3D-QSARpy: Combining variable selection strategies and machine learning techniques to build QSAR models

Abstract Quantitative Structure-Activity Relationship (QSAR) is a computer-aided technology in the field of medicinal chemistry that seeks to clarify the relationships between molecular structures and their biological activities. Such technologies allow for the acceleration of the development of new compounds by reducing the costs of drug design. This work presents 3D-QSARpy, a flexible, user-friendly and robust tool, freely available without registration, to support the generation of QSAR 3D models in an automated way. The user only needs to provide aligned molecular structures and the respective dependent variable. The current version was developed using Python with packages such as scikit-learn and includes various techniques of machine learning for regression. The diverse techniques employed by the tool is a differential compared to known methodologies, such as CoMFA and CoMSIA, because it expands the search space of possible solutions, and in this way increases the chances of obtaining relevant models. Additionally, approaches for select variables (dimension reduction) were implemented in the tool. To evaluate its potentials, experiments were carried out to compare results obtained from the proposed 3D-QSARpy tool with the results from already published works. The results demonstrated that 3D-QSARpy is extremely useful in the field due to its expressive results.

Ameliorating effects of ethanol extract of root bark of Salacia nitida on blood electrolyte and renal perturbations in Plasmodium berghei-infected mice

Abstract Malaria, a disease of public health concern is a known cause of kidney failure, and dependence on herbal medicines for its treatment is increasing due to the high cost of drugs. So this study is designed to evaluate the ameliorating effect of ethanol extract from Salacia nitida root bark on electrolyte and renal perturbations in Plasmodium berghei-infected mice. Thirty malariainfected mice divided into five groups of six mice each and another group of six uninfected mice were used for the study. 280, 430, and 580 mg/kg of extract were given to infected mice in groups B, C, and D, 4 mg/kg of artesunate given to group E mice, and 4 ml/kg of physiological saline given to group A and uninfected group F mice for five days. Serum Na+, K+, HCO3, Cl-, TB, urea, creatinine, BUN concentrations, and BUN/creatinine ratio were determined using standard methods. Results showed significant increases (p < 0.05) in Na+, K+, and HCO3 and decreases in Cl-, TB, urea, creatinine, BUN, and BUN/creatinine ratio in the infected treated mice in groups B - E. This study showed that ethanol extract of S. nitida root bark is efficient in the treatment of renal disorders and blood electrolyte perturbations

Moringa oleifera Plant as potent alternate to Chemical Coagulant in Water Purification

Abstract Quality of groundwater is threatened due to pollution by industrial, domestic and agricultural waste. A large number of populations are residing in rural areas which are unable to afford high cost water purifiers due to their low income as well as limited awareness. However, limited availability of fresh water has become a critical issue in developing countries. Around 1.2 billion population is deprived of affordable and safe water for their domestic need. Additionally, chemical coagulants which are nowadays being used for water purification pose severe and numerous health hazards to human. Thus utilization of easily accessible natural coagulant for water purification might offer a sustainable, practical and cost effective solution to the current alarming situation in developing countries. Several experimental findings have shown strong efficiency of Moringa oleifera plant extracts obtained from different solvents in the improvement of water quality parameters including physicochemical (such as pH, hardness, turbidity, metallic impurities, total dissolved solid) and biological (E.coli count) parameter. We have also highlighted the limitations and advantages of chemical coagulation in water purification. Altogether, this review summarizes one such miracle tree which has shown significant potential as a natural coagulant and its associated underlying mechanism in water purification process.

Optimization of glycerol-based medium composition for antifungal metabolites production by Bacillus subtilis

Abstract Bacillus species are promising producers of various compounds that have pronounced antimicrobial, antiviral and antitumor activities. Due to its GRAS status, Bacillus subtilis represents an excellent candidate for the usage in plant pathogens biocontrol. In this research, evaluation of antifungal metabolites biosynthesis by Bacillus subtilis ATCC 6633 and optimization of glycerol-based medium composition, using response surface methodology, for the production of compounds effective against Neurospora crassa were investigated. The results of disc-diffusion method indicate that applied Bacillus strain produces compounds with antifungal activity against tested fungus. In order to find optimal cultivation medium composition, the experiments were carried out in accordance with Box-Behnken design, and optimization was performed using the concept of desirability function combined with previously defined mathematical equation, which describes examined bioprocess. The optimization model predicts that maximum inhibition zone diameter against Neurospora crassa of 32.24 mm is achieved when initial content of glycerol, NaNO2 and K2HPO4 were 49.68 g/L, 2.90 g/L and 6.49 g/L, respectively. Additionally, the second optimization set was made to minimize the consumption of medium components and costs of medium preparation. The obtained results are the basis for further research aimed to develop medium appropriate for economically justified production of bioactive compounds at industrial scale.

