RESUMO

Modern randomization methods in clinical trials are invariably adaptive, meaning that the assignment of the next subject to a treatment group uses the accumulated information in the trial. Some of the recent adaptive randomization methods use mathematical programming to construct attractive clinical trials that balance the group features, such as their sizes and covariate distributions of their subjects. We review some of these methods and compare their performance with common covariate-adaptive randomization methods for small clinical trials. We introduce an energy distance measure that compares the discrepancy between the two groups using the joint distribution of the subjects' covariates. This metric is more appealing than evaluating the discrepancy between the groups using their marginal covariate distributions. Using numerical experiments, we demonstrate the advantages of the mathematical programming methods under the new measure. In the supplementary material, we provide R codes to reproduce our study results and facilitate comparisons of different randomization procedures.

RESUMO

BACKGROUND: Argentina currently uses a pentavalent vaccine containing diphtheria, tetanus, pertussis (whole cell), Haemophilus influenza type b and hepatitis B antigens, administered concomitantly with the inactivated polio vaccine (IPV) (DTwP-Hib-HB plus IPV) in its childhood vaccination schedule. However, hexavalent vaccines containing acellular pertussis antigens (DTaP-Hib-HB-IPV) and providing protection against the same diseases are also licensed, but are only available with a private prescription or for high-risk pre-term infants in the public health program. We analyzed the cost of switching from the current schedule to the alternative schedule with the hexavalent vaccine in Argentina, assuming similar levels of effectiveness. METHODS: The study population was infants ≤ 1 year of age born in Argentina from 2015 to 2019. The analysis considered adverse events, programmatic, logistic, and vaccine costs of both schemes from the societal perspective. The societal costs were disaggregated to summarize costs incurred in the public sector and with vaccination pre-term infants in the public sector. Costs were expressed in 2021 US Dollars (US$). RESULTS: Although the cost of vaccines with the alternative scheme would be US$39.8 million (M) more than with the current scheme, these additional costs are in large part offset by fewer adverse event-associated costs and lower programmatic costs such that the overall cost of the alternative scheme would only be an additional US$3.6 M from the societal perspective. The additional cost associated with switching to the alternative scheme in the public sector and with the vaccination of pre-term infants in the public sector would be US$2.1 M and US$84,023, respectively. CONCLUSIONS: The switch to an alternative scheme with the hexavalent vaccine in Argentina would result in marginally higher vaccine costs, which are mostly offset by the lower costs associated with improved logistics, fewer separate vaccines, and a reduction in adverse events.

Assuntos

RESUMO

Human tooth enamel (HTE) is the hardest tissue in the human body and its structural organization shows a hierarchical composite material. At the nanometric level, HTE is composed of approximately 97% hydroxyapatite [HAP, Ca10(PO4)6(OH)2] as inorganic phase, and of 3% as organic phase and water. However, it is still controversial whether the hexagonal HAP phase crystallizes in P63/m or another space group. The observance in HTE of Ca2+, Mg2+ and Na+ ions using X-ray characteristic energy-dispersive spectroscopy in the scanning electron microscope has been explained by substitutions in the HAP unit cell. Thus, Ca2+ can be replaced by Na+ and Mg2+ ions; the PO43- group can be replaced by CO32- ions; and the OH- ions can also be replaced by CO32-. A unit-cell model of the hexagonal structure of HTE is not fully defined yet. In this work, density functional theory calculations are performed to study the hexagonal HAP unit cell when substitution by OH-, CO32-, Mg2+ and Na+ ions are carried out. An approach is presented to study the crystallographic unit cell of HTE by examining the changes resulting from the inclusion of these different ions in the unit cell of HAP. Enthalpies of formation and crystallographic characteristics of the electron diffraction patterns are analysed in each case. The results show an enhancement in structural stability of HAP with OH defects, atomic substitution of Mg2+, carbonate and interstitial Na+. Simulated electron diffraction patterns of the generated structures show similar characteristics to those of human tooth enamel. Hence, the results explain the indiscernible structural changes shown in experimental X-ray diffractograms and electron diffraction patterns.

RESUMO

Historically, owing to the increase in processing capacity over the years, validation and adjustment of measurements have become imperative. In particular, concerning discussions related to data and results in analytical chemistry, there is always a need to improve their reliability. The data reconciliation technique has the objective of using measurement redundancies to obtain the best estimate of the true value and, consequently to minimize its uncertainty. Unfortunately, this powerful tool is less known and used by analytical chemists compared to other areas. This approach can be satisfactorily performed in decision-making procedures that focus on chemical analysis, chemometrics, biochemistry analysis, forensics, and environmental sciences, such as in a characterization study, regarding conformance or nonconformance with the specification, doubts related to the malfunctioning of meters and about the compatibility of test methods. This work discusses and sheds light on the importance of data reconciliation, including data reconciliation statistics and application of the technique, traditional data reconciliation in analytical chemistry, principal component analysis based on data reconciliation in analytical chemistry, and fuzzy data reconciliation in analytical chemistry.

