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1.
BJOG ; 127(1): 47-56, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31512355

RESUMO

OBJECTIVE: To describe the epidemiology of rheumatic heart disease (RHD) in pregnancy in Australia and New Zealand (A&NZ). DESIGN: Prospective population-based study. SETTING: Hospital-based maternity units throughout A&NZ. POPULATION: Pregnant women with RHD with a birth outcome of ≥20 weeks of gestation between January 2013 and December 2014. METHODS: We identified eligible women using the Australasian Maternity Outcomes Surveillance System (AMOSS). De-identified antenatal, perinatal and postnatal data were collected and analysed. MAIN OUTCOME MEASURES: Prevalence of RHD in pregnancy. Perinatal morbidity and mortality. RESULTS: There were 311 pregnancies associated with women with RHD (4.3/10 000 women giving birth, 95% CI 3.9-4.8). In Australia, 78% were Aboriginal or Torres Strait Islander (60.4/10 000, 95% CI 50.7-70.0), while in New Zealand 90% were Maori or Pasifika (27.2/10 000, 95% CI 22.0-32.3). One woman (0.3%) died and one in ten was admitted to coronary or intensive care units postpartum. There were 314 births with seven stillbirths (22.3/1000 births) and two neonatal deaths (6.5/1000 births). Sixty-six (21%) live-born babies were preterm and one in three was admitted to neonatal intensive care or special care units. CONCLUSION: Rheumatic heart disease in pregnancy persists in disadvantaged First Nations populations in A&NZ. It is associated with significant cardiac and perinatal morbidity. Preconception planning and counselling and RHD screening in at-risk pregnant women are essential for good maternal and baby outcomes. TWEETABLE ABSTRACT: Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity.


Assuntos
Complicações Cardiovasculares na Gravidez/etnologia , Cardiopatia Reumática/etnologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Renda , Havaiano Nativo ou Outro Ilhéu do Pacífico/etnologia , Nova Zelândia/epidemiologia , Nova Zelândia/etnologia , Northern Territory/epidemiologia , Northern Territory/etnologia , Paridade , Gravidez , Prevalência , Estudos Prospectivos , Adulto Jovem
2.
Eur J Vasc Endovasc Surg ; 49(3): 344-52, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25631458

RESUMO

OBJECTIVES: This study sought to compare the local tissue response and subsequent volume of intimal hyperplasia (IH) that develops throughout the maturation of an arteriovenous fistula created using continuous/interrupted polypropylene with that of a novel, metal-alloy, penetrating anastomotic clip device. MATERIALS AND METHODS: Forty-six fistulae were created in 23 sheep under a paired design using the nitinol U-Clip (n = 23) in one hind limb and continuous (n = 20) or interrupted (n = 3) polypropylene suture for the other. Animals were killed at 4 (n = 3), 14 (n = 3), 28 (n = 10), 42 (n = 3), and 180 (n = 4) days. Histological sections were evaluated for quantitative histology and immunohistochemistry. RESULTS: Compared with continuous polypropylene, U-Clip specimens demonstrated less intima-media area per unit length (IMA/L), proliferating cells, and tissue necrosis at all time points (MANOVA, F = 9.8-24.1, all p ≤ .005; observed power >82%). Specifically, values of IMA/L were reduced by 5% (p = .97), 37% (p = .02), 33% (p < .01), 9% (p = .42), and 14% (p = .22) at the time points of 4, 14, 28, 42, and 180 days respectively. Proliferating cells were reduced by 75% (p < .01), 72% (p = .03), 76% (p = .03), 27% (p = .31), and 60% (p = .01) and tissue necrosis by 67% (p < .01), 58% (p = .02), 40% (p = .33), 21% (p = .43), 77% (p = .11). In a 28-day comparison between U-Clip and interrupted polypropylene the U-Clip group demonstrated a 4% (p = .65) reduction in IMA/L, 74% (p < .01) in proliferating cells and 49% (p < .05) in tissue necrosis. CONCLUSIONS: These results provide evidence of reduced local tissue necrosis, proliferating cells, and IH, favouring arteriovenous fistulae created using the U-Clip anastomotic device over conventional polypropylene suture techniques most evident over the first 4 weeks.


