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1.
Proc Natl Acad Sci U S A ; 118(26)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34168077

RESUMO

Dual oxidase 1 (DUOX1) is an NADPH oxidase that is highly expre-ssed in respiratory epithelial cells and produces H2O2 in the airway lumen. While a line of prior in vitro observations suggested that DUOX1 works in partnership with an airway peroxidase, lactoperoxidase (LPO), to produce antimicrobial hypothiocyanite (OSCN-) in the airways, the in vivo role of DUOX1 in mammalian organisms has remained unproven to date. Here, we show that Duox1 promotes antiviral innate immunity in vivo. Upon influenza airway challenge, Duox1-/- mice have enhanced mortality, morbidity, and impaired lung viral clearance. Duox1 increases the airway levels of several cytokines (IL-1ß, IL-2, CCL1, CCL3, CCL11, CCL19, CCL20, CCL27, CXCL5, and CXCL11), contributes to innate immune cell recruitment, and affects epithelial apoptosis in the airways. In primary human tracheobronchial epithelial cells, OSCN- is generated by LPO using DUOX1-derived H2O2 and inactivates several influenza strains in vitro. We also show that OSCN- diminishes influenza replication and viral RNA synthesis in infected host cells that is inhibited by the H2O2 scavenger catalase. Binding of the influenza virus to host cells and viral entry are both reduced by OSCN- in an H2O2-dependent manner in vitro. OSCN- does not affect the neuraminidase activity or morphology of the influenza virus. Overall, this antiviral function of Duox1 identifies an in vivo role of this gene, defines the steps in the infection cycle targeted by OSCN-, and proposes that boosting this mechanism in vivo can have therapeutic potential in treating viral infections.


Assuntos
Antivirais/imunologia , Oxidases Duais/metabolismo , Imunidade Inata , Animais , Apoptose , Brônquios/patologia , Brônquios/virologia , Citocinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/patologia , Humanos , Peróxido de Hidrogênio/metabolismo , Influenza Humana/imunologia , Influenza Humana/patologia , Influenza Humana/virologia , Lactoperoxidase/metabolismo , Camundongos , Neuraminidase/química , Neuraminidase/metabolismo , Orthomyxoviridae/fisiologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Proteólise , RNA Viral/metabolismo , Tiocianatos , Proteínas Virais/química , Proteínas Virais/metabolismo , Inativação de Vírus , Internalização do Vírus , Replicação Viral
2.
J Virol ; 95(23): e0237920, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34523961

RESUMO

Influenza remains one of the most contagious infectious diseases. Approximately, 25 to 50 million people suffer from influenza-like illness in the United States annually, leading to almost 1 million hospitalizations. Globally, the World Health Organization (WHO) estimates 250,000 to 500,000 mortalities associated with secondary respiratory complications due to influenza virus infection every year. Currently, seasonal vaccination represents the best countermeasure to prevent influenza virus spread and transmission in the general population. However, presently licensed influenza vaccines are about 60% effective on average, and their effectiveness varies from season to season and among age groups, as well as between different influenza subtypes within a single season. The hemagglutination inhibition (HAI) assay represents the gold standard method for measuring the functional antibody response elicited following standard-of-care vaccination, along with evaluating the efficacy of under-development influenza vaccines in both animal models and clinical trial settings. However, using the classical HAI approach, it is not possible to dissect the complexities of variable epitope recognition within a polyclonal antibody response. In this paper, we describe a straightforward competitive HAI-based method using a combination of influenza virus and recombinant hemagglutinin (HA) proteins to dissect the HAI functional activity of HA-specific antibody populations in a single assay format. IMPORTANCE The hemagglutination inhibition (HAI) assay is a well-established and reproducible method that quantifies functional antibody activity against influenza viruses and, in particular, the capability of an antibody formulation to inhibit the binding of hemagglutinin (HA) to sialic acid. However, the HAI assay does not provide full insights on the breadth and epitope recognition of the antibody formulation, especially in the context of polyclonal sera, where multiple antibody specificities contribute to the overall observed functional activity. In this report we introduce the use of Y98F point-mutated recombinant HA (HAΔSA) proteins, which lack sialic acid binding activity, in the context of the HAI assay as a means to absorb out certain HA-directed (i.e., strain-specific or cross-reactive) antibody populations. This modification to the classical HAI assay, referred to as the competitive HAI assay, represents a new tool to dissect the magnitude and breadth of polyclonal antibodies elicited through vaccination or natural infection.


