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Background: Immunosuppression (IS) is the main treatment for most types of glomerulonephritis (GN). Quantifying the cost of IS is necessary to ensure equitable access to therapies and optimal health outcomes, but the real-world cost of IS treatment for GN is largely unknown. We examined temporal changes in the population-level IS medication costs for GN over a 14-year period in a large Canadian province. Methods: We linked a provincial pathology database (containing all GN cases from 2000 to 2012) with renal and medication administrative databases to capture clinical characteristics and IS medications, with follow-up until 2013. The primary outcome (mean IS medication cost per treated patient each year) was evaluated for trends over time. Results: The cohort included 2983 GN patients followed for a mean of 5.7 years. The yearly per-patient medication cost increased 6.8-fold from $205 to $1394 (P < 0.001), with significant increases of 3.5-11.7-fold in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis, focal segmental glomerulosclerosis, lupus nephritis, minimal change disease and membranous nephropathy (P ≤ 0.004), but no change in immunoglobulin A (IgA) nephropathy. The cost of mycophenolate mofetil, calcineurin inhibitors and rituximab increased significantly (P < 0.001) such that in 2000 they accounted for 17.6% of medication costs and were used by 2.2% of patients, which increased to 94.5% and 44.6%, respectively, in 2013. The costs of azathioprine, cyclophosphamide and prednisone increased only slightly or decreased. Patterns of drug use and contribution to cost varied by type of GN. Conclusions: These are the first population-level estimates of the IS treatment costs for GN, and demonstrate a striking increase due to changing practice patterns from older, cheaper medications to newer, more expensive therapies. These results provide important information to guide future health policy strategies and cost-effectiveness research in glomerular diseases.
Assuntos
Bases de Dados Factuais , Glomerulonefrite/economia , Imunossupressores/economia , Imunossupressores/uso terapêutico , Padrões de Prática Médica/normas , Adulto , Canadá/epidemiologia , Feminino , Glomerulonefrite/classificação , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Levamisole as an immunomodulator drug has been demonstrated to improve the immune response to hepatitis B virus vaccination in haemodialysis patients. The aim of this randomized double-blind placebo-controlled trial was to evaluate the effect of levamisole supplementation on tetanus-diphtheria (Td) vaccine response rates in haemodialysis patients. Forty haemodialysis patients who had not received tetanus vaccination in a year before investigation and had unprotective anti-tetanus immunoglobulin G (IgG) levels (<0.1 international unit/mL) were enrolled and randomized into two equal groups to receive one dose of intramuscular Td vaccine supplemented with either levamisole (100 mg) or placebo daily, for 6 days before and 6 days after vaccination. The anti-tetanus IgG levels were measured 1 and 6 months after vaccination. One month post-vaccination, four patients were excluded from the levamisole group and two from the placebo group because of either death or renal transplantation. At 1 month, 13 out of 16 (81%) patients in the levamisole group as compared with six out of 18 (33%) patients in the placebo group developed protective anti-tetanus IgG levels (relative risk = 2.44, 95% confidence interval (CI) = 1.21, 4.88). From 1 to 6 months post-vaccination, one more patient in the levamisole group and two more patients in the placebo group were excluded because of renal transplantation. At 6 months, 11 out of 15 (73%) patients in the levamisole group as compared with four out of 16 (25%) patients in the placebo group still had protective anti-tetanus IgG levels (relative risk = 2.93, 95% CI = 1.19, 7.23). Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Levamisol/administração & dosagem , Diálise Renal , Toxoide Tetânico/imunologia , Vacinação , Idoso , Anticorpos Antibacterianos/sangue , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
In the present report, six different nano-composites contaning the same amine functionalized multi-walled carbon nanotubes (NH(2)-MWCNTs) but different room temperature ionic liquids (RTILs) were prepared. Then, the efficiency of these nano-composites as supporting materials for studying the electrochemistry and electrocatalysis of choline oxidase (ChOx) as a model enzyme were compared. The corresponding cyclic voltammetric and amperometric data showed that the electrocatalytic activity and the electroanalytical performance of immobilized ChOx depends on the degree of hydrophilicity of RTILs used in the applied nano-composite. The higher stability (180 days), higher enzyme loading (6.56 mol cm(-2)), lower detection limit (3.85 µM) and wider linear range (0.005-0.8 mM) was obtained for the most hydrophilic RTIL (1-allyl-3-methylimidazolium bromide).
