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With the aim of integrating clinical pharmacology with pharmacogenomics and providing a platform to gather clinicians, academicians, diagnostic laboratory personnel and scientists from related domains, the International Conference on Clinical Pharmacology and Pharmacogenomics 2023 (ICCPP 2023) was jointly organized by the Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, India and the CANSEARCH research platform in Pediatric Oncology and Hematology, University of Geneva, Geneva, Switzerland. The conference was held on 31 August and 1 September 2023, as a continued Indo-Swiss scientific exchange event series. In this report we describe the proceedings of this conference for the benefit of peers who could not attend the conference but are interested in knowing about the scientific program in detail.
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Farmacología Clínica , Médicos , Niño , Humanos , Farmacogenética/educación , Medicina de Precisión , SuizaRESUMEN
BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.
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Ácidos Nucleicos Libres de Células , Síndrome de Down , Recién Nacido , Embarazo , Femenino , Humanos , Adulto , Lactante , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Embarazo Gemelar , Trisomía/diagnóstico , Trisomía/genética , Diagnóstico Prenatal/métodos , Síndrome de la Trisomía 18/diagnóstico , Síndrome de la Trisomía 13/diagnóstico , Síndrome de la Trisomía 13/genética , Estudios RetrospectivosRESUMEN
BACKGROUND: Headaches with marked, specific response to indomethacin occur in children, but the phenotypic spectrum of this phenomenon has not been well-studied. METHODS: We reviewed pediatric patients with headache showing ≥80% improvement with indomethacin, from seven academic medical centers. RESULTS: We included 32 pediatric patients (16 females). Mean headache onset age was 10.9 y (range 2-16 y). Headache syndromes included hemicrania continua (n = 13), paroxysmal hemicrania (n = 10), primary stabbing headache (n = 2), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (n = 1), primary exercise headache (n = 1) and primary cough headache (n = 1). Adverse events were reported in 13, most commonly gastrointestinal symptoms, which often improved with co-administration of gastro-protective agents. CONCLUSION: Indomethacin-responsive headaches occur in children and adolescents, and include headache syndromes, such as primary cough headache, previously thought to present only in adulthood. The incidence of adverse events is high, and patients must be co-treated with a gastroprotective agent.
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Neuralgia , Hemicránea Paroxística , Adolescente , Adulto , Niño , Femenino , Cefalea/diagnóstico , Cefalea/tratamiento farmacológico , Humanos , Indometacina/uso terapéutico , LágrimasRESUMEN
OBJECTIVES: Measles immunity testing, unlike that for rubella, is not currently part of prenatal screening even though immunity to both is conferred by the measles-mumps-rubella (MMR) vaccine. Although endemic transmission of measles was declared eliminated in the United States in 2001, outbreaks have continued to occur. Given the risks associated with measles infection during pregnancy, we sought to identify risk factors for measles nonimmunity (MNI) in rubella-immune (RI) pregnant individuals. METHODS: We performed a retrospective observational cross-sectional study of patients receiving prenatal care and delivering at two university hospitals and a county hospital in Southern California from April 1, 2019 to February 1, 2021. Inclusion criteria were pregnant individuals ≥18 years old who had serological testing for rubella and measles during pregnancy. Demographic data were extracted from electronic medical records, including results of serological testing and chronic medical conditions. All subjects were rubella immune, and we compared measles-immune (MI) with MNI groups. RESULTS: In total, 1,813 RI individuals were identified, with 1,467 (81%) MI and 346 (19%) MNI individuals. Variables associated with an increased risk of MNI included having public health insurance (adjusted relative risk [aRR]: 1.56; 95% confidence interval [CI]: 1.24, 1.97) and Hispanic ethnicity (aRR: 1.37; 95% CI: 1.06, 1.78). Black race was associated with a decreased risk of MNI (aRR: 0.52; 95% CI: 0.29, 0.91). Birth year before 1989 demonstrated a trend toward increased risk of MNI, but this did not reach statistical significance (aRR 1.23; 95% CI: 1.00, 1.52). No differences were seen between the two groups for medical comorbidities. CONCLUSION: Our study is the first to demonstrate risk factors for measles MNI in patients with documented rubella immunity. In the absence of universal measles serological screening recommendations, the risk factors identified could help guide clinicians in selective screening for those at risk of needing postpartum MMR vaccination. KEY POINTS: · The rate of measles nonimmunity is higher than previously reported.. · Hispanic ethnicity and use of public insurance are risk factors for measles nonimmunity.. · The current recommendation for history-based screening for measles immunity is likely insufficient..