Affordability in individuals' healthcare decision making: A concept analysis.

This concept analysis aims to define affordability within the context of healthcare decision making. Affordability is a complex concept that influences an individual's healthcare decision making. In the year's post-Affordable Care Act, the United States has seen an increase in insured individuals, but also an increase in underinsured healthcare consumers. Evidence for the concept attributes was found by searching the Cumulative Index of Nursing and Allied Health Literature, EconLit, Family & Society Studies Worldwide, Humanities Full Text, and PsychINFO databases. Literature was synthesized using the Walker and Avant approach. A new definition was derived with four defining attributes, as well as antecedents and consequences. Three cases are forwarded: the model, borderline, and contrary. In healthcare decision making, affordability is a subjective measure that individuals use in determining the ability to engage in a healthcare service or a durable good transaction. Affordability varies based on circumstances. The context of healthcare decision making of individuals stands in contrast to the decision-making in health systems and to decisions unrelated to one's health. Affordability is a determinant of an individual's ability to engage in a transaction. As such, nurses and policymakers should attempt to understand affordability from the patient's perspective.

Análise Técnico-Econômica para a produção de biofármacos de L-asparaginase / Technical-Economic analysis for the production of L-asparaginase biopharmaceuticals

A enzima L-asparaginase é comumente utilizada como biofármaco para o tratamento da Leucemia Linfoblástica Aguda e possui altas taxas de cura com o medicamento disponível no mercado. Atualmente a aquisição deste biofármaco é fruto integral de importação, não sendo realizada produção nacional, muito embora existam grupos de pesquisas nacionais que trabalham em pesquisas e no desenvolvimento de biofármacos alternativos da L-asparaginase. Assim, a presente dissertação tem como objetivo realizar análises técnico-econômicas para avaliar a viabilidade de implementação industrial de bioprocessos para a produção da L-asparaginase do tipo Erwinase PEGuilada e não PEGuilada, que foram previamente desenvolvidos na FCF-USP. As análises técnico-econômicas foram conduzidas por meio do software SuperPro Design® (Intelligen, Inc.) e permitiram adaptar o processo laboratorial para um processo piloto e possibilitaram estimar os valores de custo de produção unitário (Unity Cost of Production - UPC) de US$ 12,37/mg e US$ 3,46/mg para a L-asparaginase monoPEGuilada e nativa obtida por processo similar, respectivamente. O custo unitário de produção para a enzima peguilada foi, portanto, estimado em cerca de 4 vezes o mesmo custo para a produção da enzima peguilada, sendo tal aumento de custo devido às operações de peguilação, já que ambas as plantas foram mantidas nas mesmas dimensões. Ainda, foram obtidos indicadores econômicos, que indicam a atratividade do processo desenvolvido, muito embora tenham sido identificados diversos gargalos de processo e fatores a serem otimizados e melhorados de forma a tornar o processo mais atrativo sob os pontos de vista técnico e econômico. Em uma análise de sensibilidade preliminar um aumento factível da densidade celular já mostra que é possível reduzir em mais de 30% o UPC. De toda forma, ainda que não otimizado, o processo apresentou valores e dados compatíveis com os biofármacos de L-asparaginase já disponíveis no mercado

