A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings.

Genomic sequencing (GS) can reveal secondary findings (SFs), findings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically significant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically significant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in three phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative refinement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary (cancer) and secondary findings, with in-depth details of each finding generated from exome sequencing. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically significant SFs to patients and providers, facilitating clinical management of GS results.

Exome and genome sequencing in adults with undiagnosed disease: a prospective cohort study.

BACKGROUND: Exome and genome sequencing have been demonstrated to increase diagnostic yield in paediatric populations, improving treatment options and providing risk information for relatives. There are limited studies examining the clinical utility of these tests in adults, who currently have limited access to this technology. METHODS: Patients from adult and cancer genetics clinics across Toronto, Ontario, Canada were recruited into a prospective cohort study evaluating the diagnostic utility of exome and genome sequencing in adults. Eligible patients were ≥18 years of age and suspected of having a hereditary disorder but had received previous uninformative genetic test results. In total, we examined the diagnostic utility of exome and genome sequencing in 47 probands and 34 of their relatives who consented to participate and underwent exome or genome sequencing. RESULTS: Overall, 17% (8/47) of probands had a pathogenic or likely pathogenic variant identified in a gene associated with their primary indication for testing. The diagnostic yield for patients with a cancer history was similar to the yield for patients with a non-cancer history (4/18 (22%) vs 4/29 (14%)). An additional 24 probands (51%) had an inconclusive result. Secondary findings were identified in 10 patients (21%); three had medically actionable results. CONCLUSIONS: This study lends evidence to the diagnostic utility of exome or genome sequencing in an undiagnosed adult population. The significant increase in diagnostic yield warrants the use of this technology. The identification and communication of secondary findings may provide added value when using this testing modality as a first-line test.

[A systematic review of standardized instruments to measure the doctor-patient relationship]. / Instrumentos estandarizados para medir la relación médico-paciente: una revisión sistemática de la literatura internacional e iberoamericana.

The current health situation caused by the COVID-19 pandemic has prompted a reconfiguration of the doctor-patient relationship. We performed a systematic review to comparatively evaluate the instruments most used to study communication in the doctor-patient relationship. We identified 43 instruments assessing different aspects of the doctor-patient relationship, of which 34 correspond to Anglo-Saxon literature and nine to Latin American texts. The psychometric evidence for many of these instruments is incipient. Most of these instruments contemplate a unidirectional design and address similar dimensions of the doctor-patient relationship, particularly in the Latin American context where the relationship is mostly studied in a unidimensional way. We propose recommendations for the development, revision, or refinement of instruments that measure communication in the doctor-patient relationship.

Beyond medically actionable results: an analytical pipeline for decreasing the burden of returning all clinically significant secondary findings.

Genomic sequencing advances have increased the potential to identify secondary findings (SFs). Current guidelines recommend the analysis of 59 medically actionable genes; however, patient preferences indicate interest in learning a broader group of SFs. We aimed to develop an analytical pipeline for the efficient analysis and return of all clinically significant SFs. We developed a pipeline consisting of comprehensive gene lists for five categories of SFs and filtration parameters for prioritization of variants in each category. We applied the pipeline to 42 exomes to assess feasibility and efficiency. Comprehensive lists of clinically significant SF genes were curated for each category: (1) 90 medically actionable genes and 28 pharmacogenomic variants; (2) 17 common disease risk variants; (3) 3166 Mendelian disease genes, (4) 7 early onset neurodegenerative disorder genes; (5) 688 carrier status results. Analysis of 42 exomes using our pipeline resulted in a significant decrease (> 98%) in variants compared to the raw analysis (13,036.56 ± 59.72 raw variants/exome vs 161.32 ± 7.68 filtered variants/exome), and aided in time and costs savings for the overall analysis process. Our pipeline represents a critical step in overcoming the analytic challenge associated with returning all clinically relevant SFs to allow for its routine implementation in clinical practice.

Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy.