Assuntos
Anticorpos Antivirais/imunologia , Testes de Inibição da Hemaglutinação/métodos , Influenza Humana/diagnóstico , Animais , Antígenos Virais/genética , Antígenos Virais/imunologia , Reações Cruzadas , Modelos Animais de Doenças , Epitopos , Furões/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/virologia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/imunologia , Vacinação
3.
Am J Obstet Gynecol ; 226(2): 241.e1-241.e14, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34419453

RESUMO

BACKGROUND: Women with gestational glucose intolerance, defined as an abnormal initial gestational diabetes mellitus screening test, are at risk of adverse pregnancy outcomes even if they do not have gestational diabetes mellitus. Previously, we defined the physiological subtypes of gestational diabetes mellitus based on the primary underlying physiology leading to hyperglycemia and found that women with different subtypes had differential risks of adverse outcomes. Physiological subclassification has not yet been applied to women with gestational glucose intolerance. OBJECTIVE: We defined the physiological subtypes of gestational glucose intolerance based on the presence of insulin resistance, insulin deficiency, or mixed pathophysiology and aimed to determine whether these subtypes are at differential risks of adverse outcomes. We hypothesized that women with the insulin-resistant subtype of gestational glucose intolerance would have the greatest risk of adverse pregnancy outcomes. STUDY DESIGN: In a hospital-based cohort study, we studied women with gestational glucose intolerance (glucose loading test 1-hour glucose, ≥140 mg/dL; n=236) and normal glucose tolerance (glucose loading test 1-hour glucose, <140 mg/dL; n=1472). We applied homeostasis model assessment to fasting glucose and insulin levels at 16 to 20 weeks' gestation to assess insulin resistance and deficiency and used these measures to classify women with gestational glucose intolerance into subtypes. We compared odds of adverse outcomes (large for gestational age birthweight, neonatal intensive care unit admission, pregnancy-related hypertension, and cesarean delivery) in each subtype to odds in women with normal glucose tolerance using logistic regression with adjustment for age, race and ethnicity, marital status, and body mass index. RESULTS: Of women with gestational glucose intolerance (12% with gestational diabetes mellitus), 115 (49%) had the insulin-resistant subtype, 70 (27%) had the insulin-deficient subtype, 40 (17%) had the mixed pathophysiology subtype, and 11 (5%) were uncategorized. We found increased odds of large for gestational age birthweight (primary outcome) in women with the insulin-resistant subtype compared with women with normal glucose tolerance (odds ratio, 2.35; 95% confidence interval, 1.43-3.88; P=.001; adjusted odds ratio, 1.74; 95% confidence interval, 1.02-3.48; P=.04). The odds of large for gestational age birthweight in women with the insulin-deficient subtype were increased only after adjustment for covariates (odds ratio, 1.69; 95% confidence interval, 0.84-3.38; P=.14; adjusted odds ratio, 2.05; 95% confidence interval, 1.01-4.19; P=.048). Among secondary outcomes, there was a trend toward increased odds of neonatal intensive care unit admission in the insulin-resistant subtype in an unadjusted model (odds ratio, 2.09; 95% confidence interval, 0.99-4.40; P=.05); this finding was driven by an increased risk of neonatal intensive care unit admission in women with the insulin-resistant subtype and a body mass index of <25 kg/m2. Infants of women with other subtypes did not have increased odds of neonatal intensive care unit admission. The odds of pregnancy-related hypertension in women with the insulin-resistant subtype were increased (odds ratio, 2.09; 95% confidence interval, 1.31-3.33; P=.002; adjusted odds ratio, 1.77; 95% confidence interval, 1.07-2.92; P=.03) compared with women with normal glucose tolerance; other subtypes did not have increased odds of pregnancy-related hypertension. There was no difference in cesarean delivery rates in nulliparous women across subtypes. CONCLUSION: Insulin-resistant gestational glucose intolerance is a high-risk subtype for adverse pregnancy outcomes. Delineating physiological subtypes may provide opportunities for a more personalized approach to gestational glucose intolerance.