The enzyme L-asparaginase is commonly used as a biopharmaceutical in the treatment of Acute Lymphoblastic Leukemia, presenting high cure rates with the formulations available on the market. Nowadays, the acquisition of this biopharmaceutical is only from importation, given that there is no national production being carried out, although there are national research groups working on research and development of alternative L-asparaginase biopharmaceuticals. Thus, this project aims at carrying out technical-economic analyzes to evaluate the viability of industrial implementation of bioprocesses for the production of L-asparaginase of the PEGylated and non-PEGylated Erwinase type previously developed at FCF-USP. The technical-economic analyzes, conducted by means of the software SuperPro Design® (Intelligen, Inc.), allowed to adapt the laboratory process to a pilot process and made it possible to estimate the unit cost of production (UPC) values of US $ 12.37 / mg and US $ 3.56 / mg for monoPEGylated L-asparaginase and bare obtained by similar process, respectively. The unit cost of production for the pegylated enzyme was, therefore, estimated at about 4 times the same cost for the production of the pegylated enzyme, such an increase in cost due to pegylation operations, since both plants were maintained in the same dimensions. Moreover, economic indicators were obtained, which indicate the attractiveness of the developed process. However, several process bottlenecks and factors to be optimized and improved were identified to make the process more attractive from the technical and economic point of view. In a preliminary sensitivity analysis, a feasible increase in cell density already shows that it is possible to reduce UPC by more than 30%. Accordingly, although not optimized, the process presented values and data compatible with the L-asparaginase biopharmaceuticals already available on the market

Modeling biological and economic uncertainty on cell therapy manufacturing: the choice of culture media supplementation.

AIM: To evaluate the cost-effectiveness of autologous cell therapy manufacturing in xeno-free conditions. MATERIALS & METHODS: Published data on the isolation and expansion of mesenchymal stem/stromal cells introduced donor, multipassage and culture media variability on cell yields and process times on adherent culture flasks to drive cost simulation of a scale-out campaign of 1000 doses of 75 million cells each in a 400 square meter Good Manufacturing Practices facility. RESULTS & CONCLUSION: Passage numbers in the expansion step are strongly associated with isolation cell yield and drive cost increases per donor of $1970 and 2802 for fetal bovine serum and human platelet lysate. Human platelet lysate decreases passage numbers and process costs in 94.5 and 97% of donors through lower facility and labor costs. Cost savings are maintained with full equipment depreciation and higher numbers of cells per dose, highlighting the number of cells per passage step as the key cost driver.

Safety cost management in construction companies: A proposal classification.

BACKGROUND: Estimating health and safety costs in the construction industry presents various difficulties, including the complexity of cost allocation, the inadequacy of data available to managers and the absence of an accounting model designed specifically for safety cost management. Very often, the costs arising from accidents in the workplace are not fully identifiable due to the hidden costs involved. OBJECTIVE: This paper reviews some studies of occupational health and safety cost management and proposes a means of classifying these costs. METHODS: We conducted an empirical study in which the health and safety costs of 40 construction worksites are estimated. RESULTS: A new classification of the health and safety cost and its categories is proposed: Safety and non-safety costs. CONCLUSIONS: The costs of the company's health and safety policy should be included in the information provided by the accounting system, as a starting point for analysis and control. From this perspective, a classification of health and safety costs and its categories is put forward.

Chronic Hepatitis C treatment for genotype 2 or 3 in Brazil: cost effectiveness analysis of peginterferon plus ribavirin as first choice treatment

Brazilian Guidelines to HCV treatment (2007) recommended that the first choice treatment for patients with chronic hepatitis C (CHC) and genotype 2 or 3 is interferon alpha (IFN) plus ribavirin (RBV) for 24 weeks. The aim of this study is compare the cost and effectiveness to Hepatitis C treatment in patients with genotype 2 or 3 of peginterferon alpha (PEG) as the first choice of treatment within PEG for those that do not respond to IFN. The target population is CHC patients with genotype 2 or 3 in Brazil. The interventions are: PEG-SEC (first IFN plus RBV for 24 weeks, after, for non-responders and relapsers subsequently PEG plus RBV for 48 weeks); PEG-FIRST24 (PEG+RBV for 24 weeks). The type of the study is cost-effectiveness analysis. The data sources are: Effectiveness data from meta-analysis conducted on the Brazilian population. Treatment cost from Brazilian micro costing study is converted into USD (2010). The perspective is the Public Health System. The outcome measurements are Sustained Viral Response (SVR) and costs. PEG-FIRST24 (SVR: 87.8%, costs: USD 8,338.27) was more effective and more costly than PEG-SEC (SVR: 79.2%, costs: USD 5,852.99). The sensitivity analyses are: When SVR rates with IFN was less than 30% PEG-FIRST is dominant. On the other hand, when SVR with IFN was more then 75% PEG-SEC is dominant (SVR=88.2% and costs USD $ 3,753.00). PEG-SEC is also dominant when SVR to PEG24 weeks was less than 54%. In the Brazilian context, PEG-FIRST is more effective and more expensive than PEG-SEC. PEG-SEC could be dominant when rates of IFN therapy are higher than 75% or rates of PEG24 therapy are lower than 54%.

