RESUMO
Nanoparticles (NPs) produced from amphiphilic derivatives of poly-N-vinylpyrrolidone (Amph-PVP), composed of various molecular weight polymeric hydrophilic fragments linked into hydrophobic n-alkyl chains of varying lengths, were previously shown to exert excellent biocompatibility. Although routes of administration can be different, finally, most nanosystems enter the blood circulation or lymphatic vessels, and by this, they establish direct contact with endothelial cells. In this study, Amph-PVP NPs and fluorescently labeled Amph-PVP-based NPs, namely "PVP" NPs (Amph-PVP-NPs (6000 Da) unloaded) and "F"-NPs (Amph-PVP-NPs (6000 Da) loaded with fluorescent FITC), were synthesized to study Amph-PVP NPs interactions with HMEC-1 endothelial cells. PVP NPs were readily uptaken by HMEC-1 cells in a concentration-dependent manner, as demonstrated by immunofluorescence imaging. Upon uptake, the FITC dye was localized to the perinuclear region and cytoplasm of treated cells. The generation of lipopolysaccharide (LPS)-induced activated endothelium model revealed an increased uptake of PVPNPs, as shown by confocal microscopy. Both unloaded PVP NPs and F-NPs did not affect EC viability in the 0.01 to 0.066 mg/mL range. Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon PVPNPs treatment by assessing the expression of their E-Selectin, ICAM-1, and VCAM-1 adhesion receptors. None of the adhesion molecules were affected by NP treatments of both activated by LPS and nonactivated HMEC-1 cells, at the utilized concentrations (p = NS). In this study, PVP (6000 Da) NPs were used to encapsulate indomethacin, a widely used anti-inflammatory drug. The synthesized drug carrier complex did not affect HMEC-1 cell growth and expression of E-selectin, ICAM-1, and VCAM-1 adhesion receptors. In summary, PVP-based NPs are safe for use on both basal and activated endothelium, which more accurately mimics pathological conditions. Amph-PVP NPs are a promising drug delivery system.
Assuntos
Anti-Inflamatórios/administração & dosagem , Materiais Biocompatíveis/química , Portadores de Fármacos/química , Células Endoteliais/efeitos dos fármacos , Indometacina/administração & dosagem , Nanopartículas/química , Polímeros/química , Pirrolidinonas/química , Anti-Inflamatórios/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/metabolismo , Fluoresceína-5-Isotiocianato/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Indometacina/metabolismo , Peso Molecular , Tamanho da PartículaRESUMO
BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy recommends prophylactic pancreatic duct stent placement (PPS) and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk individuals and suggests that rectal indomethacin may decrease the risk and severity of PEP in average-risk individuals. The European Society for Gastrointestinal Endoscopy recommends rectal indomethacin for all patients undergoing ERCP. Previous surveys of European endoscopists revealed low adoption of PPS or rectal NSAIDs to prevent PEP. We sought to capture current practice in the prevention of PEP among endoscopists in the United States involved in advanced endoscopy fellowship programs. METHODS: An anonymous online 16-item survey was e-mailed to 233 advanced endoscopists involved in advanced endoscopy fellowship programs. RESULTS: Of the 233 endoscopists who were invited to participate, 62 responded (26.7%). Most respondents reported working in tertiary referral centers (57; 95.0%) and performing ERCP for greater than 5 years (44; 74.6%). All respondents (60; 100.0%) reported working with fellows. Most PPS users (41; 72.0%) reported use of PPS in high-risk patients only and using PPS for PEP in ≤25% of ERCPs (38; 64.4%). Most respondents reported using rectal NSAIDs for high-risk patients only (34; 59.7%) compared with respondents (23; 40.1%) who reported using rectal NSAIDs for prevention of PEP in average-risk patients undergoing ERCP. Most respondents (49; 83.0%) also reported using rapid intravenous fluids to prevent PEP. CONCLUSIONS: Among endoscopists involved in advanced endoscopy fellowships in the United States, rectal NSAIDs are used more frequently than PPS in the prevention of PEP. Despite mounting evidence supporting the use of rectal NSAIDs to prevent PEP in average-risk patients, less than half of the respondents in this survey reported such practice.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colangiopancreatografia Retrógrada Endoscópica , Indometacina/administração & dosagem , Ductos Pancreáticos/cirurgia , Pancreatite , Administração Retal , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Bolsas de Estudo , Gastroenterologia , Pesquisas sobre Atenção à Saúde , Humanos , Indometacina/uso terapêutico , Pessoa de Meia-Idade , Pancreatite/etiologia , Pancreatite/prevenção & controle , Prática Profissional , Implantação de Prótese , Medição de Risco , Stents , Estados UnidosRESUMO