Assuntos
Oxirredutases do Álcool/química , Eletroquímica , Interações Hidrofóbicas e Hidrofílicas , Líquidos Iônicos/química , Nanocompostos/química , Nanotubos de Carbono/química , Técnicas Biossensoriais , Eletrodos , TemperaturaRESUMO
The human immunodeficiency virus type 1 protease (HIV-1 PR) is an important enzyme in the life cycle of the HIV virus. It cleaves inactive pre-proteins of the virus and changes them into active proteins. Darunavir (DRV) suppresses the wild-type HIV-1 PR (WT-Pr) activity but cannot inhibit some mutant resistant forms (MUT-Pr). Increasing knowledge about the resistance mechanism can be helpful for designing more effective inhibitors. In this study, the mechanism of resistance of a highly MUT-Pr strain against DRV was investigated. For this purpose, complexes of DRV with WT-Pr (WT-Pr-D) and MUT-Pr (MUT-Pr-D) were studied by all-atom molecular dynamics simulation in order to extract the dynamic and energetic properties. Our data revealed that mutations increased the flap-tip flexibility due to the reduction of the flap-flap hydrophobic interactions. So, the protease's conformation changed from a closed state to a semi-open state that can facilitate the disjunction of DRV from the active site. On the other hand, energy analysis limited to the final basins of the energy landscape indicated that the entropy of binding of DRV to MUT-Pr was more favorable than that of WT-Pr. However, the enthalpy penalty overcomes it and makes binding more unfavorable relative to the WT-Pr. The unfavorable interaction of DRV with R8, I50, I84, D25', and A28' residues in MUT-Pr-D relative to WT-Pr-D is the reason for this enthalpy penalty. Thus, mutations drive resistance to DRV. The hydrogen bond analysis showed that compared with WT-Pr, the hydrogen bonds between DRV and the active-site residues of MUT-Pr were disrupted.
Assuntos
Anemia/etiologia , Neoplasias Duodenais/etiologia , Infecções por Herpesviridae/etiologia , Herpesvirus Humano 8/isolamento & purificação , Transplante de Rim/efeitos adversos , Sarcoma de Kaposi/etiologia , Infecções Tumorais por Vírus/etiologia , Idoso , Anemia/diagnóstico , Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Biópsia , Progressão da Doença , Substituição de Medicamentos , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/tratamento farmacológico , Neoplasias Duodenais/imunologia , Neoplasias Duodenais/virologia , Feminino , Gastroscopia , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/tratamento farmacológico , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/imunologia , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Imunossupressores/efeitos adversos , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/virologia , Tomografia Computadorizada por Raios X , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologiaRESUMO
In the current study, a novel electrochemical label-free immunosensor is proposed for sensitive detection of heat-labile enterotoxin (LT) from Escherichia coli. Firstly, a glassy carbon electrode (GCE) was modified by a mixture containing reduced graphene oxide/room temperature ionic liquid (rGO/RTIL) composite. Then, simultaneous electrodeposition of prussian blue and gold nanoparticles led to formation of prussian blue@gold nanoparticles (PB@GNPs) composite on the electrode surface. The modified electrode was characterized by field emission scanning electron microscopy (FE-SEM), energy dispersive spectroscopy (EDS), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. After immobilization of anti-LT and blocking the unreacted sites with BSA (bovine serum albumin), the analytical performance of the proposed immunosensor was evaluated under optimal conditions (i.e. optimal pH, incubation time and temperature of incubation). Square wave voltammetry (SWV) was used to determine different concentrations of the LT antigen. The linear dynamic range of the proposed immunosensor was from 0.01 to 50 µg/mL and the detection limit of the immunosensor was found to be 0.0023 µg/mL. An acceptable selectivity in the real sample, long-term stability and goodreproducibility made the fabricated immunosensor a good candidate for detecting LT.
