The views of European students on the inclusion of research in undergraduate Oral Health Professional curricula.

INTRODUCTION: The education of Oral Health Professionals (OHPs) is variable across Europe and consequently, there is concern that research skills are not consistently or optimally integrated into European OHP curricula. The aim of this study is to investigate the perspectives of European OHP students regarding the inclusion of research in the undergraduate curriculum. MATERIALS AND METHODS: A 21-question online survey was administered to dental, dental hygiene, and dental hygiene and therapy students across Europe. Informed consent was obtained from participants and all responses remained confidential. Quantitative and qualitative methods were used to analyse the data. RESULTS: A total of 825 student responses to the survey from 33 European countries were eligible for inclusion. The results demonstrated that OHP students recognise the importance of research in the dental field and value the inclusion of research in the curriculum. Although students indicated that they are interested to learn more about research, the survey results also showed that students had neutral opinions towards the existing curriculum providing enough training about research. CONCLUSION: European OHP students agree on the need for an open and explicit research curriculum in OHP education. The development of a research domain within an open curriculum framework would help to harmonise the teaching and assessment of OHP research skills across Europe and ultimately improve graduating OHP's research skills.

O-HEALTH-EDU: A viewpoint into the current state of Oral Health Professional education in Europe: Part 1: Programme-level data.

INTRODUCTION: Current legislation leaves Oral Health Professional (OHP) education open to wide interpretation and may result in significant variation in educational practice and resultant professional attributes across Europe. Data regarding the current state of OHP education across Europe is limited. The aim of Part 1 of this series is to provide programme-level data for Primary Dental Degree Programmes, Dental Hygiene and Postgraduate Education. METHODS: A 91-item questionnaire was developed following the Delphi method. The questionnaire and the Articulate glossary of OHP education terms were developed concurrently to facilitate a common understanding of language. Piloting was performed in multiple stages and included institutions internal and external to the research group. The questionnaire was uploaded online and converted to a data hub, allowing dental schools to control their own data and update the data provided whenever they wish. All ADEE member schools (n = 144) were invited to provide data. Forty questions relating to school details, Primary Dental Degree Programmes, Dental Hygiene and Postgraduate Education were included in this part of the series. RESULTS: Seventy-one institutions from 25 European countries provided data between June 2021 and April 2023, which represents a response rate of 49.3% of ADEE members. Programme-level data for Primary Dental Degree Programmes, Dental Hygiene and Postgraduate Education is presented including programme length, funding, languages and fees, student numbers and demographics, student admission and selection processes and permission to practice after graduation. CONCLUSION: This series of papers, as far as the authors are aware, are the first attempts to build a comprehensive picture of the current state of OHP education in Europe. A comprehensive view of the state of OHP education in Europe is not yet available but the O-Health-Edu data hub provides a means for all education providers in Europe to contribute data to reach this goal. It is anticipated that the data hub will be updated and built upon over time to continually establish a clearer picture of the state of OHP education in Europe.

O-Health-Edu: A viewpoint into the current state of oral health professional education in Europe: Part 2: Curriculum structure, facilities, staffing and quality assurance.

INTRODUCTION: Oral health professional (OHP) education is likely to vary across Europe in accordance with an EU directive that is open to broad interpretation. It is not clear how OHP curricula are structured or delivered across Europe. The objectives of Part 2 of this paper series are: (i) to provide an overview of common practices in curriculum structure, the availability of facilities, staffing (faculty) and quality assurance processes and (ii) to consider how the existing programme structures align to stakeholder guidance documents. METHODS: A total of 27 questions from a 91-item questionnaire were used for this manuscript. The questionnaire was developed following the Delphi method to establish consensus from a group of experts. Members of the research team and colleagues from other countries in Europe completed a multi-step piloting process. An online data hub was created to allow the respondents to be data controllers and respond to the questionnaire. ADEE member schools (n = 144) were invited to provide data. RESULTS: Totally, 71 institutions from 25 European countries provided data between June 2021 and April 2023, which represents a response rate of 49.3% of ADEE members. Data on curriculum approaches, teaching methods, integration of topics of interest, clinical education, staff-student ratios, access to facilities and new technologies, teaching staff (faculty) and quality assurance processes are presented for Primary Dental Degree Programmes. CONCLUSION: To the best of our knowledge, this series of papers are the first attempts to provide a comprehensive overview of OHP education in Europe. Results showed that the majority of European dental programmes are engaged in providing innovative and scientifically grounded education in order to develop quality future OHPs. Nevertheless, significant variability in the delivery of clinical education across the European OHP schools was notable in this dataset. A comprehensive view of the state of OHP education in Europe is not yet available but the O-Health-Edu data hub provides a means for all education providers in Europe to contribute data to reach this goal. It is anticipated that the data hub will be updated and built upon over time to continually establish a clearer picture of the state of OHP education in Europe.