O protocolo brasileiro de tratamento da Hepatite C (2007) recomendava como primeira escolha para pacientes com hepatite C crônica e portadores de genótipo 2 ou 3 o tratamento com interferona alfa (IFN) associada à ribavirina (RBV), por 24 semanas. O objetivo deste estudo é comparar o custo e a efetividade para pacientes com hepatite C crônica e portadores do genótipo 2 ou 3 o uso de peguinterferon (PEG) como primeiro escolha com o PEG como secunda escolha para aqueles que não responderam ao tratamento com IFN. A população alvo compreende pacientes com hepatite C crônica portadores de genótipo 2 ou 3 no Brasil. As intervenções são: PEG-SEC (IFN + RBV por 24 semanas, para os não respondedores e recidivantes tratamento subsequente com PEG + RBV por 48 semanas; PEG-FIRST24 (PEG + RBV por 24 semanas). O tipo de estudo envolvido é Análise de Custo Efetividade. Os dados de efetividade são provenientes de um metanálise de estudos brasileiros e os dados de custo do tratamento de um estudo de custo do contexto brasileiro. A perspectiva é o Sistema Público de Saúde. Os desfechos avaliados foram Resposta Viral Sustentada (RVS) e Custos. PEG-FIRST24 (RVS: 87,8%, costs: USD 8.338,27) foi mais efetivo e apresentou maior custo que PEG-SEC (RVS: 79,2%, custo USD 5.852,99). A análise de sensibilidade demonstrou que PEG-SEC é dominado por PEG-FIRST24 quando RVS com IFN for menor que 30%. Por outro lado, quando RVS com IFN for maior que 75% PEG-SEC é dominante (RVS=88.2% e custo USD $ 3.753,00). PEG-SEC é também dominante quando RVS para PEG24 for menor que 54%. Conclusão: No contexto brasileiro, PEG-FIRST é mais efetivo e mais custoso que PEG-SEC. PEG-SEC poderia ser dominante quando as taxas de RVS do tratamento com IFN forem superiores a 75% ou as taxas de PEG24 forem inferiores a 54%.

Operationalizing value-based pricing of medicines : a taxonomy of approaches.

The UK Government is proposing a novel form of price regulation for branded medicines, which it has dubbed 'value-based pricing' (VBP). The specifics of how VBP will work are unclear. We provide an account of the possible means by which VBP of medicines might be operationalized, and a taxonomy to describe and categorize the various approaches. We begin with a brief discussion of the UK Government's proposal for VBP and proceed to define a taxonomy of approaches to VBP. The taxonomy has five main dimensions: (1) what is identified as being of value, (2) how each element is measured, (3) how it is valued, (4) how the different elements of value are aggregated, and (5) how the result is then used to determine the price of a medicine. We take as our starting point that VBP will include a measure of health gain and that, as proposed by the UK Government, this will be built on the QALY. Our principal interest is in the way criteria other than QALYs are taken into account, including severity of illness, the extent of unmet need, and wider societal considerations such as impacts on carers. We set out to: (1) identify and describe the full range of alternative means by which 'value' might be measured and valued, (2) identify and describe the options available for aggregating the different components of value to establish a maximum price, and (3) note the challenges and relative advantages associated with these approaches. We review the means by which aspects of VBP are currently operationalized in a selection of countries and place these, and proposals for the UK, in the context of our taxonomy. Finally, we give an initial assessment of the challenges, pros and cons of each approach. We conclude that identifying where VBP should lie on each of the five dimensions entails value judgements: there are no simple 'right or wrong' solutions. If a wider definition of value than incremental QALYs gained is adopted, as is desirable, then a pragmatic way to aggregate the different elements of value, including both QALYs and benefits unrelated to QALYs, is to use a multi-criteria decision analysis (MCDA) approach. All approaches to VBP ultimately require the conversion of value, however assessed, into a monetary price. This requires assessment of the marginal values of all types of benefit, not just of QALYs. All stages of the VBP process are subject to uncertainty and margins of error. Consequently, the assessment of overall value can provide bounds to a price negotiation but cannot be expected to identify a precise value-based price.

