RESUMO
Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case-control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.
Assuntos
Dengue/diagnóstico , Infecção por Zika virus/diagnóstico , Adulto , Aedes/virologia , Idoso , Animais , Estudos de Casos e Controles , Estudos de Coortes , Conjuntivite Viral/diagnóstico , Conjuntivite Viral/fisiopatologia , Conjuntivite Viral/virologia , Dengue/fisiopatologia , Dengue/transmissão , Dengue/virologia , Vírus da Dengue , Diagnóstico Diferencial , Feminino , Febre/diagnóstico , Febre/fisiopatologia , Febre/virologia , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mosquitos Vetores/virologia , Mialgia/diagnóstico , Mialgia/fisiopatologia , Mialgia/virologia , Contagem de Plaquetas , Curva ROC , Singapura , Zika virus , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologiaRESUMO
BACKGROUND: Compared to electroconvulsive therapy (ECT), the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the management of treatment-resistant depression (TRD) remains unclear. OBJECTIVE/HYPOTHESIS: This study evaluated the cost-effectiveness of rTMS vs. ECT for TRD from Singapore societal perspective. METHODS: We constructed a Markov model to project the cost and benefit of rTMS compared with ECT over one year in patients with TRD. The relative treatment effects between rTMS and ECT were obtained from meta-analyses of published trials. The effectiveness and quality of life data for patients using ECT, resource use for TRD and their associated costs were derived from the national tertiary mental institution in Singapore. RESULTS: At one year, rTMS was cost-effective relative to ECT. The incremental cost-effectiveness ratio (ICER) associated with ECT was Singapore dollars (SGD) 311,024 per quality-adjusted life-year (QALY) gained. This exceeded the willingness-to-pay threshold of SGD 70,000 per QALY gained. A similar trend was observed for ICER per remission achieved (i.e., SGD 143,811 per remission achieved with ECT). In the subgroup analysis, rTMS was found to be less costly and more effective than ECT in nonpsychotic depressive patients. In the scenario analysis, ECT employed as an ambulatory service yielded a much smaller ICER (i.e., SGD 78,819 per QALY gained) compared to the standard inpatient setting. CONCLUSIONS: rTMS was a cost-effective treatment compared to ECT in TRD over one year. The cost-effectiveness of rTMS was attenuated when ECT was used in the outpatient setting.
Assuntos
Depressão/economia , Depressão/terapia , Eletroconvulsoterapia/economia , Eletroconvulsoterapia/métodos , Estimulação Magnética Transcraniana/economia , Estimulação Magnética Transcraniana/métodos , Feminino , Humanos , Masculino , Singapura/epidemiologiaRESUMO
Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting.
Assuntos
Antifúngicos/economia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/economia , Micoses/tratamento farmacológico , Micoses/economia , Adulto , Antifúngicos/uso terapêutico , Aspergillus/efeitos dos fármacos , Aspergillus/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Análise Custo-Benefício , Feminino , Fluconazol/economia , Fluconazol/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Itraconazol/economia , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/microbiologia , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Micoses/microbiologia , Micoses/mortalidade , Singapura , Análise de Sobrevida , Triazóis/economia , Triazóis/uso terapêutico , Voriconazol/economia , Voriconazol/uso terapêuticoRESUMO
BACKGROUND AND AIM: The high cost of chronic hepatitis C (HCV) direct-acting antivirals (DAAs) poses significant financial challenges for health payers, especially in Asia. A personalized treatment strategy based on individualized probability of virological response using oral DAAs as second-line therapy would seem practical but has not been studied. METHODS: We performed a Markov model to project health outcomes and costs for patients with genotype 1 HCV through 10 treatment strategies over a lifetime period. The implication of retreatment was also incorporated to reflect real-life situation. RESULTS: Using boceprevir and peginterferon/ribavirin (BOC/PR, the least costly treatment) as a base case, the all-oral therapies such as ombitasvir/paritaprevir/ritonavir-dasabuvir are cost-effective with an incremental cost-effective ratio of $US50 828. However, the all-oral DAAs would no longer be cost-effective compared with conventional therapies if retreatment were taken into account. A road map strategy using rapid virological response to guide use of BOC/PR and sofosbuvir/PR had the most favorable