Assuntos
Glicemia , Diabetes Gestacional/diagnóstico , Intolerância à Glucose/diagnóstico , Resistência à Insulina/fisiologia , Complicações na Gravidez/diagnóstico , Adulto , Estudos de Coortes , Diabetes Gestacional/sangue , Feminino , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Gravidez , Complicações na Gravidez/sangue , Resultado da Gravidez
4.
J Immunol ; 204(2): 375-385, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31811019

RESUMO

Computationally optimized broadly reactive Ags (COBRA) targeting H1 elicit a broad cross-reactive and cross-neutralizing Ab response against multiple H1N1 viral strains. To assess B cell breadth, Mus musculus (BALB/c) Ab-secreting cells elicited by a candidate COBRA hemagglutinin (HA) (termed P1) were compared with Ab-secreting cells elicited by historical H1N1 vaccine strains. In addition, to evaluate the Ab response elicited by P1 HA at increased resolution, a panel of P1 HA-specific B cell hybridomas was generated following immunization of mice with COBRA P1 and the corresponding purified mAbs were characterized for Ag specificity and neutralization activity. Both head- and stem-directed mAbs were elicited by the P1 HA Ag, with some mAbs endowed with Ab-dependent cell-mediated cytotoxicity activity. P1 HA-elicited mAbs exhibited a wide breadth of HA recognition, ranging from narrowly reactive to broadly reactive mAbs. Interestingly, we identified a P1 HA-elicited mAb (1F8) exhibiting broad hemagglutination inhibition activity against both seasonal and pandemic H1N1 influenza strains. Furthermore, mAb 1F8 recognized an overlapping, but distinct, epitope compared with other narrowly hemagglutination inhibition-positive mAbs elicited by the P1 or wild-type HA Ags. Finally, P1 HA-elicited mAbs were encoded by distinct H chain variable and L chain variable gene segment rearrangements and possessed unique CDR3 sequences. Collectively, the functional characterization of P1 HA-elicited mAbs sheds further insights into the underlying mechanism(s) of expanded Ab breadth elicited by a COBRA HA-based immunogen and advances efforts toward design and implementation of a more broadly protective influenza vaccine.


Assuntos
Anticorpos Monoclonais/metabolismo , Anticorpos Antivirais/metabolismo , Anticorpos Amplamente Neutralizantes/metabolismo , Vírus da Influenza A Subtipo H1N1/fisiologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Anticorpos Monoclonais/química , Anticorpos Antivirais/química , Anticorpos Amplamente Neutralizantes/química , Biologia Computacional , Cães , Mapeamento de Epitopos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/metabolismo , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C
5.
Am J Obstet Gynecol ; 224(5): 479-483, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33539824

RESUMO

Challenges arise when treatment to improve maternal health brings the possibility of risk to fetal health. The coronavirus disease 2019 (COVID-19) vaccine is the most recent, but hardly the only, example. Because pregnant patients are often specifically excluded from trials of new therapies, this is often the dilemma that patients and providers face when considering new treatments. In this study, we used the COVID-19 vaccine as an exemplar to question the broader issue of how society, in general, and obstetricians, in particular, should balance obligations to pregnant women's right of access to new therapeutic agents with the physician's desire to protect the fetus from potential risks. We will argue that in almost all circumstances (with few exceptions, as will also be discussed), maternal benefit and respect for autonomy create the uncertainty that absent safety data bring. Consequently, if pregnant women choose to try new interventions and treatments, such as the COVID-19 vaccination, they should be offered those new regimens and their decision supported. In addition, we will argue that the right solution to avoid the dilemma of absent data is to include pregnant individuals in clinical trials studying new treatments, drugs, and other therapies. We will also discuss the basis for our opinion, which are mainstream obstetrical ethics, precedents in law (supreme court ruling that forbids companies to exclude women from jobs that might pose a risk to the fetus), and historic events (thalidomide). The ethical framework includes the supposition that sacrifice to improve fetal outcome is a virtue and not a mandate. Denying a pregnant patient treatment because of threats to their life can create absurd and paradoxical consequences. Either requiring abortion or premature delivery before proceeding with treatments to optimize maternal health, or risking a patient's own life and ability to parent a child by delaying treatment brings clear and significant risks to fetal and/or neonatal outcomes. With rare exceptions, properly and ethically balancing such consequential actions cannot be undertaken without considering the values and goals of the pregnant patient. Therefore, active participation of both the pregnant patient and their physician in shared decision making is needed.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Tomada de Decisões , SARS-CoV-2/imunologia , Vacinação/ética , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Segurança do Paciente , Autonomia Pessoal , Gravidez
6.
BMC Pregnancy Childbirth ; 20(1): 365, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539690

RESUMO

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare but serious complication in pregnancy that places the mother and fetus at high risk for morbidity and mortality. This case illustrates novel pregnancy complications associated with this rare medical condition. CASE PRESENTATION: A 31-year-old G3P0020 at 28 weeks and 1 day was admitted with severe thrombocytopenia and was ultimately diagnosed with TTP. With therapeutic plasma exchange (TPE), maternal status improved. At 28 weeks 6 days, however, non-reassuring fetal testing prompted cesarean delivery with placental abruption noted intraoperatively. Pathology examination confirmed placental abruption and also revealed multiple placental infarcts. CONCLUSION: While medical management of TTP can significantly improve the health of the mother, this case highlights the potential role of TTP in abruption and other placental pathology and thus, the need for close fetal surveillance throughout an affected pregnancy.


