Use of Zernike moments to characterize dose conformity for radiotherapy treatment plans.

Dose conformity is an essential parameter used in radiotherapy and radiosurgery that measures the correspondence of the dose distribution derived from a Treatment Planning System (TPS) with the actual volume to be treated, the Planning Treatment Volume (PTV). The present work uses a method based on the expansion of dose distributions and PTVs by three-dimensional Zernike polynomials and further comparison of their moments to define a general criterion of dose conformity. To carry on this study, data coming from 20 patients comprising 80 datasets exported from the TPS, which included imaging data (PTVs) and dose distributions corresponding to different treatment modalities: three-dimensional conformal radiotherapy, intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), were used. The expansions in Zernike polynomials were obtained up to order 6 and reconstructed dose distributions and PTVs were obtained and compared, and several definitions for a general dose conformity index were proposed. Results indicate agreement between the proposed dose conformity index and the Conformation Number CN. The proposed method allows for a systematic approach to the analysis of dose distributions with further extensions in AI applications.

Cultural values, parenting and child adjustment in Colombia.

This study examined associations of mothers' and fathers' individualism, collectivism and conformity values with parenting (warmth, rules/limit-setting, knowledge solicitation and expectations regarding children's family obligations) and child internalising and externalising behaviours in Colombia. Mothers, fathers and children (N = 100) from Medellín, Colombia were interviewed when children were, on average, 10 years old. Higher maternal collectivism and conformity values were associated with higher maternal warmth and fewer child externalising problems, whereas higher paternal collectivism was associated with lower maternal warmth and more child externalising problems. Fathers' cultural values also were related to their expectations regarding children's family obligations. The findings suggest differences in how mothers' and fathers' cultural values are related to parenting and child adjustment in Colombia, as well as the need to examine cultural values beyond individualism, collectivism and conformity values.

Multivariate guard-bands and total risk assessment on multiparameter evaluations with correlated and uncorrelated measured values

Abstract The quality, efficacy, and safety of medicines are usually verified by analytical results. Measurement uncertainty is a critical aspect for the reliability of these analytical results. The pharmacopeial compendia usually adopt a simple acceptance rule that does not consider information from measurement uncertainty. In this work, we compared decision-making using simple acceptance and decision rules with the use of guard-band for multiparameter evaluation of ofloxacin ophthalmic solution and acyclovir topical cream. Ciprofloxacin ophthalmic solution and acyclovir topical cream samples were subject to pharmacopeial tests and assays. Multivariate guard-band widths were calculated by multiplying the standard uncertainty (u) by an appropriate multivariate coverage factor (k'). The multivariate coverage factor (k') was obtained by the Monte Carlo method. According to the simple acceptance rule, all the results obtained for ciprofloxacin ophthalmic solution and acyclovir topical cream are within the specification limits. However, the risk of false conformity decisions increases for ciprofloxacin tests. Decisions made using the simple acceptance rule and decision rules with the use of guard-band may differ. The simple acceptance rule may increase the risk of false conformity decisions when the measured value is close to the regulatory specification limits and/or when the measurement uncertainty value is inappropriately high. Nevertheless, the guard-band decision rule will always reduce the risk of false conformity decisions. Therefore, using information on measurement uncertainty in conformity assessment is highly recommended to ensure the proper efficacy, safety, and quality of medicines.

Risk of false conformity decisions due to measurement uncertainty of Active Pharmaceutical Ingredient: A multiparametric evaluation

Abstract Medicines must be subject to physical, chemical, and biological analysis to guarantee their quality, safety, and effectiveness. Despite the efforts to ensure the reliability of analytical results, some uncertainty will always be associated with the measured value, which can lead to false decisions regarding conformity/non-conformity assessment. This work aims to calculate the specific risk of false decisions regarding conformity/non-conformity of acetaminophen oral solution dosage form. The acetaminophen samples from five different manufacturers (A, B, C, D, and E) were subject to an active pharmaceutical ingredient assay, density test, and dose per drop test according to the official compendia. Based on measured values and their respective uncertainties, the risk values were calculated using the Monte Carlo method implemented in an MS Excel spreadsheet. The results for two acetaminophen oral solution samples (C and D) provided an increased total risk value of false acceptance (33.1% and 9.6% for C and D, respectively). On the other hand, the results for the other three acetaminophen samples (A, B, and E) provided a negligible risk of false acceptance (0.004%, 0.025%, and 0.045% for A, B, and E, respectively). This indicates that measurement uncertainty is very relevant when a conformity assessment is carried out, and information on the risks of false decisions is essential to ensure proper decisions.

Measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets.

Dissolution is used to determine the rate and extent of drug release from the dosage form into a dissolution medium, which allow to assess the batch-to-batch variability. Considering that the dissolution test is used to predict the vivo performance of the drug as well, it is important to guarantee the quality and reliability of dissolution test results. The aim of this work was to evaluate the measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets. Dissolution test was performed using 900 mL of purified water as dissolution medium and a dissolution apparatus equipped with paddles rotating at 50 rpm for 30 min. Quantification was performed by UV spectrophotometer. Uncertainty arising from sampling was estimated using the duplicate method (empirical approach), using 17-sampling target, two samples for each sampling target, and three replicas for each sample, totalizing 102 analyses. Uncertainty arising from analytical steps considered the uncertainty from dissolution step (estimated using Monte Carlo method and regression equation obtained using DoE) and uncertainty from quantification step. Overall uncertainty value was found to be 2.2%, which is below the target uncertainty value (ut =2.5%). The contributions of uncertainty sources in this study were as follows: 24% from sampling uncertainty, 29% from the dissolution step uncertainty, and 47% from the quantification step uncertainty. The results of dissolution test should be compared to the specification limits (Q). According to the pharmacopeia requirements, the batch of the medicine should be declared compliant if the dissolved amount of prednisone for six tablets are above the specification limits + 5% (Q+5%=85%). Since the measured values for all six tablets (96.5%, 94.0%, 96,4%, 95.3%, 96.0%, and 96.9%) were above the multivariate acceptance limit (90.2%, calculate as the standard uncertainty multiplied by multivariate coverage factor), the batch of the prednisone tablets was declared complaint, with a reduced total risk of false decision (total risk value below 5%).

Definition of multivariate acceptance limits (guard-bands) applied to pharmaceutical equivalence assessment.

The quality assessment of medicines involves multiple compliance parameters, such as identity, dosage, purity, potency, content uniformity, disintegration time, dissolution rate, among others. The measurement uncertainty associated with a measured value can affect the conformity assessment and, consequently, it impacts decision-making. Even if the particular risks are acceptable, the total risk may be significantly high. Thus, the aim of this work was to develop a procedure for the definition of acceptance (or rejection) limits applied to multiple compliance assessments, that ensure acceptable particular and total risks. The multiple compliance assessments were performed and applied in the pharmaceutical equivalence studies for cisplatin injectable solution, carboplatin injectable solution, ranitidine tablets, and acetaminophen oral solution from several manufacturers. Pharmaceutical equivalence studies were performed adopting pharmacopeial analytical procedures. All chromatographic system suitability results complied with the requirements regarding the resolution between peaks, the capacity factor, the tailing factor, the theoretical plates, and the relative standard deviation for replicate injections. Univariate and multivariate guard-bands (g and g', respectively) were calculated by multiplying the standard uncertainty (u) by an appropriate univariate and multivariate coverage factor (k and k', respectively).The values of multivariate guard band (g') were higher than the values of univariate guard bands (g), which leads to more restrictive acceptance intervals. Measured values between the conventional and the multivariate acceptance limits will ensure particular risk values below the maximum acceptable value, however, the total risk may be significantly high. On the other hand, measured values within the multivariate acceptance limits ensure that particular risk values and total risk value are below the maximum acceptable value The application of multivariate guard bands is a simple way to ensure reduced particular and total risks of false conformity decisions, which is of great interest to regulatory agencies and the manufactures of the medicines.

Measurement Uncertainty and Conformity Assessment Applied to Drug and Medicine Analyses - A Review.