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Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Enterotoxinas/análise , Imunoensaio/métodos , Nanopartículas Metálicas/química , Escherichia coli/metabolismo , HumanosRESUMO
Semiconductor photocatalysis is an effective method used to degrade organophosphorus compounds. Here, the potential of a commonly mixed oxide semiconductor, ZnO/CuO, has been examined to degrade methyl parathion. Sono-coprecipitation method was used to provide ZnO/CuO nanocomposites, and it was applied to photocatalytic and sono-photocatalytic degradation of methyl parathion under solar light irradiation. Powder x-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), the Brunauer-Emmett-Teller (BET) surface area, field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM) were used to characterize the synthesized samples. The optimal experimental conditions such as ZnO/CuO photocatalyst 90:10 M ratios, the initial concentration of 20 mg/L parathion, 1 g/L photocatalyst loading, no compressed air sparging, pH of 8, and ultrasonic power (60 W and 80 kHz) were used to degrade the parathion effectively. The parathion was fully (100% removal) degraded after 60 min sono-photoirradiation in the optimal experimental conditions. A real water sample was used to examine the ability of the ZnO/CuO photocatalyst 90:10 to remove the parathion in the water-soluble ions. Graphical abstract.
Assuntos
Paration , Óxido de Zinco , Catálise , Cobre , Águas ResiduáriasRESUMO
Patients with end stage renal disease suffer from a high incidence of infectious diseases believed to be related to their impaired immune system. To determine the antitetanus and antidiphtheria IgG antibody levels in Iranian hemodialysis patients with end stage renal disease, as well as its association with sex, age, hemoglobin, zinc serum level, serum albumin, duration of dialysis, number of dialysis per week, dialysis adequacy, erythropoietin or iron supplements such as venofer, body mass index (BMI), and underlying renal disorder, we conducted a cross-sectional study on a total of 112 hemodialysis patients with end stage renal disorder (60 male, 52 female ) and 36 healthy individuals in the control group (14 male, 22 female). The patients and the control group received no antitetanus or antidiphtheria vaccine or immunoglobulin in the year prior to the investigation. The serum antitetanus and antidiphtheria IgG antibody levels were measured using the ELISA method. We found out that only 16% of our hemodialysis patients were immune to diphtheria (19% of the control group), and this rate for tetanus was 24% (48.2% in the healthy control). Except for the hemodialysis duration, none of the mentioned factors seemed to affect immunity. We conclude that in our study, the level of the antitetanus IgG antibody (unlike the antidiphtheria IgG antibody level) is significantly different among the hemodialysis patients, the chronic hemodialysis patients, and the control group.
Assuntos
Difteria/imunologia , Imunoglobulina G/sangue , Falência Renal Crônica/imunologia , Tétano/imunologia , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise RenalRESUMO
BACKGROUND: Residents frequently encounter situations in their workplace that may induce moral distress or burnout. The objective of this study was to measure overall and rotation-specific moral distress and burnout in medical residents, and the relationship between demographics and moral distress and burnout. METHODS: The revised Moral Distress Scale and the Maslach Burnout Inventory (Human Service version) were administered to Internal Medicine residents in the 2013-2014 academic year at the University of British Columbia. RESULTS: Of the 88 residents, 45 completed the surveys. Participants (mean age 30+/-3; 46% male) reported a median moral distress score (interquartile range) of 77 (50-96). Twenty-six percent of residents had considered quitting because of moral distress, 21% had a high level of burnout, and only 5% had a low level of burnout. Moral distress scores were highest during Intensive Care Unit (ICU) and Clinical Teaching Unit (CTU) rotations, and lowest during elective rotations (p<0.0001). Women reported higher emotional exhaustion. Moral distress was associated with depersonalization (p=0.01), and both moral distress and burnout were associated with intention to leave the job. CONCLUSION: Internal Medicine residents report moral distress that is greatest during ICU and CTU rotations, and is associated with burnout and intention to leave the job.