Assuntos
Descolamento Prematuro da Placenta/etiologia , Complicações Hematológicas na Gravidez/diagnóstico , Púrpura Trombocitopênica Trombótica/complicações , Adulto , Cesárea , Feminino , Humanos , Placenta/patologia , Troca Plasmática , Gravidez , Complicações Hematológicas na Gravidez/terapia
7.
J Am Soc Nephrol ; 28(5): 1566-1574, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28008002

RESUMO

The effect of clinically recovered AKI (r-AKI) on future pregnancy outcomes is unknown. We retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General Hospital to assess whether a previous episode of r-AKI associated with subsequent adverse maternal and fetal outcomes, including preeclampsia. AKI was defined as rise in serum creatinine concentration to 1.5-fold above baseline. We compared pregnancy outcomes in women with r-AKI without history of CKD (eGFR>90 ml/min per 1.73 m2 before conception; n=105) with outcomes in women without kidney disease (controls; n=24,640). The r-AKI and control groups had similar prepregnancy serum creatinine measurements (0.70±0.20 versus 0.69±0.10 mg/dl; P=0.36). However, women with r-AKI had increased rates of preeclampsia compared with controls (23% versus 4%; P<0.001). Infants of women with r-AKI were born earlier than infants of controls (37.6±3.6 versus 39.2±2.2 weeks; P<0.001), with increased rates of small for gestational age births (15% versus 8%; P=0.03). After multivariate adjustment, r-AKI associated with increased risk for preeclampsia (adjusted odds ratio [aOR], 5.9; 95% confidence interval [95% CI], 3.6 to 9.7) and adverse fetal outcomes (aOR, 2.4; 95% CI, 1.6 to 3.7). When women with r-AKI and controls were matched 1:2 by age, race, body mass index, diastolic BP, parity, and diabetes status, r-AKI remained associated with preeclampsia (OR, 4.7; 95% CI, 2.1 to 10.1) and adverse fetal outcomes (OR, 2.1; 95% CI, 1.2 to 3.7). Thus, a past episode of AKI, despite return to normal renal function before pregnancy, associated with adverse outcomes in pregnancy.


Assuntos
Injúria Renal Aguda/terapia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Adulto , Feminino , Humanos , Pré-Eclâmpsia/epidemiologia , Gravidez , Estudos Retrospectivos , Fatores de Risco
9.
Birth ; 44(4): 315-324, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28594070

RESUMO

BACKGROUND: Although many women with physical disabilities report poor quality reproductive health care, little research has addressed labor, delivery, and anesthesia experiences of these women. This study was conducted to explore these experiences in women with significant mobility disabilities. METHODS: A qualitative descriptive study was conducted with 22 women from the United States who had delivered newborns within the prior 10 years. All had significant mobility disabilities. Two-hour, in-depth telephone interviews were conducted using a semistructured, open-ended interview protocol, which addressed many topics, including labor, delivery, and anesthesia experiences. We recruited most participants through social networks, interviewing women from 17 states. Conventional content analysis, facilitated by NVivo software, was used to identify major themes. RESULTS: The mean age of women was 34.8 ± 5.3 years. Most women were white, college educated, and used wheeled mobility aids. Four key themes emerged from participants' narratives of laboring and giving birth with a disability. These included women's preferences for type of delivery, clinicians and some women expected no labor pain, fears prompting active advocacy, and positive experiences. As participants discussed their experiences with anesthesia, four additional themes were identified: importance of consultation with the anesthesia team, decisions about epidural/spinal vs general anesthesia, failed epidural with repeated efforts, and fear of injury related to anesthesia. CONCLUSIONS: The responses of women in this study suggest that there is need to make intrapartum care better for women with physical disabilities and to improve their experiences with labor, birth, and obstetric anesthesia care.


