, Species A, Strongyloides spp., Uncinaria criniformis, and two unidentifiable but morphologically distinct nematodes. All helminths belong to the taxon Nematoda, and this is the first report of an exclusively nematode community across the badger's Eurasian distribution. Infection was not significantly influenced by the host sex, region of origin or season of sampling.


Assuntos
Animais Selvagens/parasitologia , Helmintos/isolamento & purificação , Mustelidae/parasitologia , Animais , Feminino , Helmintos/classificação , Helmintos/genética , Irlanda , Masculino
14.
Cephalalgia ; 38(6): 1015-1025, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29310444

RESUMO

Background Safety findings from a Phase 2b study of galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, for prevention of migraine (NCT02163993) are reported here. Methods Patients aged 18-65 years with episodic migraine were evaluated in this multicenter, double-blind, randomized study. After randomization, 410 patients were administered 5, 50, 120 or 300 mg of galcanezumab or placebo subcutaneously once every 4 weeks for 12 weeks, followed by a post-treatment off-drug period lasting 12 weeks. Results Treatment-emergent adverse events (TEAEs) were primarily rated as mild to moderate. Serious adverse events reported in galcanezumab dose groups were appendicitis, Crohn's disease, suicidal ideation, and congenital ankyloglossia in an infant of a paternal pregnancy; each of these were reported by one patient. Adverse events leading to discontinuation with galcanezumab treatment were abdominal pain, visual impairment, and upper limb fracture, each reported by one patient. Treatment-emergent injection-site reactions were reported significantly more frequently ( p = 0.013) with galcanezumab (13.9%) than with placebo (5.8%). Injection-site pain was the most common injection-site reaction (galcanezumab 11.4%; placebo 2.9%, p = 0.004). Upper respiratory tract infection (galcanezumab 10.0%; placebo 8.8%) and nasopharyngitis (galcanezumab 7.0%; placebo 2.2%) also occurred more frequently with galcanezumab treatment. Potential hypersensitivity events were reported at similar frequencies in galcanezumab (3.3%) and placebo (5.1%) groups. Incidence of treatment-emergent anti-drug antibodies in galcanezumab dose groups (4.6% of patients during treatment period) did not appear to have any meaningful effects on safety, the pharmacokinetics of galcanezumab, or its ability to bind to the target ligand. Conclusion The results from this 3-month Phase 2b study support the initiation of larger Phase 3 trials of longer duration.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Transtornos de Enxaqueca/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
15.
Parasitology ; 144(1): 81-94, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26670118

RESUMO

Toxocara species infect a wide range of companion, domestic and wild animals as definitive and paratenic hosts, via multiple routes of transmission, producing long-lived tissue-inhabiting larvae and resistant eggs that can survive in the external environment. Therefore Toxocara and the disease it causes in humans, toxocariasis, represents an ideal aetiological agent for the development of the one health approach. However, despite increasing awareness of the public health significance of toxocariasis, gaps in our understanding of certain key aspects of the parasite's biology and epidemiology remain. These gaps hinder our ability to integrate research effort within the veterinary, medical and environmental disciplines. This review will highlight key deficits in our understanding of nine dimensions of Toxocara epidemiology and discuss a potential scenario to develop a more integrated, one health approach to improve our understanding of the prevention and control of this complex and cryptic zoonosis.


Assuntos
Interações Hospedeiro-Parasita , Toxocara/fisiologia , Toxocaríase/epidemiologia , Animais , Gerenciamento Clínico , Cães , Meio Ambiente , Saúde Global , Humanos , Saúde Pública , Toxocara/isolamento & purificação , Toxocara canis/isolamento & purificação , Toxocaríase/parasitologia , Toxocaríase/prevenção & controle , Zoonoses
16.
J Mater Sci Mater Med ; 27(4): 79, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26914710

RESUMO

This work presents a combined experimental-numerical framework for the biomechanical characterization of highly hydrated collagen hydrogels, namely with 0.20, 0.30 and 0.40% (by weight) of collagen concentration. Collagen is the most abundant protein in the extracellular matrix of animals and humans. Its intrinsic biocompatibility makes collagen a promising substrate for embedding cells within a highly hydrated environment mimicking natural soft tissues. Cell behaviour is greatly influenced by the mechanical properties of the surrounding matrix, but the biomechanical characterization of collagen hydrogels has been challenging up to now, since they present non-linear poro-viscoelastic properties. Combining the stiffness outcomes from rheological experiments with relevant literature data on collagen permeability, poroelastic finite element (FE) models were developed. Comparison between experimental confined compression tests available in the literature and analogous FE stress relaxation curves showed a close agreement throughout the tests. This framework allowed establishing that the dynamic shear modulus of the collagen hydrogels is between 0.0097 ± 0.018 kPa for the 0.20% concentration and 0.0601 ± 0.044 kPa for the 0.40% concentration. The Poisson's ratio values for such conditions lie within the range of 0.495-0.485 for 0.20% and 0.480-0.470 for 0.40%, respectively, showing that rheology is sensitive enough to detect these small changes in collagen concentration and thus allowing to link rheology results with the confined compression tests. In conclusion, this integrated approach allows for accurate constitutive modelling of collagen hydrogels. This framework sets the grounds for the characterization of related hydrogels and to the use of this collagen parameterization in more complex multiscale models.


