RESUMO
INTRODUCTION/AIMS: Early diagnosis of a chronic neuromuscular disease such as muscular dystrophy (MD) generally excludes an individual from active-duty military service. However, it is not known whether veterans are sometimes diagnosed with milder forms of MD at a later timepoint. We aimed to determine the prevalence of MD in a veterans health system. METHODS: We abstracted clinical and genetic test data on patients who received care for a diagnosis of MD at the North Florida/South Georgia Veterans Health System between 2008 and 2021. We then determined which of these individuals would meet criteria for a definite diagnosis of MD, based on electrodiagnostic testing, muscle biopsy, and genetic testing of the individual or an affected first degree relative. RESULTS: We identified 12 patients with definite MD and 36 with possible or probable MD. The definite cases included myotonic dystrophy type 1 (4), myotonic dystrophy type 2 (3), oculopharyngeal MD (2), Becker MD (1), distal MD (1), and facioscapulohumeral MD (1). At least five of the cases classified as definite developed symptoms after discharge from active duty. DISCUSSION: Clinicians who care for veterans should be knowledgeable about, and have access to, diagnostic testing and treatment options for MD. When conducting MD surveillance, it is important to include veterans health systems as a data source. Mild cases of MD and those of later onset appear to be compatible in some cases with successful completion of military service.
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Distrofias Musculares , Veteranos , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Distrofias Musculares/diagnóstico , Distrofias Musculares/epidemiologia , Distrofias Musculares/genética , Idoso , Saúde dos Veteranos , PrevalênciaRESUMO
BACKGROUND: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. RESULTS: After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. CONCLUSIONS: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.
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COVID-19 , Diabetes Mellitus Tipo 2 , Adulto , Criança , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Estudos RetrospectivosRESUMO
Background: Data modernization efforts to strengthen surveillance capacity could help assess trends in use of preventive services and diagnoses of new chronic disease during the COVID-19 pandemic, which broadly disrupted health care access. Methods: This cross-sectional study examined electronic health record data from US adults aged 21 to 79 years in a large national research network (PCORnet), to describe use of 8 preventive health services (Nâ=â30,783,825 patients) and new diagnoses of 9 chronic diseases (Nâ=â31,588,222 patients) during 2018 through 2022. Joinpoint regression assessed significant trends, and health debt was calculated comparing 2020 through 2022 volume to prepandemic (2018 and 2019) levels. Results: From 2018 to 2022, use of some preventive services increased (hemoglobin A1c and lung computed tomography, both P < .05), others remained consistent (lipid testing, wellness visits, mammograms, Papanicolaou tests or human papillomavirus tests, stool-based screening), and colonoscopies or sigmoidoscopies declined (P < .01). Annual new chronic disease diagnoses were mostly stable (6% hypertension; 4% to 5% cholesterol; 4% diabetes; 1% colonic adenoma; 0.1% colorectal cancer; among women, 0.5% breast cancer), although some declined (lung cancer, cervical intraepithelial neoplasia or carcinoma in situ, cervical cancer, all P < .05). The pandemic resulted in health debt, because use of most preventive services and new diagnoses of chronic disease were less than expected during 2020; these partially rebounded in subsequent years. Colorectal screening and colonic adenoma detection by age group aligned with screening recommendation age changes during this period. Conclusion: Among over 30 million patients receiving care during 2018 through 2022, use of preventive services and new diagnoses of chronic disease declined in 2020 and then rebounded, with some remaining health debt. These data highlight opportunities to augment traditional surveillance with EHR-based data.
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COVID-19 , Serviços Preventivos de Saúde , Humanos , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Doença Crônica/epidemiologia , Doença Crônica/prevenção & controle , Serviços Preventivos de Saúde/estatística & dados numéricos , Serviços Preventivos de Saúde/tendências , Estudos Transversais , Adulto , Feminino , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Masculino , SARS-CoV-2 , Adulto Jovem , Registros Eletrônicos de Saúde , PandemiasRESUMO
The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000-2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 female live births (95% CI = 3.0-3.3, program range: 1.0-10.4), and 1.9 for live birth and stillbirth (≥20 weeks gestation) cases (95% CI = 1.8-2.1, program range: 0.2-3.9). Prevalence was lowest among cases born to non-Hispanic Black women compared to non-Hispanic White women (PR = 0.5, 95% CI = 0.4-0.6). Coarctation of the aorta was the most common defect (11.6% of cases), and across the cohort, individuals without hypoplastic left heart had a five-year survival probability of 94.6%. The findings from this population-based study may inform surveillance practices, prenatal counseling, and diagnosis. We also identified racial and ethnic disparities in prevalence, an observation that warrants further investigation.