Prevalence and costs of hospitalizations for poisoning and accidental intoxication in Brazilian elderly

A cross-sectional study of secondary data/information obtained from the Hospital Information System (HIS) spanning the years 2008 - 2009 was performed. The distribution of the main hospital admissions by gender, age, color/race, region and federal unit of residence, average expenditure and average length of hospital stay, year of hospitalization and mortality rates (MR) were studied. The data collected were tabulated by TabNet and keyed into Microsoft Excel 2007. It was verified that elderly males (54.3%), from 60 to 69 years old (50.6%), nonwhites (36.3%) and residents of Southeast and North regions of the country had the highest rates of hospitalization. Seniors were hospitalized for an average of 4.8 days, and the major causes were exposure to alcohol (43.7%) and to drugs (33.9%). Expenses related to hospital admissions were, on average, R$ 529,817.70. The highest mortality rates were recorded among females (MR = 4.34), in elderly, 80 years or older (MR = 10.16) and Caucasians (MR = 3.95), where pharmacological substances with action on the Autonomic Nervous System were the leading cause of death. There are demographic differences in morbi-mortality of these elderly since, although men and younger elderly were the main victims, women and elderly of advanced age have greater mortality. The leading causes of hospitalization were alcohol and drugs.

Realizou-se um estudo transversal de dados secundários obtidos no Sistema de Informação Hospitalar (SIH), nos anos 2008/2009. Estudou-se a distribuição das principais internações segundo sexo; faixa etária; cor/raça; região e unidade federativa de residência; valor médio pago e média de permanência das internações hospitalares; ano de internação e as taxas de mortalidade (TM). Os dados coletados foram tabulados por meio do TabNet e transcritos para o Programa Microsoft Excel® 2007. Verificou-se que idosos do sexo masculino (54,3%), com 60 e 69 anos de idade (50,6%), não brancos (36,3%) e residentes nas regiões Sudeste e Norte do País apresentaram os maiores percentuais de internação hospitalar. Idosos ficam em média 4,8 dias internados, sendo as principais causas a exposição ao álcool (43,7%) e a medicamentos (33,9%). Os gastos com as internações equivaleram a R$ 529.817,70. As maiores taxas de mortalidade foram registradas no sexo feminino (TM=4,34), em idosos entre 80 anos e superior (TM=10,16) e pessoas brancas (TM=3,95), sendo as substâncias farmacológicas de ação sobre o Sistema Nervoso Autônomo maiores causas do óbito. Existem diferenças demográficas na morbimortalidade desses idosos, visto que apesar de homens e idosos mais jovens serem as principais vítimas, mulheres e idosos com idade mais avançada morrem mais. Sendo as principais causas de internação o álcool e os medicamentos.

A review of cost measures for the economic impact of domestic violence.

Although economic analyses of domestic violence typically guide decisions concerning resource allocation, allowing policy makers to make better informed decisions on how to prioritize and allocate scarce resources, the methods adopted to calculate domestic violence costs have varied widely from study to study. In particular, only a few studies have reviewed the cost measures of the economic impact of domestic violence. This article reviews and compares these measures by covering approaches to categorizing costs, the cost components, and ways to estimate them and recommends an integrated framework that brings the various approaches together. Some issues still need to be addressed when further developing measures such as including omitted but significant measures and expanding the time horizons of others. The implications for future study of domestic violence costs are discussed.

Conducting economic evaluations alongside multinational clinical trials: toward a research consensus.

Demand for economic evaluations in multinational clinical trials is increasing, but there is little consensus about how such studies should be conducted and reported. At a workshop in Durham, North Carolina, we sought to identify areas of agreement about how the primary findings of economic evaluations in multinational clinical trials should be generated and presented. In this paper, we propose a framework for classifying multinational economic evaluations according to (a) the sources of an analyst's estimates of resource use and clinical effectiveness and (b) the analyst's method of estimating costs. We review existing studies in the cardiology literature in the context of the proposed framework. We then describe important methodological and practical considerations in conducting multinational economic evaluations and summarize the advantages and disadvantages of each approach. Finally, we describe opportunities for future research. Delineation of the various approaches to multinational economic evaluation may assist researchers, peer reviewers, journal editors, and decision makers in evaluating the strengths and limitations of particular studies.