ARTICULATE: A European glossary of terms used in oral health professional education.

INTRODUCTION: The Erasmus+O-Health-EDU project aims to gain a comprehensive view of oral health professional (OHP) education in Europe, through the development of web-based surveys and online toolkits. A glossary to facilitate a common language through which academic teams could cooperate and communicate more accurately was identified as a key need within the project. The aim of ARTICULATE was thus to create a shared language, with a European focus, for terms and concepts used in the field of OHP education. METHODS: The methodology was developed from those published for construction of other glossaries with a circular and iterative process: the creation of content and definitions by a group of experts in OHP education, the testing of "fitness for purpose" of the content, and stakeholder consultation. All creation steps were followed by refinements based on testing results and stakeholder comments. The final glossary was then launched as an online resource including a built-in mechanism for user feedback. RESULTS: The scope and structure of the glossary were mapped out at a workshop with 12 dental education experts from 7 European countries. A total of 328 terms were identified, of which 171 were finally included in ARTICULATE. After piloting with a close group of other colleagues, the glossary was opened for external input. Thirty European Deans or Heads of Education assessed the definition of each term as "clear" or "not clear." A total of 86 definitions were described as "clear" by all individuals. Terms deemed unclear by at least one individual were revisited and changes made to 37 of the definitions. In conjunction with the launch of the glossary, a range of stakeholder organisations were informed and asked to participate in an open global consultation by providing feedback online. Since its launch in June 2021, the ARTICULATE website (https://o-health-edu.org/articulate) has had an average of 500 visits/month. To promote community ownership, forms embedded on the ARTICULATE webpage allow users to give feedback and suggest new terms. A standing taskforce will meet regularly to consider amendments and make changes to ensure that the glossary remains a relevant and up-to-date resource over time. CONCLUSION: ARTICULATE is a unique, evolving, online glossary of terms relating to OHP education, created as a resource for all interested OHP educators. The glossary is a key output of the O-Health-Edu project, which relies on a comprehensive vision of OHP education to address the future oral health needs of the European population.

O-Health-Edu: A vision for oral health professional education in Europe.

This consensus paper reports on the process of developing a renewed vision for Oral Health Professional (OHP) education across Europe, and forms part of a larger EU-funded collaborative Erasmus+ project, "O-Health-Edu." The vision aligns with the World Health Organisation milestones (2016) and resolutions (2021), and EU4Health programme (2020) objectives - and projects 20 years into the future, to 2040. This longitudinal vision takes a multi-stakeholder perspective to deliver OHP education that acts in the best interests of both students and patients, and sits within the context of a wider strategy for general health. Included, it is an infographic to help communicate the vision to various stakeholders of OHP education.

Embedding environmental sustainability within oral health professional curricula-Recommendations for teaching and assessment of learning outcomes.

The FDI World Dental Federation suggests that "dentistry, as a profession, should integrate Sustainable Development Goals into daily practice and support a shift to a green economy in the pursuit of healthy lives and wellbeing for all, through all stages of life." This article reports on the recent activity of the Association for Dental Education in Europe Special Interest Group for Sustainability in Dentistry. Following on from the group's previous activities, which explored current educational practice, this work aimed to reach a pan-European consensus on a number of learning outcomes for environmental sustainability, in order to (i) support institutions in designing and delivering their curriculum, and (ii) to further harmonise the delivery of oral health professional education across Europe. This article presents specific learning outcomes relating to environmental sustainability and recommendations relating to curriculum development, including methods of teaching and assessment.

Combining virtual reality and 3D-printed models to simulate patient-specific dental operative procedures-A study exploring student perceptions.