Hypomyelinating leukodystrophies are genetic disorders characterized by insufficient myelin deposition during development. They are diagnosed on the basis of both clinical and MRI features followed by genetic confirmation. Here, we report on four unrelated affected individuals with hypomyelination and bi-allelic pathogenic variants in EPRS, the gene encoding cytoplasmic glutamyl-prolyl-aminoacyl-tRNA synthetase. EPRS is a bifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. It is a subunit of a large multisynthetase complex composed of eight aminoacyl-tRNA synthetases and its three interacting proteins. In total, five different EPRS mutations were identified. The p.Pro1115Arg variation did not affect the assembly of the multisynthetase complex (MSC) as monitored by affinity purification-mass spectrometry. However, immunoblot analyses on protein extracts from fibroblasts of the two affected individuals sharing the p.Pro1115Arg variant showed reduced EPRS amounts. EPRS activity was reduced in one affected individual's lymphoblasts and in a purified recombinant protein model. Interestingly, two other cytoplasmic aminoacyl-tRNA synthetases have previously been implicated in hypomyelinating leukodystrophies bearing clinical and radiological similarities to those in the individuals we studied. We therefore hypothesized that leukodystrophies caused by mutations in genes encoding cytoplasmic aminoacyl-tRNA synthetases share a common underlying mechanism, such as reduced protein availability, abnormal assembly of the multisynthetase complex, and/or abnormal aminoacylation, all resulting in reduced translation capacity and insufficient myelin deposition in the developing brain.

Othering the Chronically Ill: A Discourse Analysis of New Zealand Health Policy Documents.

It is widely recognized that chronic illnesses pose significant challenges for health care systems around the world. In response, most governments have set health policies in order to manage (or better, reduce) demand and improve the health of their populations. A discourse analysis of four policy documents that shape these strategies in New Zealand reveals that the policies construct the chronically ill as "others," that is, as deviant or different from the "normal" population. The discourse further serves to blame the chronically ill both for being sick, and for placing a serious financial burden on society. We identify problems that arise from this discourse. They relate to (a) the fact that chronic illnesses are so prevalent, (b) the fallacy of categorizing all chronic illnesses as the same,

Early versus late cardiac magnetic resonance in the diagnosis of myocardial infarction with non-obstructive coronary arteries.

INTRODUCTION AND OBJECTIVES: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is responsible for about 10% of all acute myocardial infarctions (AMI). Therapeutic strategies and prognosis depend on the underlying etiology, and a multimodal approach is essential. The objectives of this study were to characterize the group of patients diagnosed with MINOCA and to valuate the diagnostic yield of cardiovascular magnetic resonance (CMR). METHODS: This was a retrospective, observational, and analytical study, including 516 patients admitted for a non-ST-elevation MI and with no significant coronary disease on coronary angiography between January 2016 and September 2021. RESULTS: After the inclusion criteria, 163 patients remained of the 516 admitted to the study. They were divided into four groups based on the CMR results: MINOCA (n=51), Takotsubo syndrome (n=37), myocarditis (n=33), and without diagnosis (n=42). Most patients diagnosed with MINOCA were female with a mean age of 61.06±13.83 years. CMR identified the diagnosis in 74.2% of patients admitted for suspected acute MI, in which coronary angiography showed the absence of significant obstructions. The median time between hospital admission and CMR was significantly shorter in the groups that had a diagnosis compared with the group with no diagnosis (p=0.038), with a significant increase in diagnostic profitability if CMR was performed up to 14 days after admission (p=0.022). There were no deaths of cardiovascular etiology during the follow-up period. CONCLUSIONS: CMR was fundamental as it identified the diagnosis in three out of four patients; it should be performed in the first 14 days.

Structure, Process, and Mortality Associated with Acute Coronary Syndrome Management in Guatemala's National Healthcare System: The ACS-GT Registry.