Assuntos
Ligas , Derivação Arteriovenosa Cirúrgica , Artéria Femoral/cirurgia , Veia Femoral/cirurgia , Músculo Esquelético/irrigação sanguínea , Neointima , Instrumentos Cirúrgicos , Técnicas de Sutura , Animais , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/instrumentação , Derivação Arteriovenosa Cirúrgica/métodos , Proliferação de Células , Desenho de Equipamento , Artéria Femoral/patologia , Veia Femoral/patologia , Membro Posterior , Hiperplasia , Modelos Animais , Necrose , Polipropilenos , Ovinos , Técnicas de Sutura/efeitos adversos , Técnicas de Sutura/instrumentação , Suturas , Fatores de Tempo
3.
Ann Oncol ; 24(7): 1936-1942, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23553058

RESUMO

BACKGROUND: In phase II trials of cytotoxic agents, a multinomial phase II design incorporating early progression and response end points was shown to perform more efficiently than designs based only on response. We undertook a study to evaluate the performance of these designs in trials of targeted agents using the actual phase II data. PATIENTS AND METHODS: Using best response data from sequentially enrolled patients in 15 NCIC Clinical Trials Group and 7 European Organization for Research and Treatment of Cancer trials of targeted agents, we determined that trials would have been stopped at the end of stage I of accrual by applying rules generated by the multinomial and Fleming designs. Two variants of the multinomial design were studied: to stop accrual after stage I of enrolment, Variant A required either response or progression criteria to be met, whereas Variant B required that both response and progression criteria to be met. RESULTS: Using early progression, null/alternate hypotheses of 60% and 40% (60/40), the multinomial A variant recommended early stopping more often than the Fleming design. In most of the cases, this recommendation was correct given the final trial outcome. In contrast, the multinomial B variant never led to recommendations for early stopping and changing progression hypotheses did not improve the performance of this design. CONCLUSIONS: The multinomial A design using 60/40 hypotheses carried out better than the Fleming design in appropriately stopping trials of inactive targeted agents early. The multinomial B design was not useful for early stopping decisions. The multinomial A design may be favored over response-based designs in phase II trials of targeted agents.


Assuntos
Ensaios Clínicos Fase II como Assunto/métodos , Término Precoce de Ensaios Clínicos , Neoplasias/tratamento farmacológico , Humanos , Terapia de Alvo Molecular , Avaliação de Programas e Projetos de Saúde
4.
Osteoporos Int ; 24(10): 2581-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23563933

RESUMO

SUMMARY: Fractures in post-menopausal osteoporosis cause significant morbidity; however, animal models for post-menopausal fracture healing lack the effect of ageing. Therefore, we developed a model using aged animals with chronic oestrogen deficiency, which demonstrates inferior fracture repair (decreased healing histologically, bone mineral density and content and strength). This novel model may help develop molecular strategies for osteoporotic fracture repair. INTRODUCTION: The femur is susceptible to damage by both systemic conditions such as osteoporosis and locally by traumatic injury. The capacity for fracture repair decreases with age, while the risk of fracture increases. As studies of osteoporotic fracture healing in rats traditionally use a period of 3 months or less of oestrogen deficiency prior to fracturing, we aimed to establish a osteoporosis model in rats with chronic oestrogen deficiency by 12 months to better mimic human female osteoporosis. METHODS: Seventy female Sprague-Dawley rats (10 weeks old) were ovariectomised or sham operated and housed for 12 months. The right femur was fractured by way of an open osteotomy and fixed with an intramedullary Kirschner wire. Animals were sacrificed at 1, 3 and 6 weeks for radiography, dual-energy X-ray absorptiometry, tensile testing and histology. RESULTS: Bone mineral density and bone mineral content were lower by 60 and 63 %, respectively, (p < 0.05) in the bilaterally ovariectomized (OVX) groups than those in the sham groups at 6 weeks in the right fractured femurs. Maximum breaking force of the OVX group was lower than that of the sham group, with the greatest difference seen at 6 weeks following osteotomy. Histologically, the OVX groups demonstrated a delay in cellular differentiation within the fracture callus and the presence of bone resorption. The sham animals had a superior histological healing pattern with an Allen score of 4 at 6 weeks compared to a score of 1 for the OVX groups (p < 0.01). CONCLUSIONS: Long-term ovariectomy has a deleterious effect on fracture healing in a rodent model.


Assuntos
Estrogênios/deficiência , Fraturas do Fêmur/fisiopatologia , Consolidação da Fratura/fisiologia , Fraturas por Osteoporose/fisiopatologia , Absorciometria de Fóton , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Densidade Óssea/fisiologia , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/patologia , Calo Ósseo/fisiopatologia , Modelos Animais de Doenças , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/patologia , Osteoporose/fisiopatologia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/patologia , Ovariectomia , Ratos , Ratos Sprague-Dawley , Estresse Mecânico
5.
Int J Sports Med ; 34(1): 74-80, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22893324