Analytical results are often used in scientific research, industrial and clinical applications to support decision making. Despite all efforts to ensure the reliability of analytical results (including method validation, internal quality control, use of certified reference materials, proficiency tests, and ISO 17025 accreditation), there will always be an uncertainty associated with the measured value. The measurement uncertainty expresses the quality of the analytical result and allows the comparability between analytical results or between the measured value and the specification limit(s). This work discusses the importance of measurement uncertainty, including the steps involved in the measurement uncertainty evaluation, the bottom-up and top-down approaches used in measurement uncertainty calculation, the measurement uncertainty evaluation in drug and medicine analyses, and the application of measurement uncertainty in conformity assessment for quality control, stability studies, and pharmaceutical equivalence.

Conformity assessment of medicines containing antibiotics - A multivariate assessment.

Pharmaceutical products must meet quality requirements to ensure the efficacy and safety of pharmacological treatment. Non-compliance of medicines can cause economic losses and compromise the patient's health. In this work, the risks of false compliance/non-compliance decisions for parenteral antibiotics (cephalothin, ciprofloxacin and metronidazole) were evaluated on the basis of analytical results, measurement uncertainties and specification limits. Physicochemical and biological quality assays were performed according to pharmacopeial procedures. Measurement uncertainties were determined using the bottom-up approach or the probability of false-positive/false-negative results. The risks of false compliance/non-compliance decisions were estimated using the frequentist approach and Monte Carlo simulations. Guard-bands were determined through a validated spreadsheet for calculating univariate and multivariate acceptance limits. All risk values (particular risks and total risk, consumer's or producer's risk) were below the maximum permissible risk value. The univariate and multivariate guard-bands defined more restrictive specification values, reducing the risks of false compliance/non-compliance decisions. One antibiotic presented unsatisfactory results regarding the drug content and was classified as out of specification product. The application of risk management tools in the pharmaceutical area contributes to improving the quality and safety of products and supports decision-making.

Memory conformity for high-confidence recognition of faces.

Memory judgments made by an individual may be affected by the memory judgments made by another individual, a phenomenon named memory conformity. It is unclear, however, whether memory conformity affects the well demonstrated positive relationship between accuracy and confidence, and more importantly, whether it affects the accuracy of high-confidence memory judgments. Here, we investigated these possibilities in three experiments wherein participants performed recognition followed by confidence judgments of studied and novel faces, after being exposed to the recognition responses of a fictional participant whose responses could be valid or invalid (74% and 26% of the responses, respectively). In all three experiments, accuracy for high confidence "old" and "new" responses was affected by the responses of the fictitious participant, with invalid responses producing consistent decreases in high confidence accuracy. In addition, confidence-accuracy characteristics (CAC) analysis revealed that invalid responses were particularly impactful on the assignment of confidence for faces judged as "new," a pattern that sheds light on prior findings regarding the effects of cueing on mean confidence. Thus, further than demonstrating that the exposition to the memory judgments of another person affects high confidence recognition, we show that such exposition produces distinct effects on the assignment of confidence for "new" versus "old" memory judgments.

Risk of false pharmaceutical equivalence (non-equivalence) decisions due to measurement uncertainty.

The pharmaceutical equivalence between test (generic or similar) and reference medicine is evaluated through in vitro quality tests involving multiple compliance parameters. Despite efforts to ensure the reliability of the analytical results obtained in the pharmaceutical equivalence studies, measurement uncertainties lead to a risk of false decisions. Thus, the aim of this work was to evaluate the measurement uncertainties associated with the analytical results obtained in the pharmaceutical equivalence studies of different pharmaceutical forms and to estimate the risks of false decisions in the evaluation of pharmaceutical equivalence. The measurement uncertainties associated with the test results were evaluated using the bottom-up and top-down approaches. The consumer's or producer's combined particular risks and combined total risks were estimated using the Monte Carlo method implemented in MS-Excel spreadsheet (available as supplemental material). Considering the seven pharmaceutical equivalence studies performed in this work, three studies were not conclusive (risk of false pharmaceutical equivalence decisions higher than 5 %). Moreover, we concluded pharmaceutical equivalence and pharmaceutical non-equivalence in one and three studies, respectively. The particular and total combined risks are useful to make decisions regarding the evaluation of pharmaceutical equivalence between the test (generic or similar) and reference medicines. Regulatory bodies and pharmaceutical equivalence centers are very interested in the estimation of the risks of false decisions, particularly to evaluate the quality of medicines that are not submitted to bioequivalence studies.