PURPOSE: Existing knowledge of medicines that increase the risk of an adverse event may be corroborated and augmented by population studies specifically assessing the risk associated with the concurrent use of these medicines and use by patients with existing comorbidity. An American Heart Association review recently identified a variety of medicines that may cause or exacerbate heart failure (HF), many with evidence from limited evaluation of population data. We assessed the risk of first-time HF associated with the use of 50 of these medicines by New Zealand's primary care population. METHODS: Case-control study utilising national pharmaceutical use and hospital admissions data 2007-2015; 22,989 patients with first-time HF 2008-2015 were matched with 114 498 control patients. The primary outcome was first-time HF and its association with medicine exposure in the prior 90 days, estimated using conditional logistic regression. We also assessed the risk associated with new use of medicines in the prior month, concurrent use, and in patients with existing comorbidity. RESULTS: Eleven medicines were significantly associated with HF with several other infrequently used medicines providing signals of increased risk. A high risk was associated with the use of salbutamol (adjusted odds ratio 2.63; 95% CI, 2.48-2.78), clozapine (2.70; 2.46-4.98), diltiazem (1.52; 1.44-1.60), indomethacin (2.51; 1.54-4.10), pioglitazone (1.50; 1.16-1.95), and antifungal medicines. New use of medicines and use of medicine combinations increased this risk in many cases. CONCLUSIONS: Our study provides further evidence to inform cautious use of these medicines in patients with HF or at risk of developing HF.
Assuntos
Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Insuficiência Cardíaca/induzido quimicamente , Hospitalização/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Albuterol/administração & dosagem , Albuterol/efeitos adversos , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Estudos de Casos e Controles , Clozapina/administração & dosagem , Clozapina/efeitos adversos , Diltiazem/administração & dosagem , Diltiazem/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Indometacina/administração & dosagem , Indometacina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Pioglitazona/administração & dosagem , Pioglitazona/efeitos adversos , Pontuação de Propensão , Fatores de RiscoRESUMO
OBJECTIVE: We aimed to evaluate the results in our case series of AP ERCP over the last three years. The prophylaxis for acute pancreatitis (AP) post-endoscopic retrograde cholangiopancreatography (ERCP) consists of rectal indomethacin, but some studies are not concordant. PATIENTS AND METHODS: We compared 241 ERCP performed from January 2014 to February 2015 with intravenous gabexate mesylate (Group A), with the 387 ERCP performed from March 2015 to December 2016 with rectal indomethacin (Group B) as prophylaxis for AP post-ERCP. RESULTS: There were 8 (3.31%) AP post-ERCP in Group A vs. 4 (1.03%) in Group B. CONCLUSIONS: Rectal indomethacin shows a better statistically significant performance than intravenous gabexate mesylate in the prophylaxis of AP post-ERCP, besides being cheaper.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Gabexato/administração & dosagem , Gabexato/uso terapêutico , Indometacina/administração & dosagem , Indometacina/uso terapêutico , Pancreatite/etiologia , Pancreatite/prevenção & controle , Inibidores de Serina Proteinase/administração & dosagem , Inibidores de Serina Proteinase/uso terapêutico , Doença Aguda , Administração Intravenosa , Administração Retal , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/economia , Colangiopancreatografia Retrógrada Endoscópica/economia , Custos e Análise de Custo , Feminino , Gabexato/economia , Humanos , Indometacina/economia , Masculino , Pessoa de Meia-Idade , Pancreatite/economia , Estudos Retrospectivos , Inibidores de Serina Proteinase/economiaRESUMO
PURPOSE: The efficacy and safety of indomethacin (IM) oral spray (OS) as a pain control therapy for oropharyngeal mucositis due to anticancer chemo- and radiotherapy were assessed in patients with head and neck carcinomas and haematological tumours. METHOD: We observed 35 patients (male/female, 20/15; 53 ± 17 years) with oropharyngeal mucositis who were treated with IM-OS preparation for pain relief at University of Tsukuba Hospital, Japan. Analgesic effects were assessed using the six-grade face scale for pain in 28 patients at the start of IM oral spray treatment. Systemic exposure was assessed by determining urinary excretions of IM in seven patients. RESULTS: Pain relief was achieved in 26 (93%) patients at 25 (5-60) min after applying the IM-OS preparation (15.6 ± 3.4 µg/kg) and analgesic effects were maintained for 120 (10-360) min. The pain was significantly decreased after using the spray (3.6 ± 0.7 vs. 2.4 ± 0.9, p < 0.01). Moreover, urinary IM excretion rates after applying the IM spray preparation were 1.8 ± 0.8% of the IM oral spray dose (130.5 ± 77.7 µg/kg/day), which was markedly lower than that following oral administration of IM (60%). No adverse events were observed following application of the spray. CONCLUSIONS: The present IM spray is an effective and safe preparation for pain relief and can be used as an alternative therapeutic option for oropharyngeal mucositis in cancer patients.
Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Indometacina/administração & dosagem , Sprays Orais , Manejo da Dor/métodos , Dor/tratamento farmacológico , Faringite/tratamento farmacológico , Estomatite/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Feminino , Neoplasias Hematológicas/terapia , Humanos , Indometacina/efeitos adversos , Japão , Masculino , Pessoa de Meia-Idade , Orofaringe/efeitos dos fármacos , Orofaringe/patologia , Orofaringe/efeitos da radiação , Dor/etiologia , Faringite/etiologia , Lesões por Radiação/complicações , Lesões por Radiação/tratamento farmacológico , Estomatite/etiologiaRESUMO
The care of extremely premature neonates with suspected or confirmed diagnosis of patent ductus arteriosus (PDA) is a frequent challenge for pediatric nurses. It is important for nurses to have adequate knowledge of the normal postnatal changes in cardiovascular and pulmonary function to recognize any adverse symptoms. Nurses caring for these vulnerable neonates must have a thorough understanding of the pathophysiology of a PDA in order to assess, plan, and implement patient-centered care. Recognition of characteristic symptoms of PDA in a timely manner is essential for optimal management and outcomes. Understanding the science behind treatment options is also imperative for pediatric nurses to provide the best care and effectively educate parents. Pediatric nurses are a significant resource in managing extremely premature neonates through comprehensive assessment, effective parent education, and high-quality patient-centered care.
Assuntos
Permeabilidade do Canal Arterial/enfermagem , Lactente Extremamente Prematuro , Doenças do Prematuro/enfermagem , Avaliação em Enfermagem , Enfermagem Pediátrica/educação , Inibidores de Ciclo-Oxigenase/administração & dosagem , Permeabilidade do Canal Arterial/fisiopatologia , Permeabilidade do Canal Arterial/terapia , Humanos , Indometacina/administração & dosagem , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/terapia , Enfermagem Pediátrica/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Guias de Prática Clínica como AssuntoRESUMO
Management of the patent ductus arteriosus (PDA) represents an ongoing challenge in the care of extremely premature neonates. Determining the optimal treatment strategy requires careful consideration of the potential risks and benefits of available therapies. Surgical ligation results in reliable ductal closure, but may result in numerous short-term complications and have a negative impact on long-term outcome. Intravenous indomethacin was the first pharmacologic agent widely utilized for PDA closure. Intravenous indomethacin effectively closes the ductus arteriosus and prevents pulmonary hemorrhage and severe intraventricular hemorrhage, but fails to mitigate short-term morbidities and improve long-term outcomes. Intravenous ibuprofen represents an alternative therapy with fewer renal adverse effects. However, intravenous ibuprofen does not prevent severe intraventricular hemorrhage and also has concerning adverse effects, including bilirubin displacement and the potential to increase the risk of chronic lung disease. Enteral ibuprofen has also been investigated, although gastrointestinal adverse effects limit widespread utilization. Acetaminophen (paracetamol) represents an enticing novel therapy due to wide availability, low cost, and an appealing safety profile. Ongoing investigation is required to determine the role of this agent in PDA treatment algorithms. Pending these results, clinicians must weigh the potential risks and benefits of each therapy for individual neonates considering all available evidence.