Assuntos

RESUMO

Abstract Introduction: The methods most frequently used at the present time in Colombia for the administration of general anesthesia are based on halogenated and intravenous drugs. However, in view of the lack of differential clinical outcomes, the existence of cost variations between the two is not clear. Objective: To determine the expected cost of the use of both techniques in patients taken to surgery, within the framework of the Colombian national health system. Methods: A cost minimization study was carried out using the decision tree as the analytical model. A time frame of 6 postoperative hours was used as the assumption. Only direct healthcare-related costs were included using a case study approach. An econometric model was used based on the frequency with which each technology is applied and the type of drug used, and a deterministic and probabilistic sensitivity analysis was performed. Results: For the case study, total intravenous anesthesia (TIVA) is more costly than the inhalational technique, with an incremental cost of $102,718 per patient. The deterministic analysis shows that both the incidence of postoperative nausea and vomiting (PONV) as well as the use of target controlled infusion (TCI) techniques are the main cost determinants. The probabilistic analysis shows that the cost difference can even be nil in more than 50% of the simulated settings, when the difference in the risk of PONV is higher. Conclusions: Although the total intravenous technique can be more costly than the inhalational technique, this difference is offset by a lower cost of the postanesthesia care unit, given the lower risk of postoperative nausea and vomiting.

Resumen Introducción: Actualmente, los métodos más usados en Colombia para la administración de anestesia general son las técnicas basadas en halogenados y en medicamentos intravenosos. No obstante, y ante la falta de desenlaces clínicos diferenciales, no es claro si existe una variación en los costos. Objetivo: Determinar el costo esperado del uso de ambas técnicas en pacientes llevados a cirugía bajo la perspectiva del sistema nacional de salud colombiano. Métodos: Se realizó un estudio de minimización de costos. Se empleó el árbol de decisión como modelo analítico. Se asumió un horizonte temporal de 6 horas postoperatorio. Se incluyeron solo los costos sanitarios directos mediante un caso tipo. Se empleó un modelo econométrico basado en la frecuencia de uso de cada tecnología y medicamento empleado y se realizó análisis de sensibilidad determinístico y probabilístico. Resultados: Para el caso tipo, la técnica total endovenosa es más costosa que la técnica basada en halogenados, con un costo incremental de $102.718 por paciente. El análisis determinístico muestra que tanto la incidencia de náuseas y vómito postoperatorio como el uso de tecnologías TCI (targetcontrolled infution) son los principales determinantes de estos costos. El análisis probabilístico muestra que la diferencia de costos puede ser incluso de cero pesos en más del 50 % de los escenarios simulados cuando se tiene una mayor diferencia del riesgo de náuseas y vómito postoperatorio. Conclusiones: Aunque la técnica total endovenosa puede ser más costosa que la basada en halogenados, esto se compensa con un costo inferior en la unidad de recuperación postanestésica debido a un menor riesgo de náuseas y vómito postoperatorio.

Assuntos

RESUMO

BACKGROUND: This study aimed to estimate the economic impact of replacing the current Peruvian primary immunization scheme for infants under 1 year old with an alternative scheme with similar efficacy, based on a hexavalent vaccine. METHODS: A cost-minimization analysis compared the costs associated with vaccine administration, adverse reactions medical treatment, logistical activities, and indirect social costs associated with time spent by parents in both schemes. A budgetary impact analysis assessed the financial impact of the alternative scheme on healthcare budget. RESULTS: Incorporating the hexavalent vaccine would result in a 15.5% net increase in healthcare budget expenditure ($48,281,706 vs $55,744,653). Vaccination costs would increase by 54.1%, whereas logistical and adverse reaction costs would be reduced by 59.8% and 33.1%, respectively. When including indirect social costs in the analysis, the budgetary impact was reduced to 8.7%. Furthermore, the alternative scheme would enable the liberation of 17.5% of national vaccines storage capacity. CONCLUSIONS: Despite of the significant reduction of logistical and adverse reaction costs, including the hexavalent vaccine into the National Immunization Program of Peru in place of the current vaccination scheme for infants under 1 year of age would increase the public financial budget of the government as it would represent larger vaccine acquisition costs. Incorporating the indirect costs would reduce the budgetary impact demonstrating the social value of the alternative scheme. This merits consideration by government bodies, and future studies investigating such benefits would be informative.