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Coartação Aórtica , Síndrome de Turner , Lactente , Feminino , Gravidez , Humanos , Estados Unidos/epidemiologia , Síndrome de Turner/epidemiologia , Síndrome de Turner/genética , Prevalência , Coartação Aórtica/epidemiologia , Etnicidade , Grupos RaciaisRESUMO
BACKGROUND: Concerns have been raised about prenatal exposure to magnetic resonance imaging with gadolinium-based contrast agents because of nonclinical findings of gadolinium retention in fetal tissue and 1 population-based study reporting an association with adverse pregnancy outcomes. OBJECTIVE: This study aimed to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death and neonatal intensive care unit admission. STUDY DESIGN: We constructed a retrospective cohort of >11 million Medicaid-covered pregnancies between 1999 and 2014 to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death (primary endpoint) and neonatal intensive care unit admissions (secondary endpoint). Medicaid claims data were linked to medical records, Florida birth and fetal death records, and the National Death Index to validate the outcomes and gestational age estimates. Pregnancies with multiples, concurrent cancer, teratogenic drug exposure, magnetic resonance imaging focused on fetal or pelvic evaluation, undetermined gadolinium-based contrast agent use, or those preceded by or contemporaneous with congenital anomaly diagnoses were excluded. We adjusted for potential confounders with standardized mortality ratio weighting using propensity scores. RESULTS: Among 5991 qualifying pregnancies, we found 11 fetal or neonatal deaths in the gadolinium-based contrast agent magnetic resonance imaging group (1.4%) and 73 in the non-gadolinium-based contrast agent magnetic resonance imaging group (1.4%) with an adjusted relative risk of 0.73 (95% confidence interval, 0.34-1.55); the neonatal intensive care unit admission adjusted relative risk was 1.03 (0.76-1.39). Sensitivity analyses investigating the timing of magnetic resonance imaging or repeat magnetic resonance imaging exposure during pregnancy and simulating the impact of exposure misclassification corroborated these results. CONCLUSION: This study addressed the safety concerns related to prenatal exposure to gadolinium-based contrast agents used in magnetic resonance imaging and the risk thereof on fetal and neonatal death or the need for neonatal intensive care unit admission. Although the results on fatal or severe acute effects are reassuring, the impact on subacute outcomes was not evaluated.
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Morte Perinatal , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Recém-Nascido , Feminino , Humanos , Estudos Retrospectivos , Unidades de Terapia Intensiva Neonatal , Meios de Contraste/efeitos adversos , Gadolínio/efeitos adversos , Recém-Nascido Pequeno para a Idade Gestacional , Feto , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The VARIVAX® Pregnancy Registry was established in 1995 to monitor pregnancy outcomes of women who received varicella vaccine (ie, VARIVAX) inadvertently while pregnant. METHODS: Health care providers and consumers sent voluntary reports about women who received VARIVAX 3 months before or during pregnancy. Follow-up occurred to evaluate pregnancy outcomes for birth defects. Outcomes from prospectively reported pregnancy exposures (ie, reports received before the outcome of the pregnancy was known) among varicella-zoster virus (VZV)-seronegative women were used to calculate rates and 95% confidence intervals (CIs). RESULTS: From 17 March 1995 through 16 October 2013, 1601 women were enrolled-966 prospectively-among whom there were 819 live births. Among 164 infants born to women who were VZV seronegative at the time of vaccination, no cases of congenital varicella syndrome (CVS) were identified (rate, 0 per 100, 95% CI, 0.0-2.2) and the birth prevalence of major birth defects was 4.3 per 100 liveborn infants (95% CI 1.7-8.6) with no pattern suggestive of CVS. No defects consistent with CVS were identified in any registry reports. CONCLUSIONS: Data collected through the VARIVAX pregnancy registry do not support a relationship between the occurrence of CVS or major birth defects and varicella vaccine exposure during pregnancy, although the small numbers of exposures cannot rule out a low risk. VARIVAX remains contraindicated during pregnancy.