Assuntos
Permeabilidade do Canal Arterial/tratamento farmacológico , Acetaminofen/administração & dosagem , Análise Custo-Benefício , Inibidores de Ciclo-Oxigenase/administração & dosagem , Permeabilidade do Canal Arterial/fisiopatologia , Humanos , Ibuprofeno/administração & dosagem , Indometacina/administração & dosagem , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Infusões Intravenosas , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background Our goal was to evaluate the hemodynamic status of very low-birth-weight infants (VLBWIs) with patent ductus arteriosus (PDA) by measuring the vena contracta width (VCW) and effective shunt orifice area (ESOA) using the proximal isovelocity surface area (PISA) on color Doppler imaging. Method and Results In this study, 34 VLBWIs with PDA (median weight: 949 g) were studied. We measured VCW and ESOA using the PISA on echocardiography. PDA-VCW was measured at the narrowest PDA flow region. ESOA determined using PISA (PDA-ESOA) was defined as the hemispheric area of laminar flow with aliased velocities on color Doppler flow imaging: PDA-ESOA = 2π (PDA radius) 2 × aligning velocity/PDA velocity. Of the 34 VLBWIs, 26 received indomethacin (IND) for symptomatic PDA. Comparing echocardiographic parameters between infants who did versus did not receive IND, significant differences were seen in the left atrial-to-aortic root ratio (LA/AO), PDA-VCW, and PDA-ESOA. Receiver operating characteristic curve analysis to differentiate between IND usage status produced statistically significant results for PDA-VCW (area under the curve [AUC] = 0.880), PDA-ESOA (AUC = 0.813), and LA/AO (AUC = 0.769). Conclusion PDA-VCW and PDA-ESOA may allow noninvasive assessment of PDA severity, and are useful when determining the timing of clinical decision making for IND administration.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/tratamento farmacológico , Indometacina/administração & dosagem , Recém-Nascido de muito Baixo Peso , Ecocardiografia Doppler em Cores , Feminino , Hemodinâmica , Humanos , Recém-Nascido , Japão , Modelos Logísticos , Masculino , Análise Multivariada , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Common standard practice after complex arthroscopic elbow surgery includes hospital admission for 72 h. The authors hypothesized that an expedited care pathway, with 24 h of hospital admission and ambulatory brachial plexus analgesia and continuous passive motion at home, results in equivalent elbow range of motion (ROM) 2 weeks after surgery compared with standard 72-h hospital admission. METHODS: A randomized, single-blinded study was conducted after obtaining approval from the research ethics board. Forty patients were randomized in a 1:1 ratio using a computer-generated list of random numbers into an expedited care pathway group (24-h admission) and a control group (72-h admission). They were treated equally aside from the predetermined hospital length of stay. RESULTS: Patients in the control (n = 19) and expedited care pathway (n = 19) groups achieved similar elbow ROM 2 weeks (119 ± 18 degrees and 121 ± 15 degrees, P = 0.627) and 3 months (130 ± 18 vs. 130 ± 11 degrees, P = 0.897) postoperatively. The mean difference in elbow ROM at 2 weeks was 2.6 degrees (95% CI, -8.3 to 13.5). There were no differences in analgesic outcomes, physical function scores, and patient satisfaction up to 3 months postoperatively. Total hospital cost of care was 15% lower in the expedited care pathway group. CONCLUSION: The results suggest that an expedited care pathway with early hospital discharge followed by ambulatory brachial plexus analgesia and continuous passive motion at home is a cost-effective alternative to 72 h of hospital admission after complex arthroscopic elbow surgery.