incremental cost-effective ratio ($US27 782) relative to BOC/PR. Nevertheless, the trade-off with the cost-effectiveness of the road map strategy is an increased number of liver-related deaths compared with all-oral DAAs (52 vs 10-20 per 10 000 patients) by incorporating retreatment. CONCLUSIONS: The 12-week all-oral DAAs were cost-effective options using conventional drug-to-drug comparison. However, they cease to be cost-effective when treatment strategies incorporating DAA retreatment for interferon failures are incorporated. HCV management can be optimized by adopting individualized treatment algorithm providing a practical solution to health payers to make oral DAAs accessible to those who need them most.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Administração Oral , Antivirais/administração & dosagem , Antivirais/economia , Ásia , Análise Custo-Benefício , Custos de Medicamentos/estatística & dados numéricos , Quimioterapia Combinada/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hepatite C Crônica/economia , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/economia , Cirrose Hepática/virologia , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Econométricos , Medicina de Precisão/economia , Anos de Vida Ajustados por Qualidade de Vida , Sensibilidade e Especificidade , Resposta Viral Sustentada , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJECTIVES: Effective formulary management in healthcare institutions safeguards rational drug use and optimizes health outcomes. We implemented a formulary management program integrating the principles of health technology assessment (HTA) to improve the safe, appropriate, and cost-effective use of medicine in Singapore. METHODS: A 3-year formulary management program was initiated in 2011 in five public healthcare institutions. This program was managed by a project team comprising HTA researchers. The project team worked with institutional pharmacy and therapeutics (P&T) committees to: (i) develop tools for formulary drug review and decision making; (ii) enhance the HTA knowledge and skills of formulary pharmacists and members of P&T committees; (iii) devise a prioritization framework to overcome resource constraints and time pressure; and (iv) conceptualize and implement a framework to review existing formulary. RESULTS: Tools that facilitate drug request submission, drug review, and decision making were developed for formulary drug inclusion. A systematic framework to review existing formulary was also developed and tested in selected institutions. A competency development plan was rolled out over 2 years to enhance formulary pharmacists' proficiency in systematic literature search and review, meta-analysis, and pharmacoeconomic evaluation. The plan comprised training workshops and on-the-job knowledge transfer between the project team and institutional formulary pharmacists through collaborating on selected drug reviews. A resource guide that consolidated the tools and templates was published to encourage the adoption of best practices in formulary management. CONCLUSIONS: Based on the concepts of HTA, we implemented an evidence-based approach to optimize formulary management.
Assuntos
Tomada de Decisões , Custos de Medicamentos , Formulários de Hospitais como Assunto , Comitê de Farmácia e Terapêutica/organização & administração , Avaliação da Tecnologia Biomédica/organização & administração , Humanos , Capacitação em Serviço , Farmacêuticos/organização & administração , SingapuraRESUMO
Vitamin D level is linked to susceptibility to infections, but its relevance in candidemia is unknown. We aimed to investigate the in vivo sequelae of vitamin D3 supplementation in systemic Candida infection. Implicating the role of vitamin D in Candida infections, we showed that candidemic patients had significantly lower 25-OHD concentrations. Candida-infected mice treated with low-dose 1,25(OH)2D3 had reduced fungal burden and better survival relative to untreated mice. Conversely, higher 1,25(OH)2D3 doses led to poor outcomes. Mechanistically, low-dose 1,25(OH)2D3 induced proinflammatory immune responses. This was mediated through suppression of SOCS3 and induction of vitamin D receptor binding with the vitamin D-response elements in the promoter of the gene encoding interferon γ. These beneficial effects were negated with higher vitamin D3 doses. While the antiinflammatory effects of vitamin D3 are well described, we found that, conversely, lower doses conferred proinflammatory benefits in Candida infection. Our study highlights caution against extreme deviations of vitamin D levels during infections.