Assuntos
Colágeno/química , Hidrogéis/química , Fenômenos Biomecânicos , Simulação por Computador , Análise de Elementos Finitos , Modelos Biológicos , Reologia , Engenharia Tecidual
17.
BMC Psychiatry ; 15: 65, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25886006

RESUMO

BACKGROUND: Olanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a cluster of symptoms termed post-injection delirium/sedation syndrome (PDSS) in a small percentage (~2%) of patients during clinical trials. The objective of this analysis was to evaluate the rate and clinical characteristics of PDSS since olanzapine LAI entered commercial use. METHODS: Cases of PDSS were identified from all reported adverse events during worldwide commercial use of olanzapine LAI through to 1 March 2014. Data sources included two ongoing post-marketing safety studies as well as spontaneously reported adverse events from routine clinical practice over a 5-year period (1 March 2009 to 1 March 2014). RESULTS: A total of 338 PDSS events were identified. Of these, 91% occurred within 1 hour of injection, and 52% of these occurred within 15 minutes. None of the PDSS events in this analysis were fatal, and most resolved within 72 hours. The most common symptoms (occurring in >30% of cases) were sedation (61%), confusion (56%), dysarthria (54%), somnolence (46%), dizziness (45%) and disorientation (35%). Overall, PDSS occurred with approximately 0.07% of injections and in 0.46-1.03% of patients (reporting and incidence rates from spontaneous reports and post-marketing safety studies, respectively). CONCLUSIONS: The PDSS events reported during routine clinical use of olanzapine LAI are generally similar in incidence and presentation to those reported in clinical trials. Caution should be applied when interpreting spontaneously reported rates of adverse events, however, due to potential under-reporting. Implemented risk-minimisation activities may contribute substantially to the identification and appropriate management of patients with PDSS in clinical practice.


Assuntos
Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Delírio/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Inconsciência/induzido quimicamente , Adulto , Antipsicóticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/uso terapêutico , Distúrbios do Sono por Sonolência Excessiva/induzido quimicamente , Tontura/induzido quimicamente , Disartria/induzido quimicamente , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Olanzapina , Fatores de Risco , Síndrome
18.
BMC Psychiatry ; 15: 278, 2015 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-26567159

RESUMO

BACKGROUND: Depot antipsychotics are a treatment option for medication nonadherence in patients with schizophrenia. Nonadherence can lead to increased relapse and hospitalization rates. This article reports hospitalization data before and after initiation of olanzapine long-acting injection (LAI), a depot antipsychotic. METHODS: Data were assessed from an ongoing, multinational, prospective, observational post-authorisation safety study being conducted to evaluate post-injection delirium/sedation syndrome (PDSS), an adverse reaction that can occur following injection of olanzapine LAI. Eligible patients were aged ≥18 years, diagnosed with schizophrenia, were prescribed olanzapine LAI, and lived outside the United States. Psychiatric hospitalization and medication data were collected retrospectively for the 6-month period before study entry and prospectively throughout the study. Paired t-tests and McNemar's tests were used to assess changes in hospitalization incidence and duration. Stepwise Cox proportional hazards models assessed factors associated with hospitalizations. Analyses were based on data from the first 3 years of the continuously enrolling study (N = 668). RESULTS: The average duration of olanzapine LAI exposure for all patients was 0.768 years. Of the 529 patients who received at least 1 injection of olanzapine LAI and were not hospitalized at study entry, 8.1% had at least 1 subsequent psychiatric hospitalization with a mean duration of 2.0 days. Of the 288 patients who had a >6-month follow-up, 8.3% had at least 1 post-baseline psychiatric hospitalization with a mean duration of 2.3 days. The incidence of hospitalizations in the 6-month period after treatment was significantly lower than that in the 6-month period prior to treatment (8.3 vs 32.6%, respectively; P < 0.001). Furthermore, mean hospitalization duration decreased from 11.5 days in the 6-month period before treatment to 2.3 days in the 6-month period after treatment (P < 0.001). Psychiatric hospitalization in the prior 12 months (P < 0.0001) and recreational drug use within 24 h of baseline visit (P = 0.015) were identified as potential predictors of time to first psychiatric hospitalization after beginning to take olanzapine LAI. At the time of interim analysis, 5 PDSS events had occurred, which was too few for a full analysis of those events. CONCLUSIONS: Results indicate a significant reduction in the incidence and days of hospitalization from the 6-month period before to the 6-month period after olanzapine LAI initiation, which suggests reduced relapse and hospitalization during treatment. Results should be interpreted with caution due to the observational nature of the study and use of retrospective baseline data.


Assuntos
Benzodiazepinas , Delírio/induzido quimicamente , Tempo de Internação/estatística & dados numéricos , Esquizofrenia , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Delírio/terapia , Feminino , Humanos , Hipnóticos e Sedativos , Injeções Intramusculares , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Olanzapina , Avaliação de Resultados em Cuidados de Saúde , Modelos de Riscos Proporcionais , Estudos Prospectivos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Prevenção Secundária/métodos , Fatores de Tempo , Estados Unidos
19.
J Acoust Soc Am ; 137(5): EL355-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25994733

RESUMO

The image source method in acoustics is well known to simulate reverberation. It has also been recently used for characterization of seafloor sound-speed structure. The idea is to detect image sources by imaging techniques to obtain information about the environment. In this paper, the idea is to use the detection of image sources to remove reflections from plane interfaces in recorded signals and perform imaging with this filtered signal. This imaging process highlights scatterers because their wave front shapes are different than those from plane interfaces. Applications can be in seafloor buried object detection or scattering analysis from interface roughnesses or volume heterogeneities.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA