Enhancing Pharmaceutical Product Quality With a Comprehensive Corrective and Preventive Actions (CAPA) Framework: From Reactive to Proactive.

Corrective and preventive actions (CAPA) are crucial components of quality assurance (QA) within the pharmaceutical industry, essential for maintaining product quality, safety, and regulatory compliance. The review explores the multifaceted role of CAPA in pharmaceutical manufacturing, emphasizing its structured approach to detecting, addressing, and preventing quality issues. CAPA systems are integral to the broader quality management system (QMS), functioning as a dual-loop mechanism that is reactive and proactive approach aligned with continuous improvement principles outlined by the International Organization for Standardization (ISO) 9001:2000. It details the three distinct phases of CAPA: correction or remedial action, corrective action (CA), and preventive action (PA). It highlights the importance of root cause analysis and the necessity for immediate corrections and long-term preventive measures to avoid recurring issues. Regulatory expectations, such as those from the Food and Drug Administration (FDA) under the Code of Federal Regulations (CFR) title 21 part 820 and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q10, are discussed, underscoring the need for a comprehensive CAPA plan that integrates data analysis and ongoing process enhancements. Additionally, the paper introduces the 8D methodology as a structured problem-solving approach to complement CAPA efforts. By providing an in-depth examination of CAPA procedures and their implementation, this article aims to contribute to the understanding and effectiveness of quality systems in pharmaceutical manufacturing.

Data quality in an HIV vaccine efficacy clinical trial in South Africa: through natural disasters and with discipline.

BACKGROUND: To produce quality data that informs valid clinical trial results and withstands regulatory inspection, trial sites should adhere to many complex and dynamic requirements. Understanding non-conformance to requirements informs the emerging field of improvement science. We describe protocol deviations in South Africa's largest HIV vaccine efficacy trial. METHODS: We analysed data from the HVTN 702 trial using mixed methods. We obtained descriptive statistics, from protocol deviation case report forms collected from 2016-2022, of deviation by participant, trial site, and time to site awareness. We thematically analysed text narratives of deviation descriptions, corrective and preventive actions, generating categories, codes and themes which emerged from the data. RESULTS: For 5407 enrollments, 4074 protocol deviations were reported (75 [95% CI: 73.0-77.6] deviations per 100 enrolments). There was a median of 1 protocol deviation per participant (IQR 1-2). Median time from deviation to site awareness was 31 days (IQR 0-146). The most common category of deviation type was omitted data and/or procedures (69%), and 54% of these omissions were stated to have arisen because of the national lockdown at the beginning of the COVID-19 pandemic. The ratio of protocol deviations to cumulative enrolments was highest in the year 2020 (0.34). Major themes of deviations were: COVID-19 and climate disasters giving rise to deviation trends, subroutines introducing an opportunity for deviation, and document fragmentation (such as requirements dispersed across multiple guidance documents) as an obstacle. Preventive action categories were: no preventive measures; discipline, training and/or awareness; quality review, checking and verifying and changing the process and/or implementation tools. Major themes of preventive actions were that systems-based actions are unusual, with people-based actions dominating, and that root cause analysis was rarely mentioned. CONCLUSIONS: In the age of infectious and climate disaster risks, trials may benefit from simple study designs and trial-related documents. To optimise protocol adherence, sponsors and sites should consider ongoing training, and routinely review deviation reports with a view to adjusting processes. These data quality lessons may inform future trial design, training and implementation. TRIAL REGISTRATION: HVTN 702 was registered with the South African National Clinical Trials Register (DOH-27-0916-5327) and ClinicalTrials.gov ( NCT02968849 ).

Effects of self-efficacy on the intention to take preventive actions against infectious diseases: Focusing on dental hygiene students in South Korea.

OBJECTIVE: This study aimed to determine the impact of self-efficacy on the intention to take preventive actions against infectious diseases, focusing on dental hygiene students during the COVID-19 pandemic. METHODS: A survey was conducted through a questionnaire distributed to 300 dental hygiene students at the Department of Dental Hygiene, Gangneung Yeongdong College in South Korea. In total, 251 students completed the survey (response rate: 83.6%). The survey data were analysed via exploratory and confirmatory factor analyses, path analysis and structural equation modelling. RESULTS: The analysis showed that self-efficacy positively affected students' intentions to take preventive actions against infectious diseases. CONCLUSIONS: This study confirmed that self-efficacy positively affected dental hygiene students' intentions for preventive actions against infections. Furthermore, it suggested that self-efficacy should be classified into psychological (confidence and judgement) and behavioural (drive and task challenge) categories, and a systematic survey to formalize the concept of self-efficacy should be developed. The results of this study should enable a better understanding of the impact of self-efficacy on the intention to take preventive actions against infectious diseases.

Exploring the Mediating Role of Situation Awareness and Crisis Emotions Between Social Media Use and COVID-19 Protective Behaviors: Cross-Sectional Study.

Background: In an outbreak of an infectious disease especially, online media would usually be an important channel for people to get first-hand knowledge and evaluate risks of the specific emergency. Although there has been increasing attention to the effect of social media use during epidemics and outbreaks, relatively little is known about the underlying mechanism by which social media plays a role in people's cognitive, affective and preventive responses. Objective: With an objective to advance current knowledge surrounding social media effects on people's cognition, affection and health protective behaviors during epidemics, we aim to examine the associations between social media exposure to COVID-19 risks related information and preventive behavior of the public, and also the role that situation awareness and crisis emotions including anxiety and fear played. Methods: An online cross-sectional survey was conducted in China a total of 632 participants were recruited. Measures included exposure to COVID-19 information through social media, situation awareness, anxiety, fear and protective behaviors that participants have taken. We have performed the descriptive statistical analysis, correlation and mediation analysis to test the research hypotheses. Results: Findings indicated that situation awareness was positively associated with social media use (B = 0.54, p < 0.001), anxiety (B = 0.95, p < 0.001) and fear (B = 0.87, p < 0.001), and preventive behavior (B = 0.68, p < 0.001). Social media use would also have an indirect effect on anxiety (indirect effect = 0.40; 95% CI = [0.34, 0.46]) and fear (indirect effect = 0.35; 95% CI = [0.29, 0.42]) through situation awareness. The serial mediation effect of situation awareness and fear in the correlation between social media use and preventive behavior has been testified (indirect effect = 0.04, 95% CI = [0.01, 0.08]). Conclusions: Social media use might influence the adoption of preventive behaviors through triggering situation awareness and fear. Therefore, health communication regarding COVID-19 prevention should target people with less internet access and low eHealth literacy. Understanding the positive role of negative crisis emotions during outbreaks could also help communicators and policymakers develop appropriate strategies to make people proactive to avoid the remaining health hazard.

The Paradox of Conspiracy Theory: The Positive Impact of Beliefs in Conspiracy Theories on Preventive Actions and Vaccination Intentions during the COVID-19 Pandemic.

This study aims to analyze the direct and indirect impact of beliefs in conspiracy theories on COVID-19-related preventive actions and vaccination intentions. The dominant theory in the literature is that beliefs in conspiracy theories have negative consequences. In particular, strong beliefs in conspiracy theories lower people's intentions to engage in preventive actions and get vaccinated. Previous studies indicated that this dominant theory applies in Korea as well. However, we find that this dominant theory does not apply in Korea. Based on an analysis of survey data, we find that beliefs in conspiracy theories have positive impact on preventive actions and vaccination intentions. In addition, beliefs in conspiracy theories play indirect roles in these two responses to COVID-19. Specifically, when perceived benefits and trust in the government or science enhance preventive actions or increase vaccination intentions, strong beliefs in conspiracy theories promote this effect. This positive role of conspiracy theories is paradoxical because they are generally viewed as negative.

The role of online news and social media in preventive action in times of infodemic from a social capital perspective: The case of the COVID-19 pandemic in South Korea.

Infodemic, the spread of false information during the COVID-19 pandemic, has been raised as one of the major concerns aggravating the confusion in the global society. In this regard, the role of media as an information channel in delivering the reliable information and motivating the active participation of citizens in complying with government's preventive actions becomes much more important. In this study, the role of online news and social media on people's preventive actions considering the role of trust in citizens and government from the perspective of social capital is investigated. For the empirical study, a structural equation modeling is employed by using survey material gathered from South Korea in the early days of the COVID-19 outbreak. South Korea was selected as its COVID-19 prevention strategy focused not only on the provision of medical support, but also on the enhancement of social trust through active engagement with people through media channels. Our results reveal that the perceived characteristics of online news and social media influence preventive actions through the trust in citizens or in government. In addition, while online news media enhances trust in both the citizens and the government, social media only influences trust in citizens. Based on our findings, the role of media in preventing the spread of COVID-19 is dicussed.

Managing Deviating EQA Results: A Survey to Assess the Corrective and Preventive Actions of Medical Laboratories Testing for Oncological Biomarkers.

Laboratories testing predictive biomarkers in lung and colorectal cancer are advised to participate in external quality assessment (EQA) schemes. This study aimed to investigate which corrective actions were taken by laboratories if predetermined performance criteria were not met, to ultimately improve current test practices. EQA participants from the European Society of Pathology between 2014 and 2018 for lung and colorectal cancer were contacted, if they had at least one analysis error or test failure in the provided cases, to complete a survey. For 72.4% of 514 deviating EQA results, an appropriate action was performed, most often including staff training (15.2%) and protocol revisions (14.6%). Main assigned persons were the molecular biologist (40.0%) and pathologist (46.5%). A change in test method or the use of complex techniques, such as next-generation sequencing, required more training and the involvement of dedicated personnel to reduce future test failures. The majority of participants adhered to ISO 15189 and implemented suitable actions by designated staff, not limited to accredited laboratories. However, for 27.6% of cases (by 20 laboratories) no corrective action was taken, especially for pre-analytic problems and complex techniques. The surveys were feasible to request information on results follow-up and further recommendations were provided.

Blood School.

OBJECTIVES: To describe and evaluate a laboratory-based nursing education activity on transfusion to improve patient safety, an often-neglected opportunity. METHODS: Our transfusion service developed a day-long "Blood School" to provide knowledge, skills, and behaviors to nurses in four aspects of transfusion: blood ordering, sample collection, transfusion procedures, and recognition and reporting of transfusion reactions. We collected survey data on methods and effects of training and hard data on the number of reported patient safety events. RESULTS: Nurses want more hands-on experience to understand transfusion concepts, practice hospital procedures, recognize latent problems, and have behaviors to act effectively. We observed that engagement and understanding are best where participation is highest. Reported patient safety events were lower even as self-reported nursing mistakes increased. CONCLUSIONS: Blood School is a well-received and effective site for nursing education in transfusion. We seek ways to extend and improve laboratory-based nursing training to improve patient safety.

Skin cancer risk perception and sun protection behavior at work, at leisure, and on sun holidays: a survey for Danish outdoor and indoor workers.

BACKGROUND: To prevent occupational skin cancer, it is essential that the sun-protective behavior of outdoor workers is adequate. The aim is to study the sun-protective behavior of Danish outdoor workers at work, at leisure, and on sun holiday and compare it to that of indoor workers. METHODS: This is a cross-sectional study, based on a 53-item survey completed by Danish outdoor (n = 380) and indoor workers (n = 119) in 2016-2017. Status as outdoor or indoor worker was decided based on self-report and behavioral differences were tested using (paired) t tests and multiple regression adjusted for age, sex, educational level, history of smoking, and skin type. RESULTS: Danish outdoor workers at work use sun protection less than they do at leisure and on sun holiday (α < .05) where their sun protection behavior is similar to that of indoor workers. The proportion of Danish outdoor workers that always/often use sun protection at work is for shade seeking around noon 4.2%, sunscreen 34.5%, wide-brimmed hat 25.3%, and long trousers and shirt with sleeves 42.4%. Of Danish outdoor workers, 49.5% do not think about the risk of occupational skin cancer and 11.8% think the risk is insignificant, 32.4% think that the use of sun protection is of low or no importance, 84.2% consider sunburn important as skin cancer risk factor still 88.9% have a history of sunburn at work, > 80.0% agree that risk of skin cancer is reduced by the use of sun protection, and only 4.0% dismiss the possibility of sun protection use at work. CONCLUSIONS: Skin cancer risk and use of sun protection at work are largely neglected in Danish outdoor workers, more so than at leisure and on sun holiday where their risk behavior resembles that of indoor workers. This indicates an untapped workplace preventive potential.

Compliance with recommended protective actions during an H7N9 emergency: a risk perception perspective.

This study investigates the factors determining an individual's response to official recommended protective measures, based on the Health Belief Model and the Protective Action Decision Model, to understand the adoption of protective behaviour during an H7N9 (Avian Influenza A) emergency. A public survey involving 1,375 respondents was conducted in Anhui Province, China, during the 2013 H7N9 outbreak to test the research model and hypotheses. The results indicate that protective, stakeholder, and risk perceptions influence positively an individual's willingness to take recommended actions. Protective and stakeholder perceptions also have a positive bearing on lay people's risk perceptions. A stakeholder perception is a vital determinant of a protective perception. More importantly, the effects of protective and stakeholder perceptions on behavioural responses to recommendations are mediated in part by risk perception. These findings can help public health officials to develop messages to encourage members of the population to protect themselves effectively during an influenza crisis.

Analysis of Patient's Satisfaction with Phlebotomy Services in NABH Accredited Neuropsychiatric Hospital: An Effective Tool for Improvement.

INTRODUCTION: Patient's satisfaction is the need of the hour and one of the most important quality indicators in the laboratory medicine. AIM: To assess the patient's satisfaction with phlebotomy services in a neuropsychiatric hospital by a structured questionnaire with grading scale. Also, identify the problems causing dissatisfactions and to undertake necessary Corrective and Preventative Action (CAPA). MATERIALS AND METHODS: Total 1200 patients were randomly selected over a period of two months (June and July 2016). A structured self designed questionnaire (feedback form) was devised in both Hindi and English languages containing ten questions with a grading scale for each question. It also included suggestions from the users. All the selected patients or their attendants filled up this questionnaire. At the same time, they were also interviewed by phlebotomy staff. A statistical analysis was conducted using SPSS version 16.0 software and Likert scale. RESULTS: A total of 94% of the patients were satisfied with the phlebotomy services. Almost 30.0% patients found the phlebotomy services to be very good, but the majority of them (40.5%) found it to be good and another 23.5% found it to be satisfactory while, 4% found the services to be poor and 2% found it to be very poor. The highest rate of satisfaction (4.21) was noted in case of parameter-ease to find collection sample room and lowest rate of satisfaction (3.92) was scored by the parameter-staff's wearing proper uniform. Depending upon the deficient areas some corrective actions were suggested such as strict compliance of personal protective equipments, regular training to improve technical skill, knowledge and behaviour with emphasis on cleanliness of work area. CONCLUSION: Even though the overall patient's satisfaction was high, there were areas which needed our attention such as waiting time for phlebotomy procedure, lack of proper sitting arrangement, techniques of sample collection, knowledge of universal precautions etc. Appropriate corrective and preventive actions were taken to solve the problems. Thereby, feedback proved effective in maintenance and improvement of phlebotomy services.

A Toolkit for the Management of Protocol Deviations.

BACKGROUND: The DIA's Good Clinical Practice and Quality Assurance Community (DIA GCP/QA) created a working group to develop templates for a protocol deviation standard operating procedure (SOP) and protocol deviation handling plan (PDHP). METHODS: The working group consisted of QA auditors, data managers, statisticians, and clinical monitors from several pharmaceutical companies, academia, and independent auditing firms. Various examples of standard operating procedures, data handling plans, and auditing plans were examined, and the core elements extracted into the initial PD SOP and PDHP templates. The draft templates were presented at a workshop at the DIA 51st Annual Meeting held in June 2015 in Washington, DC, and feedback was incorporated. The workshop came at the heels of a previously published position paper, "The Lifecycle and Management of Protocol Deviations." RESULTS: The PD SOP and the PDHP templates are presented in this article. They are a starting point, and each company will need to modify to suit its individual needs. CONCLUSIONS: This article expands on the position paper to include concrete tools for the management of protocol deviations, including best practices for detection, classification, mitigation, and management of protocol deviations with a goal to reduce the impact on subject safety and data integrity.

The Life Cycle and Management of Protocol Deviations.

Clinical trials are designed to evaluate the efficacy, safety, or other characteristics associated with medical products. Trials are usually complex and require a large group of professionals to follow a clinical trial protocol, standard operating procedures, and study-specific manuals, guidelines, and plans. Clinical trial protocols prospectively describe the background and rationale for conducting the trial, the objectives of the trial, the trial design, the equipment to be used, the procedures to be performed, and the statistical methods on how the trial data are to be analyzed. Deviations from the protocol can result in harm to subjects, biased or inaccurate results, and possible rejection of all or part of the trial data by the sponsor or regulatory authorities. Despite preventive efforts, protocol deviations are likely to occur in most trials. This position paper proposes a common definition of protocol deviations and recommends best practices for their detection, classification, and management as part of their life cycle, with a goal of reducing their impact on subject safety and data integrity. The information contained herein is drawn globally from industry experts within the DIA Good Clinical Practice and Quality Assurance community, an industry-wide survey, and presentations with discussions at various industry meetings.

Role of a quality management system in improving patient safety - laboratory aspects.

OBJECTIVES: The aim of this study is to describe how implementation of a quality management system (QMS) based on ISO 15189 enhances patient safety. DESIGN AND METHODS: A literature review showed that several European hospitals implemented a QMS based on ISO 9001 and assessed the impact on patient safety. An Internet search showed that problems affecting patient safety have occurred in a number of laboratories across Canada. The requirements of a QMS based on ISO 15189 are outlined, and the impact of the implementation of each requirement on patient safety is summarized. The Quality Management Program - Laboratory Services in Ontario is briefly described, and the experience of Ontario laboratories with Ontario Laboratory Accreditation, based on ISO 15189, is outlined. RESULTS: Several hospitals that implemented ISO 9001 reported either a positive impact or no impact on patient safety. Patient safety problems in Canadian laboratories are described. Implementation of each requirement of the QMS can be seen to have a positive effect on patient safety. Average laboratory conformance on Ontario Laboratory Accreditation is very high, and laboratories must address and resolve any nonconformities. Other standards, practices, and quality requirements may also contribute to patient safety. CONCLUSION: Implementation of a QMS based on ISO 15189 provides a solid foundation for quality in the laboratory and enhances patient safety. It helps to prevent patient safety issues; when such issues do occur, effective processes are in place for investigation and resolution. Patient safety problems in Canadian laboratories might have been prevented had effective QMSs been in place. Ontario Laboratory Accreditation has had a positive impact on quality in Ontario laboratories.