False reports of an accomplice in a crime scene: conformity effects on memory confidence and accuracy / Relatos falsos sobre um cúmplice na cena do crime: efeitos da conformidade na confiança e na acurácia da memória / Informes falsos de un cómplice en la escena del crimen: efectos de conformidad en la confianza y precisión de la memoria

The memory reports of a given individual may be altered by preceding memory reports of another individual, a phenomenon termed memory conformity. To investigate this phenomenon, 58 undergraduate students were separated in two groups which watched one of two slightly different movies of a crime scene (one included an accomplice). Subsequently, pairs containing one participant from each group discussed the movie, and then participants responded individually whether there was an accomplice in the scene. The frequency of false reports and their confidence for the presence/absence of the accomplice were analyzed. Only false reports of seeing an accomplice were produced (by 31% of those who saw no accomplice), and confidence were as high for these responses as for correct "no-accomplice" responses. The data is consistent with prior findings, and show that confidence on false reports can be high when involving "insertion" of elements to witnessed events. (AU)

O relato sobre fatos vivenciados por um indivíduo pode ser alterado por relatos anteriores apresentados por outro indivíduo, fenômeno denominado conformidade de memória. Para investigar esse fenômeno, 58 estudantes de graduação foram separados em dois grupos, os quais assistiram cada um a um vídeo ligeiramente diferente de um mesmo crime (em um havia um cúmplice). Posteriormente, foram formados pares de discussão contendo participantes que assistiram às diferentes versões do vídeo, para, em seguida, responderem individualmente sobre se havia um cúmplice na cena testemunhada. A frequência de relatos incorretos e a confiança na presença/ausência do cúmplice foi analisada. Somente relatos falsos da presença do cúmplice foram verificados (por 31% daqueles que não viram o cúmplice no vídeo), e a confiança foi tão alta quanto as respostas corretas. Os resultados confirmam experimentos anteriores e mostram que a confiança em relatos falsos pode ser alta quando se trata de "inserção" de elementos em um evento testemunhado. (AU)

El informe de memoria sobre hechos vividos por un determinado individuo pueden ser modificados por informes de memoria de otro individuo, este fenómeno es denominado conformidad de memoria. Para investigar este fenómeno, 58 estudiantes universitarios fueron divididos en dos grupos, cada uno vio una película de una misma escena del crimen con sutiles diferencias (una de las versiones incluía un cómplice). Posteriormente, se conformaron parejas de discusión con un participante de cada grupo, y luego, de forma individual, cada persona contestó sí hubo un cómplice en la escena presenciada. Fue analizado la frecuencia de los informes falsos y su confianza en la presencia / ausencia del cómplice. Solo fueron analizados los informes falsos de la existencia del cómplice (por el 31% de los que no vieron el cómplice en el video), y la confianza fue tan alta para estas respuestas, como para las respuestas correctas de "no cómplices". Los resultados confirman los experimentos anteriores y muestran que la confianza en los informes falsos puede ser alta cuando se trata de "insertar" elementos en los eventos atestiguados. (AU)

Risk of false conformity assessment applied to automotive fuel analysis: A multiparameter approach.

The low-quality of automotive fuels may lead to the generation of pollutants harmful to both environmental and human health. The quality evaluation of automotive fuels requires a multiparameter conformity assessment, which may lead to an increased total risk of false conformity decisions even if all parameters comply with the acceptance limits. Thus, the aim of this work was to propose the establishment of multivariate acceptance limits in order to ensure a reduced total risk of false conformity decisions applied to automotive fuels analysis. Particular and total (consumers' and/or producers') risks were estimated using frequentist (specific) and Bayesian (global) approaches. Multivariate acceptance limits were estimated using Monte Carlo method, adopting an appropriate multivariate coverage factor (k') defined using MS Excel Solver function. The definition of multivariate acceptance limits ensures a total risk below the maximum admissible risk (typically 5%) and was successfully employed in the conformity assessment of automotive fuels (diesel and gasoline). The employment of the multivariate acceptance limits may be useful in the conformity assessment of several multiparameter products.