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Infecção pelo Vírus da Varicela-Zoster , Vacinas Virais , Humanos , Lactente , Gravidez , Feminino , Estados Unidos , Vacina contra Varicela , Herpesvirus Humano 3 , Sistema de Registros , Vacinas Atenuadas , Centers for Disease Control and Prevention, U.S.RESUMO
Limited data are available about the potential health effects of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pregnant women and their developing offspring. We established the International Registry of Coronavirus Exposure in Pregnancy (IRCEP) to provide data on the risk of major adverse obstetric and neonatal outcomes among women with varying degrees of severity and timing of coronavirus disease 2019 (COVID-19) during pregnancy. We describe here the cohort and share the lessons learned. The IRCEP enrolls women tested for SARS-CoV-2 or with a clinical diagnosis of COVID-19 during pregnancy and obtains information using an online data collection system. By March 2021, 17,532 participants from 77 countries had enrolled; 54% enrolled during pregnancy and 46% afterward. Among women with symptomatic COVID-19 with a positive SARS-CoV-2 test (n = 4,934), symptoms were mild in 41%, moderate in 52%, and severe in 7%; 7.7% were hospitalized for COVID-19 and 1.7% were admitted to an intensive care unit. The biggest challenges were retention of participants enrolled during pregnancy and the potential bias introduced when participants enroll after pregnancy outcomes are known. Multiple biases need to be considered and addressed when estimating and interpreting the effects of COVID-19 in pregnancy in these types of cohorts.
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COVID-19 , Complicações Infecciosas na Gravidez , COVID-19/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Sistema de Registros , SARS-CoV-2Assuntos
Vacinas contra Vírus Sincicial Respiratório , Humanos , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Medição de Risco , Feminino , Gravidez , Recém-Nascido , LactenteRESUMO
Physiological, mechanical, and immunologic alterations in pregnancy could potentially affect the susceptibility to and the severity of COVID-19 during pregnancy. Owing to the lack of comparable incidence data and the challenges with disentangling differences in the susceptibility from different exposure risks, the data are insufficient to determine whether pregnancy increases the susceptibility to SARS-CoV-2 infection. The data support pregnancy as a risk factor for severe disease associated with COVID-19; some of the best evidence comes from the United States Centers for Disease Control and Prevention COVID-19 surveillance system, which reported that pregnant persons were more likely to be admitted to an intensive care unit, require invasive ventilation, require extracorporeal membrane oxygenation, and die than nonpregnant women of reproductive age. Although the intrauterine transmission of SARS-CoV-2 has been documented, it appears to be rare. It is possibly related to low levels of SARS-CoV-2 viremia and the decreased coexpression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 needed for SARS-CoV-2 entry into cells in the placenta. Evidence is accumulating that SARS-CoV-2 infection during pregnancy is associated with a number of adverse pregnancy outcomes including preeclampsia, preterm birth, and stillbirth, especially among pregnant persons with severe COVID-19 disease. In addition to the direct impact of COVID-19 on pregnancy outcomes, there is evidence that the pandemic and its effects on healthcare systems have had adverse effects such as increased stillbirths and maternal deaths on the pregnancy outcomes. These trends may represent widening disparities and an alarming reversal of recent improvements in maternal and infant health. All the 3 COVID-19 vaccines currently available in the United States can be administered to pregnant or lactating persons, with no preference for the vaccine type. Although the safety data in pregnancy are rapidly accumulating and no safety signals in pregnancy have been detected, additional information about the birth outcomes, particularly among persons vaccinated earlier in pregnancy, are needed.