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OBJECTIVE: To describe outcomes associated with monoclonal antibody use in pregnant persons with mild-to-moderate coronavirus disease 2019 (COVID-19). METHODS: We present a retrospective case series of pregnant patients who received anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody infusions at a single center from April 1, 2021, through October 16, 2021. Pregnant patients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) test result and mild-to-moderate COVID-19 symptoms were eligible for monoclonal antibody infusion. Exclusion criteria for administration included need for supplemental oxygen, hospitalization due to COVID-19, and positive SARS-CoV-2 PCR test result more than 7 days before screening. All patients received either bamlanivimab plus etesevimab or casirivimab plus imdevimab based on availability and dosing instructions of the product and emerging resistance patterns in the community. RESULTS: During the study period, monoclonal antibody infusions were administered to 450 individuals at our institution, of whom 15 were pregnant. Of the 15 pregnant persons receiving monoclonal antibody, six (40%) had full-vaccination status at the time of infusion. Two individuals (13%, CI 0-31%) experienced systemic reactions during the infusion, both resulting in temporary changes in the fetal heart rate tracing that recovered with maternal and intrauterine resuscitative efforts. One patient delivered after infusion for worsening maternal and fetal status; the remainder of the patients did not require admission for COVID-19. CONCLUSION: In this case series, pregnant persons who received anti-SARS-CoV-2 monoclonal antibody infusions had generally favorable outcomes.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Neutralizantes/efectos adversos , Tratamiento Farmacológico de COVID-19 , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Combinación de Medicamentos , Femenino , Corazón Fetal/efectos de los fármacos , Humanos , Sobretratamiento , Embarazo , Estudios RetrospectivosRESUMEN
Tocilizumab (TCZ) is used to treat rheumatoid arthritis and other systemic inflammatory disorders. There is some evidence suggesting the occurrence of pancreatitis following TCZ use. We aimed to determine the reporting of pancreatitis following TCZ use in comparison with other drugs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We extracted adverse event reports submitted to FAERS during 2013-2019. A reporting odds ratio (ROR) with the lower bound 95% confidence interval (CI) > 1 and a lower limit of a two-sided 95% interval of information component (IC025) more than zero was considered significant. Following deduplication, 3,383,910 adverse event reports were available; 144 (0.004%) reports were of pancreatic adverse events associated with TCZ use, and 15,907 (0.47%) associated with other drugs. Of the 144 cases, 74 (51.39%) received concomitant medications with pancreatotoxic potential. The likelihood of reporting of pancreatic events, compared with any other adverse event, with TCZ use was 1.32 times higher than that with other drugs. The lower bound of the 95% CI of the ROR and IC remained above the criteria of significance throughout the study period, except 2013. The findings suggest disproportionately high reporting of pancreatitis in patients receiving TCZ as compared with other drugs. This marginally high reporting is not likely to be of immediate clinical concern and needs to be interpreted cautiously.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Pancreatitis/inducido químicamente , Receptores de Interleucina-6/antagonistas & inhibidores , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