Assuntos
Analgésicos/administração & dosagem , Artroscopia , Plexo Braquial/efeitos dos fármacos , Cotovelo/cirurgia , Bombas de Infusão , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/administração & dosagem , Acetaminofen/economia , Acetaminofen/uso terapêutico , Adulto , Analgesia/economia , Analgesia/métodos , Analgésicos/economia , Analgésicos/uso terapêutico , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/economia , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/economia , Analgésicos Opioides/uso terapêutico , Análise de Variância , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/economia , Anti-Inflamatórios não Esteroides/uso terapêutico , Análise Custo-Benefício , Equipamentos Descartáveis , Feminino , Seguimentos , Humanos , Indometacina/administração & dosagem , Indometacina/economia , Indometacina/uso terapêutico , Pacientes Internados , Tempo de Internação/estatística & dados numéricos , Masculino , Oxicodona/administração & dosagem , Oxicodona/economia , Oxicodona/uso terapêutico , Satisfação do Paciente/estatística & dados numéricos , Amplitude de Movimento Articular , Método Simples-CegoRESUMO
OBJECTIVES: The aim of the present study was to perform a comparative cost-effectiveness analysis of the different strategies used to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis. METHODS: We performed a cost-effectiveness decision analysis of 4 prophylactic strategies (nonsteroidal anti-inflammatory drugs or NSAIDs, pancreatic stent, stent plus rectal indomethacin, and no prophylaxis) in a simulated cohort of 300 patients during 1 year. Treatment effectiveness was defined as the number of patients who did not develop post-ERCP pancreatitis. RESULTS: The baseline costs of each strategy were as follows: rectal NSAID $359,098, pancreatic stent $426,504, stent plus rectal indomethacin $479,153, and no prophylaxis $491,275. The mean number of cases developing post-ERCP pancreatitis was 16, 21, 23, and 37 for the strategies rectal NSAID, pancreatic stent, stent plus rectal indomethacin, and no prophylaxis, respectively. Taking rectal NSAID prophylaxis as the reference strategy, the odds ratio of an episode of post-ERCP acute pancreatitis after pancreatic stent placement was 1.33 (95% confidence interval [CI], 0.68-2.61); after stent plus indomethacin, it was 1.40 (95% CI, 0.72-2.73), and after no prophylaxis, it was 2.49 (95% CI, 1.35-4.59). CONCLUSIONS: Rectal NSAID administration proved to be the most cost-effective prophylactic strategy used to prevent post-ERCP pancreatitis. The strategy of no prophylaxis for this complication should be avoided.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/economia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/economia , Custos de Medicamentos , Custos Hospitalares , Pancreatite/economia , Pancreatite/prevenção & controle , Stents/economia , Administração Retal , Terapia Combinada , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Árvores de Decisões , Diclofenaco/administração & dosagem , Diclofenaco/economia , Feminino , Humanos , Indometacina/administração & dosagem , Indometacina/economia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Método de Monte Carlo , Razão de Chances , Pancreatite/etiologia , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Acute peripheral arterial thrombosis can be threatening to life and limb. Dissolution of the thrombus local catheter-directed intra-arterial infusion of fibrinolytic agents such as urokinase is the standard therapy for thrombosis; however, this method is time-intensive, and amputation of the affected limb is still needed in 10-30% of cases. Furthermore, thrombolytic therapy carries the risk of bleeding complications. The use of small gas-filled bubbles, or ultrasound contrast agents (UCAs), in combination with ultrasound has been investigated as an improved thrombolytic therapy in acute coronary and cerebral arterial thrombosis. The authors describe a porcine model of acute peripheral arterial occlusion to test contrast-enhanced sonothrombolysis approaches that combine ultrasound, UCAs and fibrinolytic agents and recommend a strategy for preventing severe allergic reactions to UCAs in the pigs.
Assuntos
Meios de Contraste/farmacologia , Trombólise Mecânica/métodos , Doença Arterial Periférica/terapia , Trombose/terapia , Anafilaxia/induzido quimicamente , Anafilaxia/prevenção & controle , Animais , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/economia , Fármacos Cardiovasculares/farmacologia , Feminino , Indometacina/administração & dosagem , Indometacina/economia , Indometacina/farmacologia , Lipídeos/efeitos adversos , Microbolhas/efeitos adversos , Doença Arterial Periférica/patologia , Pré-Medicação , Suínos , Trombose/patologiaRESUMO
The aim of the study was to assess the small intestine permeability by using lactulose as a sugar probe and blood metabolites in sheep after a challenge with repeated indomethacin injections. According to a changeover design, 7 adult sheep (4 males and 3 females) were subjected to 4 intramuscular injections (every 12 h) of saline [control (CRT); 7 animals] or indomethacin (INDO; 7 animals). Two hours after the last injection, 30 g of lactulose were administered orally to both CTR and INDO. Blood samples were collected daily for the analysis of the metabolic profile and 5 samples were collected at 2-h intervals following lactulose ingestion to monitor changes in blood levels of lactulose as an index of intestinal permeability. The INDO challenge induced clinical symptoms such as lack of appetite, dullness, weakness, depression, and diarrhea with traces of blood in the feces. In INDO group, haptoglobin and ceruloplasmin increased (P < 0.01) after INDO challenge whereas a decrease (P < 0.05) of negative acute phase reactants (e.g., cholesterol, albumin, and paraoxonase) was observed. Reactive oxygen metabolites increased (P < 0.01) from 60 to 204 h after the INDO challenge start, with a decrease of vitamin E concentration from 12 (P < 0.01) to 132 h (P < 0.05). Blood lactulose concentrations were increased (P < 0.05) in INDO animals and the highest mean values (17.67 µg/mL in INDO vs. 0.17 µg/mL in CRT; P < 0.01) were observed 6 h after oral dosage of lactulose. These changes indicate that the INDO challenge led to severe inflammatory responses with oxidative stress by enhancing small intestinal permeability in sheep that allowed lactulose to enter in blood. The results of this experiment demonstrate that lactulose can be used as a probe to assess gastrointestinal permeability in adult ruminants to test the consequences of stressing conditions on animal welfare. For this purpose, the most suitable time for blood sampling is between 2 and 8 h after the oral dosage of lactulose.