Assuntos
Candidíase/tratamento farmacológico , Colecalciferol/farmacologia , Vitamina D/sangue , Animais , Candidíase/imunologia , Colecalciferol/administração & dosagem , Estudos de Coortes , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Interferon gama/metabolismo , Leucócitos Mononucleares , Camundongos , Camundongos Endogâmicos BALB C , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismoAssuntos
Autoanticorpos , Síndromes de Imunodeficiência , Humanos , Interferon gama , Tailândia , Estados UnidosRESUMO
PURPOSE: This study aimed to evaluate the cost-effectiveness of statins for primary prevention of stroke and myocardial infarction (MI) in the elderly in Singapore. METHODS: A Markov model was developed to investigate the lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) of statin treatment in those aged 65 years and older without a history of stroke or MI from the perspective of Singapore's healthcare system, using elderly-specific clinical data and local costs from hospital databases. A lifetime horizon was used and all costs and health outcomes were discounted at 3% annually. RESULTS: In the base-case analysis, statin treatment prevented an additional four strokes and eight MIs among 1,000 "healthy" elderly individuals compared with no treatment. Statin treatment resulted in a QALY gain of 0.26 and additional costs of SGD 11,314 per person, yielding an ICER of SGD 43,925 (USD 33,495) per QALY gained. The results were sensitive to statin effectiveness, particularly statins' effect on all-cause mortality, and cost of statin medication. Probabilistic sensitivity analysis demonstrated that the probability of statin treatment being cost-effective was 72% at a willingness-to-pay threshold of SGD 65,000 (USD 49,546) per QALY gained. Shortening the time horizon from lifetime to 10 years (simulating limited life expectancy) considerably increased the ICER to SGD 291,313 (USD 167,171) per QALY. Female gender and younger age were also associated with higher ICERs owing to a lower baseline risk of cardiovascular disease (CVD) and higher costs to manage events in these subgroups. CONCLUSIONS: Statin treatment for the primary prevention of CVD in the elderly was cost-effective. However, treatment warrants re-evaluation when the prognosis of the individual is considered less than ten years; other goals may take precedence over CVD prevention.
Assuntos
Análise Custo-Benefício/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Prevenção Primária/economia , Acidente Vascular Cerebral/prevenção & controle , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Modelos Econômicos , Infarto do Miocárdio/economia , Anos de Vida Ajustados por Qualidade de Vida , Caracteres Sexuais , Singapura , Acidente Vascular Cerebral/economiaRESUMO
OBJECTIVE: To systematically review the efficacy and tolerability of 4 prostaglandin analogues (PGAs) as first-line monotherapies for intraocular pressure (IOP) lowering in adult patients with primary open-angle glaucoma or ocular hypertension. DATA SOURCES: A literature search was performed in PubMed (1965-June 2013) and the Cochrane Library (1980-June 2013) using the search terms ocular hypertension, open-angle glaucoma, prostaglandin analogues, bimatoprost, latanoprost, tafluprost, and travoprost. Additional studies were searched from the reference lists of identified publications. STUDY SELECTION AND DATA EXTRACTION: In all, 32 randomized controlled trials comparing between PGAs (bimatoprost 0.03%, latanoprost 0.005%, tafluprost 0.0015%, and travoprost 0.004%) or PGA with timolol were selected. DATA SYNTHESIS: A network meta-analysis was conducted. Using timolol as reference, the relative risks (RRs) of achieving treatment success, defined as the proportion of patients achieving at least 30% IOP reduction, with 95% CIs, were as follows: bimatoprost, 1.59 (1.28-1.98); latanoprost, 1.32 (1.00-1.74); travoprost, 1.33 (1.03-1.72); and tafluprost, 1.10 (0.85-1.42). The mean IOP reductions after 1 month were 1.98 (1.50-2.47), 1.01 (0.55-1.46), 1.08 (0.59-1.57), and 0.46 (-0.41 to 1.33) mm Hg, respectively, and the results were sustained at 3 months. Bimatoprost was associated with the highest risk of developing hyperemia, whereas latanoprost had the lowest risk, with RRs (95% CI) of 4.66 (3.49-6.23) and 2.30 (1.76-3.00), respectively. CONCLUSIONS: Bimatoprost achieved the highest efficacy in terms of IOP reduction, whereas latanoprost had the most favorable tolerability profile. This review serves to guide selection of the optimal PGA agent for individual patient care in clinical practice.