OBJECTIVE: This study was aimed to evaluate the role of intertwin discrepancy in middle cerebral artery peak systolic velocity (MCA-PSV) and cerebroplacental ratio (CPR) for the prediction of adverse outcomes in monochorionic-diamniotic (MCDA) twin pregnancies. STUDY DESIGN: A retrospective cohort study of MCDA pregnancies that underwent ultrasound surveillance at a perinatal referral center from 2007 to 2017. Intertwin MCA-PSV discrepancy (MCA-ΔPSV-MoM) was defined as the absolute difference of MCA-PSV multiple of the median (MoM) for gestational age between twins. Intertwin CPR discrepancy (CPR-Δ) was defined as the absolute difference of CPR between twins. The maximum MCA-ΔPSV-MoM and CPR-Δ before and after 26 weeks of gestation were assessed as predictors of pregnancy and neonatal outcomes through simple logistic regression models and Pearson's correlation coefficients. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of maximum MCA-ΔPSV-MoM and CPR-Δ. RESULTS: A total of 143 MCDA pregnancies met inclusion criteria. There was a significant association between MCA-ΔPSV-MoM at <26 weeks and the development of twin anemia-polycythemia sequence (TAPS; p = 0.007), intrauterine fetal demise (IUFD; p = 0.009), and neonatal intensive care unit (NICU) admission (p < 0.05). MCA-ΔPSV-MoM at ≥26 weeks was associated with the development of TAPS (p < 0.001). CPR-Δ at <26 weeks was associated with the development of twin-twin transfusion syndrome (TTTS; p = 0.03) and NICU admission (p = 0.02). MCA-ΔPSV-MoM at ≥26 weeks was highly predictive of TAPS (area under curve [AUC] = 0.92). A cut-off of 0.44 would identify TAPS with 100% sensitivity and 73% specificity. CONCLUSION: In MCDA pregnancies, intertwin MCA and CPR discrepancies are associated with adverse pregnancy and neonatal outcomes, including TAPS, TTTS, IUFD, and NICU admission. Evaluation of intertwin MCA and CPR differences demonstrated the potential for clinical predictive utility in the surveillance of MCDA twin pregnancies. KEY POINTS: · Intertwin discrepancy of MCA-PSV and CPR is associated with adverse pregnancy outcomes.. · Intertwin differences in Doppler ultrasound may occur prior to meeting diagnostic criteria for TTTS or TAPS.. · There is potential clinical predictive utility in MCA and CPR surveillance of MCDA twin pregnancies..
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Velocidad del Flujo Sanguíneo , Enfermedades en Gemelos , Arteria Cerebral Media/diagnóstico por imagen , Resultado del Embarazo , Gemelos Monocigóticos , Ultrasonografía Prenatal , Arterias Umbilicales/diagnóstico por imagen , Anemia/epidemiología , Anemia/etiología , Enfermedades en Gemelos/diagnóstico , Enfermedades en Gemelos/epidemiología , Femenino , Transfusión Feto-Fetal/epidemiología , Humanos , Arteria Cerebral Media/fisiología , Policitemia/epidemiología , Embarazo , Embarazo Gemelar , Curva ROC , Estudios Retrospectivos , Ultrasonografía Doppler , Arterias Umbilicales/fisiologíaRESUMEN
AIMS: Small group teaching in Pharmacology offers an effective platform to encourage interaction amongst peers and self-directed learning. The present study is an attempt to assess and compare the effectiveness and perception of students on two different pedagogical methods: Crossword puzzles and Student Led Objective Tutorials (SLOT). METHODS: Second year undergraduate students who gave their informed consent were divided randomly into two groups: one which received crossword puzzle as a teaching learning method and the other had SLOT during which the students conducted an interactive quiz with multiple choice questions prepared by themselves. The students' perceptions were recorded using a self-administered questionnaire. One week later, a unit test was conducted for both the groups and the performance of the students was compared. Statistical analysis was done using independent Student's T test with SPSS version 15.0. RESULTS: Analyses revealed a statistical significant difference (P<0.001) between the mean marks obtained in the SLOT group (n= 74; 6.5±3.8) and the marks obtained in the crossword group (n= 87; 4.2±2.9), with the students in the tutorial group performing better. The students opined that SLOT sessions helped them to understand Pharmacology better whereas crossword sessions enabled them to memorize the names of the drugs. CONCLUSION: The present study revealed that SLOT sessions fared better compared to the crossword puzzles in terms of improving the students' test scores. It fostered teamwork, self-directed learning skills and critical thinking. Crossword puzzles make the session more student friendly as it is fun and engaging but a careful design is inevitable as it may fail to test in-depth learning in students.