Assuntos
Trato Gastrointestinal/efeitos dos fármacos , Indometacina/efeitos adversos , Lactulose/sangue , Ovinos , Proteínas de Fase Aguda/metabolismo , Animais , Feminino , Trato Gastrointestinal/fisiologia , Indometacina/administração & dosagem , Lactulose/administração & dosagem , Lactulose/metabolismo , Masculino , Estresse Oxidativo , Permeabilidade/efeitos dos fármacos , Ovinos/sangueRESUMO
OBJECTIVES: A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach. METHODS: We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both. RESULTS: After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP. CONCLUSIONS: This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Indometacina/uso terapêutico , Pancreatite/prevenção & controle , Stents/economia , Administração Retal , Adulto , Idoso , Colangiopancreatografia Retrógrada Endoscópica/economia , Análise Custo-Benefício , Feminino , Humanos , Indometacina/administração & dosagem , Indometacina/economia , Masculino , Pessoa de Meia-Idade , Pancreatite/economia , Pancreatite/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
The objective of this study was to evaluate the influence of the ratios or the hydrophile-lipophile balance (HLB) values of Cremophor EL and Span 80 on the phase behavior of the O/W microemulsions and the percutaneous absorption and penetration of indomethacin microemulsions. The existence of microemulsion regions is investigated in quaternary systems composed of soybean oil/Cremophor EL and Span 80 (mixed surfactants)/diethylene glycol monoethyl ether (cosurfactant)/water by constructing pseudo-ternary phase diagrams at various Cremophor EL/Span 80 ratios. In addition, five microemulsion formulations with various mixed surfactants HLB values were evaluated by in vitro penetration experiments using mouse skin and Franz diffusion cells. The flux and amount of indomethacin penetration from 5 microemulsion formulations were significantly different from the control, and the enhance ratios ranged from 2.38 to 4.68 and 2.11 to 4.23, respectively. The HLB value of mixed surfactants in the formulations was a principal factor in determining the percutaneous penetration of the drug. The flux and amount of drug penetration increased gradually with increasing content of the lipophilic surfactant Span 80 and skin retention was highest for mixed surfactants with a HLB value of 7.6. Therefore, it is suggested that the presence of mixed surfactants was beneficial in the formation of O/W microemulsions and enhanced percutaneous penetration of indomethacin.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Indometacina/farmacocinética , Óleo de Soja/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Emulsões , Excipientes , Glicerol/análogos & derivados , Hexoses , Técnicas In Vitro , Indometacina/administração & dosagem , Camundongos , Absorção Cutânea , TensoativosRESUMO
OBJECTIVES: Acute gouty arthritis is often treated with NSAIDs, but recent studies have suggested that treatment with prednisolone has at least equivalent analgesic efficacy and fewer adverse effects. No formal economic analysis has been performed earlier. In this study, we aimed to compare the economic impact of oral indomethacin therapy and oral prednisolone therapy in the treatment of acute gout in patients presenting to an emergency department in Hong Kong. METHODS: Data from a previously published randomized controlled trial were used to compare the costs of the two treatment options. Direct, incremental costs incurred in the 2 weeks after the initial presentation were considered from the perspective of the healthcare provider. Costs were subdivided into those incurred in the emergency department phase; admission on day 1 to the emergency department's observation ward; admission subsequently to the general medical ward for adverse events and reattendance to the hospital outpatients' or emergency department. RESULTS: The prednisolone strategy resulted in cost savings in the emergency department of HK$5.67 (US$0.73; pound0.37) and in medical admissions of HK$1727.48 (US$221.47; pound111.45) per patient treated. Overall, the average saving with prednisolone was HK$1235 (US$158.33; pound79.68) per patient treated, which was equivalent to one admission bed/day saved for every two patients treated. Treatment for each of the six patients in the indomethacin group admitted for serious adverse effects cost the healthcare provider HK$13 244 (US$1697.95; pound854.45). CONCLUSION: Treatment of acute gouty arthritis with a 5-day course of prednisolone is significantly more cost-effective than treatment with indomethacin.