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Vacinas contra COVID-19/uso terapêutico , COVID-19/epidemiologia , Pré-Eclâmpsia/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Natimorto/epidemiologia , COVID-19/fisiopatologia , COVID-19/prevenção & controle , COVID-19/terapia , Suscetibilidade a Doenças , Feminino , Disparidades em Assistência à Saúde , Humanos , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/terapia , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Prevention of prenatal exposures to teratogenic drugs is a significant clinical and public health concern. With the enactment of the US Food and Drug Administration Amendments Act in 2007, the US Food and Drug Administration has begun to require manufacturers to implement Risk Evaluation and Mitigation Strategies to prevent prenatal exposures. Among 12 risk evaluation and mitigation strategy drugs, several had predecessor risk mitigation plans (eg, isotretinoin) and some were newly required (eg, mycophenolate). Only a small proportion of teratogenic drugs are currently subject to Risk Evaluation and Mitigation Strategies, and the extent of prenatal exposure to the universe of teratogenic drugs compared with drugs subject to Risk Evaluation and Mitigation Strategies is unknown. Moreover, the effectiveness of such advanced risk mitigation programs in preventing prenatal exposure is not clear. OBJECTIVE: This study aimed to characterize the epidemiology of prenatal exposures to definite and potential teratogens during the risk evaluation and mitigation strategy era. STUDY DESIGN: We constructed a time-series of pregnancies identified from a national private insurance claims database (IBM MarketScan) to estimate prenatal exposures to teratogenic drugs (2006-2017). Pregnancy outcomes, gestational age, and the onset of pregnancy were determined with previously validated algorithms. The Teratology Information Service and Clinical Pharmacology databases were used to identify drugs with definite (n=141) or potential (n=65) teratogenic effects, and drugs with debatable risks such as benzodiazepines, statins, tetracyclines, sex hormones, infertility treatments, and gonadotropin-releasing hormone analogs were excluded. We defined prenatal exposure as ≥1 prescription fill or medical encounter involving administration of drugs with a definite teratogenic risk (including 12 for which there is a "current or discontinued" risk evaluation and mitigation strategy) or a potential teratogenic risk. We evaluated secular trends and modeled the effects of age, preconception exposure, and state healthcare quality rankings on prenatal exposure, adjusting for demographic factors and clinical conditions. RESULTS: The cohort included 3,445,612 pregnancies (2,532,444 live deliveries). Prenatal exposures to definite teratogens decreased slightly during the study years from 1.86 to 1.24 per 100 pregnancies between 2006 and 2017, whereas exposure increased for potential teratogens from 3.40% to 5.33%. Prenatal exposure prevalences were higher during the first trimester and for pregnancies that ended in nonlive outcomes. Drugs subject to Risk Evaluation and Mitigation Strategies had low background utilization and contributed to a small proportion of prenatal exposures (15.1 per 100,000 pregnancies). We also observed fewer prenatal exposures to risk evaluation and mitigation strategy drugs among women of childbearing age who used these treatments (0.14% vs 0.36% for any definite teratogen). Age extremes and low state-level healthcare quality rankings were independent predictors of prenatal exposure. CONCLUSION: Fetuses in more than 1 in 16 pregnancies continued to be exposed to teratogenic drugs during the past decade. Drugs with Risk Evaluation and Mitigation Strategies imposed a small burden of prenatal exposure because of the low background utilization rates and lower pregnancy prevalence among women of childbearing age who used these drugs. Although the declining exposure rates to teratogenic drugs with definite risk are encouraging, the rising prenatal exposure to drugs with potential risk calls for more assessments. Future research is needed to elucidate the health outcomes of fetuses exposed to potential risk drugs, understand the effectiveness of risk evaluation and mitigation strategy programs, and prioritize teratogenic drugs for advanced risk mitigation.
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Anormalidades Induzidas por Medicamentos , Efeitos Tardios da Exposição Pré-Natal , Teratogênese , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Induzidas por Medicamentos/prevenção & controle , Feminino , Humanos , Gravidez , Resultado da Gravidez , Avaliação de Risco e Mitigação , TeratogênicosRESUMO
The COVID-19 pandemic has magnified longstanding health care and social inequities, resulting in disproportionately high COVID-19-associated illness and death among members of racial and ethnic minority groups (1). Equitable use of effective medications (2) could reduce disparities in these severe outcomes (3). Monoclonal antibody (mAb) therapies against SARS-CoV-2, the virus that causes COVID-19, initially received Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA) in November 2020. mAbs are typically administered in an outpatient setting via intravenous infusion or subcutaneous injection and can prevent progression of COVID-19 if given after a positive SARS-CoV-2 test result or for postexposure prophylaxis in patients at high risk for severe illness. Dexamethasone, a commonly used steroid, and remdesivir, an antiviral drug that received EUA from FDA in May 2020, are used in inpatient settings and help prevent COVID-19 progression§ (2). No large-scale studies have yet examined the use of mAb by race and ethnicity. Using COVID-19 patient electronic health record data from 41 U.S. health care systems that participated in the PCORnet, the National Patient-Centered Clinical Research Network,¶ this study assessed receipt of medications for COVID-19 treatment by race (White, Black, Asian, and Other races [including American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, and multiple or Other races]) and ethnicity (Hispanic or non-Hispanic). Relative disparities in mAb** treatment among all patients (805,276) with a positive SARS-CoV-2 test result and in dexamethasone and remdesivir treatment among inpatients§§ (120,204) with a positive SARS-CoV-2 test result were calculated. Among all patients with positive SARS-CoV-2 test results, the overall use of mAb was infrequent, with mean monthly use at 4% or less for all racial and ethnic groups. Hispanic patients received mAb 58% less often than did non-Hispanic patients, and Black, Asian, or Other race patients received mAb 22%, 48%, and 47% less often, respectively, than did White patients during November 2020-August 2021. Among inpatients, disparities were different and of lesser magnitude: Hispanic inpatients received dexamethasone 6% less often than did non-Hispanic inpatients, and Black inpatients received remdesivir 9% more often than did White inpatients. Vaccines and preventive measures are the best defense against infection; use of COVID-19 medications postexposure or postinfection can reduce morbidity and mortality and relieve strain on hospitals but are not a substitute for COVID-19 vaccination. Public health policies and programs centered around the specific needs of communities can promote health equity (4). Equitable receipt of outpatient treatments, such as mAb and antiviral medications, and implementation of prevention practices are essential to reducing existing racial and ethnic inequities in severe COVID-19-associated illness and death.