OBJETIVOS: O ensino de farmacologia em pequenos grupos oferece uma plataforma eficaz para estimular a interação entre pares e a aprendizagem autodirigida. O presente estudo procurou avaliar e comparar a eficácia e percepção dos alunos em dois métodos pedagógicos diferentes: palavras cruzadas e tutoriais objetivos conduzido pelo aluno (SLOT). MÉTODOS: Alunos do segundo ano de graduação, que deram seu consentimento informado, foram divididos aleatoriamente em dois grupos: um que recebeu palavras cruzadas como método de ensino-aprendizagem e o outro teve SLOT onde os alunos realizaram um questionário interativo com questões de múltipla escolha elaborado por si mesmos. As percepções dos alunos foram registradas por meio de um questionário autoaplicável. Uma semana depois, um teste foi realizado para ambos os grupos e o desempenho dos alunos foi comparado. A análise estatística foi feita usando o teste T de student de amostras independentes. RESULTADOS: As análises revelaram uma diferença estatisticamente significativa (P <0,001) entre as notas médias obtidas no grupo SLOT (n = 74; 6,5±3,8) e as notas obtidas no grupo de palavras cruzadas (n = 87; 4,2±2,9), com os alunos do grupo tutorial tendo melhor desempenho. Os alunos opinaram que as sessões de tutoria objetiva conduzida pelos alunos os ajudaram a entender melhor a Farmacologia, ao passo que as sessões de palavras cruzadas lhes permitiram memorizar os nomes dos medicamentos. CONCLUSÃO: O presente estudo revelou que as sessões do SLOT se saíram melhor comparativamente àquelas com as palavras cruzadas em termos de melhorar as pontuações dos alunos nos testes, assim como promoveu o trabalho em equipe, habilidades de aprendizagem autodirigida e pensamento crítico. As palavras cruzadas tornam a sessão mais amigável ao aluno, pois é divertida e envolvente, mas um design cuidadoso é inevitável, pois pode falhar em testar o aprendizado em profundidade nos alunos.
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Educación de Pregrado en Medicina , EnseñanzaRESUMEN
BACKGROUND: There are 2 prediction nomograms for vaginal birth after cesarean delivery. The first is based on variables that are available at the first prenatal visit, and the second includes variables at the time of admission. OBJECTIVE: The purpose of this study was to compare the accuracy of prediction scores that are calculated by the intake and admission prediction nomograms in a modern cohort of racially and ethnically diverse women. STUDY DESIGN: This is a retrospective cohort study that analyzed the data for women with at least 1 previous cesarean delivery who attempted a trial of labor from 2007-2016 at a tertiary medical center. Participants were stratified into 3 probability-of-success groups: low (<35%), moderate (35-65%), and high (>65%). The primary outcome was the difference between the intake- and admission-predicted success scores in the 3 groups. Secondary outcomes were characteristics that were associated with successful vaginal birth after cesarean delivery . RESULTS: Of the 614 women included in the analysis, 444 (72.3%) had a successful vaginal birth after cesarean delivery . Predicted vaginal birth after cesarean delivery success rate ranged from 14.4-96.2%. Patients were stratified into 3 groups by intake predicted success rates: low (<35%; n=21), moderate (35-65%; n=136), and high (>65%; n=457). The change in predicted success rates was compared between the intake and admission nomograms. Women in the low and moderate groups improved their prediction score by approximately 7-8% when variables at the time of admission were included. As a result, more than one-half of these women (172/307; 56%) shifted to a higher predicted success group. The admission nomogram, as compared with the intake nomogram, more accurately predicted vaginal birth after cesarean delivery success in all groups. Analysis of admission variables showed that cervical dilation >2 cm compared with a closed cervix was the strongest predictor of successful vaginal birth after cesarean delivery (relative risk, 1.79; 95% confidence interval, 1.11-2.89). CONCLUSION: The admission prediction nomogram was more accurate and showed higher predicted success compared with the intake nomogram for the same cohort. Because prediction scores may improve at the time of admission, additional counseling on the risks and benefits of trial of labor may be helpful at that time.