Assuntos
Anti-Inflamatórios/economia , Artrite Gotosa/tratamento farmacológico , Serviço Hospitalar de Emergência/economia , Custos de Cuidados de Saúde , Indometacina/economia , Prednisolona/economia , Administração Oral , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Análise Custo-Benefício , Hong Kong , Humanos , Indometacina/administração & dosagem , Prednisolona/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: One barrier to economic evaluation alongside neonatal randomized controlled trials is the expense of collecting detailed patient resource information. To reduce this data collection burden, we identified the key resource items that predict daily ancillary costs for extremely low birth weight infants. METHODS: Participants were 385 infants enrolled in the Trial of Indomethacin Prophylaxis for Preterms in nine tertiary level neonatal intensive care units in Canada. Information on eighty-nine nonpersonnel resource items was abstracted from the hospital chart from admission to tertiary hospital discharge. Unit costs were derived from a provincially standardized cost accounting system. Using stepwise linear regression, models correlating total daily ancillary costs with key resource items were constructed for each of five periods of admission. Models were derived in a randomly split half of the total sample of patient days and validated against the remainder. RESULTS: The 385 infants contributed resource information from 23,354 admission days. The regression model for weeks one to twelve included the covariates surfactant, chest radiograph, red blood cell transfusion, cranial ultrasound, abdominal radiograph, parenteral amino acid infusion, surgery, platelet transfusion, and echocardiogram and explained 91% of the variability in daily nonpersonnel costs (P<.0001). Models for other admission periods similarly included between four and eight covariates, were highly significant (P<.0001) and explained between 76% and 94% of daily ancillary cost variability. The regression equations showed excellent predictive power when applied to the second half of the patient data set. CONCLUSIONS: Daily nonpersonnel costs for extremely low birth weight infants are driven by a limited number of key resource variables. The ability to predict total ancillary costs with minimal data collection will facilitate inclusion of economic evaluations in neonatal trials.
Assuntos
Serviços Técnicos Hospitalares/economia , Custos Hospitalares/estatística & dados numéricos , Unidades de Terapia Intensiva Neonatal/economia , Modelos Econométricos , Serviços Técnicos Hospitalares/estatística & dados numéricos , Anti-Inflamatórios não Esteroides/administração & dosagem , Canadá , Custos e Análise de Custo , Humanos , Indometacina/administração & dosagem , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Modelos LinearesRESUMO
Although laparoscopic cholecystectomy (LC) is known to be safe in the treatment of acute cholecystitis (AC), the optimal timing of laparoscopic intervention remains controversial. The objective of this study is to prospectively compare the safety and cost effectiveness of early versus delayed LC in AC. Our study population consisted of 43 patients presenting with AC (localized tenderness, white blood cell count >10.0 or temperature >38.0 degrees C, and ultrasound confirmation) who were prospectively randomized to early versus delayed LC during their first admission. Exclusion criteria included a history of peptic ulcer disease or evidence of gallbladder perforation. All patients were treated with bowel rest and antibiotics (piperacillin 2 g intravenous piggyback every 6 hours). Early treatment patients underwent LC as soon as the operating schedule allowed. Delayed treatment patients received anti-inflammatory medication (indomethacin 50 mg per rectum every 12 hours) in addition to bowel rest and antibiotics and underwent operation after resolution of symptoms or within 5 days if symptoms failed to resolve. Early LC was performed in 21 patients, whereas 22 patients underwent delayed LC. There was no difference in age, temperature, or white blood cell count on admission between groups. Early LC slightly reduced operative time and conversion rate. There was no difference in complications. Estimated blood loss was significantly lower in those receiving early LC. There was also a significant reduction in total hospital stay and hospital charges with early LC. We conclude that delay in operation combined with anti-inflammatory medication showed no advantage with regard to operative time, conversion, or complication rate. Furthermore, early laparoscopic intervention significantly reduced operative blood loss, hospital days, and hospital charges.