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Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, is overexpressed in many cancers such as head-neck, breast, prostate, and skin cancers for this reason it is a good target in cancer therapy and diagnosis. In nanobody-based cancer diagnosis and treatment, nanobodies with high affinity toward receptor (e.g. EGFR) results in effective treatment or diagnosis of cancer. In this regard, the main aim of this study is to develop a method based on molecular dynamic (MD) simulations for designing of 7D12 based nanobody with high affinity compared with wild-type nanobody. By surveying electrostatic and desolvation interactions between different residues of 7D12 and EGFR, the critical residues of 7D12 that play the main role in the binding of 7D12 to EGFR were elucidated and based on these residues, five logical variants were designed. Following the 50 ns MD simulations, pull and umbrella sampling simulation were performed for 7D12 and all its variants in complex with EGFR. Binding free energy of 7D12 (and all its variants) with EGFR was obtained by weighted histogram analysis method. According to binding free energy results, GLY101 to GLU mutation showed the highest binding affinity but this variant is unstable after 50 ns MD simulations. ALA100 to GLU mutation shows suitable binding enhancement with acceptable structural stability. Suitable position and orientation of GLU in residue 100 of 7D12 against related amino acids of EGFR formed some extra hydrogen and electrostatic interactions which resulted in binding enhancement.
Assuntos
Receptores ErbB/química , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida/métodos , Anticorpos de Domínio Único/química , Motivos de Aminoácidos , Afinidade de Anticorpos , Especificidade de Anticorpos , Sítios de Ligação , Cristalografia por Raios X , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Mutação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Anticorpos de Domínio Único/genética , Anticorpos de Domínio Único/metabolismo , Eletricidade Estática , TermodinâmicaRESUMO
A simple mono-enzyme biosensor has been developed for specific determination of paraoxon (POX). In this biosensor, choline oxidase (ChOx) was introduced and used as a new recognition element. Besides, by application of Prussian blue (PB), as an electron mediator, the necessity of applying oxygen or hydrogen peroxide sensor, as the internal transducer, was abated. The method was based on PB chemically modified screen-printed electrode coupled with ChOx for detection of POX as inhibitor. The concentration of H(2)O(2) produced by ChOx was electrochemically determined by the PB modified electrode at -50 mV versus the internal screen-printed Ag pseudo-reference electrode. The decrease in current caused by the addition of inhibitor was used for evaluation of POX concentration. The experimental parameters such as the quantity of enzyme, substrate concentration and incubation time were optimized for ChOx inhibition. At the incubation time of 5 min, the biosensor response was linear from 0.1 to 1 microM of POX with a detection limit of 0.1 microM.
Assuntos
Oxirredutases do Álcool/química , Técnicas Biossensoriais/instrumentação , Eletroquímica/instrumentação , Eletrodos , Monitoramento Ambiental/instrumentação , Poluentes Ambientais/análise , Paraoxon/análise , Desenho de Equipamento , Análise de Falha de Equipamento , Inseticidas/análise , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Patients with end stage renal disease have higher incidence of infection diseases that is thought to be related to impaired immune system. OBJECTIVE: To determine the antitetanus IgG antibody level in Iranian hemodialysis patients with end stage renal disease and to find its association with sex, age, blood hemoglobin, serum albumin, duration of dialysis, time of dialysis per week, dialysis adequacy, erythropoietin, or iron supplementation, body mass index (BMI) and underlying renal disorder. METHODS: We conducted a cross sectional study on a total of 108 Iranian hemodialysis patients with end stage renal disorder, and 36 healthy individuals in the control group matched with the patient group. The patients and controls did not receive any antitetanus vaccine or immunoglobulins a year prior to the investigation. The serum antitetanus IgG antibody levels were measured by an ELISA method. RESULTS: We found 74.3% of patients to have unprotected antitetanus IgG antibody level compared with 52.8% of the control group. Except hemodialysis duration, none of the contributing factors seemed to affect immunity. CONCLUSION: We conclude that in our study, there is a significant difference in the antitetanus IgG antibody level between hemodialysis patients and the control group and also in the chronic hemodialysis patients.