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Trabajo de Parto , Parto Vaginal Después de Cesárea , Cesárea , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Esfuerzo de PartoAsunto(s)
Malformaciones Arteriovenosas/complicaciones , Gasto Cardíaco Elevado/etiología , Insuficiencia Cardíaca/etiología , Hemodinámica , Complicaciones Cardiovasculares del Embarazo , Gemelos , Adulto , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/fisiopatología , Malformaciones Arteriovenosas/terapia , Gasto Cardíaco Elevado/diagnóstico por imagen , Gasto Cardíaco Elevado/fisiopatología , Gasto Cardíaco Elevado/terapia , Cesárea , Diuréticos/uso terapéutico , Embolización Terapéutica , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Humanos , Nacimiento Vivo , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico por imagen , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Complicaciones Cardiovasculares del Embarazo/terapia , Embarazo Gemelar , Resultado del TratamientoRESUMEN
AIMS: To determine the learning approach of second-year undergraduate medical students and whether a surface or deep approach to learning had any correlation with the pharmacology sessional and university examination marks obtained. METHODS: A cross-sectional study was conducted among second-year medical students in their fifth semester. To determine the students' learning approach, whether superficial or deep, we used the Revised Two Factor Study Process Questionnaire (R-SPQ-2F), which contains 20 items in the form of a five-point Likert scale and is suitable for use in higher education settings. Cronbach's alpha was calculated using the scores obtained from a sample of 20 students to determine the internal consistency. To determine the relationship between the learning approach and examination scores, the average of the individual sessional examination marks and the university examination scores obtained by the students were calculated. RESULTS: Of the 170 students who participated in the study, 87 (51.2%) were females. The Cronbach's alpha value was considered acceptable for both surface and deep approach. While the academic performance was significantly better in females (U=2571.5; p=0.001), no difference was seen in the learning approach based on gender. Fifty (29.4%) students had a higher score for the surface approach. This group had lower examination scores compared with those with equal scores for surface and deep approach or higher scores for the deep approach. A weak negative correlation was seen between the examination marks and surface approach (τb=-0.167; p=0.002). When analyzed based on gender, the correlation was statistically significant only in females (τb=-0.173; p=0.02). CONCLUSIONS: A weak negative correlation was seen between the examination marks and surface approach to learning. Although statistically significant, the actual difference between the groups was of a small magnitude. Hence, whether promoting deep learning approach improves academic performance in terms of marks obtained in the examination needs to be confirmed by further studies.