RESUMO

Platelet Rich Plasma (PRP) therapies require blood to be processed prior to application, however, the full assessment of the output of platelet sequestration devices is lacking. In this study the products of the Autologous Fluid Concentrator (Circle BiologicsTM, Minneapolis, MN) and the Gravitational Platelet Separation System (GPS, Biomet, Warsaw, IN, USA) were evaluated in terms of platelet viability and PRP constituents. The AFC and GPS produced 6.4 (±1.0) ml and 6.3 (±0.4) ml of PRP, with platelet recovery of 46.4% (±14.7%) and 59.8% (±24.2%) producing fold increases of platelets of 4.19 (±1.62) and 5.19 (±1.62), respectively. Fibrinogen concentration was increased above baseline PPP produced with the AFC. pH was lower for both of the processed samples than for whole blood. White Blood Cell count was increased around 5 fold. Functional tests showed preserved viability with both devices. This represents essential knowledge that every treating physician should have before they can confidently administer PRP therapy produced by any method. These are the first published results of platelet function for the GPS system and the first performance results of the AFC system. The PRP produced is classified according to broad classifications as Leukocyte-PRP (L-PRP) for both devices.


Assuntos
Plaquetas/metabolismo , Fibrinogênio/metabolismo , Plasma Rico em Plaquetas/química , Separação Celular/métodos , Sobrevivência Celular , Desenho de Equipamento , Humanos , Concentração de Íons de Hidrogênio , Contagem de Leucócitos , Contagem de Plaquetas , Testes de Função Plaquetária
6.
Ann Oncol ; 23(1): 238-244, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21447615

RESUMO

BACKGROUND: The purpose of the study was to assess the safety, tolerability, recommended phase II dose (RPTD), and preliminary antitumor activity of the combination of carboplatin-paclitaxel (Taxol)-temsirolimus. MATERIALS AND METHODS: Patients with solid malignancies suitable for carboplatin-paclitaxel (CP) chemotherapy and two or less prior lines of chemotherapy received 15, 20, or 25 mg of temsirolimus per week with CP given every 21 days. Thirty-eight eligible patients were entered into six dose levels with the first two levels administering temsirolimus on days 8 and 15 and the subsequent four dose levels switching to days 1 and 8 temsirolimus administration. RESULTS: Days 8 and 15 administration of temsirolimus was not feasible due to myelosuppression on day 15. CP on day 1 with temsirolimus on days 1 and 8 was well tolerated. Dose-limiting toxicity (DLT) was grade 4 thrombocytopenia (n=2) and grade 3 fatigue (n=1). Relative dose intensities for carboplatin, paclitaxel, and temsirolimus at the RPTD were 92%, 82%, and 56%, respectively. Non-DLT treatment-related adverse events occurring in >20% of patients included fatigue, mucositis, alopecia, neuropathy, nausea, neutropenia, thrombocytopenia, and infection. Grade 3/4 non-hematological toxicity was rare. Partial responses (PRs) and disease stabilization were seen in 46% and 49% of patients, respectively. Nine of 11 (82%) endometrial cancer patients had objective PRs. CONCLUSION: Carboplatin-paclitaxel-temsirolimus is well tolerated and the RPTD is carboplatin area under the curve 5 mg/ml/min, paclitaxel 175 mg/m2, both given on day 1 with temsirolimus 25 mg on days 1 and 8.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados
7.
Eur J Vasc Endovasc Surg ; 43(2): 224-31, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22104322

RESUMO

OBJECTIVES: The aim of this study was to create an ovine arteriovenous fistula (AVF) model which would closely replicate a human forearm fistula and use this to quantify the degree of intimal hyperplasia in those created with the U-Clip compared to a conventional sutured anastomosis. MATERIALS AND METHODS: Twenty AVFs were created in 10 Border Leicester-Merino sheep between the superficial femoral artery and vein of each hind limb. On one side the U-Clip and on the other a continuous polypropylene suture was used to perform the anastomosis. The animals were sacrificed at 2 (n = 3), 4 (n = 4), 6 (n = 3) weeks and histological slices were taken of each AVF in cross section to determine the intimal media area per unit length (IMA/L). RESULTS: Intimal hyperplasia (IH) was observed at all time points with one AVF found occluded with thrombus at the time of harvest. The IMA/L was significantly lower in the U-Clip groups by 24% at 2 weeks, 32% at 4 weeks and 23% at 6 weeks (Two-way ANOVA, p = 0.019, observed power = 0.825, time or side p ≥ 0.766, type p = 0.001; Paired t-test, p < 0.001 between matched anastomotic types). Time taken to perform the anastomosis was similar between the two anastomotic techniques (Polypropylene 14(8-18) vs. U-Clip 15.3(11-23) min; p = 0.47). CONCLUSION: This ovine AVF model results in IH similar to that seen in a human AVF. The IH that occurs with the U-Clip is less than that of continuous polypropylene suture.


