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The Lancet. Oncology Dec 2020Oncogenic human papillomavirus (HPV) infections cause most cases of cervical cancer. Here, we report long-term follow-up results for the Costa Rica Vaccine Trial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Oncogenic human papillomavirus (HPV) infections cause most cases of cervical cancer. Here, we report long-term follow-up results for the Costa Rica Vaccine Trial (publicly funded and initiated before licensure of the HPV vaccines), with the aim of assessing the efficacy of the bivalent HPV vaccine for preventing HPV 16/18-associated cervical intraepithelial neoplasia grade 2 or worse (CIN2+).
METHODS
Women aged 18-25 years were enrolled in a randomised, double-blind, controlled trial in Costa Rica, between June 28, 2004, and Dec 21, 2005, designed to assess the efficacy of a bivalent vaccine for the prevention of infection with HPV 16/18 and associated precancerous lesions at the cervix. Participants were randomly assigned (1:1) to receive an HPV 16/18 AS04-adjuvanted vaccine or control hepatitis A vaccine. Vaccines were administered intramuscularly in three 0·5 mL doses at 0, 1, and 6 months and participants were followed up annually for 4 years. After the blinded phase, women in the HPV vaccine group were invited to enrol in the long-term follow-up study, which extended follow-up for 7 additional years. The control group received HPV vaccine and was replaced with a new unvaccinated control group. Women were followed up every 2 years until year 11. Investigators and patients were aware of treatment allocation for the follow-up phase. At each visit, clinicians collected cervical cells from sexually active women for cytology and HPV testing. Women with abnormal cytology were referred to colposcopy, biopsy, and treatment as needed. Women with negative results at the last screening visit (year 11) exited the long-term follow-up study. The analytical cohort for vaccine efficacy included women who were HPV 16/18 DNA-negative at vaccination. The primary outcome of this analysis was defined as histopathologically confirmed CIN2+ or cervical intraepithelial neoplasia grade 3 or worse associated with HPV 16/18 cervical infection detected at colposcopy referral. We calculated vaccine efficacy by year and cumulatively. This long-term follow-up study is registered with ClinicalTrials.gov, NCT00867464.
FINDINGS
7466 women were enrolled in the Costa Rica Vaccine Trial; 3727 received the HPV vaccine and 3739 received the control vaccine. Between March 30, 2009, and July 5, 2012, 2635 women in the HPV vaccine group and 2836 women in the new unvaccinated control group were enrolled in the long-term follow-up study. 2635 women in the HPV vaccine group and 2677 women in the control group were included in the analysis cohort for years 0-4, and 2073 women from the HPV vaccine group and 2530 women from the new unvaccinated control group were included in the analysis cohort for years 7-11. Median follow-up time for the HPV group was 11·1 years (IQR 9·1-11·7), 4·6 years (4·3-5·3) for the original control group, and 6·2 years (5·5-6·9) for the new unvaccinated control group. At year 11, vaccine efficacy against incident HPV 16/18-associated CIN2+ was 100% (95% CI 89·2-100·0); 34 (1·5%) of 2233 unvaccinated women had a CIN2+ outcome compared with none of 1913 women in the HPV group. Cumulative vaccine efficacy against HPV 16/18-associated CIN2+ over the 11-year period was 97·4% (95% CI 88·0-99·6). Similar protection was observed against HPV 16/18-associated CIN3-specifically at year 11, vaccine efficacy was 100% (95% CI 78·8-100·0) and cumulative vaccine efficacy was 94·9% (73·7-99·4). During the long-term follow-up, no serious adverse events occurred that were deemed related to the HPV vaccine. The most common grade 3 or worse serious adverse events were pregnancy, puerperium, and perinatal conditions (in 255 [10%] of 2530 women in the unvaccinated control group and 201 [10%] of 2073 women in the HPV vaccine group). Four women in the unvaccinated control group and three in the HPV vaccine group died; no deaths were deemed to be related to the HPV vaccine.
INTERPRETATION
The bivalent HPV vaccine has high efficacy against HPV 16/18-associated precancer for more than a decade after initial vaccination, supporting the notion that invasive cervical cancer is preventable.
FUNDING
US National Cancer Institute.
Topics: Adolescent; Adult; Costa Rica; Double-Blind Method; Female; Human papillomavirus 16; Human papillomavirus 18; Humans; Immunization; Neoplasm Grading; Papillomavirus Infections; Papillomavirus Vaccines; Time Factors; Treatment Outcome; Uterine Cervical Neoplasms; Vaccines, Combined; Young Adult; Uterine Cervical Dysplasia
PubMed: 33271093
DOI: 10.1016/S1470-2045(20)30524-6 -
American Journal of Obstetrics and... May 1976The results of the Schiller test were recorded in 87 patients before conization and in 100 healthy control women having normal cytologic examinations. Large proportions...
The results of the Schiller test were recorded in 87 patients before conization and in 100 healthy control women having normal cytologic examinations. Large proportions of quadrants with iodine-unstained areas were found in both the experimental and the control series. In the 87 patients, the histologic examination of the cone specimens revealed false positive Schiller tests in 32 per cent of the patients with unstained quadrants, and false negative tests in 60 per cent of the patients with iodine-stained quadrants. The Schiller test proved to be unreliable in detecting or rejecting dysplasia or carcinoma in situ at the surgical margin of the conization specimens.