Conformidade em Memória de Reconhecimento: Revisão Breve e Potenciais Direções de Pesquisa / Memory Conformity in Recognition: Brief Review and Research Directions

Resumo Conformidade de memória é o fenômeno em que relatos de memória de uma pessoa são modificados após exposição aos relatos de outra pessoa. Estudos sobre conformidade de memória são importantes tanto no âmbito puro quanto aplicado, especialmente quando os estímulos são carregados emocionalmente. No entanto, estudos de conformidade de memória com estímulos emocionais ainda são escassos. Além disso, os poucos estudos sobre o tema apresentam resultados contraditórios. Nesta revisão, apresentamos um breve resumo de pesquisas sobre conformidade de memória em tarefas de reconhecimento e avaliamos o papel moderador da emocionalidade na conformidade. Sugerimos como possível direção de pesquisas futuras a avaliação de duas variáveis, intervalo de retenção e distintividade dos estímulos, que podem ser cruciais para elucidar as inconsistências empíricas.

Abstract Memory conformity refers to the phenomenon in which memory reports from one person are modified by memory reports from another person. The study of memory conformity is important both in basic and applied settings, especially when the stimuli are emotionally-laden. Research on memory conformity for emotional stimuli, however, is surprisingly scarce. Here we briefly review research on memory conformity in recognition tasks and assess the modulatory role of emotionality on conformity effects. We also propose further research based on the manipulation of two variables, retention interval and stimulus distinctiveness, that could help to reconcile the discrepant findings in the literature.

Indústria cultural: o pensar cristalizado / Cultural industry: crystallized thinking / Industria cultural: el pensar cristalizado

Este artigo discute como a indústria cultural, tal como conceituada por Adorno e Horkheimer, se consolidou como um dos elementos socializadores mais importantes na contemporaneidade, pois tem um papel formativo na subjetividade dos indivíduos e na conservação do sistema capitalista de produção. Nesse sentido, discorremos sobre a indústria cultural e a obra de arte autêntica, e suas relações com a organização subjetiva do indivíduo contemporâneo. Para explicitar como esses conceitos operam, recorremos ao exemplo do Jornalismo Policial televisivo, que encarna muitos dos processos apontados pela crítica à indústria cultural. A partir destas considerações, conclui- se que a indústria cultural, ao colonizar os mais diversos aspectos da vida individual, promove uma profunda reificação da personalidade. O indivíduo que assim se produz é o contrário do sujeito autônomo e independente, pois é incapaz de um julgamento crítico sobre sua própria condição.

This article discusses how the cultural industry, as conceptualized by Adorno and Horkheimer, has consolidated itself as one of the most important socializing elements in contemporary times, since it has a formative role in the subjectivity of individuals and in the conservation of the capitalist system of production. In this sense, we discuss the cultural industry and the authentic work of art, and its relations with the subjective organization of the contemporary individual. To explain how these concepts operate we resort to the example of television police journalism, which embodies many processes pointed out by critics of the cultural industry. From these considerations, it is concluded that the cultural industry, by colonizing the most diverse aspects of the individual life, promotes a deep reification of the personality. The individual thus produced is the opposite of the autonomous and independent subject, for he is incapable of a critical judgment on his own condition.

Este artículo discute cómo la industria cultural, tal como lo conceptualizan Adorno y Horkheimer, se ha consolidado como uno de los elementos de socialización más importantes en los tiempos contemporáneos, ya que tiene un papel formativo en la subjetividad de los individuos y en la conservación del sistema de producción capitalista. En este sentido, discutimos la industria cultural y la auténtica obra de arte, y sus relaciones con la organización subjetiva del individuo contemporáneo. Para explicar cómo operan estos conceptos, recurrimos al ejemplo del periodismo policial televisivo, que encarna varios procesos señalados por los críticos de la industria cultural. De estas consideraciones, se concluye que la industria cultural, al colonizar los aspectos más diversos de la vida individual, promueve una profunda reificación de la personalidad. El individuo así producido es lo opuesto al sujeto autónomo e independiente, ya que es incapaz de un juicio crítico sobre su propia condición.