Background: Acute coronary syndromes (ACS) include ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA). The leading cause of mortality in Guatemala is acute myocardial infarction (AMI) and there is no established national policy nor current standard of care. Objective: Describe the factors that influence ACS outcome, evaluating the national healthcare system's quality of care based on the Donabedian health model. Methods: The ACS-Gt study is an observational, multicentre, and prospective national registry. A total of 109 ACS adult patients admitted at six hospitals from Guatemala's National Healthcare System were included. These represent six out of the country's eight geographic regions. Data enrolment took place from February 2020 to January 2021. Data was assessed using chi-square test, Student's t-test, or Mann-Whitney U test, whichever applied. A p-value < 0.05 was considered statistically significant. Results: One hundred and nine patients met inclusion criteria (80.7% STEMI, 19.3% NSTEMI/UA). The population was predominantly male, (68%) hypertensive (49.5%), and diabetic (45.9%). Fifty-nine percent of STEMI patients received fibrinolysis (alteplase 65.4%) and none for primary Percutaneous Coronary Intervention (pPCI). Reperfusion success rate was 65%, and none were taken to PCI afterwards in the recommended time period (2-24 hours). Prognostic delays in STEMI were significantly prolonged in comparison with European guidelines goals. Optimal in-hospital medical therapy was 8.3%, and in-hospital mortality was 20.4%. Conclusions: There is poor access to ACS pharmacological treatment, low reperfusion rate, and no primary, urgent, or rescue PCI available. No patient fulfilled the recommended time period between successful fibrinolysis and PCI. Resources are limited and inefficiently used.

Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial.

INTRODUCTION: Genomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, which refer to genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance. High-quality evidence evaluating health outcomes and costs of receiving incidental results is critical for the adoption of genomic sequencing into clinical care and to understand the unintended consequences of adoption of genomic sequencing. We aim to evaluate the health outcomes and costs of receiving incidental results for patients undergoing genomic sequencing. METHODS AND ANALYSIS: We will compare health outcomes and costs of receiving, versus not receiving, incidental results for adult patients with cancer undergoing genomic sequencing in a mixed-methods randomised controlled trial. Two hundred and sixty patients who have previously undergone first or second-tier genetic testing for cancer and received uninformative results will be recruited from familial cancer clinics in Toronto, Ontario. Participants in both arms will receive cancer-related results. Participants in the intervention arm have the option to receive incidental results. Our primary outcome is psychological distress at 2 weeks following return of results. Secondary outcomes include behavioural consequences, clinical and personal utility assessed over the 12 months after results are returned and health service use and costs at 12 months and 5 years. A subset of participants and providers will complete qualitative interviews about utility of incidental results. ETHICS AND DISSEMINATION: This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System that provides ethical review and oversight for multiple sites participating in the same clinical trial in Ontario.Results from the trial will be shared through stakeholder workshops, national and international conferences, and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03597165.

Instrumentos estandarizados para medir la relación médico-paciente: una revisión sistemática de la literatura internacional e iberoamericana / A systematic review of standardized instruments to measure the doctor-patient relationship

The current health situation caused by the COVID-19 pandemic has prompted a reconfiguration of the doctor-patient relationship. We performed a systematic review to comparatively evaluate the instruments most used to study communication in the doctor-patient relationship. We identified 43 instruments assessing different aspects of the doctor-patient relationship, of which 34 correspond to Anglo-Saxon literature and nine to Latin American texts. The psychometric evidence for many of these instruments is incipient. Most of these instruments contemplate a unidirectional design and address similar dimensions of the doctor-patient relationship, particularly in the Latin American context where the relationship is mostly studied in a unidimensional way. We propose recommendations for the development, revision, or refinement of instruments that measure communication in the doctor-patient relationship.

General health and perceived/feared discrimination in the lgbt+ community / Saúde geral e discriminação percebida e temida na comunidade lgbt+ / Salud general y discriminación percibida y temida en la comunidad lgbt+

ABSTRACT Objective: to analyze the relationship of perceived and feared discrimination with general health in LGBT+ people according to schooling level, gender identity and socioeconomic level. Method: a cross-sectional and correlational study was conducted. The sample consisted of 120 participants of legal age from the Maule region (Chile) who belonged to the LGBT+ community and answered an online survey due to the SARS-CoV-2 pandemic. The survey also included an open question for the participants to share discrimination experiences regarding the treatment received from the Nursing personnel. The quantitative data were examined by means of descriptive and inferential analyses (means difference and correlation tests). The results extracted were analyzed following the thematic and discursive analysis techniques. Results: although perceived discrimination had low prevalence in the sample, 44.17%, 38.33% and 32.51% manifested fear of not being loved, of not finding a job and of being rejected by their family for being part of the LGBT+ community, respectively. Likewise, discrimination was higher in the group of trans people and was mainly reflected in unjustified dismissals, difficulties finding a job or ill-treatment in the provision of health services. Finally, it was found that the participants exposed to more discrimination also reported worse general health. Conclusions: discrimination is a problem that affects the LGBT+ community, particularly the trans collective. The severe implications of discrimination for people's health evidence the need to design strategies, policies and regulations aimed at fostering tolerance and integration.