INTRODUCTION: Students face a number of challenges in translating the skills acquired in pre-clinical simulation environments to the delivery of real patient care. These are particularly emphasised for complex operative procedures such as tooth preparations for indirect restorations. This paper reports student perceptions of a novel approach designed to improving student confidence when undertaking operative procedures on patients for the first time, by providing patient-specific simulation using virtual reality (VR) and 3D-printed models of the student's real clinical case. MATERIALS AND METHODS: Students practised on patient-specific models, in the presence of a clinical tutor, firstly using VR simulation then with 3D-printed models in a clinical skills laboratory. The students then carried out the operative procedure on their patients, on the third occasion of practice. After providing the treatment for their patients, students attended a semi-structured interview to discuss their experiences. The qualitative data were analysed using two forms of inductive analysis. RESULTS: Students most frequently cited: the value of the educator, increased confidence and efficiency during the clinical procedure, improved patient confidence and the complementary benefits of the two simulation modalities. Thematic analysis of participants' responses uncovered five key themes: The value of virtual reality dental simulators The value of clinical skills laboratory simulation with 3D-printed models The value of educator engagement The impact on the clinical procedure and the patient The VR and clinical skills laboratory balance CONCLUSION: This paper reports the early findings of an intervention that improves dental student confidence through the use of patient-specific VR exercises and 3D-printed models. These provided an incremental learning experience for an operative clinical procedure, prior to treatment of the live patient. Early results suggest this is a positive experience for the students, providing a valuable contribution to their confidence and preparedness.

Re-defining the virtual reality dental simulator: Demonstrating concurrent validity of clinically relevant assessment and feedback.

INTRODUCTION: Virtual reality (VR) dental simulators are gaining momentum as a useful tool to educate dental students. To date, no VR dental simulator exercise has been designed which is capable of reliably providing validated, meaningful clinical feedback to dental students. This study aims to measure the concurrent validity of the assessment and the provision of qualitative feedback, pertaining to cavity preparations by VR dental simulators. METHODS: A cavity preparation exercise was created on a VR dental simulator, and assessment criteria for cavity preparations were developed. The exercise was performed 10 times in order to demonstrate a range of performances, and for each, the simulator feedback was recorded. The exercises were subsequently three-dimensionally printed, and 12 clinical teachers were asked to assess the preparations according to the same criteria. Inter-rater reliability (IRR) between clinical teachers was measured using a free-marginal multirater kappa value. Clinical teacher assessment responses were compared with the VR simulator responses and percentage agreements calculated. RESULTS: IRR values for each exercise ranged from 0.39 to 0.77 (69.39%-88.48%). The assessment of smoothness (κfree 0.58, 78.79%) and ability to follow the outline (κfree 0.56, 77.88%) demonstrated highest agreement between clinical teachers, whilst the assessment of undercut (κfree 0.15, 57.58%) and depth (κfree 0.28, 64.09%) had the lowest agreement. The modal percentage agreement between clinical teachers and the VR simulator was, on average, 78% across all exercises. CONCLUSION: The results of this study demonstrate that it is possible to provide reliable and clinically relevant qualitative feedback via a VR dental simulator. Further research should look to employ this technique across a broader range of exercises that help to develop other complex operative dental skills.

Defining dental operative skills curricula: An ADEE consensus paper.

This paper reports on the recent activity of the pan-European consensus of the ADEE Special Interest Group for Pre-Clinical Operative Skills. Following the previous recommendations from the group, and in order to support teachers and to harmonise the delivery of skills training across Europe, a more formal curriculum relating to pre-clinical operative skills needs to be created. This paper reports European consensus surrounding the categorisation (level of importance, and difficulty) of basic operative dental clinical skills within the undergraduate curriculum and provides recommendations relating to session structure and timing of curricular elements for basic operative dental clinical skills teaching.

O-HEALTH-EDU: A scoping review on the reporting of oral health professional education in Europe.