OBJETIVOS: Investigar a abordagem de aprendizagem de estudantes de medicina do segundo ano de graduação e se uma abordagem superficial ou profunda teve alguma correlação com as notas obtidas na disciplina de farmacologia e nos exames universitários. MÉTODOS: Um estudo transversal foi conduzido entre estudantes do segundo ano de medicina em seu quinto semestre. Para determinar a abordagem de aprendizagem dos alunos, como superficial ou profunda, usamos o questionário Revised Two Factor Study Process Questionnaire (R-SPQ-2F), que contém 20 itens em forma de uma escala Likert de cinco pontos, sendo o seu uso adequado para ambientes de ensino superior. O alfa de Cronbach foi calculado usando as pontuações obtidas de uma amostra de 20 alunos para determinar a consistência interna. Para determinar a relação entre a abordagem de aprendizagem e as pontuações do exame, calculou-se a média das notas dos exames individuais e as pontuações dos exames universitários obtidas pelos alunos. RESULTADOS: Dos 170 alunos que participaram do estudo, 87 (51,2%) eram do gênero feminino. O alpha de Cronbach foi considerado bom tanto para a abordagem superficial quanto profunda. Enquanto o desempenho acadêmico foi significativamente melhor em mulheres (U=2571,5; p=0,001), nenhuma diferença baseada no gênero foi observada na abordagem de aprendizagem. Cinquenta (29,4%) estudantes tiveram uma pontuação mais alta para a abordagem superficial. Esse grupo teve escores de exame mais baixos em comparação com aqueles com escores iguais para abordagem superficial e profunda ou escores mais altos para a abordagem profunda. Uma fraca correlação negativa foi observada entre as notas do exame e a abordagem superficial (τb=-0,167; p=0,002). Quando analisada com base no gênero, encontrou-se uma correlação de magnitude fraca e negativa apenas no gênero feminino (τb=-0,173; p=0,02). CONCLUSÕES: Uma fraca correlação negativa foi observada entre as notas do exame e a abordagem superficial para a aprendizagem. Embora estatisticamente significativa, a diferença real entre os grupos foi de pequena magnitude. Portanto, se a promoção de uma abordagem de aprendizagem profunda melhora o desempenho acadêmico em termos de notas obtidas no exame, isso precisa ser confirmado por outros estudos.
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Rendimiento Académico , Farmacología , Estudiantes de Medicina , MedicinaRESUMEN
OBJECTIVE: To investigate factors associated with abnormal cell-free DNA (cfDNA) results for sex chromosomes (SCs). STUDY DESIGN: This is a retrospective cohort study of abnormal cfDNA results for SC at a referral practice from March 2013 to July 2015. Cell-free DNA results were abnormal if they were positive for SC aneuploidy (SCA), inconclusive, or discordant with ultrasound (US) findings. Primary outcome was concordance with karyotype or postnatal evaluation. RESULTS: Of 50 abnormal cfDNA results for SC, 31 patients (62%) were positive for SCA, 13 (26%) were inconclusive, and 6 (12%) were sex discordant on US. Of SCA results, 19 (61%) were reported as 45,X and 12 (39%) were SC trisomy. Abnormal karyotypes were confirmed in 8/23 (35%) of SC aneuploidy and 1/5 (20%) of inconclusive results. Abnormal SC cfDNA results were associated with in vitro fertilization (P = .001) and twins (P < .001). Sex discordance between cfDNA and US was associated with twin gestation (P < .001). CONCLUSIONS: In our cohort, abnormal SC cfDNA results were associated with in vitro fertilization and twins. Our results indicate cfDNA for sex prediction in twins of limited utility. Positive predictive value and sensitivity for SC determination were lower than previously reported.
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Ácidos Nucleicos Libres de Células/análisis , Pruebas de Detección del Suero Materno , Aberraciones Cromosómicas Sexuales , Adulto , Reacciones Falso Positivas , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Cromosomas SexualesRESUMEN
OBJECTIVE: To describe the clinically relevant findings detected by the first trimester ultrasound (FTU) and to determine the additional value of the FTU compared to cell free DNA (cfDNA) alone. METHOD: Retrospective cohort study of patients undergoing a FTU at a maternal-fetal medicine referral practice. Fetal, gynecologic, and placental findings detected by ultrasound were analyzed with available cfDNA and diagnostic testing results. A subgroup analysis of positive ultrasound findings and cfDNA results was performed to assess the additional benefit of ultrasound evaluation in FT prenatal screening. RESULTS: There were 1906 FTU between 1 October 2013 and 1 October 2014. CfDNA results were available for 959 (50%) patients. FTU detected: 42 fetal (2.2%), 286 gynecologic (15.0%), and 317 placental (16.6%) findings. CfDNA results were discordant with invasive testing results in 8/61 cases (13%) and with ultrasound findings in 18/42 (42%) cases. There were six false positive and two false negative cfDNA results confirmed by diagnostic testing. Subgroup analysis revealed that cfDNA as the sole method of prenatal screening in the FT would miss 95% of the fetal findings detected with ultrasound. CONCLUSION: The comprehensive FTU provides valuable clinical information about fetal and maternal anatomy that cannot be detected with cfDNA alone. © 2016 John Wiley & Sons, Ltd.
