Retracción de artículos biomédicos y sus implicaciones éticas / Retraction of Biomedical Articles and its Ethical Implications / Retratação de artigos médicos e suas implicações éticas

Resumen La retracción es un mecanismo que permite la corrección de la literatura científica. Este artículo pretende demostrar que las retracciones han aumentado de manera progresiva, y sobresalen las del ámbito médico. Metodológicamente es un artículo de revisión bibliográfica, cuyos datos estadísticos se obtuvieron de estudios sobre artículos retractados, publicados entre el 2012 y el 2017, en inglés, desde las bases de datos de PubMed y Google Scholar. Entre los resultados sobresalientes se encuentran como causas más frecuentes de retracción: plagio, mala conducta, errores, fabricación y duplicación. La mayor incidencia reportada fue en Estados Unidos (EE. UU.), India, China, Japón y Alemania. El mayor índice de retracción fue para las revistas de factor de impacto bajo. El tiempo transcurrido para la retracción es largo, aunque ha disminuido. Esto permite que se citen estos artículos y se origine así una mala ciencia. Se concluye que se requiere de uniformidad en las notas y las reglas de retracción, así como señalizar de forma adecuada los artículos retractados, además de disminuir el tiempo para que esta se efectúe. En relación con la bioética, se revela un grave problema en la integridad de la literatura científica, así como un posible impacto de las retracciones en la salud de las personas.

Abstract Retraction is a mechanism to correct scientific literature. This article aims to demonstrate that retractions have gradually increased, especially in the medical field. Methodologically, it is a literature review article whose statistical data were obtained from studies on retraction articles published in English between 2012 to 2017 in the PubMed and Google Scholar databases. Some of the most frequent causes of retraction found were plagiarism, misconduct, errors, fabrication and duplication. The highest incidence rate was reported in the United States, India, China, Japan and Germany. The highest retraction rate was for low-impact journals. The time for retraction is long but has decreased, which allows these articles to be cited and bad science to arise. It is concluded that uniformity is needed in notes and rules of retraction, retracted articles should be marked appropriately, and time for retraction must be reduced. In relation to bioethics, there is a serious problem in the integrity of scientific literature and a possible impact of retractions on the health of people.

Resumo A retratação é um mecanismo que permite a correção da literatura científica. Este artigo pretende demonstrar que as retratações vêm aumentando e que as do âmbito médico têm se ressaltado. Trata-se de um artigo de revisão bibliográfica, cujos dados estatísticos foram obtidos de estudos sobre artigos retratados, publicados entre 2012 e 2017, em inglês, das bases de dados de PubMed e Google Scholar. Entre os resultados destacados, encontram-se como causas mais frequentes de retratação: plágio, má conduta, erros, fabricação e duplicação. A maior incidência relatada foi nos Estados Unidos, na Índia, na China, no Japão e na Alemanha. O maior índice de retratação foi para as revistas de fator de impacto baixo. O tempo transcorrido para a retratação é longo, embora tenha diminuído. Isso permite que esses artigos sejam citados e seja originada uma má ciência. Conclui-se que se requer de padronização nas notas de retratação ou erratas, bem como indicar, de forma adequada, os artigos retratados, além de diminuir o tempo para que isso ocorra. Quanto à bioética, revela-se um grave problema na integridade da literatura científica e um possível impacto das retratações na saúde das pessoas.

Omisiones detectadas en 150 casos de muerte materna en la Ciudad de México / Omissions detected in 150 cases of maternal death in Mexico City

Resumen OBJETIVO: Identificar y describir, en una muestra poblacional acotada, las omisiones en el proceso de atención a la salud en casos de muerte materna. MATERIALES Y MÉTODOS: Estudio descriptivo y retrospectivo para el que se seleccionaron cuatro hospitales federales de referencia, ubicados en la Ciudad de México, para revisión de los casos de muerte materna ocurridos entre enero de 2010 y diciembre de 2017. Para la identificación de las omisiones en el proceso de atención, se estudiaron 11 variables del dictamen de muerte materna: oportunidad del diagnóstico clínico, tratamiento otorgado, atención de complicaciones, atención prenatal, oportunidad de la atención médica, registro de datos en el expediente, previsibilidad de la muerte materna y muertes susceptibles de evitarse por el hospital. RESULTADOS: Se analizaron 150 casos de muerte materna. El 36% de los casos se dictaminaron como muertes que pudieron evitarse por el hospital y 71% como muertes susceptibles de prevención mediante diagnóstico. No recibieron atención prenatal 92 pacientes (61%); en 52 casos (35%) los registros médicos en el expediente clínico estaban incompletos. CONCLUSIONES: Los dictámenes elaborados por los comités señalan las acciones que no se llevaron a cabo durante el proceso de atención. El subregistro de datos en los expedientes clínicos es una omisión que afecta negativamente el análisis de los casos y la integración de los dictámenes por parte de los comités. El porcentaje elevado de evitabilidad y previsibilidad de los casos refleja probables deficiencias durante la atención en diferentes áreas y permite definir acciones correctivas para disminuir su ocurrencia.

Abstract OBJECTIVE: Identify and describe, in a limited population sample, the omissions in the health care process in cases of maternal death. MATERIALS AND METHODS: This is a descriptive and retrospective study. Four federal referral hospitals were selected, located in Mexico City and the cases of maternal death occurred between January 2010 and December 2017. For the identification of the omissions in the care process, 11 variables of the opinion were studied. of maternal death: opportunity of clinical diagnosis, treatment granted, care of complications, prenatal care, opportunity for medical attention, record of data in the file, predictability of maternal death and avoidable deaths by the hospital. RESULTS: 150 cases of maternal death were reviewed. 36% of the cases were ruled as preventable deaths by the hospital and 71% as preventable deaths by diagnosis. Ninety-two patients (61%) did not receive prenatal care; in 52 cases (35%), the medical records in the clinical file were incomplete. CONCLUSIONS: The opinions drawn up by the Committees indicate the actions that were not carried out during the care process. The underreporting of data in the clinical files is an omission that negatively affects the analysis of the cases and the integration of the opinions by the committees. The high percentage of preventability and predictability of the cases, reflects probable deficiencies during the attention in different areas and allows to define corrective actions to reduce their occurrence.

Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.

The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.

Organic cation transporter variation and response to smoking cessation therapies.

INTRODUCTION: We evaluated chr6q25.3 organic cation transporter gene (SLC22A1, SLC22A2, SLC22A3) variation and response to smoking cessation therapies. The corresponding proteins are low-affinity transporters of choline, acetylcholine and monoamines, and smoking cessation pharmacotherapies expressed in multiple tissues. METHODS: We selected 7 common polymorphisms for mega-regression analysis. We assessed additive model association of polymorphisms with 7-day point prevalence abstinence overall and by assigned pharmacotherapy at end of treatment and at 6 months among European-ancestry participants of 7 randomized controlled trials adjusted for demographic, population genetic, and trial covariates. RESULTS: Initial results were obtained in 6 trials with 1,839 participants. Nominally statistically significant associations of 2 SLC22A2 polymorphisms were observed: (1) with rs316019 at 6 months, overall ([c.808T>G; p.Ser270Ala], OR = 1.306, 95% CI = 1.034-1.649, p = .025), and among those randomized to nicotine replacement therapy (NRT) (OR = 1.784, 95% CI = 1.072-2.970, p = .026); and (2) with rs316006 (c.1502-529A>T) among those randomized to varenicline (OR = 1.420, 95% CI = 1.038-1.944, p = .028, OR = 1.362, 95% CI = 1.001-1.853, p = .04) at end of treatment and 6 months. Individuals randomized to NRT from a seventh trial were genotyped for rs316019; rs316019 was associated with a nominally statistically significant effect on abstinence overall at 6 months among 2,233 participants (OR = 1.249, 95% CI = 1.007-1.550, p = .043). CONCLUSIONS: The functional OCT2 Ser270Ala polymorphism is nominally statistically significantly associated with abstinence among European-ancestry treatment-seeking smokers after adjustments for pharmacotherapy, demographics, population genetics, and without adjustment for multiple testing of 7 SNPs. Replication of these preliminary findings in additional randomized controlled trials of smoking cessation therapies and from multiple continental populations would describe another pharmacogenetic role for SLC22A2/OCT2.

Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype.

Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.

OBJECTIVE: To evaluate the association of nicotinic acetylcholine receptor (nAChR) single nucleotide polymorphism (SNP) with 7-day point prevalence abstinence (abstinence) in randomized clinical trials of smoking cessation therapies in individuals grouped by pharmacotherapy randomization to inform the development of personalized smoking cessation therapy. MATERIALS AND METHODS: We quantified association of four SNPs at three nAChRs with abstinence in eight randomized clinical trials. Participants were 2633 outpatient treatment-seeking, self-identified European ancestry individuals smoking at least 10 cigarettes/day, recruited through advertisement, prescribed pharmacotherapy, and provided with behavioral therapy. Interventions included nicotine replacement therapy (NRT), bupropion, varenicline, placebo (PLA), or combined NRT and bupropion, and five modes of group and individual behavioral therapy. Outcome measures tested in multivariate logistic regression were end of treatment and 6 month (6MO) abstinence, with demographic, behavioral, and genetic covariates. RESULTS: 'Risk' alleles previously associated with smoking heaviness were significantly (P<0.05) associated with reduced abstinence in the PLA pharmacotherapy group (PG) at 6MO [for rs588765, odds ratio (95% confidence interval) 0.41 (0.17-0.99)], and at end of treatment and at 6MO [for rs1051730, 0.42 (0.19-0.93) and 0.31 (0.12-0.80)], and with increased abstinence in the NRT PG at 6MO [for rs588765, 2.07 (1.11-3.87) and for rs1051730, 2.54 (1.29-4.99)]. We observed significant heterogeneity in rs1051730 effects (F=2.48, P=0.021) between PGs. CONCLUSION: chr15q25.1 nAChR SNP risk alleles for smoking heaviness significantly increase relapse with PLA treatment and significantly increase abstinence with NRT. These SNP-PG associations require replication in independent samples for validation, and testing in larger sample sizes to evaluate whether similar effects occur in other PGs.

Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

CONTEXT: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. OBJECTIVE: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. DATA SOURCES: Primary data. STUDY SELECTION: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DATA EXTRACTION: Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. DATA SYNTHESIS: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). CONCLUSION: These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

Chronic psychosocial stressors and salivary biomarkers in emerging adults.

We investigated whole saliva as a source of biomarkers to distinguish individuals who have, and who have not, been chronically exposed to severe and threatening life difficulties. We evaluated RNA and DNA metrics, expression of 37 candidate genes, and cortisol release in response to the Trier Social Stress Test, as well as clinical characteristics, from 48 individuals stratified on chronic exposure to psychosocial stressors within the last year as measured by the Life Events and Difficulties Schedule. Candidate genes were selected based on their differential gene expression ratio in circulating monocytes from a published genome-wide analysis of adults experiencing different levels of exposure to a chronic stressor. In univariate analyses, we observed significantly decreased RNA integrity (RIN) score (P = 0.04), and reduced expression of glucocorticoid receptor-regulated genes (Ps < 0.05) in whole saliva RNA from individuals exposed to chronic stressors, as compared to those with no exposure. In those exposed, we observed significantly decreased BMI (P < 0.001), increased ever-smoking and increased lifetime alcohol abuse or dependence (P ≤ 0.03), and a reduction of cortisol release. In post hoc multivariate analyses including clinical and biospecimen-derived variables, we consistently observed significantly decreased expression of IL8 (Ps<0.05) in individuals exposed, with no significant association to RIN score. Alcohol use disorders, tobacco use, a reduced acute stress response and decreased salivary IL8 gene expression characterize emerging adults chronically exposed to severe and threatening psychosocial stressors.

Resequencing of nicotinic acetylcholine receptor genes and association of common and rare variants with the Fagerström test for nicotine dependence.

Common single-nucleotide polymorphisms (SNPs) at nicotinic acetylcholine receptor (nAChR) subunit genes have previously been associated with measures of nicotine dependence. We investigated the contribution of common SNPs and rare single-nucleotide variants (SNVs) in nAChR genes to Fagerström test for nicotine dependence (FTND) scores in treatment-seeking smokers. Exons of 10 genes were resequenced with next-generation sequencing technology in 448 European-American participants of a smoking cessation trial, and CHRNB2 and CHRNA4 were resequenced by Sanger technology to improve sequence coverage. A total of 214 SNP/SNVs were identified, of which 19.2% were excluded from analyses because of reduced completion rate, 73.9% had minor allele frequencies <5%, and 48.1% were novel relative to dbSNP build 129. We tested associations of 173 SNP/SNVs with the FTND score using data obtained from 430 individuals (18 were excluded because of reduced completion rate) using linear regression for common, the cohort allelic sum test and the weighted sum statistic for rare, and the multivariate distance matrix regression method for both common and rare SNP/SNVs. Association testing with common SNPs with adjustment for correlated tests within each gene identified a significant association with two CHRNB2 SNPs, eg, the minor allele of rs2072660 increased the mean FTND score by 0.6 Units (P=0.01). We observed a significant evidence for association with the FTND score of common and rare SNP/SNVs at CHRNA5 and CHRNB2, and of rare SNVs at CHRNA4. Both common and/or rare SNP/SNVs from multiple nAChR subunit genes are associated with the FTND score in this sample of treatment-seeking smokers.

Límites de la autonomía en el paciente pediátrico / Limits of the principle of autonomy in pediatric patients

No puede hablarse del paciente pediátrico como si fuera una circunstancia única, o una entidad patológica. Todo paciente es un individuo (indivisible en cuanto a su naturaleza), y es único e irrepetible en cuanto a su existencia y en cuanto a su esencia. Pero además, el paciente pediátrico variará, de acuerdo a su edad y a su grado de madurez, para tomar decisiones. En este artículo se expone lo que significa una decisión libre, y la posibilidad real que existe en el niño de tomar una decisión de esa naturaleza. Además se aclara la diferencia entre autonomía y libertad.