Aspectos teóricos e implicações práticas da conformidade de memória: uma revisão / Theoretical aspects and practical implications of memory conformity: a review / Aspectos teóricos e implicaciones prácticas de la conformidad de memoria: una revisión

A conformidade de memória consiste em alterações dos relatos de memória de um indivíduo provocadas por relatos de memória de outro(s) indivíduo(s). Considerando a importância deste fenômeno no âmbito forense, especialmente na entrevista de testemunhas oculares, o objetivo do presente estudo é compreender melhor o fenômeno da conformidade de memória, e discutir suas implicações nas práticas de inquérito policial. Para isto, realizamos uma revisão narrativa de estudos de laboratório sobre conformidade de memória e de estudos sobre práticas de inquérito. A literatura indica que embora a investigação científica da conformidade de memória tenha apresentado grande avanço nas últimas duas décadas, a incorporação destes achados na prática forense brasileira ainda é lenta. No Brasil, a adoção de práticas de entrevista de testemunhas baseadas em evidência ainda depende de infraestrutura adequada, além de alterações legislativas e em procedimentos administrativos, policiais e jurídicos.

Memory conformity consists of changes in the memory reports of an individual caused by the memory reports of another individual. Considering the importance of this phenomenon to forensic practices, especially to eyewitness testimony interview, the goal of the present study was to discuss the current scientific knowledge about this phenomenon, and to consider its implications to public inquiry practices. For this purpose, the current narrative review included laboratory studies on memory conformity and studies on public inquiry practices. The literature suggests that although the scientific investigation on memory conformity has made great progress in the last two decades, the inclusion of the knowledge produced by this progress in Brazilian forensic practices remains scant. That is, the adoption of evidence-based eyewitness interview practices in Brazil still depends on infrastructure improvements, as well as changes on legislation and on several legal procedures.

La conformidad de memoria consiste en cambios en los informes de memoria de un individuo causados por los informes de memoria de otro individuo. Considerando la importancia de este fenómeno en la esfera forense, especialmente en la entrevista de testigos, el objetivo del presente estudio es mejor comprender el fenómeno de conformidad de memoria y discutir sus implicaciones en las prácticas de investigación policial. Para este propósito, llevamos a cabo una revisión narrativa en estudios de laboratorio sobre la conformidad de memoria y estudios sobre las prácticas de investigación. La literatura indica que, aunque la investigación científica de la conformidad de memoria ha avanzado mucho en las últimas dos décadas, la incorporación de estos hallazgos en la práctica forense brasileña aún es lenta. En Brasil, la adopción de prácticas de entrevista a testigos presentadas en este artículo todavía depende de una infraestructura adecuada, además de los cambios legislativos y los procedimientos administrativos, policiales y legales.

Radiotherapy for the treatment of pituitary adenomas: A dosimetric comparison of three planning techniques.

AIM: Our goal was to compare conformal 3D (C3D) radiotherapy (RT), modulated intensity RT (IMRT), and volumetric modulated arc therapy (VMAT) planning techniques in treating pituitary adenomas. BACKGROUND: RT is important for managing pituitary adenomas. Treatment planning advances allow for higher radiation dosing with less risk of affecting organs at risk (OAR). MATERIALS AND METHODS: We conducted a 5-year retrospective review of patients with pituitary adenoma treated with external beam radiation therapy (C3D with flattening filter, flattening filter-free [FFF], IMRT, and VMAT). We compared dose-volume histogram data. For OARs, we recorded D2%, maximum, and mean doses. For planning target volume (PTV), we registered V95%, V107%, D95%, D98%, D50%, D2%, minimum dose, conformity index (CI), and homogeneity index (HI). RESULTS: Fifty-eight patients with pituitary adenoma were included. Target-volume coverage was acceptable for all techniques. The HI values were 0.06, IMRT; 0.07, VMAT; 0.08, C3D; and 0.09, C3D FFF (p < 0.0001). VMAT and IMRT provided the best target volume conformity (CI, 0.64 and 0.74, respectively; p < 0.0001). VMAT yielded the lowest doses to the optic pathway, lens, and cochlea. The position of the neck in extreme flexion showed that it helps in planning mainly with VMAT by allowing only one arc to be used and achieving the desired conformity, decreasing the treatment time, while allowing greater protection to the organs of risk using C3D, C3DFFF. CONCLUSIONS: Our results confirmed that EBRT in pituitary adenomas using IMRT, VMAT, C3D, C3FFF provide adequate coverage to the target. VMAT with a single arc or incomplete arc had a better compliance with desired dosimetric goals, such as target coverage and normal structures dose constraints, as well as shorter treatment time. Neck extreme flexion may have benefits in treatment planning for better preservation of organs at risk. C3D with extreme neck flexion is an appropriate treatment option when other treatment techniques are not available.