Topics: Biopsy; Carcinoma in Situ; Cervix Uteri; Colposcopy; Evaluation Studies as Topic; False Negative Reactions; False Positive Reactions; Female; Histological Techniques; Humans; Iodine; Photography; Uterine Cervical Neoplasms
PubMed: 775993
DOI: 10.1016/0002-9378(76)90900-5 -
Schweizerische Medizinische... Mar 1961
Topics: Face; Iodides; Iodine; Mouth
PubMed: 15445605
DOI: No ID Found -
Fertility and Sterility 1964
Topics: Carcinoma; Carcinoma, Squamous Cell; Conization; Cytodiagnosis; Female; Humans; Infertility; Infertility, Female; Iodine; Neoplasms; Pathology; Surgical Procedures, Operative; Uterine Cervical Neoplasms
PubMed: 14105094
DOI: 10.1016/s0015-0282(16)35108-1 -
Prevention Science : the Official... Apr 2018In this article, we introduce the special issue entitled Innovation and Integrity in Intervention Science. Its focus is on essential problems and prospects for...
In this article, we introduce the special issue entitled Innovation and Integrity in Intervention Science. Its focus is on essential problems and prospects for intervention research examining two related topics, i.e., methodological issues and research integrity, and challenges in the transfer of research knowledge into practice and policy. The main aims are to identify how to advance methodology in order to improve research quality, examine scientific integrity in the field of intervention science, and discuss future steps to enhance the transfer of knowledge about evidence-based intervention principles into sustained practice, routine activities, and policy decisions. Themes of the special issue are twofold. The first includes questions about research methodology in intervention science, both in terms of research design and methods, as well as data analyses and the reporting of findings. Second, the issue tackles questions surrounding the types of knowledge translation frameworks that might be beneficial to mobilize the transfer of research-based knowledge into practice and public policies. The issue argues that innovations in methodology and thoughtful approaches to knowledge translation can enable transparency, quality, and sustainability of intervention research.
Topics: Adolescent Health; Child Health; Concept Formation; Evidence-Based Medicine; Policy Making; Preventive Medicine; Research Design; Translational Research, Biomedical
PubMed: 29411196
DOI: 10.1007/s11121-018-0868-7 -
Chemical Communications (Cambridge,... Apr 2014Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic... (Review)
Review
Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed.
Topics: Animals; Carbon Monoxide; Coordination Complexes; Delayed-Action Preparations; Humans
PubMed: 24556640
DOI: 10.1039/c3cc49196j -
Frontiers in Pharmacology 2022
PubMed: 35784759
DOI: 10.3389/fphar.2022.947511 -
Pharmacotherapy Dec 2014
Topics: Drug Utilization Review; Humans; Pharmacists; Quality Improvement
PubMed: 25521846
DOI: 10.1002/phar.1515 -
Progress in Brain Research 2018There has been a controversy on the moral import of music and art in general. On the one hand, the moralist view contends that there is some sort of link between art and... (Review)
Review
There has been a controversy on the moral import of music and art in general. On the one hand, the moralist view contends that there is some sort of link between art and morality, even if the way to specify this link may be highly diverse. It comprises most of the classical views of art, from Schiller's view of the role of artistic education in moral development, to any view that declares a form of art as corrupt or degenerated, or enlightening. What it is assumed minimally in all of them is that the moral import of an artwork contributes to its aesthetic value. On the other hand, formalist views claim that the aesthetic value of an artwork is genuine and autonomous, and therefore it is independent of any other value. In this chapter we focus on music, as the most difficult case for the moralist standpoint, given the lack of representational content of music. We argue for a variety of the moralist's view according to which the moral import of a musical artwork is not derived from its content (obviously, as it lack any), but from its pragmatics: the context and the intentions that guide its composition and performance, by analogy with any other intentional action, and point to the emotional impact of music as the common ground that bridges moral and aesthetic values. As a provisional conclusion, we outline a research program for brain studies that follows from this proposal, as a way test its predictions, focusing both on the emotional grounds of valuation and their context-dependency.
Topics: Brain; Emotions; Esthetics; Humans; Morals; Music
PubMed: 29779750
DOI: 10.1016/bs.pbr.2018.03.015 -
Journal of Biomedical Informatics May 2022In the present systematic review we identified and summarised current research activities in the field of time series forecasting and imputation with the help of... (Review)
Review
In the present systematic review we identified and summarised current research activities in the field of time series forecasting and imputation with the help of generative adversarial networks (GANs). We differentiate between imputation which describes the filling of missing values at intermediate steps and forecasting defining the prediction of future values. Especially the utilisation of such methods in the biomedical domain was to be investigated. To this end, 1057 publications were identified with the help of PubMed, Web of Science and Scopus. All studies that describe the use of GANs for the imputation/forecasting of time series were included irrespective of the application domain. Finally, 33 records were identified as eligible and grouped according to the topologies, losses, inputs and outputs of the presented GANs. In combination with a summary of all described application domains, this grouping served as a basis for analysing the peculiarities of the method in the biomedical context. Due to the broad spectrum of biomedical research, nearly all recognised methodologies are also applied in this domain. We could not identify any approach that proved itself superior in the biomedical area. Although GANs were initially designed to work in the image domain, many publications show that they are capable of imputing/forecasting non-visual time series.
Topics: Bibliometrics; Forecasting; Neural Networks, Computer; Research Design; Time Factors
PubMed: 35346855
DOI: 10.1016/j.jbi.2022.104058