Assuntos
Anestesia , Pessoas com Deficiência/psicologia , Trabalho de Parto , Parto , Adulto , Parto Obstétrico/métodos , Feminino , Humanos , Recém-Nascido , Entrevistas como Assunto , Pessoa de Meia-Idade , Limitação da Mobilidade , Gravidez , Pesquisa Qualitativa , Estados Unidos
11.
Am J Obstet Gynecol ; 215(3): B17-22, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27560600

RESUMO

This document builds upon recommendations from peer organizations and outlines a process for identifying maternal cases that should be reviewed. Severe maternal morbidity is associated with a high rate of preventability, similar to that of maternal mortality. It also can be considered a near miss for maternal mortality because without identification and treatment, in some cases, these conditions would lead to maternal death. Identifying severe morbidity is, therefore, important for preventing such injuries that lead to mortality and for highlighting opportunities to avoid repeat injuries. The two-step screen and review process described in this document is intended to efficiently detect severe maternal morbidity in women and to ensure that each case undergoes a review to determine whether there were opportunities for improvement in care. Like cases of maternal mortality, cases of severe maternal morbidity merit quality review. In the absence of consensus on a comprehensive list of conditions that represent severe maternal morbidity, institutions and systems should either adopt an existing screening criteria or create their own list of outcomes that merit review.


Assuntos
Complicações na Gravidez/diagnóstico , Cuidado Pré-Natal/normas , Qualidade da Assistência à Saúde/normas , Feminino , Humanos , Morte Materna , Mortalidade Materna , Gravidez
12.
Am J Obstet Gynecol ; 214(5): 607.e1-607.e12, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26704895

RESUMO

BACKGROUND: Hospital readmissions are costly, frequent, and increasingly under public scrutiny. With increased financial constraints on the medical environment, understanding the drivers of unscheduled readmissions following gynecologic surgery will become increasingly important to value-driven care. OBJECTIVE: The current study was conducted to identify risk factors for 30-day readmission following hysterectomy for benign and malignant indications. STUDY DESIGN: A retrospective cohort study was conducted from 2008 through 2010 of all nongravid hysterectomies at a single tertiary care academic medical center. Clinical, perioperative, and physician characteristics were collected. Multivariable logistic regression models were used to identify predictors of 30-day readmission, stratified by malignant and benign indications for hysterectomy. RESULTS: Among 1649 women who underwent a hysterectomy (1009 for benign indications and 640 for malignancy), 6% were subsequently readmitted within 30 days (8.9% for malignancy vs 4.2% for benign; P < .0001). The mean time to readmission was 13 days (15 days for malignancy vs 10 days for benign; P = .004). The most common reasons for readmission were gastrointestinal (38%) and infectious (34%) etiologies, and 11.6% of readmitted patients experienced a perioperative complication. Among women undergoing hysterectomy for benign indications, a history of a laparotomy, including cesarean delivery (adjusted odds ratio [AOR], 2.12; 95% confidence interval [CI], 1.06-4.25; P = .03), as well as a perioperative complication (AOR, 2.41; 95% CI, 1.00-6.04; P = .05) were both associated with a >2-fold increased odds of readmission. Among women undergoing hysterectomy for malignancy, an American Society of Anesthesiologists Physical Status Classification of III or IV (AOR, 1.92; 95% CI, 1.05-3.50; P = .03), a longer length of initial hospitalization (3 days AOR, 7.83; 95% CI, 1.33-45.99; P = .02), and an estimated blood loss >500 mL (AOR, 3.29; 95% CI, 1.28-8.45; P = .01) were associated with a higher odds of readmission; however, women who underwent a laparoscopic hysterectomy (AOR, 0.32; 95% CI, 0.12-0.86; P = .02) and who were discharged on postoperative day 1 (AOR, 0.16; 95% CI, 0.03-0.82; P = .02) were at a decreased risk of readmission. Physician and operative characteristics were not significant predictors of readmission. CONCLUSION: This study found that malignancy, perioperative complications, and prior open abdominal surgery, including cesarean delivery, are significant risk factors for consequent 30-day readmission following index hysterectomy. It may be possible to identify patients at highest risk for readmission at the time of hysterectomy, which can assist in developing interventions to reduce such events.