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Tratamento Farmacológico da COVID-19 , Minorias Étnicas e Raciais/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde/etnologia , Determinantes Sociais da Saúde , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Estados UnidosRESUMO
PURPOSE OF REVIEW: To review updates regarding teratogens and give pediatric healthcare providers insight into the prevention of teratogenic exposures. RECENT FINDINGS: Application of the principles of teratology can help to assess the potential for exposures to be teratogenic. Identification of Zika virus as a teratogen, the most recent teratogenic agent identified, allowed public health measures to be put in place to mitigate its spread. Risk management strategies for teratogenic medications have resulted in a decrease but often not elimination of prenatal exposures. The failure to include pregnant persons in clinical trials results in their being less likely to receive needed medications and vaccines in a timely manner. SUMMARY: Pediatricians play an important role in the prevention of teratogenic exposures. Ensuring optimal management of patients with chronic illnesses that might increase their risk of birth defects during pregnancy due to the illness itself or its treatment is essential. For patients with pregnancy potential who are on teratogenic medications, ensuring effective contraception is also important. Inclusion of pregnant persons in clinical trials and research studies will be critical to advancing our knowledge of the safety of medications and other exposures during pregnancy.
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Teratologia , Vacinas , Infecção por Zika virus , Zika virus , Gravidez , Feminino , Humanos , Criança , Teratogênicos , Anticoncepção , Pessoal de SaúdeRESUMO
Victor McKusick's contributions to the field of medical genetics are legendary and include his contributions as a mentor, as creator of Mendelian Inheritance in Man (now Online Mendelian Inheritance in Man [OMIM®]), and as a leader in the field of medical genetics. McKusick's full bibliography includes 772 publications. Here we review the 453 papers authored by McKusick and indexed in PubMed, from his earliest paper published in the New England Journal of Medicine in 1949 to his last paper published in American Journal of Medical Genetics Part A in 2008. This review of his bibliography chronicles McKusick's evolution from an internist and cardiologist with an interest in genetics to an esteemed leader in the growing field of medical genetics. Review of his bibliography also provides a historical perspective of the development of the discipline of medical genetics. This field came into its own during his lifetime, transitioning from the study of interesting cases and families used to codify basic medical genetics principles to an accredited medical specialty that is expected to transform healthcare. Along the way, he helped to unite the fields of medical and human genetics to focus on mapping the human genome, culminating in completion of the Human Genome Project. This review confirms the critical role played by Victor McKusick as the founding father of medical genetics.
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Bases de Dados Genéticas/história , Genética Médica/história , Genoma Humano/genética , História do Século XX , História do Século XXI , Projeto Genoma Humano/história , Humanos , Estados UnidosRESUMO
Victor McKusick's many contributions to medicine are legendary, but his magnum opus is Mendelian Inheritance in Man (MIM), his catalog of Mendelian phenotypes and their associated genes. The catalog, originally published in 1966 in book form, became available on the internet as Online Mendelian Inheritance in Man (OMIM®) in 1987. The first of 12 editions of MIM included 1486 entries; this number has increased to over 25,000 entries in OMIM as of April 2021, which demonstrates the growth of knowledge about Mendelian phenotypes and their genes through the years. OMIM now has over 20,000 unique users a day, including users from every country in the world. Many of the early decisions made by McKusick, such as to maintain MIM data in a computer-readable format, to separate phenotype entries from those for genes, and to give phenotypes and genes MIM numbers, have proved essential to the long-term utility and flexibility of his catalog. Based on his extensive knowledge of genetics and vision of its future in the field of medicine, he developed a framework for the capture and summary of information from the published literature on phenotypes and their associated genes; this catalog continues to serve as an indispensable resource to the genetics community.