Assuntos
Colecistectomia Laparoscópica , Colecistite/cirurgia , Doença Aguda , Administração Retal , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Perda Sanguínea Cirúrgica , Colecistectomia Laparoscópica/economia , Colecistectomia Laparoscópica/métodos , Análise Custo-Benefício , Nutrição Enteral , Feminino , Hidratação , Preços Hospitalares , Humanos , Indometacina/administração & dosagem , Indometacina/uso terapêutico , Injeções Intravenosas , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Penicilinas/administração & dosagem , Penicilinas/uso terapêutico , Piperacilina/administração & dosagem , Piperacilina/uso terapêutico , Estudos Prospectivos , Segurança , Fatores de TempoRESUMO
BACKGROUND: Although researchers have reported that postoperative pain in patients undergoing excimer laser photorefractive keratectomy (PRK) surgery is common in the first 24 hours after excimer surgery, factors associated with increased postoperative pain have not been reported. The purpose of this study was to prospectively document self-reported pain following excimer laser surgery and explore associated factors. METHODS: Consecutive patients undergoing excimer laser photorefractive keratectomy (PRK) surgery to correct myopia and/or myopic astigmatism were asked to prospectively grade, on a four-point scale, the amount of pain they were experiencing immediately after treatment and again 2, 4, 8, 24, and 48 hours after surgery. They were also asked to record the type and dose of all medication taken during that time period. RESULTS: Pain questionnaires were returned by 62 patients (72%), ranging in age from 20 to 54 years. The mean self-reported pain overall peaked 24 hours after treatment. Amount of myopia and prior excimer experience were not related to use of analgesia or self-reported pain (both p > 0.10). Patients who had three additional topical drops of indomethacin postoperatively reported significantly less pain 24 hours after treatment (t = 5.95, p = 0.0001). CONCLUSION: These results have implications for the education of patients about the likely course of healing after PRK. A course of five drops of topical indomethacin should be evaluated with a randomized clinical trial to assess efficacy in inhibiting ocular pain after PRK.
Assuntos
Medição da Dor/métodos , Dor Pós-Operatória/fisiopatologia , Ceratectomia Fotorrefrativa , Administração Tópica , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Humanos , Indometacina/administração & dosagem , Lasers de Excimer , Masculino , Pessoa de Meia-Idade , Miopia/cirurgia , Inquéritos e Questionários , Fatores de TempoRESUMO
PURPOSE: A Monte Carlo simulation study was done to investigate the effects of high intrasubject variation in clearance (CL), and volume of distribution (V) on the calculation of the 90% confidence interval (CI) for Cmax for single dose and multiple dose studies. METHODS: Simulations were done for both immediate release and sustained release scenarios. The simulated data were compared with clinical data from bioequivalence studies performed on indomethacin and verapamil. RESULTS: Previous reviews and simulations have shown that the probability of failure for the Cmax for single dose studies was always greater than that for multiple dose studies. However, the results for the simulated scenarios currently investigated indicate that if intra-subject (period-to-period) variation in CL and V is high (% CV's above 25%, and 12%, respectively), multiple dose studies can exhibit a higher probability of failure for Cmax than do single dose studies. Furthermore, Cmax values from studies performed with a sustained release scenario are more sensitive to changes in Ka, CL, and V than are results of studies on immediate release products. As an example, the probability of failure for immediate release products in simulated single dose studies is about 11% and 21% when the mean difference in Ka is 10% and 20%, respectively; while, the probability of failure for multiple dose studies is about 36% regardless of the difference in Ka. The corresponding values for the probability of failure for sustained release products were 25%, 53% for single dose studies and 39% for multiple dose studies. The simulations also indicate that changes in the fraction absorbed have a greater effect on the estimation of Cmax in multiple dose regimens than in single dose studies. CONCLUSIONS: The results from these investigations indicate that multiple dose studies do not necessarily always reduce variability in Cmax.