Assuntos
Doenças dos Genitais Femininos/cirurgia , Histerectomia/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Centros Médicos Acadêmicos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Cesárea/estatística & dados numéricos , Estudos de Coortes , Doenças do Sistema Digestório/etiologia , Feminino , Humanos , Histerectomia/métodos , Laparoscopia , Laparotomia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos , Centros de Atenção Terciária
13.
Am J Obstet Gynecol ; 215(2): B2-B12.e1, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27103153

RESUMO

Approximately 0.5% of all births occur before the third trimester of pregnancy, and these very early deliveries result in the majority of neonatal deaths and more than 40% of infant deaths. A recent executive summary of proceedings from a joint workshop defined periviable birth as delivery occurring from 20 0/7 weeks to 25 6/7 weeks of gestation. When delivery is anticipated near the limit of viability, families and health care teams are faced with complex and ethically challenging decisions. Multiple factors have been found to be associated with short-term and long-term outcomes of periviable births in addition to gestational age at birth. These include, but are not limited to, nonmodifiable factors (eg, fetal sex, weight, plurality), potentially modifiable antepartum and intrapartum factors (eg, location of delivery, intent to intervene by cesarean delivery or induction for delivery, administration of antenatal corticosteroids and magnesium sulfate), and postnatal management (eg, starting or withholding and continuing or withdrawing intensive care after birth). Antepartum and intrapartum management options vary depending upon the specific circumstances but may include short-term tocolytic therapy for preterm labor to allow time for administration of antenatal steroids, antibiotics to prolong latency after preterm premature rupture of membranes or for intrapartum group B streptococci prophylaxis, and delivery, including cesarean delivery, for concern regarding fetal well-being or fetal malpresentation. Whenever possible, periviable births for which maternal or neonatal intervention is planned should occur in centers that offer expertise in maternal and neonatal care and the needed infrastructure, including intensive care units, to support such services. This document describes newborn outcomes after periviable birth, provides current evidence and recommendations regarding interventions in this setting, and provides an outline for family counseling with the goal of incorporating informed patient preferences. Its intent is to provide support and guidance regarding decisions, including declining and accepting interventions and therapies, based on individual circumstances and patient values.


Assuntos
Viabilidade Fetal , Apresentação no Trabalho de Parto , Trabalho de Parto Prematuro , Resultado da Gravidez , Aconselhamento , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Mortalidade Perinatal , Gravidez
14.
Am J Obstet Gynecol ; 212(4): 456.e1-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25530596

RESUMO

Physicians across the United States are engaged in training in the identification, isolation, and initial care of patients with Ebola. Some will be asked to do more. The issue this viewpoint will address is the moral obligation of physicians to participate in these activities. In order to do so the implicit contract between society and its physicians will be considered, as will many of the arguments that are redolent of those that were litigated 30 years ago when acquired immune deficiency syndrome (AIDS) was raising public fears to similar levels, and some physicians were publically proclaiming their unwillingness to render care to those individuals. We will build the case that if steps are taken to reduce risks-optimal personal protective equipment and training-to what is essentially the lowest possible level then rendering care should be seen as obligatory. If not, as in the AIDS era there will be an unfair distribution of risk, with those who take their obligations seriously having to go beyond their fair measure of exposure. It would also potentially undermine patients' faith in the altruism of physicians and thereby degrade the esteem in which our profession is held and the trust that underpins the therapeutic relationship. Finally there is an implicit contract with society. Society gives tremendously to us; we encumber a debt from all society does and offers, a debt for which recompense is rarely sought. The mosaic of moral, historical, and professional imperatives to render care to the infected all echoes the words of medicine's moral leaders in the AIDS epidemic. Arnold Relman perhaps put it most succinctly, "the risk of contracting the patient's disease is one of the risks that is inherent in the profession of medicine. Physicians who are not willing to accept that risk…ought not be in the practice of medicine."


Assuntos
Síndrome da Imunodeficiência Adquirida/terapia , Altruísmo , Atitude do Pessoal de Saúde , Ética Médica , Doença pelo Vírus Ebola/terapia , Obrigações Morais , Recusa em Tratar/ética , Humanos , Relações Médico-Paciente/ética , Médicos/ética , Médicos/psicologia , Estados Unidos
15.
Am J Obstet Gynecol ; 212(3): 337.e1-14, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25265405