[Prospective payment in medical rehabilitation]. / Pauschalierte Vergütung in der medizinischen Rehabilitation.

After introducing DRGs (Diagnosis-Related Groups) in the prospective payment system for German hospitals, the use of per-case reimbursement for medical rehabilitation as well is being discussed. In particular two systems have already been tested internationally. FIM-FRG were especially developed for a prospective payment system for inpatient rehabilitation facilities. RUG-III are used for reimbursing long-term care in nursing homes and are based on a per-day payment. It is recommended to test the FIM-FRG or one of the refined systems in Germany in a pilot project.

Immunization registries: costs and savings.

OBJECTIVES: The objectives of this study were to quantify the actual costs of developing, maintaining, and operating the Boston Immunization Information System (BIIS), an electronic registry and tracking system, and to compare the registry's costs with those of performing the same functions manually. METHODS: Cost data were obtained from 23 BIIS health care sites, the city health department, and 13 control sites. Actual costs of developing and operating BIIS in 1998 and projected 1999 costs for a hypothetical expanded registry were measured. Total costs of registry-supported immunization activities were compared with the costs of similar types and volumes of manual activities. RESULTS: The total annual cost of developing, maintaining, and operating BIIS in 1998 was $345,556. Annual total cost per record was $5.45 for all children aged <23 years and $10 when costs were distributed only among active users (children <8 years old). Operating BIIS saved $26,768 in 1998, compared with manual performance. The hypothetical projected total cost of an expanded BIIS in 1999 would have been $577,919, with a projected savings of $689,403 compared with manual costs. CONCLUSIONS: Electronic immunization registries potentially offer an efficient tool for the delivery of immunization services. Registries can save substantial funds if their data are kept up-to-date, and if caregivers are willing and able to use the registries routinely.

Preparación cervical en el aborto del primer trimestre: médica versus mecánica / Cervical priming in first trimester abortion: medical versus mechanical

Objetivo: El objetivo fue comparar la efectividad en la preparación cervical antes de la evacuación quirúrgica de los análogos de prostaglandinas E2 (PGE2) con los tallos higroscópicos (dilapan, lamicel, laminaria) intracervicales en abortos del primer trimestre.Diseño: Se diseñó un estudio prospectivo randomizado con enfermas ingresadas en el Servicio de Obstetricia del Hospital Universitario La Fe de Valencia por aborto.Método: El material lo integran un grupo de 140 gestantes a las que se le administró una dosis intracervical de 0,5 mg de PGE2 (dinoprostona) en forma de gel y otro grupo de 135 embarazadas a las que se les insertó intracervicalmente tallos osmóticos al menos 8 horas antes del legrado quirúrgico. Se valoró el efecto sobre la dilatación inicial y los efectos secundarios (náuseas, vómitos, diarrea, sangrado, fiebre, etc.), así como las complicaciones en abortos incompletos y diferidos antes de la semana 14 de gestación. También se valoró el impacto económico.Resultados: Hubo diferencias significativas en la capacidad de dilatar el cérvix entre las PGE2 y los tallos (p 0,05). La frecuencia de efectos adversos digestivos fue significativamente mayor en las prostaglandinas, tanto en vómito y diarrea (p < 0,05) como en náuseas (p < 0,01). Las complicaciones sistémicas sólo se observaron en las PGE2, mientras que las locales se objetivaron únicamente con los tallos, siendo mayores con el dilapan que con el lamicel (p < 0,05). La necesidad de dilatación posterior en abortos incompletos fue sólo significativamente mayor con PGE2, en amenorreas inferiores a 9 semanas (p < 0,01) tanto en primigestas (p < 0,01) como plurigestas (p < 0,05). En los abortos diferidos las diferencias sólo fueron significativamente mayores con PGE2 en amenorrea inferior a 9 semanas (p < 0,05), primigestas (p < 0,01) y con BhCG sérica menor de 5.000 mU/ml (p < 0,01). No hubo diferencias en cuanto a edad mayor o menor de 35 años. El coste económico por paciente fue menor con dilapan y lamicel que con laminaria (p < 0,05).Conclusiones: La inserción de tallos osmóticos sintéticos supera a las PGE2 en rapidez de dilatación, pero no los osmóticos naturales (laminaria). Las prostaglandinas se asocian a mayores efectos secundarios. Los tallos son económicamente más baratos, pero las PGE2 son más fáciles de administrar. En aborto incompleto los tallos osmóticos sintéticos superan a las PGE2 en primigestas de embarazos precoces. En aborto diferido los tallos sólo superan a las PGE2 si la primigesta de corta edad gestacional tiene gonadotrofina coriónica (BhCG) sérica baja (AU)

Costing interventions in primary care.