Frequentist approach for estimation of false decision risks in conformity assessment based on measurement uncertainty of liquid chromatography analytical procedures.

The measurement uncertainty (MU) related to analytical results can lead to false decisions in conformity assessment, such as accepting or rejecting incorrectly a medicine lot (consumer's and producer's risks, respectively). These risks can be global or specific. It is important to understand the different types of conformity decision risks, and the different approaches to estimate them to ensure the reliability of the analytical results. Thus, the aim of this work was to estimate the specific consumer's and producer's risks from the MU values of 64 liquid chromatography analytical procedures for antibiotic or antifungal assays, in order to evaluate their performances in conformity assessment. The specific risks of the analytical procedures were estimated by the frequentist approach following normal distribution using Microsoft Excel® software, and in addition a spreadsheet was created to be available as supplementary material to estimate specific risks by this approach. Moreover, the global risks of the analytical procedures were estimated using Bayesian approach, assuming a uniform scenario of production process. And finally, the estimation of specific risks by Bayesian and frequentist approaches was compared. Only 39 % of the evaluated analytical procedures had MU within the recommended. When the result is close to the specification limit, the risk can be significant, in such cases, a strategy is to adopt guard bands to reduce or expand the specification limits, minimizing the risks. The spreadsheet created shows the risk of false decision for a MU value, considering results within and outside the specification limits, allowing to verify the risk according to the analytical result obtained. The global risks values were practically equal to the expanded uncertainty values, as there is no tendency of the production process between lots within or outside the specification, but once the analytical result is known, the frequentist approach provides a more reliable risk estimate (specific risk). The specific risks estimated by Bayesian and frequentist approaches were divergent by the influence of the production process information on the first approach, which may overestimate or underestimate the consumer's and producer's risks regarding the frequentist approach. Failures in medicine conformity assessment can cause much damage, therefore, preventive actions such as developing, evaluating and/or optimizing analytical procedures, are essential in order to guarantee measurement uncertainties below or equal to the target and adopt routine strategies to minimize the risk of false decisions in conformity assessment.

Measurement uncertainty and risk of false conformity decision in the performance evaluation of liquid chromatography analytical procedures.

Liquid chromatography is one of the main techniques used in pharmaceutical quality control analytical procedures. However, there will always be a measurement uncertainty (MU) associated with them, that can lead to the approval of an out of specification lot (consumer risk) or rejection of a lot within specification (producer risk). Thus, the aim of this study was to evaluate the performance of liquid chromatography analytical procedures based on their measurement uncertainty and to estimate the risk of false conformity decisions. The uncertainties of the analytical procedures were estimated based on the results of validation (trueness and precision). Then, the ratio between overall uncertainty and specification range (U/T%) was calculated. It was noted that in most cases (73%), random errors (precision) contributes more significantly to the overall uncertainty when compared to systematic errors (trueness). Monte Carlo method was used, generating different manufacturing processes scenarios, and analytical results based on the MU of each analytical procedure. Then, consumer's and producer's risks were estimated from the simulated values. Pharmaceutical dosage forms that require more steps in sample preparation had higher measurement uncertainties, often above the recommended target uncertainty. As most of the analytical procedures showed U/T% values above recommended, the majority presented high estimated risk values and did not fit for purpose. Therefore, it is important to considerate the measurement uncertainty as part of analytical procedures validation, since trueness and precision values affect directly the measurement uncertainty and the risk of false conformity decisions.