Assuntos
Ligas , Anastomose Cirúrgica/instrumentação , Fístula Arteriovenosa/cirurgia , Instrumentos Cirúrgicos , Suturas , Túnica Íntima/patologia , Anastomose Cirúrgica/métodos , Animais , Modelos Animais de Doenças , Hiperplasia/patologia , Ovinos
8.
Heart Lung Circ ; 21(10): 632-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22726405

RESUMO

Three priority areas in the prevention, diagnosis and management of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) were identified and discussed in detail: 1. Echocardiography and screening/diagnosis of RHD ­ Given the existing uncertainty it remains premature to advocate for or to incorporate echocardiographic screening for RHD into Australian clinical practice. Further research is currently being undertaken to evaluate the potential for echocardiography screening. 2. Secondary prophylaxis ­ Secondary prophylaxis (long acting benzathine penicillin injections) must be seen as a priority. Systems-based approaches are necessary with a focus on the development and evaluation of primary health care-based or led strategies incorporating effective health information management systems. Better/novel systems of delivery of prophylactic medications should be investigated. 3. Management of advanced RHD ­ National centres of excellence for the diagnosis, assessment and surgical management of RHD are required. Early referral for surgical input is necessary with multidisciplinary care and team-based decision making that includes patient, family, and local health providers. There is a need for a national RHD surgical register and research strategy for the assessment, intervention and long-term outcome of surgery and other interventions for RHD.


Assuntos
Atenção à Saúde/métodos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Atenção Primária à Saúde/métodos , Cardiopatia Reumática , Doença Aguda , Antibacterianos/uso terapêutico , Austrália/epidemiologia , Congressos como Assunto , Atenção à Saúde/normas , Feminino , Humanos , Masculino , Penicilina G Benzatina/uso terapêutico , Atenção Primária à Saúde/normas , Febre Reumática/diagnóstico , Febre Reumática/epidemiologia , Febre Reumática/prevenção & controle , Febre Reumática/terapia , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/epidemiologia , Cardiopatia Reumática/prevenção & controle , Cardiopatia Reumática/terapia
9.
Br J Cancer ; 104(5): 756-62, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21285985

RESUMO

BACKGROUND: SB939 is an orally available, competitive histone deacetylase (HDAC) inhibitor selective for class I, II and IV histone deacetylases. Preclinical evaluation of SB939 revealed a profile suggesting improved efficacy compared to other HDAC inhibitors. This phase I study was carried out to determine the safety, dose-limiting toxicity, recommended phase II dose (RPTD), as well as pharmacokinetic (PK) and pharmacodynamic (PD) profiles of SB939 in a daily × 5 schedule in advanced solid tumours. METHODS: Sequential dose-escalating cohorts of patients were enrolled into 8 dose levels. At dose level 1, SB939 was taken on days 1-3 and 15-17 every 4 weeks, then on days 1-5 and 15-19 for other dose levels. Detailed PK sampling was performed in cycle 1, days 1 and 5. Peripheral blood mononuclear cells (PBMCs) were collected on cycle 1 at various time points for determination of acetylated histone H3 (AcH3) levels. RESULTS: In total, 38 patients received a total of 96 cycles of treatment. The maximal administered dose was 90 mg and the RPTD was 60 mg given 5 consecutive days every 2 weeks. The most frequent non-hematologic adverse events (AEs) of at least possible attribution to SB939 were fatigue, nausea, vomiting, anorexia and diarrhoea. Pharmacokinetic analysis showed dose-proportional increases in AUC across the doses evaluated. Elimination half-life was 5.6-8.9 h. There was no clear relationship between AcH3 changes and dose level or anti-tumour response. CONCLUSIONS: SB939 is well tolerated in patients with advanced solid tumours. The RPTD of this drug is 60 mg on a schedule of 5 consecutive days every 2 weeks. The toxicities of SB939 are consistent with other HDAC inhibitors.


Assuntos
Antineoplásicos/uso terapêutico , Benzimidazóis/uso terapêutico , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/farmacocinética , Neoplasias/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Benzimidazóis/farmacocinética , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Inibidores de Histona Desacetilases/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/metabolismo , Vômito/induzido quimicamente
10.
Cleft Palate Craniofac J ; 48(5): 532-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21091369