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ADN/sangre , Diagnóstico Prenatal/métodos , Ultrasonografía Prenatal , Adulto , Errores Diagnósticos/estadística & datos numéricos , Femenino , Feto/química , Edad Gestacional , Humanos , Pruebas de Detección del Suero Materno/métodos , Persona de Mediana Edad , Embarazo , Primer Trimestre del Embarazo , Diagnóstico Prenatal/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
BACKGROUND: Since its commercial release in 2011 cell-free DNA screening has been rapidly adopted as a routine prenatal genetic test. However, little is known about its performance in actual clinical practice. OBJECTIVE: We sought to investigate factors associated with the accuracy of abnormal autosomal cell-free DNA results. STUDY DESIGN: We conducted a retrospective cohort study of 121 patients with abnormal cell-free DNA results from a referral maternal-fetal medicine practice from March 2013 through July 2015. Patients were included if cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, or microdeletions (if reported by the laboratory) were positive or nonreportable. The primary outcome was confirmed aneuploidy or microarray abnormality on either prenatal or postnatal karyotype or microarray. Secondary outcomes were identifiable associations with in vitro fertilization, twins, ultrasound findings, testing platform, and testing laboratory. Kruskal-Wallis or Fisher exact tests were used as appropriate. RESULTS: A total of 121 patients had abnormal cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, and/or microdeletions. In all, 105 patients had abnormal cell-free DNA results for trisomy 21, trisomy 18, and trisomy 13. Of these, 92 (87.6%) were positive and 13 (12.4%) were nonreportable. The results of the 92 positive cell-free DNA were for trisomy 21 (48, 52.2%), trisomy 18 (22, 23.9%), trisomy 13 (17, 18.5%), triploidy (2, 2.2%), and positive for >1 parameter (3, 3.3%). Overall, the positive predictive value of cell-free DNA was 73.5% (61/83; 95% confidence interval, 63-82%) for all trisomies (by chromosome: trisomy 21, 83.0% [39/47; 95% confidence interval, 69-92%], trisomy 18, 65.0% [13/20; 95% confidence interval, 41-84%], and trisomy 13, 43.8% [7/16; 95% confidence interval, 21-70%]). Abnormal cell-free DNA results were associated with positive serum screening (by group: trisomy 21 [17/48, 70.8%]; trisomy 18 [7/22, 77.8%]; trisomy 13 [3/17, 37.5%]; nonreportable [2/13, 16.7%]; P = .004), and abnormal first-trimester ultrasound (trisomy 21 [25/45, 55.6%]; trisomy 18 [13/20, 65%]; trisomy 13 [6/14, 42.9%]; nonreportable [1/13, 7.7%]; P = .003). There was no association between false-positive rates and testing platform, but there was a difference between the 4 laboratories (P = .018). In all, 26 patients had positive (n = 9) or nonreportable (n = 17) microdeletion results. Seven of 9 screens positive for microdeletions underwent confirmatory testing; all were false positives. CONCLUSION: The positive predictive value of 73.5% for cell-free DNA screening for autosomal aneuploidy is lower than reported. The positive predictive value for microdeletion testing was 0%. Diagnostic testing is needed to confirm abnormal cell-free DNA results for aneuploidy and microdeletions.