RESUMO Objetivo: analisar a relação entre a discriminação percebida e temida e a saúde geral das pessoas LGBT+ de acordo com seu nível educacional, identidade de gênero e nível socioeconômico. Método: realizou-se um estudo transversal e correlacional. A amostra foi composta por 120 participantes adultos da região de Maule (Chile), pertencentes à comunidade LGBT+, que responderam a uma pesquisa virtual devido à pandemia de SARS CoV-2. A pesquisa também incluiu uma pergunta aberta que proporcionou um espaço para os participantes compartilharem experiências de discriminação em relação ao tratamento recebido da equipe de enfermagem. Os dados quantitativos foram examinados por meio de análises descritivas e inferenciais (testes de diferença de médias e correlações). As histórias extraídas foram analisadas segundo técnicas de análise temática e discursiva. Resultados: embora a discriminação percebida tenha uma baixa prevalência na amostra, 44,17% expressaram medo de não serem amados, 38,33% de não encontrar emprego e 32,51% de serem rejeitados pela família por fazerem parte da comunidade LGBT+. Da mesma forma, a discriminação foi maior no coletivo de pessoas trans e se refletiu principalmente em demissões injustificadas, dificuldades em encontrar emprego ou maus-tratos na prestação de serviços de saúde. Por fim, verificou-se que os participantes expostos a mais discriminação também relataram pior estado geral de saúde. Conclusões: a discriminação é um problema que afeta a comunidade LGBT+, principalmente o coletivo de pessoas trans. As graves implicações da discriminação para a saúde das pessoas evidenciam a necessidade de desenhar estratégias, políticas e regulamentações que visem promover a tolerância e a integração.

RESUMEN Objetivo: analizar la relación entre la discriminación percibida y temida, y la salud general de personas LGBT+ de acuerdo a su nivel educativo, identidad de género y nivel socio-económico. Método: se realizó un estudio transversal y correlacional. La muestra constó de 120 personas participantes mayores de edad de la región del Maule (Chile), pertenecientes a la comunidad LGBT+, que respondieron una encuesta de manera virtual debido a la pandemia por SARS CoV-2. La encuesta también incluyó una pregunta abierta que proporcionó un espacio para que las personas participantes compartieran experiencias de discriminación con respecto al trato recibido del personal de enfermería. Los datos cuantitativos se examinaron mediante análisis descriptivos e inferenciales (pruebas de diferencia de medias y correlaciones). Los relatos extraídos se analizaron siguiendo técnicas de análisis temático y discursivo. Resultados: si bien la discriminación percibida tuvo una prevalencia baja en la muestra, un 44,17% expresó temor a no ser querido, 38,33% a no encontrar trabajo, y 32,51% a ser rechazado por su familia por ser parte de la comunidad LGBT+. Asimismo, la discriminación fue mayor en el grupo de personas trans y se reflejó principalmente en despidos injustificados, dificultades para encontrar empleo o maltratos en la provisión de servicios de salud. Finalmente, se encontró que las personas participantes expuestas a mayor discriminación también reportaron una peor salud general. Conclusiones: la discriminación es un problema que afecta a la comunidad LGBT+, particularmente al colectivo trans. Las serias implicaciones de la discriminación para la salud de las personas ponen de manifiesto la necesidad de diseñar estrategias, políticas y reglamentaciones tendientes a fomentar la tolerancia y la integración.

Ten years of research on psychosocial risks, health, and performance in Latin America: a comprehensive systematic review and research agenda / Diez años de investigación sobre riesgos psicosociales, salud y desempeño en América Latina: una revisión sistemática integradora y agenda de investigación

Most systematic reviews of the relationships between work-related psychosocial risks, health, and performance have only considered papers in English, thus ignoring, to a considerable extent, studies conducted in Latin America. In addition, most systematic reviews that have indeed included Latin-American studies have focused on only one occupation and one kind of psychosocial risk, which contributes to producing scattered empirical evidence of this relationship. This paper reports the results of a comprehensive and critical systematic review of 85 studies that examined the relationships between psychosocial risks, health, and performance across a wide range of organizational contexts in Latin America over the last ten years. The paper contributes to the organizational psychology literature by critically reviewing and integrating the most recent studies on this topic in Latin America, identifying their main limitations, and proposing future lines of research that update the debate on this relationship and move this field of study forward (AU)

La mayoría de las revisiones sistemáticas sobre las relaciones entre los riesgos psicosociales en el trabajo, la salud y el desempeño solo han considerado artículos en inglés, ignorando así, en gran medida, los estudios realizados en América Latina. Además, la mayoría de las revisiones sistemáticas que efectivamente han incluido estudios latinoamericanos se han centrado en una sola ocupación y en un solo tipo de riesgo psicosocial, lo que ha contribuido a producir evidencia empírica dispersa y atomizada de esta relación. Este artículo reporta los resultados de una revisión sistemática integradora y crítica de 85 estudios que examinaron las relaciones entre los riesgos psicosociales, la salud y el desempeño en una amplia gama de contextos organizacionales en América Latina durante los últimos diez años. El artículo contribuye a la literatura de psicología organizacional dado que revisa críticamente e integra los estudios más recientes sobre este tema en América Latina, identifica sus principales limitaciones y propone líneas futuras de investigación que actualicen el debate sobre esta relación y promuevan el avance de este campo de estudio (AU)

Psychosocial risks and job satisfaction in Argentinian scholars: exploring the moderating role of work engagement / Los riesgos psicosociales y la satisfacción laboral en los académicos argentinos: exploración del rol moderador del entusiasmo laboral

The increasing psychosocial risks imposed on today's scholars have turned their profession into a highly stressful career path. Drawing on evidence collected in a sample of 177 scholars from an Argentinian public university, this study explores the buffering role of work engagement in the relationship between perceived exposure to six work-related psychosocial risk factors, namely psychological demands, insufficient autonomy, lack of social support and leadership, insufficient esteem, double presence, and job insecurity, and job satisfaction. Hierarchical regression analyses resulted in three out of six possible interaction effects, revealing that work engagement indeed moderates the effects of psychological demands, lack of social support and leadership, and insufficient esteem on scholars' job satisfaction. We discuss the findings in relation to directions proposed for future research

Los crecientes riesgos psicosociales impuestos a los académicos actuales han convertido su profesión en una carrera muy estresante. Basándose en la evidencia recopilada en una muestra de 177 académicos de una universidad pública argentina, este estudio explora el rol moderador del entusiasmo laboral en la relación entre la percepción de exposición a seis factores de riesgo psicosociales relacionados con el trabajo, demandas psicológicas, autonomía insuficiente, falta de apoyo y liderazgo, falta de estima, doble presencia e inseguridad laboral, y satisfacción laboral. Los análisis de regresión jerárquica dieron como resultado tres de seis posibles efectos de interacción, revelando que el trabajo realmente modera los efectos de las demandas psicológicas, la falta de apoyo social y liderazgo y la falta de estima en la satisfacción laboral de los académicos. Se discuten los hallazgos en relación con las indicaciones propuestas para futuras investigaciones

Riesgos psicosociales e integración profesional de médicos extranjeros: Un estudio sobre el manejo del conflicto en Chile / Psychosocial risks and professional integration of foreign physicians: a study on conflict management in Chile