RESUMO

OBJECTIVE: To investigate the use of intravenous ketorolac and iliac crest bupivacaine infusion in the management of iliac crest donor-site pain in the pediatric cleft population. The null hypothesis was there is no difference with respect to pain scores between ketorolac and iliac crest bupivacaine infusion as analgesic adjuncts to intravenous opioids. METHODS: A total of 54 children and adolescents (27 boys, 27 girls) undergoing alveolar cleft repair or Le Fort I osteotomy were assigned randomly in a prospective, single-blinded fashion to one of three groups: intravenous ketorolac plus iliac crest normal saline infusion, intravenous ketorolac plus iliac crest bupivacaine infusion, or iliac crest bupivacaine infusion alone. Iliac crest infusions and ketorolac were administered for 48 hours or until discharge, whichever occurred first. All patients received morphine via a patient-controlled analgesia device. MAIN OUTCOME MEASURE(S): Primary outcome was pain score, and secondary outcomes were morphine consumption and satisfaction scores. RESULTS: Pain scores, morphine consumption, and satisfaction scores were not significantly different among groups. Estimated costs were significantly higher for bupivacaine infusion than intravenous ketorolac. CONCLUSIONS: Iliac crest donor-site pain is well managed in this patient population. Intravenous ketorolac and iliac crest bupivacaine infusion provide comparable analgesia for iliac crest bone graft donor-site pain in children and adolescents.


Assuntos
Anestésicos Locais/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Transplante Ósseo , Bupivacaína/uso terapêutico , Fissura Palatina/cirurgia , Ílio/transplante , Cetorolaco/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Adolescente , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Bupivacaína/administração & dosagem , Criança , Feminino , Humanos , Infusões Intravenosas , Cetorolaco/administração & dosagem , Masculino , Morfina/administração & dosagem , Morfina/uso terapêutico , Osteotomia de Le Fort , Medição da Dor , Satisfação do Paciente , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento
11.
Vet Comp Orthop Traumatol ; 24(3): 197-204, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21373716

RESUMO

OBJECTIVES: The bone-patellar tendon-bone complex is routinely harvested for anterior cruciate ligament reconstruction in humans. Patella infera may ensue. However, the contribution from resection of the central one-third of the patellar tendon (PT) to potentially altered patellofemoral kinematics, in addition to those induced by a positional shift of the patella, are yet to be distinguished. Objectives of this study were to characterize changes in intraoperative patellar kinematics and PT length in nine sheep immediately following unilateral resection of the central one-third PT, and again at six, 12 and 24 weeks postoperatively. METHODS: Following implantation of bone-screws into the patella and tibia, electromagnetic receivers were anchored to these, and then passively-induced, unloaded patellar kinematics were captured. Patellar kinematics were referenced to the tibial coordinate frame and analysed using non-parametric tests (Wilcoxon Signed Rank Test). RESULTS: Resection alone did cause significant alteration in kinematics at the time of surgery (p <0.05). Postoperatively, a mean increase in PT length of 2.6 mm was detected in the operated stifles, reflected partly as a net 2.8 mm proximal patellar shift (p <0.001). This was accompanied by a mean net six degree medial shift in the patellar tilt pattern (p <0.001). Significant changes to patellar spin in the latter parts of flexion were also observed (p <0.005). Kinematic and length changes did not recover up to 24 weeks postoperatively. CLINICAL SIGNIFICANCE: The data obtained in this study suggests that both the patellar height and integrity of the PT are important determinants of patellar kinematics in the ovine stifle joint.


Assuntos
Patela/anatomia & histologia , Patela/fisiologia , Ligamento Patelar/cirurgia , Ovinos/cirurgia , Joelho de Quadrúpedes/cirurgia , Animais , Fenômenos Biomecânicos , Masculino , Projetos Piloto , Reprodutibilidade dos Testes
12.
Lung Cancer ; 147: 115-122, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32688194

RESUMO

BACKGROUND: The Lung Cancer Screening Trial demonstrated improved overall survival (OS) and lung cancer specific survival (LCSS), likely due to finding early-stage NSCLC. The purpose of our investigation is to evaluate whether long-term surveillance strategies (4+ years after surgical resection of the initial lung cancer(1LC)) would be beneficial in NSCLC patients by assessing the rates of second lung cancers(2LC) and the OS/LCSS in patients undergoing definitive surgery in 1LC as compared to 2LC (>48 months after 1LC) populations. METHODS: SEER13/18 database was reviewed for patients during 1998-2013. Log-rank tests were used to determine the OS/LCSS differences between the 1LC and 2LC in the entire surgical group(EG) and in those having an early-stage resectable tumors (ESR, tumors <4 cm, node negative). Joinpoint analysis was used to determine rates of second cancers 4-10 year after 1LC using SEER-9 during years 1985-2014. RESULTS: The rate of 2LCs was significantly less than all other second cancers until 2001 when the incidence of 2LCs increased sharply and became significantly greater than all other second cancers in females starting in year 2005 and in men starting in year 2010. OS/LCSS, adjusted for propensity score by using inverse probability weighting, demonstrated similar OS, but worse LCSS for 2LCs in the EG, but similar OS/LCSSs in the ESR group. CONCLUSION: Because the rate of 2LCs are increasing and because the OS/LCSS of the 1LC and 2LC are similar in early-stage lesions, we feel that continued surveillance of patients in order to find early-stage disease may be beneficial.