INTRODUCTION: The variability in oral health professional education is likely to impact on the management of oral health needs across Europe. This scoping review forms the initial part of a larger EU-funded collaborative Erasmus + project, 'O-Health-Edu'. The aim of this scoping review is to investigate how oral health professional education in Europe is reported. METHODS: The PRISMA and Arksey & O'Malley methodological frameworks for scoping reviews were used to guide reviewers in answering the research question "How is oral health professional education reported in Europe?". The search strategy encompassed published literature searches, internet searches and further searching of relevant documents from educational organisations, regulators and professional bodies. Once the search strategy was developed, it was sent to key stakeholders for consultation. Sources were reviewed by two authors (JD, JF) and included in the review if they reported on oral health professional education in Europe. RESULTS: A total of 508 sources were retrieved from all of the searches. A total of 405 sources were excluded as they did not report on the topic of interest, leaving 103 sources that reported on oral health professional education in Europe. Handsearching the references of published sources lead to a further 41 sources being screened, of which, 15 were included. In total, 33 duplications were removed and the final number of included sources was 85. The average year of publication for the included sources was 2007, with sources most commonly published in journals dedicated to dental education. Surveys represented the most common form of reporting. From the data obtained, four broad themes of reporting were evident: dental education at a programme level, dental education at a discipline level, other oral health professional education, and postgraduate education and continuous professional development. CONCLUSION: The reporting of dental and oral health professional education in Europe is limited. Whilst there are many useful documents that provide guidelines on dental education, there is limited knowledge on how education is implemented and delivered. There is a greater need for comprehensive educationally driven programme-level data on oral health professional education across Europe.

Embedding environmental sustainability within the modern dental curriculum- Exploring current practice and developing a shared understanding.

INTRODUCTION: Evidence concerning the interactions between human health and planetary health has grown extensively in recent years. In turn, the perceived importance of environmental sustainability within higher education is growing at a rapid rate. This paper provides a summary of key elements as they apply to dentistry, and provides an introduction to the reader of an early consensus of how sustainability could be included as part of the dental curriculum. METHODS: The consensus opinion within this paper largely centres around discussion at the ADEE sustainability workshop at the annual conference in Berlin (August 2019). In order to help inform discussions at the workshop, a brief scoping questionnaire was circulated to potential participants regarding their understanding and current teaching practices in sustainability. An infographic was designed to help delegates remember the important elements of sustainable dentistry. Delegates discussed the concept of sustainability alongside the infographic, and how they could link these with the Graduating European Dentist (GED) curriculum. RESULTS: The discussions within the workshop largely centred around 4 main themes: Disease prevention and health promotion, Patient education and empowerment, Lean service delivery and Preferential use of strategies with lower environmental impact. DISCUSSION: It is apparent that there is a widespread need for teaching materials relating to environmental sustainability; this includes specific learning outcomes relating to the 4 educational domains of the Graduating European Dentist curriculum, and methods for teaching and assessing these outcomes. CONCLUSION: This paper reports consensus on the first phase of a pan-European working group on Sustainability in dental education.

COVID-19: The immediate response of european academic dental institutions and future implications for dental education.

The COVID-19 pandemic has had an immediate and dramatic impact on dental education. The Association of Dental Education in Europe decided to carry out an investigation to assess the immediate response of European Academic Dental Institutions. An online survey was sent to both member and non-member dental schools to investigate the impact on non-clinical and clinical education, assessment and the well-being/pastoral care measures implemented. The preliminary findings and discussion are presented in this paper, for the responses collected between the 25 March and 5 April 2020. The survey at this time of publication is ongoing, and detailed results can be accessed https://adee.org/covid-19-european-dental-education%E2%80%99s-immediate-response.

Environmental sustainability: the attitudes and experiences of UK students in the oral health care profession.

Objective This study aims to provide insight into the attitudes and perspectives of undergraduate dental students from UK dental schools regarding environmental sustainability in dentistry (ESD) and the manner and extent in which ESD is included in the current undergraduate oral health care curricula.Methods This study is a multi-centre, nationally representive study involving a cross-sectional online survey of undergraduate Bachelor of Dental Surgery and dental hygiene and therapy students in UK-based dental schools. Data analysis was conducted through descriptive statistics and thematic analysis.Results In total, 263 students from 13 UK schools completed the survey, resulting in a national school response rate of 68.4%. Key findings are: 97.3% of students believe that the dental profession should be more actively engaged in environmental sustainability but students currently have very little exposure to ESD at an undergraduate level; and 76.8% of students expressed that they are concerned about the impact that oral health care provision has on the environment, but only 23% of students have independently researched ESD.Conclusions Students identify that oral health care professionals should become more engaged in efforts to mitigate the negative impacts from our activities on the environment, principally via education at all levels. The data from this study provide insight into the current level of awareness and concerns for the environmental impacts of oral health care provision, and are a powerful driver for the inclusion of ESD into the undergraduate curriculum in UK based dental schools.

Curriculum content for Environmental Sustainability in Dentistry.