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Ocular/tratamento farmacológico , Prostaglandinas Sintéticas/uso terapêutico , Amidas/efeitos adversos , Amidas/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bimatoprost , Cloprostenol/efeitos adversos , Cloprostenol/análogos & derivados , Cloprostenol/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Latanoprosta , Hipertensão Ocular/fisiopatologia , Prostaglandinas F/efeitos adversos , Prostaglandinas F/uso terapêutico , Prostaglandinas F Sintéticas/efeitos adversos , Prostaglandinas F Sintéticas/uso terapêutico , Prostaglandinas Sintéticas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Timolol/uso terapêutico , TravoprostRESUMO
BACKGROUND: High-alert medications can cause significant patient harm when used in error. A multicenter, multidisciplinary, high-alert medication collaborative was established in Singapore in 2009 to identify and maintain a current list of high-alert medications and to create systematic approaches for preventing and reducing the risk of medication errors and adverse drug events (ADEs) for high-alert medications. METHODS: The collaborative was led by a core multidisciplinary team consisting of pharmacists, nurses, and physicians, as well as clinical services and quality personnel, from six primary and acute care institutions. Multidisciplinary work groups were formed to drive the improvement efforts using the Plan-Do-Study-Act (PDSA) cycles. Tracking of improvement work was conducted with an adaptation of the Institute for Healthcare Improvement Trigger Tool method. RESULTS: A localized high-alert medication list was developed through local ADE reports, literature review, an online survey of health care professionals, and expert opinion. Some 130 interventions were proposed to prevent, detect, and mitigate harm from the use of high-alert medications for 10 drug classes/drugs. A significant number of these interventions were tested and revised during the PDSA cycles before implementation throughout the institution and subsequent spread to other institutions. Outcome audits identified areas for improvement. The interventions, which were subsequently incorporated into the change packages, led to a 50% and 67% decline in the ADE rates for radiocontrast agents and heparin, respectively. CONCLUSION: The collaborative has provided a sound framework for ongoing development and refinement of high-alert medication change packages and for sharing of ADE data and best practices across the participating institutions.
Assuntos
Erros de Medicação/prevenção & controle , Segurança do Paciente , Melhoria de Qualidade , Sistemas de Notificação de Reações Adversas a Medicamentos , Comportamento Cooperativo , Pesquisa sobre Serviços de Saúde , Humanos , Sistemas de Medicação no Hospital , SingapuraRESUMO
Vitamin D(3) affects both the innate as well as adaptive immune responses. Epidemiological studies have established that vitamin D(3) deficiency plays an important role in tuberculosis (TB) and viral influenza prevalence as well as susceptibility to active disease in TB. Vitamin D(3) status has been associated with the clinical course of HIV infection and drug interaction with anti-retroviral therapy. This article reviews the immunomodulatory capacity of vitamin D(3) and examines the impact of vitamin D(3) supplementation as a preventive or therapeutic intervention with the intent to uncover its potential therapeutic application in infectious diseases and to identify novel areas for future research. We present a review of randomized, controlled clinical studies conducted in humans which included assessment of the immune function or clinical outcome as study end points. Current data support vitamin D(3) supplementation as risk-modifying intervention in tuberculosis and viral respiratory tract infection, but the optimal dosage regimen remains to be determined. However, to date the knowledge on its role in fungal infection and sepsis is limited although a potential benefit could be harnessed from its ability to curtail the unrestrained pro-inflammatory response and therefore prevent excessive collateral tissue damage.