Assuntos
Neoplasias Pulmonares , Segunda Neoplasia Primária , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Estadiamento de Neoplasias , Segunda Neoplasia Primária/epidemiologia , Pneumonectomia , Modelos de Riscos Proporcionais , Programa de SEER
13.
Ann Oncol ; 19(4): 746-51, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18056648

RESUMO

BACKGROUND: The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer. PATIENTS AND METHODS: This was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered orally twice daily continuously. Primary end point was prostate-specific antigen (PSA) 'response' defined as a > or =50% decrease for > or =4 weeks. RESULTS: In all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance status was zero or one in 19 and 9 patients. Two patients had no metastases, and 26 had bone and/or lymph node disease. A median of two cycles (range 1-8) was delivered. Adverse events were typical for sorafenib. The PSA response rate was 3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one patient (baseline = 10 000 and nadir = 1643 microg/l). No measurable disease responses occurred in eight patients. Time to PSA progression was 2.3 months (95% CI 1.8-6.4). Of 16 patients who discontinued sorafenib and then did not receive any immediate therapy, 10 had postdiscontinuation PSA declines of 7%-52%. CONCLUSIONS: Sorafenib has limited activity using current PSA criteria. The declines in PSA observed on treatment discontinuation indicate an effect on PSA production/secretion. Further study may be warranted but needs to consider the limitations of PSA as an indicator of progression and response.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Antineoplásicos/administração & dosagem , Benzenossulfonatos/administração & dosagem , Biomarcadores Tumorais/análise , Canadá , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/irrigação sanguínea , Neoplasias Hormônio-Dependentes/química , Neoplasias Hormônio-Dependentes/imunologia , Neoplasias Hormônio-Dependentes/patologia , Neovascularização Patológica/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/química , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Sorafenibe , Resultado do Tratamento
14.
Bone Marrow Transplant ; 40(8): 759-64, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17680015

RESUMO

Long-term survivors after autologous peripheral blood stem cell transplantation (APBSCT) for lymphoma or Hodgkin's disease are known to have a high risk of developing myelodysplastic syndrome (MDS), but the risk of MDS is not clear for patients transplanted for myeloma. We reviewed the outcomes for 82 myeloma patients who underwent APBSCT at our center. The group included 47 men and 35 women of median age 56 years (range: 37-74 years). Median time from diagnosis to APBSCT was 8.2 months (range: 2.6-86.1 months). Before coming to transplantation, 28% had received oral melphalan (MEL), 98% received other chemotherapy and 34% received radiation. A single APBSCT was provided for 68, and 32% underwent APBSCT more than once. High-dose MEL alone was used as the preparative regimen for 83%, and the remainder received at least one APBSCT with a more intensive preparative regimen. Ten patients (12%) developed MDS. The 5-year cumulative incidence is 18% (95% confidence interval, 9-30%). There were no demographic factors associated with an increased risk of developing MDS. Median survival after the diagnosis of MDS was 18 months. There is a relatively high risk of MDS after APBSCT for myeloma, and optimal therapy has not been established for these patients.


Assuntos
Mieloma Múltiplo/cirurgia , Síndromes Mielodisplásicas/etiologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo
15.
J Biomed Mater Res A ; 80(2): 435-43, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17013857

RESUMO

An initial study showed that morselized human bone grafts were osteoconductive and osteoinductive when implanted in nude rat tibial window defects, and 25 kGy of gamma-irradiation significantly reduced those properties. The mechanism of the osteoinductivity and the influence of gamma-irradiation required further investigation. In this study we assessed the paraffin sections of seven morselized human bone grafts implanted into rat tibial defects for 3 weeks after being treated with 0, 15, or 25 kGy gamma-radiation respectively. Osteoclast-like cell counting and protein expressions of bone morphogenetic protein-7 (BMP-7), core binding factor alpha1 (CBFA1), and proliferating cell nuclear antigen (PCNA) were investigated and the positive signals were quantitatively analyzed. More new bone formation was observed in the 0 and 15 kGy groups compared with 25 kGy groups. The newly formed bones were found mainly from the intact cortex into the defects bridged by the implanted grafts. A dense staining of BMP-7 and CBFA1 was noted in the osteoblast-like cells in those areas. The BMP-7 and CBFA1 staining was also seen in the cells surrounding the implanted grafts in the centre areas of the defects in distance from the intact cortex. Quantitative analysis of immunohistochemical staining of the centre areas of the defects showed that gamma-irradiation (15 and 25 kGy) significantly reduced the expression of CBFA1 and BMP-7. In conclusion, morselized human bone grafts may contain some factors, which induced osteoblast lineage differentiation and bone formation and gamma-irradiation damages those bone inducing factors.