OBJECTIVES: (i) To identify suitable strategies and opportunities to embed Environmental Sustainability (ES) within an existing Oral Health Professional (OHP) curriculum through a series of focus groups with students and academic staff and (ii) To create high-level evidence-based and subject-specific ES content through an approach grounded in evidence and collaboration with key stakeholders in OHP education. METHODS: Focus groups were used to explore academic staff and student views on appropriate teaching and assessment methods for ES. Content statements were developed from an extensive literature search, mapped to curriculum subjects, and validated through consultation with students, discipline-experts and education-experts. RESULTS: Five themes were identified from the focus groups: ES transcends all disciplines of dentistry and oral healthcare; baseline knowledge transmission with relevant practical application; viewing and modifying existing teaching and assessment events through a different lens; normalising the topic of ES to support attitude and behaviour change and safeguarding against misinformation and disinformation. Forty-four content statements were developed and mapped to nineteen curriculum subjects. CONCLUSIONS: This study identifies for the first time a comprehensive strategy for the inclusion and delivery of ES (method and content) in the curriculum. A novel method to define and map curriculum content has been explored and validated using a range of complementary methodologies. A comprehensive and robust list of evidence-based and subject-specific educational content statements have been defined in the field of Environmental Sustainability in dentistry and oral healthcare. CLINICAL SIGNIFICANCE: Oral healthcare has a significant environmental impact, the key to all mitigation strategies is educating the profession at all levels.

Relative contributions to patient effective dose in SPECT-CT hybrid imaging.

Medical imaging using ionising radiation, while commonplace, has an associated risk of cancer induction. In trying to manage this risk it is beneficial to be able to quantify it through the use of effective dose. Estimates of effective dose resulting from radiopharmaceutical administration are well established in published data but the equivalent data for the computed tomography (CT) component of nuclear medicine hybrid imaging is less well-known. This study aims to estimate the absolute and relative contributions to effective dose from radiopharmaceutical and CT components of common single photon emission computed tomography (SPECT)-CT procedures. Using patient dose-audit data from three SPECT-CT systems we estimated the effective dose resulting from radiopharmaceutical administration by scaling the published effective dose data according to administered activity. The corresponding effective dose resulting from the CT component was estimated using the ImPACT CT dosimetry tool. Absolute effective dose from radiopharmaceutical administrations ranged from 0.2 (Tc-99m colloid head and neck sentinel lymph node imaging) to 14.2 mSv (dual-isotope Tc-99m sestamibi/I-123 sodium iodide parathyroid imaging). Effective dose from the CT components ranged from 0.3 (Tl-201 chloride brain scans - scan range covering the brain) to 4.4 mSv (Tc-99m HYNIC Ty3-Octreotide scans which use a scan range from the top of the brain to bottom of pelvis). Relative contributions (radiopharmaceutical/CT) ranged from 11/89 (Tc-99m colloid head and neck sentinel lymph node imaging) to 98/2% (Tl-201 chloride brain scans). There is a wide range of effective dose from radiopharmaceutical and CT components of hybrid imaging and both aspects can benefit from optimisation efforts, with the largest benefit coming from the CT components.

Five years of treatment with adefovir dipivoxil in Chinese patients with HBeAg-positive chronic hepatitis B.

BACKGROUND: Adefovir dipivoxil (ADV) is a nucleotide analogue with proven efficacy in chronic hepatitis B (CHB). AIMS: This study investigated long-term ADV treatment in HBeAg-positive patients. METHODS: A total of 480 Chinese subjects with HBeAg-positive CHB who participated in a 1-year, double-blind, placebo-controlled study of ADV 10 mg daily were offered open-label continuation for a further 208 weeks. RESULTS: A total of 390 subjects completed 5 years of treatment. Baseline median hepatitis B virus (HBV) DNA was 8.8 log(10) copies/ml and alanine aminotransferase (ALT) 2.6 × upper limit of normal. Treatment with ADV resulted in sustained suppression of median HBV DNA by 4.8, 5.0, 5.1, 5.4 and 5.5 log(10) copies/ml after 1, 2, 3, 4 and 5 years respectively. Continuous treatment with ADV led to a progressive increase in the proportion of subjects achieving undetectable HBV DNA, from 28% after 1 year to 58% after 5 years. HBeAg seroconversion rates increased cumulatively from 11% after 1 year to 29% after 5 years. HBsAg seroconversion was achieved by 1.0% of patients. ADV resulted in ALT normalization that was maintained throughout this study in 75-79% of subjects. Virological breakthrough associated with ADV resistant mutations (rtN236T and rtA181V) occurred in 14.6% of subjects. ADV was well tolerated. CONCLUSION: Five years of ADV treatment in Chinese subjects with HBeAg-positive CHB resulted in increasing virological and serological responses and sustained biochemical responses over time. Virological resistance was identified in 14.6% of patients. Urgent switch or add-on therapy with a nucleoside analogue is necessary if ADV resistant mutations are detected, particularly rtN236T. Treatment was well tolerated.