Assuntos

RESUMO

This review aims to evaluate the production and processing chain of camu-camu (Myrciaria dubia), giving suggestions to maximize the valorization of raw materials, demonstrating new product possibilities from processing to distribution and highlighting the suggested contributions. It is clear that despite the camu-camu pulp has important properties, a large part of its raw material, considered waste (around 50%) and formed by important bioactive compounds, can give rise to new products, such as bioactive extracts to be used by pharmaceutical, chemical and food industries, ingredients for bakery products, dairy and several others sectors, which constitutes opportunities, in addition to contributing to the reduction of agro-industrial waste and the preservation of the environment.

Assuntos

RESUMO

Rapadura is an artisanal candy obtained from concentrated sugarcane juice. In this study, a differentiation between South American rapadura producers has been tried using a Kurtosis-based projection pursuit analysis (kPPA) concerning essential minerals, acrylamide, moisture contents, pH, and color. These parameters revealed significant inter- and intra-country differences. Based on the employed measurements, a multivariate exploration with kPPA extracted information from rapadura even though it is a very artisanal product and was effective in separating classes, especially Brazilian and Ecuadorian rapadura, where principal component analysis failed. Moreover, ellipse confidence regions showed significant differences between non-organic and organic rapadura from Colombia and Peru in granulated form. From a chemometric point of view, the application of kPPA can be used in cases when other metrics (as based on the variance) fail and can be useful in the exploratory analysis of complex multivariate chemical data.

Assuntos

RESUMO

OBJECTIVES: To evaluate cost implications of a hexavalent vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]-inactivated polio vaccine [IPV]-hepatitis B [HB]-Haemophilus influenzae type B [Hib] polysaccharide conjugated to T protein [PRP∼T]) as an alternative to DT-whole-cell pertussis (wP)-HB//Hib, DTwP, IPV, and oral polio vaccines in the Expanded Program on Immunization schedule in Colombia. METHODS: Primary vaccination (DTaP-IPV-HB-PRP∼T or DTwP-HB-Hib + IPV [2, 4, 6 months]) and booster (DTaP-IPV-HB-PRP∼T or DTwP + oral polio vaccine [18 months]) (scenario 1) and primary vaccination only (DTaP-IPV-HB-PRP∼T or DTwP-HB-Hib + IPV) (scenario 2) were evaluated. An estimated cost-minimization analysis was based on a micro costing technique for vaccination-associated activities. Adverse event (AE)-associated costs, out-of-pocket costs, and productivity losses for caregivers were included. A budget impact (12-month temporal horizon) was estimated according to the distribution of full-term and premature infants. A 5% annual discount rate was used. A 2-way univariate (tornado) analysis evaluated which variables had the greatest impact on the overall cost. RESULTS: DTaP-IPV-HB-PRP∼T resulted in a cost increase of 29.38% (scenario 1) and 22.19% (scenario 2) for full-term infants and a decrease of 0.99% (scenario 1) and 18.88% (scenario 2) for premature infants, probably because of the higher incidence of wP-related AEs and associated costs in premature infants. With a 100% replacement rate, the budget impact for full-term infants and full-term plus premature infants was 23.73% and 21.80% (scenario 1), respectively, and 13.02% and 11.14% (scenario 2), respectively, of the national immunization program budget. The variables with most impact were the hexavalent vaccine price and costs associated with the pentavalent safety profile. CONCLUSIONS: Incorporation of the hexavalent vaccine in the Expanded Program on Immunization schedule would lead to an increase in spending largely mitigated by reduced AE incidence and reduced logistic and social costs.

Assuntos

RESUMO

Aims: Cost-minimization analysis (CMA) comparing the teledermatology service of the State of Santa Catarina, Brazil with the provision of conventional care, from the societal perspective. Patients & methods: All costs related to direct patient care were considered in calculation of outpatient costs. The evaluation was performed using the parameters avoided referrals and profile of hospitalizations. The economic analysis was developed through a decision tree. Results: Totally, 40% of 79,411 tests performed could be managed in primary care, avoiding commuting and expanding the patients' access. The CMA showed the teledermatology service had a cost per patient of US$196.04, and the conventional care of US$245.66. Conclusion: In this scenario, teledermatology proved to be a cost-saving alternative to conventional care, reducing commuting costs.

Lay abstract Diagnosis and treatment of skin diseases through teledermatology avoid patient referrals, improves accessibility to specialized care, as well as the skin care provided by physicians. This study compared the costs of the teledermatology service of the State of Santa Catarina, Brazil with the costs of the provision of conventional care, to check which of them was more efficient. All costs related to direct patient care were considered in the calculation of costs. Totally, 40% of 79,411 dermatological tests performed could be locally managed in primary care, avoiding commuting, and expanding the patients' access to care. The teledermatology service had a cost per patient of US$196.04, compared with the cost of conventional care of US$245.66. In this evaluation, teledermatology proved to be cheaper than conventional care, reducing commuting costs.

Assuntos