Atendimento pré-hospitalar ao idoso vítima de violência em cinco capitais brasileiras / Pre-hospital attendance to elders victims of violence in five Brazilian capitals

This article reviews the characteristics and operation in the daily routine of a pre-hospital care to the elderly victims of violence and accidents in five capitals (Manaus, Recife, Brasília, Rio de Janeiro and Curitiba). Besides that, it analyses their abilities, and potential obstacles. It was based on the triangulation of quantitative and qualitative methods analyzing data from 80 departments of mobile and fixed pre-hospitals: 32 in Manaus, 18 in Recife, 10 in Brasilia, 12 in Rio de Janeiro and eight in Curitiba. Among the findings are the differences in size and diversity of occupational categories and difficulties of the teams to identify, serve and report cases for lack of training, limited preventive action, almost no involvement and guidance to the family, practically no attention to the perpetrator; incipient articulation and partnership network, especially regarding on pre-hospital services and the hospital.

Este artigo analisa as características e a operacionalização no cotidiano da atenção pré-hospitalar aos idosos vítimas de violências e acidentes de cinco capitais (Manaus, Recife, Brasília, Rio de Janeiro e Curitiba), abordando ainda suas capacidades, seus obstáculos e potencialidades. Pautou-se na triangulação de métodos quantitativos e qualitativos. Analisaram-se dados de oitenta serviços da atenção pré-hospitalar móvel e fixa: 32 em Manaus; 18 em Recife; dez em Brasília; 12 no Rio de Janeiro e oito em Curitiba. Entre os achados estão as diferenças (de tamanho e diversidade de categorias profissionais) e dificuldades das equipes para identificar, atender e notificar os casos por falta de capacitação; pouca atuação preventiva; quase nenhum envolvimento com a família e orientação a ela; praticamente nenhum atendimento ao autor da agressão; incipiente articulação e parcerias da rede, sobretudo dos serviços pré-hospitalares com os hospitalares.

Good clinical practice regulatory inspections: Lessons for Indian investigator sites.

Regulatory inspections are important to evaluate the integrity of the data submitted to health authorities (HAs), protect patient safety, and assess adequacy of site/sponsor quality systems to achieve the same. Inspections generally occur after submission of data for marketing approval of an investigational drug. In recent years, there has been a significant increase in number of inspections by different HAs, including in India. The assessors/inspectors generally do a thorough review of site data before inspections. All aspects of ICH-GCP, site infrastructure, and quality control systems are assessed during the inspection. Findings are discussed during the close out meeting and a detailed inspection report issued afterward, which has to be responded to within 15-30 days with effective Corrective and Preventive Action Plan (CAPA). Protocol noncompliance, inadequate/inaccurate records, inadequate drug accountability, informed consent issues, and adverse event reporting were some of the most common findings observed during recent Food and Drug Administration (FDA) inspections. Drug development is being increasingly globalized and an increased number of patients enrolled in studies submitted as part of applications come from all over the world including India. Because of the steep increase in research activity in the country, inexperienced sites, and more stakeholders, increased efforts will be required to ensure continuous quality and compliance. HAs have also made clear that enforcement will be increased and be swift, aggressive, and effective.

Conocimientos, actitudes y prácticas sobre el test de Papanicolau (PAP) en mujeres embarazadas consultantes de hospitales públicos del Departamento de Alto Paraná, Paraguay / Knowledge, attitudes and practices on the Papanicolau smear test (PAP) in pregnant women attending public hospitals of the Department of Alto Parana, Paraguay