The pediatric patient is not a single circumstance or a pathological entity. The nature of each patient is to have individuality and uniqueness that is not duplicated in their essence and existence. The pediatric patient will also show variations with age and psychological maturity to be able to make decisions. This paper reveals the significance of free decisions and the real possibility that a child may make these types of decisions. The difference between freedom and autonomy is explained.

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain.

BACKGROUND: Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. METHODS: Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. RESULTS: The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. CONCLUSIONS: Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.

The economic burden of gynecologic cancers in California, 1998.

OBJECTIVE: Our aim was to estimate the direct and indirect costs of gynecologic cancers including cervical, ovarian, and uterine cancer in California in 1998. METHODS: Hospitalization costs, including costs of primary and secondary diagnoses of each of the gynecologic cancers, are derived from the California Patient Discharge dataset. Charges are converted to costs using hospital-specific cost-to-charge ratios and an imputed cost for HMO hospitalizations. Other direct medical costs are derived from the 1997 Medical Expenditure Panel Survey. Indirect mortality costs are the product of the number of deaths and the expected value of a female's future earnings, including an imputed value of housekeeping services. RESULTS: The total cost of the three gynecologic cancers in California is estimated at $624 million for 1998. Indirect costs or losses in productivity due to premature death are twice the direct medical care costs. Hospitalization inpatient costs account for more than half of total direct costs for each of these cancers. Total costs for ovarian cancer are highest among the three cancers. CONCLUSIONS: The estimates presented here highlight the need for studies that identify cost-effective screening methods and the relationship between treatment protocols and outcomes. The methods presented here could be used to develop stage- or treatment-specific costs that would be useful for such analyses. Only through early detection and more effective management of gynecologic cancers can there be a reduction in the morbidity, premature death, and high costs of cervical, ovarian, and uterine cancers.

The economic burden of prostate cancer, California, 1998.

BACKGROUND: Prostate cancer is the most common malignancy diagnosed among men in the United States. This article reviews previous studies of the annual cost of all cancers and of prostate cancer in the United States and California and estimates the direct and indirect costs of prostate cancer in California in 1998. METHODS: Hospitalization costs, including costs of primary and secondary diagnoses of prostate cancer, were derived from the California Hospital Discharge data set (CHDS). Charges were converted to costs using hospital specific cost-to-charge ratios and an imputed cost for Health Maintenance Organization hospitalizations. Other direct medical costs were derived from the 1997 Medical Expenditure Panel Survey. Indirect mortality costs are the product of the number of deaths and the expected value of a male's future earnings taking into account age at death, earning patterns at successive ages, labor force participation, imputed value of housekeeping services, and a 3% discount rate. RESULTS: Prostate cancer direct health care costs in California were estimated at 180 million dollars, and lost productivity from premature death was estimated at 180 million dollars, for a total cost of 360 million dollars in 1998. The disease is largely one of older men; hospitalization costs account for three-fifths of total direct costs, and Medicare and private health insurance share almost equally in paying for hospital care. CONCLUSIONS: It is critical to identify cost-effective screening efforts that permit early detection of prostate cancer to reduce illness, premature deaths, and the high costs of prostate cancer.

Estandarización de los datos reportados en estudios de nasofaringoscopía y fluoroscopía del esfínter velofaríngeo / Stantardization of data reported in studies of nasopharyngoscopy and fluoroscopy of the velopharyngeal sphincter

Existe una gran inquietud mundial por inicar el informe de los hallazgos obtenidos con la endoscopía con fibra óptica y con la fluoroscopía en el esfínter velofaríngeo. La evolución debe ser realizada por un médico especialista (foniatría). Nasofaringoscopía: el equipo necesario es el nasofaringoscopio con frente de luz. La videograbación es deseable, pero no indispensable. El reporte debe ser discriptivo y llegar a conclusiones precisas sobre 1) fosa nasal: 2) meatro; 3) orificio de la salida de la trompa de eustaquio; 4) orofaringeo; 5) esfinter velofaríngeo (paredes faríngeas posterior y laterales y velo de paladar), 6)patrón de cierre (forma y cada estructura por separado, en reposo y fonación); 7) laringe. Flouroscopía; útil para valorar las parederes faríngeas laterales y el nivel de cierre del esfínter velofaríngeo. No se requiere en todos los casos, pero es completamente para la nasofaringoscopía. La videograbación no es indispensable. Siempre se deben realizar las incidencias frontal, lateral y basal