RESUMO

OBJECTIVE: Chronic hypertension is a common medical condition in pregnancy. The purpose of the study was to examine the association between maternal chronic hypertension and the risk of congenital malformations in the offspring. STUDY DESIGN: We defined a cohort of 878,126 completed pregnancies linked to infant medical records using the Medicaid Analytic Extract. The risk of congenital malformations was compared between normotensive controls and those with treated and untreated chronic hypertension. Confounding was addressed using propensity score matching. RESULTS: After matching, compared with normotensive controls, pregnancies complicated by treated chronic hypertension were at increased risk of congenital malformations (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.5), as were pregnancies with untreated chronic hypertension (OR 1.2; 95% CI, 1.1-1.3). In our analysis of organ-specific malformations, both treated and untreated chronic hypertension was associated with a significant increase in the risk of cardiac malformations (OR, 1.6; 95% CI, 1.4-1.9 and OR, 1.5; 95% CI, 1.3-1.7, respectively). These associations persisted across a range of sensitivity analyses. CONCLUSION: There is a similar increase in the risk of congenital malformations (particularly cardiac malformations) associated with treated and untreated chronic hypertension that is independent of measured confounders. Studies evaluating the teratogenic potential of antihypertensive medications must control for confounding by indication. Fetuses and neonates of mothers with chronic hypertension should be carefully evaluated for potential malformations, particularly cardiac defects.


Assuntos
Anormalidades Congênitas/etiologia , Hipertensão , Complicações Cardiovasculares na Gravidez , Adolescente , Adulto , Anti-Hipertensivos/uso terapêutico , Doença Crônica , Estudos de Coortes , Feminino , Cardiopatias Congênitas/etiologia , Humanos , Hipertensão/tratamento farmacológico , Recém-Nascido , Modelos Logísticos , Razão de Chances , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Pontuação de Propensão , Fatores de Risco , Adulto Jovem
16.
Am J Obstet Gynecol ; 213(5): 604-14, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26506448

RESUMO

Approximately 0.5% of all births occur before the third trimester of pregnancy, and these very early deliveries result in the majority of neonatal deaths and more than 40% of infant deaths. A recent executive summary of proceedings from a joint workshop defined periviable birth as delivery occurring from 20 0/7 weeks to 25 6/7 weeks of gestation. When delivery is anticipated near the limit of viability, families and health care teams are faced with complex and ethically challenging decisions. Multiple factors have been found to be associated with short-term and long-term outcomes of periviable births in addition to gestational age at birth. These include, but are not limited to, nonmodifiable factors (eg, fetal sex, weight, plurality), potentially modifiable antepartum and intrapartum factors (eg, location of delivery, intent to intervene by cesarean delivery or induction for delivery, administration of antenatal corticosteroids and magnesium sulfate), and postnatal management (eg, starting or withholding and continuing or withdrawing intensive care after birth). Antepartum and intrapartum management options vary depending upon the specific circumstances but may include short-term tocolytic therapy for preterm labor to allow time for administration of antenatal steroids, antibiotics to prolong latency after preterm premature rupture of membranes or for intrapartum group B streptococci prophylaxis, and delivery, including cesarean delivery, for concern regarding fetal well-being or fetal malpresentation. Whenever possible, periviable births for which maternal or neonatal intervention is planned should occur in centers that offer expertise in maternal and neonatal care and the needed infrastructure, including intensive care units, to support such services. This document describes newborn outcomes after periviable birth, provides current evidence and recommendations regarding interventions in this setting, and provides an outline for family counseling with the goal of incorporating informed patient preferences. Its intent is to provide support and guidance regarding decisions, including declining and accepting interventions and therapies, based on individual circumstances and patient values.

17.
Depress Anxiety ; 32(10): 774-82, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26130074

RESUMO

INTRODUCTION: The relationship between gestational diabetes mellitus (GDM) and postpregnancy mental health disorders has been inconsistently reported. Additionally, race/ethnicity data are limited. We sought to elucidate the intersection of these relationships. METHODS: We analyzed 18,109 women aged 18-40 with self-reported race/ethnicity. Women with (n = 659) and without (n = 14,461) GDM were followed for a median of 4.4 (interquartile range 1.4-6.8) and 4.0 (1.5-6.4) years, respectively, for incident mental health disorders. Multivariable repeated measures analyses were conducted to examine associations between GDM and postpregnancy mental health disorders, race/ethnicity, and the interaction of these factors. RESULTS: Women with compared to women without GDM were older (mean ± standard deviation, 32 ± 5 vs. 30 ± 5 years; P < .001) and had higher body mass index (29.0 ± 7.2 vs. 25.3 ± 5.2 kg/m(2) ; P < .001). GDM was associated with increased risk for depression and anxiety after adjusting for age and pregnancy complications; however, loss of significance in the fully adjusted model for depression (odds ratio [95% CI]: 1.29 [0.98, 1.70]; P = .064) and anxiety (1.14 [0.83, 1.57], P = .421) suggested that clinical and socioeconomic factors influence this relationship. Hispanic compared to white women had a greater risk for depression (1.40 [1.15, 1.72]; P = .001), even after multivariable adjustment. The interaction between GDM and race was evident in complication-adjusted but not fully adjusted models. CONCLUSIONS: The incidence of mental health disorders subsequent to GDM was attenuated after adjustment for clinical and socioeconomic factors. Moreover, race/ethnicity influenced this relationship. Further investigation is warranted to clarify potential underlying mechanisms.