Assuntos
Proteínas Morfogenéticas Ósseas/análise , Transplante Ósseo , Subunidade alfa 1 de Fator de Ligação ao Core/análise , Raios gama/efeitos adversos , Osteogênese/efeitos da radiação , Animais , Proteína Morfogenética Óssea 7 , Proteínas Morfogenéticas Ósseas/efeitos da radiação , Contagem de Células , Subunidade alfa 1 de Fator de Ligação ao Core/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Masculino , Osteoclastos/citologia , Osteoclastos/efeitos da radiação , Ratos , Ratos Endogâmicos , Tíbia , Transplante Heterólogo
16.
Proc Inst Mech Eng H ; 221(5): 489-98, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17822151

RESUMO

Cartilage has an extremely poor capacity to heal, which has lead to intensive research into biomaterials and tissue engineering for the purpose of regenerating cartilage in vivo. Many of these techniques have shown great promise in vitro; however, the results do not always carry across to the in-vivo scenario. Healthy cartilage autografts often do not integrate with the adjacent cartilage, suggesting that cartilage is rarely capable of healing even under ideal conditions. It is hypothesized in this study that the surgical creation of defects in cartilage causes significant damage to the adjacent tissues, leading to further degradation of the cartilage and poor outcome for the repair in general. This study compares the healing response of osteochondral defects created with either a punch or a drill in the weight-bearing region of the sheep knee at 4 and 26 weeks following surgery. The use of a drill to create the defect creates a more aggressive inflammatory response at 4 weeks compared with a punch. However, by 26 weeks, defects created with a punch scored higher on the O'Driscoll cartilage grading scale. Tissue damage at the time of surgery plays an important part in the sequence of events for healing of cartilage defects. This knowledge will help to characterize and refine the ovine model for cartilage regeneration and may have an influence on surgical technique and instrumentation for clinical cartilage repair.


Assuntos
Cartilagem Articular/patologia , Cartilagem Articular/fisiopatologia , Modelos Animais de Doenças , Fraturas de Cartilagem/patologia , Fraturas de Cartilagem/fisiopatologia , Cicatrização/fisiologia , Animais , Cartilagem Articular/lesões , Masculino , Ovinos
17.
Violence Vict ; 22(1): 52-70, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17390563

RESUMO

While sexual victimization continues to be a problem on college campuses, recent attention has been drawn to understanding gender differences in victimization rates and consequences. To date, these studies remain relatively few in number. The current study surveyed 651 male and female undergraduate students about unwanted sexual experiences during 1 academic year. Comparison of men and women revealed expected differences in incidence rates, with women reporting higher rates of unwanted contact. Within the subsample of reported victims, however, there was gender similarity in terms of the context of unwanted sexual experiences. Analyses also revealed the negative consequences of these experiences for both men and women and low rates of disclosure regardless of gender. Across the full sample of students surveyed, there were interesting gender differences in knowledge of campus support services, with women more likely to have attended a prevention program and to have indicated greater knowledge of rape crisis services.


Assuntos
Coito/psicologia , Vítimas de Crime/estatística & dados numéricos , Relações Interpessoais , Estupro/estatística & dados numéricos , Serviços de Saúde para Estudantes/organização & administração , Estudantes/estatística & dados numéricos , Adulto , Vítimas de Crime/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Estupro/psicologia , Fatores de Risco , Fatores Sexuais , Percepção Social , Estudantes/psicologia , Inquéritos e Questionários , Estados Unidos/epidemiologia , Universidades , Saúde da Mulher
18.
J Perinatol ; 37(3): 288-290, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27831548

RESUMO

OBJECTIVE: Screening for critical congenital heart disease (CCHD) using pulse oximetry has been endorsed by the American Academy of Pediatrics and the American Heart Association. The recommended screening requires two saturation readings. We sought to determine the incidence of undetected CCHD in Tennessee for the 2 years following implementation of an algorithm that assigned an immediate pass to a single lower extremity saturation of 97% or higher. STUDY DESIGN: State Genetic Screening records and reports of missed cases from the Tennessee Initiative for Perinatal Quality Care were used to determine if CCHD cases were missed by the new screening algorithm. RESULT: During the study, 232 infants failed the screen with 51 or 22% true positives, 13 infants had undetected CCHD (10 coarctations, 2 anomalous veins and 1 Tetralogy of Fallot). CONCLUSION: This approach eliminated over 150 000 pulse oximetry determinations in Tennessee without affecting the ability of pulse oximetry to detect CCHD before discharge.