El cáncer de cuello uterino es el más frecuente entre las mujeres en nuestro país y la manera más eficaz para detectar en forma precoz es la realización del test de Papanicolau. El objetivo de este trabajo es identificar conocimientos, actitudes y prácticas sobre el papanicolau en mujeres consultantes de Centros Asistenciales Públicos de Alto Paraná. Estudio descriptivo. Se aplicó un cuestionario estructurado llenado en entrevista a 1049 embarazadas en Hospitales Públicos principales del Dpto. Alto Paraná. Procesamiento utilizando el Paquete Informático para las Ciencias Sociales (SPSS). La participación de las mujeres fue voluntaria y anónima. El 66.3% (695/1049) escuchó hablar del PAP. A las preguntas Que es el PAP? ha respondido correctamente el 15.5% (108), imprecisa el 38.7% (120), errónea el 7.2% (50) y no sabe el 33.7% (383); Para que sirve?, en forma correcta 12.8% (89),errónea 37.3%(258), imprecisa, 37.0% (257) y 11.4% (79) no sabe. Alrededor del 40.0% cree que debe hacerlo cada 6 meses y cada año. El 54.0.5%(372) considera que debe empezar a hacerse "al iniciar las relaciones sexuales y el 41.4% (288) antes de los 20 años. Las principales fuentes de información sobre el PAP son el médico 32.7% (228); familiar 24.3% (169) y enfermera 19.2% (133). El 46.4% (487/1049) del total y el 70.1% (487/ 695) de las que mencionaron conocer se realizó alguna vez. El 16.0% una sola vez. Es alto el porcentaje que no tienen conocimiento sobre el PAP y que dieron respuestas imprecisas y erróneas y que nunca se han realizado el test.

The cervical cancer is the most common among women in our country and the most effective way to early detect it is the PAP. The objective of this work was to identify knowledge, attitudes and practices on the PAP smear test in women attending Public Hospitals of the Department of Alto Paraná. It is a descriptive study which applied structured questionnaires filled in during interviews with 1049 pregnant women in the main public hospitals of Alto Parana. For the processing, it was used the Software Package for Social Sciences (SPSS). The participation of the women was voluntary and anonymous. The 66.3% (695/1049) heard about the PAP. To the question what is the PAP? 15.5% (108) has responded properly, 38.7% (120) imprecisely, 7.2% (50) erroneously 33.7% (383) did not know anything. In relation to the question what is it for? 12.8% (89) answered correctly, 37.3% (258) erroneously, 37.0% (257) imprecisely and 11.4% (79) did not know. Around 40.0% believed they should have it every 6 months and each year, 54.0.5% (372) considered that they should begin to have it at becoming sexually active and 41.4% (288) before 20 years old. The main sources of information about the PAP were: doctor 32.7% (228); family 24.3% (169) and nurse 19.2% (133); The 46.4% (487/1049) of the total and 70.1 % (487/695) of those who said they knew it said they have had it some time; 16.0% only once. There was a high percentage of women that did not have any knowledge about the PAP and that provided imprecise and wrong answers and that have never had the test.

Effects of curcumin on reflux esophagitis in rats.

The preventive effect of curcumin, a compound isolated from the rhizome of Curcuma longa, on experimental reflux esophagitis in rats was investigated in order to validate its potential therapeutic use for gastroesophageal reflux disease. Curcumin (20 mg/kg, i.d.), the antioxidative agent dimethyl sulfoxide (DMSO) (1 ml/kg, i.p.) or the proton pump inhibitor lansoprazole (1 mg/kg, i.d.) inhibited the formation of acute acid reflux esophagitis by 52.5, 61.5 and 70.9% respectively. Curcumin alone was not effective in preventing chronic acid reflux esophagitis, but the combination of curcumin and DMSO reduced the mortality rate and the severity of the esophagitis ulcer index to the same extent (56.5%) as did the lansoprazole (53.9%). Intraduodenal administration of curcumin also markedly prevented the formation of acute mixed reflux esophagitis, together with reducing the incidence or the severity of neutrophil infiltration, when compared to a control group. In contrast, lansoprazole tended to increase the severity of all histopathological changes, when compared to either the control or the curcumin-treated group. Aminoguanidine, a specific inducible nitric oxide synthase inhibitor, had no preventive effect against both types of acute reflux esophagitis models, and increased the mortality in the chronic acid reflux esophagitis model. From these results, it is indicated that curcumin can effectively prevent acute reflux esophagitis formation. Although curcumin is less potent than lansoprazole in inhibiting acid reflux esophagitis, it is superior to lansoprazole in inhibiting mixed reflux esophagitis. The antiulcerogenic mechanisms are considered to be closely associated with its antioxidant nature and antiinflammatory property.