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Bases de Dados Genéticas/história , Genética Médica/história , Mapeamento Cromossômico , História do Século XX , História do Século XXI , HumanosRESUMO
BACKGROUND: Yersinia pestis continues to cause sporadic cases and outbreaks of plague worldwide and is considered a tier 1 bioterrorism select agent due to its potential for intentional use. Knowledge about the clinical manifestations of plague during pregnancy, specifically the maternal, fetal, and neonatal risks, is very limited. METHODS: We searched 12 literature databases, performed hand searches, and consulted plague experts to identify publications on plague during pregnancy. Articles were included if they reported a case of plague during pregnancy and at least 1 maternal or fetal outcome. RESULTS: Our search identified 6425 articles, of which 59 were eligible for inclusion and described 160 cases of plague among pregnant women. Most published cases occurred during the preantibiotic era. Among those treated with antimicrobials, the most commonly used were sulfonamides (75%) and streptomycin (54%). Among cases treated with antimicrobials, maternal mortality and fetal fatality were 29% and 62%, respectively; for untreated cases, maternal mortality and fetal fatality were 67% and 74%, respectively. Five cases demonstrated evidence of Y. pestis in fetal or neonatal tissues. CONCLUSIONS: Untreated Y. pestis infection during pregnancy is associated with a high risk of maternal mortality and pregnancy loss. Appropriate antimicrobial treatment can improve maternal survival, although even with antimicrobial treatment, there remains a high risk of pregnancy loss. Limited evidence suggests that maternal-fetal transmission of Y. pestis is possible, particularly in the absence of antimicrobial treatment. These results emphasize the need to treat or prophylax pregnant women with suspected plague with highly effective antimicrobials as quickly as possible.
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Peste , Yersinia pestis , Antibacterianos/uso terapêutico , Bioterrorismo , Surtos de Doenças , Feminino , Humanos , Peste/diagnóstico , Peste/tratamento farmacológico , Peste/epidemiologia , GravidezRESUMO
BACKGROUND: Birth defects are established risk factors for childhood cancer. Nonetheless, cancer epidemiology in children with birth defects is not well characterized. METHODS: Using data from population-based registries in 4 US states, this study compared children with cancer but no birth defects (n = 13,111) with children with cancer and 1 or more nonsyndromic birth defects (n = 1616). The objective was to evaluate cancer diagnostic characteristics, including tumor type, age at diagnosis, and stage at diagnosis. RESULTS: Compared with the general population of children with cancer, children with birth defects were diagnosed with more embryonal tumors (26.6% vs 18.7%; q < 0.001), including neuroblastoma (12.5% vs 8.2%; q < 0.001) and hepatoblastoma (5.0% vs 1.3%; q < 0.001), but fewer hematologic malignancies, including acute lymphoblastic leukemia (12.4% vs 24.4%; q < 0.001). In age-stratified analyses, differences in tumor type were evident among children younger than 1 year and children 1 to 4 years old, but they were attenuated among children 5 years of age or older. The age at diagnosis was younger in children with birth defects for most cancers, including leukemia, lymphoma, astrocytoma, medulloblastoma, ependymoma, embryonal tumors, and germ cell tumors (all q < 0.05). CONCLUSIONS: The results indicate possible etiologic heterogeneity in children with birth defects, have implications for future surveillance efforts, and raise the possibility of differential cancer ascertainment in children with birth defects. LAY SUMMARY: Scientific studies suggest that children with birth defects are at increased risk for cancer. However, these studies have not been able to determine whether important tumor characteristics, such as the type of tumor diagnosed, the age at which the tumor is diagnosed, and the degree to which the tumor has spread at the time of diagnosis, are different for children with birth defects and children without birth defects. This study attempts to answer these important questions. By doing so, it may help scientists and physicians to understand the causes of cancer in children with birth defects and diagnose cancer at earlier stages when it is more treatable.