Assuntos
Erros de Diagnóstico/estatística & dados numéricos , Cardiopatias Congênitas/epidemiologia , Triagem Neonatal/métodos , Oximetria/estatística & dados numéricos , Algoritmos , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Triagem Neonatal/economia , Assistência Perinatal/normas , Tennessee/epidemiologia
19.
Plast Reconstr Surg ; 139(5): 1084-1089, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28445356

RESUMO

BACKGROUND: Breast augmentation surgery poses many challenges, and meeting the patient's expectations is one of the most important. Previous reports equate 100 cc to a one-cup-size increase; however, no studies have confirmed this between commercially available bras. The aim of this study was to identify the volume increase between cup sizes across different brands and the relationship with implant selection. METHODS: Five bra cup sizes from three different companies were analyzed for their volume capacity. Three methods were used to calculate the volume of the bras: (1) linear measurements; (2) volume measurement by means of water displacement; and (3) volume calculation after three-dimensional reconstruction of serial radiographic data (computed tomography). The clinical arm consisted of 79 patients who underwent breast augmentation surgery from February 1, 2014, to June 30, 2016. Answers from a short questionnaire in combination with the implant volume were analyzed. RESULTS: Across all three brands, the interval volume increase varied between sizes, but not all were above 100 cc. There was some variation in the volume capacity of the same cup size among the different brands. The average incremental increase in bra cup size across all three brands in the laboratory arm was 135 cc. The mean volume increase per cup size was 138.23 cc in the clinical arm. CONCLUSIONS: This article confirms that there is no standardization within the bra manufacturing industry. On the basis of this study, patients should be advised that 130 to 150 cc equates to a one-cup-size increase. Bras with narrower band widths need 130 cc and wider band widths require 150 cc to increase one cup size.


Assuntos
Implantes de Mama , Vestuário , Imageamento Tridimensional , Mamoplastia/métodos , Tomografia Computadorizada por Raios X , Mama/anatomia & histologia , Feminino , Humanos , Tamanho do Órgão , Desenho de Prótese
20.
J Plast Reconstr Aesthet Surg ; 70(5): 673-685, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28262513

RESUMO

BACKGROUND: Spring-assisted cranioplasty (SAC) has become an accepted treatment for patients with sagittal craniosynostosis; however, the early effects of springs on skull dimensions have never been assessed with objective measurements in the literature. The present study evaluated the changes in skull dimensions and intracranial volume (ICV) during the first 3 months after SAC for sagittal synostosis. METHODS: Sixteen patients with sagittal synostosis underwent SAC. The cephalic index (CI) and the distance between the spring foot plates were chronologically measured until spring removal at 3 months. Pre- and post-treatment CT scans available for 6 patients were used to assess changes in head shape. Thirteen patients underwent objective aesthetic assessment using pre- and post-operative photographs. Statistical analysis was performed using the linear mixed model for chronological data, t-test statistics for normative data comparisons and Wilcoxon's signed rank test for non-parametric data. RESULTS: For scaphocephalic patients, pre-operative and post-operative CIs were 0.70 and 0.74 (p = 0.001), respectively. Cranial widening towards normative values was observed (p = 0.0005). A continuous expansion in the distance between the spring foot plates was observed over the treatment period. Frontal and occipital angles were not affected by SAC despite apparent clinical improvements in frontal bossing and occipital prominence. CT analysis demonstrated relative reduction in the anterior cranial volume (p = 0.01) and relative expansion of the superior occipital volume (p = 0.03). CONCLUSIONS: Spring expansion was most marked in the hours following spring insertion. The expansion rate reduced to the minimum by day 1 post-operatively. Clinical benefits of SAC resulted from an increase in the bi-temporal width that camouflaged the frontal bossing. Improvement in occipital prominence was due to superior occipital volume expansion, allowing the occiput to remodel to a more rounded shape.


Assuntos
Suturas Cranianas/cirurgia , Craniossinostoses/cirurgia , Procedimentos de Cirurgia Plástica/instrumentação , Cefalometria/métodos , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/patologia , Feminino , Humanos , Lactente , Tempo de Internação , Masculino , Tamanho do Órgão , Cuidados Pós-Operatórios , Procedimentos de Cirurgia Plástica/métodos , Crânio/diagnóstico por imagem , Crânio/patologia , Instrumentos Cirúrgicos , Tomografia Computadorizada por Raios X
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