Against a background of increasing demands on limited resources, studies that relate benefits of health interventions to the resources they consume will be an important part of any decision-making process in primary care, and an accurate assessment of costs will be an important part of any economic evaluation. Although there is no such thing as a gold standard cost estimate, there are a number of basic costing concepts that underlie any costing study. How costs are derived and combined will depend on the assumptions that have been made in their derivation. It is important to be clear what assumptions have been made and why in order to maintain consistency across comparative studies and prevent inappropriate conclusions being drawn. This paper outlines some costing concepts and principles to enable primary care practitioners and researchers to have a basic understanding of costing exercises and their pitfalls.

Utilidad de la profilaxis antibiótica en la reducción de la infección de herida en la reparación de la hernia inguinal o crural mediante malla de polipropileno / Utility of antibiotic prophylaxis in reducing wound infection in inguinal or femoral hernia repair using polypropylene mesh

Objetivo. Valorar, mediante un estudio prospectivo aleatorizado, la influencia de la profilaxis antibiótica sobre la incidencia de infección de herida quirúrgica, en la reparación de la hernia inguinal o crural mediante la utilización de prótesis sintéticas de polipropileno. Pacientes y método. Desde junio de 1994 a junio de 1997, fueron intervenidos de forma programada 554 pacientes con hernia inguinal o crural. Treinta pacientes fueron excluidos del estudio por diferentes razones: cirugía urgente (11), tra tamiento con citostáticos o corticoides (5), portadores de VIH/sida (2), portadores de neoplasias concomitantes (1), incumplimiento de la aleatoriedad del protocolo de inclusión (2), falta de seguimiento postoperatorio (2) y colocación de drenaje (7). La selección de pacientes fue aleatoria y doble ciego en dos grupos: cefazolina y placebo. Se realizó una estratificación de los pacientes según su riesgo biológico individual, medido por la clasificación de ASA. El seguimiento de los pacientes fue de 12 meses. La determinación de la homogeneidad de la muestra se realizó mediante tablas 2 * 2. El cálculo del riesgo relativo y odds ratio para un intervalo de confianza del 95 por ciento fue: RR = 1,13 (0,53-2,44). Las pruebas utilizadas fueron la *2 y la t de Student. Resultados. La edad media de los pacientes fue de 54,2 años (rango 17-87). La distribución por sexos fue de 471 varones (89,9 por ciento) y 53 mujeres (10,1 por ciento). El grupo con profilaxis se compuso de 233 pacientes con una tasa de infección de herida del 1,7 por ciento (4 casos). En el grupo placebo se incluyeron 281 pacientes con una tasa de infección de herida del 2,1 por ciento (6 casos) (*2 = 0,737; diferencia no estadísticamente significativa). La estratificación según la clasificación ASA fue la siguiente: ASA-I, 224 (42,7 por ciento); ASA-II, 219 (41,8 por ciento); ASA-III, 78 (14,9 por ciento). La morbilidad general de la serie fue del 7,7 por ciento, con 40 complicaciones (hematomas, 2,7 por ciento; seromas: 2,1 por ciento; infección de herida, 1,9 por ciento [10 casos]; neuropatía inguinal, 0,2 por ciento). De los 10 pacientes con infección de herida, 4 desarrollaron una sepsis local crónica que obligó a la retirada de la malla. Otras variables estudiadas y relacionadas con la infección de herida fueron la edad, duración de la intervención y el ASA, no encontrando diferencias significativas. Conclusiones. La utilización de profilaxis antibiótica no demostró una disminución significativa de la tasa de infección de la herida quirúrgica. Los pacientes con un mayor riesgo individual (ASA-III) parecen tener también un mayor riesgo de infección de herida, aunque en nuestro estudio la diferencia no fue significativa, probablemente por el reducido número de pacientes. La profilaxis antibiótica podría evitarse en un gran número de intervenciones al ser la hernioplastia inguinal uno de los procedimientos más frecuentes, lo que permitiría una reducción del gasto farmaceútico (AU)