Assuntos
Anormalidades Congênitas/diagnóstico , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Adolescente , Criança , Pré-Escolar , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/patologia , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/patologia , Hepatoblastoma/complicações , Hepatoblastoma/diagnóstico , Hepatoblastoma/epidemiologia , Hepatoblastoma/patologia , Humanos , Lactente , Recém-Nascido , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Neoplasias/complicações , Neoplasias/patologia , Neuroblastoma/complicações , Neuroblastoma/diagnóstico , Neuroblastoma/epidemiologia , Neuroblastoma/patologia , Sistema de Registros , Fatores de Risco , Estados Unidos/epidemiologiaAssuntos
Mudança Climática , Saúde , Prática de Saúde Pública , Medicina Ambiental/métodos , Feminino , Humanos , Lactente , Gravidez , Inquéritos e QuestionáriosRESUMO
Coronavirus disease 2019 is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about coronavirus disease 2019 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (ie, severe acute respiratory syndrome and the Middle East respiratory syndrome) might provide insights into coronavirus disease 2019's effects during pregnancy. Coronaviruses cause illness ranging in severity from the common cold to severe respiratory illness and death. Currently the primary epidemiologic risk factors for coronavirus disease 2019 include travel from mainland China (especially Hubei Province) or close contact with infected individuals within 14 days of symptom onset. Data suggest an incubation period of â¼5 days (range, 2-14 days). Average age of hospitalized patients has been 49-56 years, with a third to half with an underlying illness. Children have been rarely reported. Men were more frequent among hospitalized cases (54-73%). Frequent manifestations include fever, cough, myalgia, headache, and diarrhea. Abnormal testing includes abnormalities on chest radiographic imaging, lymphopenia, leukopenia, and thrombocytopenia. Initial reports suggest that acute respiratory distress syndrome develops in 17-29% of hospitalized patients. Overall case fatality rate appears to be â¼1%; however, early data may overestimate this rate. In 2 reports describing 18 pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnant adults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of in utero transmission was seen. Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratory syndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in 4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanical ventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended in spontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks' gestation delivered preterm. For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmission was seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently no coronavirus-specific treatments have been approved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk for pregnancy complications, management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue to follow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html).
Assuntos
Infecções por Coronavirus , Coronavirus , Conhecimentos, Atitudes e Prática em Saúde , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Pandemias , Pneumonia Viral , Complicações Infecciosas na Gravidez/prevenção & controle , Betacoronavirus , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Surtos de Doenças , Feminino , Humanos , Recém-Nascido , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Nascimento Prematuro , SARS-CoV-2RESUMO
Infants are at increased risk for pertussis-associated morbidity and mortality, and pregnant women and their infants are more likely than other patient populations to experience severe influenza-related illness (1,2). The Advisory Committee on Immunization Practices (ACIP) recommends that all women receive the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during each pregnancy, preferably during the early part of gestational weeks 27-36 (3). ACIP also recommends that women who are or might be pregnant during the influenza season receive the inactivated influenza vaccine at any time during pregnancy (4). Despite these recommendations, coverage with Tdap and influenza vaccines during pregnancy has been low, with approximately one half of women receiving each vaccine and only one third receiving both, based on a survey during March-April 2019 (5). Data obtained through a retrospective chart review of randomly selected pregnant women who delivered at the University of Florida Health Shands Hospital in Gainesville, Florida, from January 1, 2016, to December 31, 2018, were analyzed to assess vaccination coverage by insurance type. Because the Florida Medicaid policy at that time did not cover these vaccines during pregnancy, the hospital system offered Tdap and influenza vaccines at no additional cost to mothers during the immediate postpartum hospital stay. Among 341 women, 68.6% of privately insured and 13.4% with Medicaid received Tdap during pregnancy, and among 316 women, 70.4% of privately insured and 35.6% with Medicaid received influenza vaccine during pregnancy. Many women, especially those with Medicaid, were vaccinated in the immediate postpartum period, when vaccination was available at no cost, increasing Tdap vaccination rates to 79.3% for privately insured and 51.7% for women with Medicaid; influenza vaccination rates rose to 72.0% for privately insured and 43.5% for women with Medicaid. These data suggest that the state Medicaid policy to not cover these vaccines during pregnancy might have significantly reduced coverage among its enrollees.