Invasive lobular carcinoma: response to neoadjuvant letrozole therapy.

Invasive lobular cancer (ILC) responds poorly to neoadjuvant chemotherapy but appears to respond well to endocrine therapy. We examined the effectiveness of neoadjuvant letrozole in postmenopausal women (PMW) with estrogen receptor (ER)-rich ILC. PMW were considered for treatment with neoadjuvant letrozole if they had ER-rich, large operable, or locally advanced cancers, or were unfit for surgical therapy. Tumor volume was estimated at diagnosis and at 3 months using calipers (clinical), ultrasound, and mammography. At 3 months, if physically fit, women were assessed for surgery. Responsive women with cancers too large for breast-conserving surgery continued with letrozole. Patients had surgery or were switched to alternative therapy if tumor volume was increasing. Sixty-one patients (mean age, 76.2 years) with 63 ILCs were treated with letrozole for ≥ 3 months. The mean reduction in tumor volume at 3 months was 66% (median, 76%) measured clinically, 61% (median, 73%) measured by ultrasound, and 54% (median, 60%) measured by mammography. Surgery was possible at 3 months in 24 cancers in 24 patients, and all but two of the remaining patients continued with letrozole therapy for a median duration of 9 months. At the time of this publication, 40 patients with a total of 41 cancers have undergone surgery. The rate of successful breast conservation was 81% (25/31). Twenty-one patients have continued with letrozole monotherapy, and 19 remain controlled on letrozole at a median of 2.8 years. There is a high rate of response to letrozole in PMW with ER-rich ILC.

Complicating factors in complete dentures: assessing case complexity.

This article aims to describe common complicating factors that impact on the success of complete denture treatment and present an overview of the challenges these pose in practice. The authors present a range of medical, oral and social factors to consider when providing treatment to edentulous patients, allowing the practitioner to identify cases which may require referral. The information is applicable to all dental practitioners, and is a useful aid to highlight complicating factors in individual patients and to make well-informed clinical decisions.

Predicting conversion to wet age-related macular degeneration using deep learning.

Progression to exudative 'wet' age-related macular degeneration (exAMD) is a major cause of visual deterioration. In patients diagnosed with exAMD in one eye, we introduce an artificial intelligence (AI) system to predict progression to exAMD in the second eye. By combining models based on three-dimensional (3D) optical coherence tomography images and corresponding automatic tissue maps, our system predicts conversion to exAMD within a clinically actionable 6-month time window, achieving a per-volumetric-scan sensitivity of 80% at 55% specificity, and 34% sensitivity at 90% specificity. This level of performance corresponds to true positives in 78% and 41% of individual eyes, and false positives in 56% and 17% of individual eyes at the high sensitivity and high specificity points, respectively. Moreover, we show that automatic tissue segmentation can identify anatomical changes before conversion and high-risk subgroups. This AI system overcomes substantial interobserver variability in expert predictions, performing better than five out of six experts, and demonstrates the potential of using AI to predict disease progression.

Lamivudine for patients with chronic hepatitis B and advanced liver disease.

BACKGROUND: The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown. METHODS: Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to receive lamivudine (100 mg per day) or placebo for a maximum of five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive placebo. The primary end point was time to disease progression, defined by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or death related to liver disease. An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data. RESULTS: We randomly assigned 651 patients (98 percent Asian and 85 percent male) to receive lamivudine or placebo. The study was terminated after a median duration of treatment of 32.4 months (range, 0 to 42) owing to a significant difference between treatment groups in the number of end points reached. End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo (hazard ratio for disease progression, 0.45; P=0.001). The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo (hazard ratio, 0.45; P=0.02), whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group (hazard ratio, 0.49; P=0.047). Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine, and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine (7 percent vs. <1 percent). Overall, 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events. CONCLUSIONS: Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.