Assuntos
Colecalciferol/farmacologia , Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis/tratamento farmacológico , Fatores Imunológicos/farmacologia , Colecalciferol/administração & dosagem , Humanos , Fatores Imunológicos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/prevenção & controle , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controleRESUMO
BACKGROUND: Our interest in immunological effects produced by vitamin D(3) (1,25(OH)(2)D(3)) and its therapeutic potential prompted us to examine the role of 1,25(OH)(2)D(3) on cytokine production by Candida albicans. METHODS: Peripheral blood mononuclear cells (PBMC) with stimulated C. albicans and 1,25(OH)(2)D(3), cytokine concentrations were measured in supernatant. Quantitative polymerase chain reaction (qPCR) was performed for T cell transcription factors, SOCS1 and 3. TLR2/4, Dectin-1, and mannose receptor expression was studied using flow cytometry and qPCR. An ex-vivo stimulation study was carried out in healthy volunteers to investigate the seasonality of immune response to C. albicans. RESULTS: Upon in vitro C. albicans stimulation, 1,25(OH)(2)D(3) induced a dose-dependent, down-regulation of IL-6, TNFα, IL-17, and IFNγ. It also increased IL-10 production. The shift in cytokine profile was not due to 1,25(OH)(2)D(3) augmenting expression of either Thelper differentiation factors or SOCS1 and SOCS3 mRNA. 1,25(OH)(2)D(3) inhibited TLR2, TLR4, Dectin-1, and MR mRNA and protein expression. In our seasonality study, both IL-17 and IFNγ levels were suppressed in summer when 25(OH)D(3) levels were elevated. CONCLUSION: Vitamin D(3) skews cytokine responses toward an antiinflammatory profile, mediated by suppression of TLR2, TLR4, Dectin-1, and MR transcription, leading to reduced surface expression. The biological relevance of these effects has been confirmed by the seasonality of cytokine responses.
Assuntos
Calcitriol/farmacologia , Candida albicans/imunologia , Citocinas/metabolismo , Fatores Imunológicos/farmacologia , Adulto , Células Cultivadas , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Lectinas Tipo C/análise , Leucócitos Mononucleares/química , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Masculino , Receptor de Manose , Lectinas de Ligação a Manose/análise , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/análise , Receptores de Superfície Celular/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estações do Ano , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/análise , Receptor 2 Toll-Like/análise , Receptor 4 Toll-Like/análiseRESUMO
Vitamin D3 is known to induce regulatory T (Treg) cells by rendering antigen-presenting cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here, we investigated if and how 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] can directly affect the proliferation and function of human naturally occurring Treg cells in vitro. First, we demonstrated that these Treg cells express vitamin D receptors that were up-regulated following anti-CD3/CD28-bead stimulation. 1,25(OH)2D3 inhibited proliferation of Treg cells even when exogenous interleukin-2 was provided. Treg cells were more susceptible to the inhibitory effect of 1,25(OH)2D3 than conventional T cells(.) 1,25(OH)2D3 neither affected the anergic state nor the suppressive function of Treg cells but induced a subtle increase in interleukin-10-secreting cells. The cell-division-inhibiting effect of 1,25(OH)2D3 on Treg cells was also demonstrated in vivo by supplementing vitamin D-deficient HIV-1-infected patients with 2000 IU cholecalciferol (vitamin D3). Increased serum 1,25(OH)2D3 levels were associated with a drop in the number and percentage of Treg cells, which may be attributed to a decrease in the proliferating Foxp3+ Treg cell population. In conclusion, 1,25(OH)2D3 directly affects Treg cell growth and promotes interleukin-10 production without apparent effects on activation status and suppressive phenotype whereas in vivo, high serum 1,25(OH)2D3 levels are associated with reduced Treg cell proliferation and a reduced number of Treg cells.