Background: The way in which communicative conflicts are confronted, as part of the acculturation process, can constitute a psychosocial risk factor that may affect the effectiveness of health care delivery. Aim: To describe the levels of dominance, adaptability and evasion as indicators of the way in which conflict situations are faced in the workplace by foreign physicians in the management of communicative conflicts. Materials and Methods: A self-report questionnaire was answered by 51 foreign physicians (63% women, 76% Venezuelans, 64% aged between 31 and 40 years old) who work in public healthcare institutions in a southern region of Chile. Results: The highest scores were recorded for the adaptable style of conflict management (69%), while the lowest scores were recorded for the evasive style (6%). Higher levels of dominance were identified for women than for men. There was a positive association between dominance and time progression, where the level of dominance increased as participants gained greater professional experience and workplace seniority. Conclusions: The foreign physicians who participated in this study have a clear constructive attitude towards the negotiation of conflicts. However, this effort to adapt can also become a psychosocial risk factor that affects professional integration in intercultural workplace contexts.

Fluoride varnishes and decrease in caries incidence in preschool children: a systematic review.

The objective of this systematic review was to evaluate whether there is conclusive evidence that the professional application of fluoride varnish decreases the incidence of dental caries in preschool children. We searched the BBO, LILACS, MEDLINE and Cochrane electronic databases to identify controlled clinical trials that evaluated the development of cavitated caries lesions in children up to six years of age. Two researchers performed a critical appraisal of the studies selected for inclusion. Five-hundred and thirteen articles were found, but only eight met our inclusion criteria. Most of these eight studies were of poor methodological quality. They were also heterogeneous in relation to participants' previous caries experience, type of intervention performed on the control group, children's exposure to other sources of fluoride, and varnish application interval. The absolute differences between caries incidences in the control and test groups ranged from 0.30 to 1.64 and the preventive fractions varied from 5% to 63%. Fluoride varnish may be effective to decrease the incidence of dental caries in preschoolers, but more randomized clinical trials with better methodological quality are necessary to provide conclusive evidence in this respect.

O uso de vernizes fluoretados e a redução da incidência de cárie dentária em pré-escolares: uma revisão sistemática / Fluoride varnishes and decrease in caries incidence in preschool children: a systematic review

O objetivo desta revisão sistemática foi verificar se existe evidência conclusiva de que o verniz fluoretado reduz a incidência de cárie dentária em pré-escolares. Foram feitas buscas nas bases eletrônicas BBO, LILACS, MEDLINE e Cochrane para identificar ensaios clínicos controlados que avaliassem o desenvolvimento de lesões cavitadas de cárie em crianças com até seis anos de idade. Dois pesquisadores analisaram criticamente os trabalhos selecionados para inclusão. Foram encontrados 513 artigos e oito foram incluídos. Esses estudos apresentaram problemas quanto ao desenho e, além disso, eram heterogêneos quanto à experiência prévia de cárie dos participantes, ao tipo de intervenção administrada ao grupo controle, à exposição das crianças a outras fontes de fluoretos, e ao intervalo entre as aplicações de verniz. As diferenças absolutas entre as incidências de cárie nos grupos controle e teste e as frações prevenidas variaram de 0,30 a 1,64 e de 5 a 63 por cento, respectivamente. O verniz fluoretado parece ser efetivo para reduzir a incidência de cárie dentária em pré-escolares, mas outros ensaios clínicos de melhor qualidade metodológica são necessários para se obter evidência conclusiva a esse respeito.

The objective of this systematic review was to evaluate whether there is conclusive evidence that the professional application of fluoride varnish decreases the incidence of dental caries in preschool children. We searched the BBO, LILACS, MEDLINE and Cochrane electronic databases to identify controlled clinical trials that evaluated the development of cavitated caries lesions in children up to six years of age. Two researchers performed a critical appraisal of the studies selected for inclusion. Five-hundred and thirteen articles were found, but only eight met our inclusion criteria. Most of these eight studies were of poor methodological quality. They were also heterogeneous in relation to participants' previous caries experience, type of intervention performed on the control group, children's exposure to other sources of fluoride, and varnish application interval. The absolute differences between caries incidences in the control and test groups ranged from 0.30 to 1.64 and the preventive fractions varied from 5 percent to 63 percent. Fluoride varnish may be effective to decrease the incidence of dental caries in preschoolers, but more randomized clinical trials with better methodological quality are necessary to provide conclusive evidence in this respect.