Adherence to fibromyalgia treatment: challenges and impact on the quality of life / Adesão ao tratamento da fibromialgia: desafios e impactos na qualidade de vida

ABSTRACT BACKGROUND AND OBJECTIVES: Fibromyalgia is a chronic and idiopathic syndrome, characterized by a general distributed pain, more prevalent in women. Its pathophysiology remains unclear. Its chronicity implies an exclusively symptomatic treatment, often unsatisfactory. The lack of adherence to the established treatment is quite common. The objective of this study is to present a review of the adherence to the fibromyalgia syndrome treatment. CONTENTS: The concept of adherence to the fibromyalgia syndrome treatment, its classification, the identification of its measurement options, and the detection of its causes are detailed, revised and updated. CONCLUSION: The review of the literature regarding the adherence to the fibromyalgia syndrome treatment points to a large number of nonconformity of prescription, in general with the prevalence of the adoption of the reduction of the recommended dose and the interruption of the treatment, over possible overdoses and self-medication. The study of the causes that led to the non-adherence to the treatment elects the characteristics of the syndrome as the great villain for its occurrence. However, other associated factors such as the age of the subject with fibromyalgia, the intensity of the pain, the established polypharmacy, the quality of the doctor-patient relationship and the socioeconomic variables were also listed. The patient's quality of life was always higher in patients with higher adherence to treatment and persistence. Patients' quality of life indices may indicate the level of commitment to treatment adherence, and vice versa.

RESUMO JUSTIFICATIVA E OBJETIVOS: A fibromialgia é uma síndrome crônica e idiopática, caracterizada por queixa dolorosa de distribuição generalizada, mais prevalente em mulheres. A sua fisiopatologia continua não totalmente esclarecida. Sua cronicidade implica em tratamento exclusivamente sintomático e muitas vezes insatisfatório. A falta de adesão ao tratamento instituído é bastante comum. O objetivo deste estudo foi apresentar uma revisão sobre a adesão do tratamento da síndrome fibromiálgica. CONTEÚDO: O conceito de adesão ao tratamento da síndrome fibromiálgica, sua classificação, a identificação das opções de sua mensuração, e a detecção de suas causas são detalhados, revisados e atualizados. CONCLUSÃO: A revisão da literatura referente à adesão ao tratamento da síndrome fibromiálgica mostra um grande contingente de inconformidade de prescrição, em geral predominando a adoção da redução da dose orientada e a interrupção do próprio tratamento, sobre possíveis sobredoses e automedicações. O estudo das causas que levaram à falta de adesão ao tratamento elege as características da própria síndrome como a grande vilã para sua ocorrência; embora, tenham sido também elencados outros fatores associados como a idade do portador da síndrome fibromiálgica, a intensidade da dor, a polifarmácia instituída, a qualidade da relação médico-paciente, e as variáveis socioeconômicas. A qualidade de vida dos pacientes sempre foi maior naqueles cuja adesão e persistência ao tratamento foram maiores. Os índices de qualidade vida dos pacientes podem indicar o nível de comprometimento com a adesão ao tratamento, e vice-versa.

Measurement uncertainty for the potency estimation by rapid microbiological methods (RMMs) with correlated data.

Recently, rapid microbiological methods (RMM) have often been used to determinate the potency of antibiotic drugs. Since all the standard and sample preparations are assayed into the same analytical conditions, it is expected that the correlations among the inhibitions zone sizes are not negligible. However, the procedures adopted in uncertainty estimations do not consider the correlation of data. The aim of this work was to study the impact of the correlation of data in the measurement uncertainty and, consequently, in the risk of false conformity decisions. RMM for the determination of the potency of cephalosporin antibiotics in pharmaceutical products were performed using an agar diffusion method. The shared analytical effects on inhibition resulted in correlation of data, which significantly decreased the combined measurement uncertainties, and therefore, the risk of false conformity decisions. Due to the lognormal distribution of potency values, measurement uncertainties were reported as a multiplicative uncertainty factor (UF). A MS-Excel spreadsheet is provided as supplementary material and may be used to estimate the measurement uncertainty and the risk of false conformity decisions for results obtained from RMM.