Assuntos
Células Apresentadoras de Antígenos , Linfócitos T Reguladores , Vitamina D/análogos & derivados , Apresentação de Antígeno/efeitos dos fármacos , Apresentação de Antígeno/imunologia , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Interleucina-10/biossíntese , Interleucina-10/imunologia , Interleucina-2/imunologia , Ativação Linfocitária/efeitos dos fármacos , Receptores de Calcitriol/biossíntese , Receptores de Calcitriol/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Vitamina D/imunologia , Vitamina D/farmacologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/imunologiaRESUMO
A well-known association between vitamin D(3) and infection with Mycobacterium tuberculosis has previously been reported, but little is known regarding the underlying mechanisms. We have investigated how 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] affects the proinflammatory cytokine production induced by M. tuberculosis. Furthermore, we explored whether 1,25(OH)(2)D(3) influence the production of the protective antimycobacterial peptide cathelicidin. Upon in vitro stimulation with M. tuberculosis, 1,25(OH)(2)D(3) induced a dose-dependent down-regulation of IL-6, TNFα and IFNγ, while increasing the production of IL-10 in culture supernatant as well as cathelicidin mRNA expression. This effect on cytokine response was not due to modulation of T-helper cell differentiation, as T-bet, GATA3, Foxp3 and ROR-γt mRNA expression remained unaffected. Similarly, 1,25(OH)(2)D(3) did not affect suppressor of cytokine signaling (SOCS)1 and SOCS3 mRNA expression. The mechanism whereby 1,25(OH)(2)D(3) inhibited the proinflammatory cytokine response was through reduced expression of the pattern recognition receptors (PRR) - TLR2, TLR4, Dectin-1 and mannose receptor, whose mRNA and protein expression were both reduced. The suppression of PRRs could be restored by a VDR antagonist. Upon M. tuberculosis stimulation, 1,25(OH)(2)D(3) modulates the balance in cytokine production towards an anti-inflammatory profile by repression of TLR2, TLR4, Dectin-1 and mannose receptor expression, while increasing cathelicidin production. These two effects may have beneficial consequences, by reducing the collateral tissue damage induced by proinflammatory cytokines, while the antibacterial effects of cathelicidin are enhanced.
Assuntos
Catelicidinas/biossíntese , Colecalciferol/farmacologia , Citocinas/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/microbiologia , Mycobacterium tuberculosis/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Receptores de Reconhecimento de Padrão/genética , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
AIM: Neurostimulation techniques are effective treatments for major depressive disorders (MDD). However, the optimal sequence of electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) as part of antidepressant treatment algorithm is unclear. We examined the cost-effectiveness of ECT and TMS in MDD. METHODS: A decision-analytic model was developed to determine total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) for 10 strategies. Each strategy comprised four treatment lines with ECT and TMS incorporated as second, third, or fourth line. A scenario analysis that explored the cost-effectiveness of maintenance approach by continuing ECT and TMS after acute treatment was performed. RESULTS: In the base case, fourth-line TMS after three preceding trials of antidepressants was least costly at US$ 5523 yielding 1.424 QALYs. Compared with this strategy, fourth-line ECT and third-line TMS followed by ECT were cost-effective with ICERs of US$ 7601 per QALY gained and US$ 11 388 per QALY gained, respectively. In the scenario analysis where continuation treatments of ECT and TMS were provided, third-line TMS followed by ECT was cost-effective, with an ICER of US$ 17 198 per QALY gained. Effectiveness of ECT and cost of managing severe depression were influential parameters affecting the cost-effectiveness results. CONCLUSIONS: In acute treatment of MDD, fourth-line ECT was the most cost-effective strategy. In maintenance treatment, the strategy that incorporated third-line TMS and fourth-line ECT was cost-effective. The overall findings confirmed the value of neurostimulation therapies which should be offered early in the process of managing depression.
Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Antidepressivos/uso terapêutico , Análise Custo-Benefício , Transtorno Depressivo Maior/tratamento farmacológico , Eletroconvulsoterapia/métodos , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Estimulação Magnética Transcraniana/métodosRESUMO
Serial galactomannan (GM) monitoring can aid the diagnosis of invasive aspergillosis (IA) and optimise treatment decisions. However, widespread adoption of mould-active prophylaxis has reduced the incidence of IA and challenged its use. We evaluated the cost-effectiveness of prophylaxis-biomarker strategies. A Markov model simulating high-risk patients undergoing routine GM surveillance with mould-active versus non-mould-active prophylaxis was constructed. The incremental cost for each additional quality-adjusted life-year (QALY) gained over a lifetime horizon was calculated. In 40- and 60-year-old patients receiving mould-active prophylaxis coupled with routine GM surveillance, the total cost accrued was the lowest at SGD 11,227 (USD 8255) and SGD 9234 (USD 6790), respectively, along with higher QALYs gained (5.3272 and 1.1693). This strategy, being less costly and more effective, dominated mould-active prophylaxis with no GM monitoring or GM surveillance during non-mould-active prophylaxis. The prescription of empiric antifungal treatment was influential in the cost-effectiveness. When the GM test sensitivity was reduced from 80% to 30%, as might be anticipated with the use of mould-active prophylactic agents, the conclusion remained unchanged. The likelihood of GM surveillance with concurrent mould-active prophylaxis being cost-effective was 77%. Routine GM surveillance remained cost-effective during mould-active prophylaxis despite lower IA breakthroughs. Cost-saving from reduced empirical antifungal treatment was an important contributing factor.
RESUMO
Both interferon-gamma-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the relative importance of the Th1 versus Th17 cellular immune pathways for the human anti-Aspergillus host defence. Using human peripheral blood mononuclear cells and a system consisting of monocyte-derived macrophages with lymphocytes, we found that Aspergillus fumigatus is a weak inducer of human IL-17 but induces a strong Th1 response. These data were validated by the very low IL-17 levels in bronchoalveolar lavage fluid and serum of patients with invasive aspergillosis. Surprisingly, live A. fumigatus reduced IL-17 production induced by mitogenic stimuli. This effect was mediated through the propensity of A. fumigatus to metabolize tryptophan and release kynurenine, which modulates the inflammatory response through inhibition of IL-17 production. In conclusion, A. fumigatus does not stimulate production of IL-17 and human host defence against aspergillosis may not rely on potent Th17 responses.
Assuntos
Aspergilose/imunologia , Aspergillus fumigatus/imunologia , Interleucina-17/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Células Th1/imunologia , Separação Celular , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Interleucina-17/biossíntese , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/metabolismoRESUMO
CONTEXT: Coconut oil is rich in medium-chain fatty acids and has been claimed to have numerous health benefits. OBJECTIVE: This review aimed to examine the evidence surrounding coconut oil consumption and its impact on cardiovascular health. DATA SOURCES: A systematic literature search of the PubMed, Embase, the Cochrane Library, and CINAHL databases, up to May 2019, was performed. DATA EXTRACTION: Study characteristics including study design, population, intervention, comparator, outcome, and source of funding were summarized. DATA ANALYSIS: Meta-analyses included 12 studies to provide estimates of effects. Subgroup analyses were performed to account for any differences in the study-level characteristics. When compared with plant oils and animal oils, coconut oil was found to significantly increase high-density lipoprotein cholesterol (HDL-C) by 0.57 mg/dL (95%CI, 0.40-0.74 mg/dL; I2 = 6.7%) and 0.33 mg/dL (0.01-0.65 mg/dL; I2 = 0%), respectively. Coconut oil significantly raised low-density lipoprotein cholesterol (LDL-C) by 0.26 mg/dL (0.09-0.43 mg/dL; I2 = 59.7%) compared with plant oils and lowered LDL-C (-0.37 mg/dL; -0.69 to -0.05 mg/dL; I2 = 48.1%) compared with animal oils. No significant effects on triglyceride were observed. Better lipid profiles were demonstrated with the virgin form of coconut oil. CONCLUSION: Compared with animal oils, coconut oil demonstrated a better lipid profile n comparison with plant oils, coconut oil significantly increased HDL-C and LDL-C.
Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Óleo de Coco/farmacologia , Óleo de Coco/metabolismo , Humanos , Óleos de Plantas/farmacologia , Triglicerídeos/sangueRESUMO
OBJECTIVES: Nosocomial infection is an ongoing concern in the COVID-19 outbreak. The effective screening of suspected cases in the healthcare setting is therefore necessary, enabling the early identification and prompt isolation of cases for epidemic containment. We aimed to assess the cost and health outcomes of an extended screening strategy, implemented in Singapore on 07 February 2020, which maximizes case identification in the public healthcare system. METHODS: We explored the effects of the expanded screening criteria which allow clinicians to isolate and investigate patients presenting with undifferentiated fever or respiratory symptoms or chest x-ray abnormalities. We formulated a cost appraisal framework which evaluated the treatment costs averted from the prevention of secondary transmission in the hospital setting, as determined by a branching process infection model, and compared these to the costs of the additional testing required to meet the criteria. RESULTS: In the base case analysis, an R0 of 2.5 and incubation period of 4 days, an estimated 239 (95% CI: 201-287) cases could be averted over 150 days within the hospital setting through ESC. A corresponding $2.36 (2-2.85) million USD in costs could be averted with net cost savings of $124,000 (95% CI: -334,000 to 516,000). In the sensitivity analyses, when positive identification rates (PIR) were above 7%, regardless of R0 and incubation period, all scenarios were cost-saving. CONCLUSION: The expanded screening criteria can help to identify and promptly isolate positive COVID cases in a cost-saving manner or within acceptable cost margins where the costs incurred from the testing of negative patients could be negated by the averted costs. Outbreak control must be sustainable and effective; the proposed screening criteria should be considered to mitigate nosocomial transmission risk within healthcare facilities.
Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico/economia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adulto , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/economia , Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/prevenção & controle , Feminino , Custos de Cuidados de Saúde , Humanos , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , SARS-CoV-2 , Adulto JovemRESUMO
AIM: Compared with second-generation durable polymer drug-eluting stents (DP-DES), the cost-effectiveness of biodegradable polymer drug-eluting stents (BP-DES) remains unclear in the real-world setting. We assessed the cost-effectiveness of BP-DES in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS: We developed a decision-analytic model to compare the cost-effectiveness of BP-DES to DP-DES over 1 year and 5 years from healthcare payer perspective. Relative treatment effects during the first year post-PCI were obtained from a real-world population analysis while clinical event risks in the subsequent 4 years were derived from a meta-analysis of published studies. RESULTS: At 1 year, based on the clinical data analysis of 497 propensity-score matched pairs of patients, BP-DES were associated with an incremental cost-effectiveness ratio (ICER) of USD20 503 per quality-adjusted life-year (QALY) gained. At 5 years, BP-DES yielded an ICER of USD4062 per QALY gained. At the willingness-to-pay threshold of USD50 400 (one gross domestic product per capita in Singapore in 2015), BP-DES were cost-effective. Sensitivity analysis showed that the cost of stents had a significant impact on the cost-effectiveness of BP-DES. Threshold analysis demonstrated that if the cost difference between BP-DES and DP-DES exceeded USD493, BP-DES would not be cost-effective in patients with 1 year of follow-up. CONCLUSIONS: Biodegradable polymer drug-eluting stents were cost-effective compared with DP-DES in patients with coronary artery disease at 1 year and 5 years after PCI. It is worth noting that the cost of stents had a significant impact on the findings.