Assuntos
Diabetes Gestacional/psicologia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Transtornos Mentais/etnologia , Complicações na Gravidez/psicologia , População Branca/psicologia , População Branca/estatística & dados numéricos , Adulto , Índice de Massa Corporal , Diabetes Gestacional/epidemiologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Incidência , Razão de Chances , Gravidez , Complicações na Gravidez/epidemiologia , Risco
18.
Acta Obstet Gynecol Scand ; 94(2): 133-40, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25417861

RESUMO

OBJECTIVE: Little is known about how functional impairments might affect the pregnancies of women with mobility disability. We aimed to explore complications that arise during pregnancy that are specifically related to physical functional impairments of women with significant mobility disabilities. DESIGN: Qualitative descriptive analysis. SETTING: Telephone interviews with women from 17 USA states. SAMPLE: 22 women with significant mobility difficulties who had delivered babies within the prior 10 years; most participants were recruited through social networks. METHODS: We conducted 2-h, in-depth telephone interviews using a semi-structured, open-ended interview protocol. We used NVIVO software to sort interview transcript texts for conventional content analyses. MAIN OUTCOME MEASURES: Functional impairment-related complications during pregnancy. RESULTS: The women's mean (standard deviation) age was 34.8 (5.3) years. Most were white, well-educated, and higher income; eight women had spinal cord injuries, four cerebral palsy, and 10 had other conditions; 18 used wheeled mobility aids; and 14 had cesarean deliveries (eight elective). Impairment-related complications during pregnancy included: falls; urinary tract and bladder problems; wheelchair fit and stability problems that reduced mobility and compromised safety; significant shortness of breath, sometimes requiring respiratory support; increased spasticity; bowel management difficulties; and skin integrity problems (this was rare, but many women greatly increased skin monitoring during pregnancy to prevent pressure ulcers). CONCLUSIONS: In addition to other pregnancy-associated health risks, women with mobility disabilities appear to experience problems relating to their functional impairments. Pre-conception planning and in-depth discussions during early pregnancy could potentially assist women with mobility disabilities to anticipate and address these difficulties.


Assuntos
Pessoas com Deficiência , Limitação da Mobilidade , Complicações na Gravidez , Resultado da Gravidez , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Traumatismos da Medula Espinal , Vértebras Torácicas/lesões , Infecções Urinárias
19.
Matern Child Health J ; 19(6): 1364-75, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25421328

RESUMO

Growing numbers of reproductive-age US women with chronic physical disabilities (CPD) raise questions about their pregnancy experiences. Little is known about the health risks of women with versus without CPD by current pregnancy status. We analyzed cross-sectional, nationally-representative National Health Interview Survey data from 2006 to 2011, which includes 47,629 civilian, noninstitutionalized women ages 18-49. NHIS asks about specified movement difficulties, current pregnancy, and various health and health risk indicators, including tobacco use and body mass index (BMI). We used responses from eight movement difficulty and other questions to identify women with mobility difficulties caused by chronic physical health conditions. Across all women regardless of CPD, women reporting current pregnancy are significantly less likely to currently smoke tobacco and report certain mental health problems. Among currently pregnant women only, women with CPD are more likely to smoke cigarettes every day (12.2 %) versus 6.3 % for pregnant women without CPD (p ≤ 0.001). Among currently pregnant women, 17.7 % of women with CPD have BMIs in the non-overweight range, compared with 40.1 % of women without CPD (p ≤ 0.0001). Currently pregnant women with CPD are significantly more likely to report having any mental health problems, 66.6 % compared with 29.7 % among women without CPD (p ≤ 0.0001). For all women, currently pregnant women appear to have fewer health risks and mental health concerns than nonpregnant women. Among pregnant women, women with CPD have higher rates than other women of health risk factors that could affect maternal and infant outcomes.


Assuntos
Pessoas com Deficiência/estatística & dados numéricos , Nível de Saúde , Saúde Mental/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Gravidez , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Adulto Jovem
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