Elective delivery at 34 weeks vs routine obstetric care in fetal gastroschisis: randomized controlled trial.

OBJECTIVE: To evaluate whether elective preterm delivery (ED) at 34 weeks is of postnatal benefit to infants with isolated gastroschisis compared with routine obstetric care (RC). METHODS: Between May 2013 and September 2015, all women with a sonographic diagnosis of fetal gastroschisis referred to a single tertiary center, before 34 weeks' gestation, were invited to participate in this study. Eligible patients were randomized to ED (induction of labor at 34 weeks) or RC (spontaneous labor or delivery by 37-38 weeks, based on standard obstetric indications). The primary outcome measure was length of time on total parenteral nutrition (TPN). Secondary outcomes were time to closure of gastroschisis and length of stay in hospital. Outcome variables were compared using appropriate statistical methods. Analysis was based on intention-to-treat. RESULTS: Twenty-five women were assessed for eligibility, of whom 21 (84%; 95% CI, 63.9-95.5%) agreed to participate in the study; of these, 10 were randomized to ED and 11 to RC. The trial was stopped at the first planned interim analysis due to patient safety concerns and for futility; thus, only 21 of the expected 86 patients (24.4%; 95% CI, 15.8-34.9%) were enrolled. Median gestational age at delivery was 34.3 (range, 34-36) weeks in the ED group and 36.7 (range, 27-38) weeks in the RC group. One patient in the ED group delivered at 36 weeks following unsuccessful induction at 34 weeks. Neonates of women who underwent ED, compared to those in the RC group, showed no difference in the median number of days on TPN (54 (range, 17-248) vs 21 (range, 9-465) days; P = 0.08), number of days to closure of gastroschisis (7 (range, 0-15) vs 5 (range, 0-8) days; P = 0.28) and length of stay in hospital (70.5 (range, 22-137) vs 31 (range, 19-186) days; P = 0.15). However, neonates in the ED group were significantly more likely to experience late-onset sepsis compared with those in the RC group (40% (95% CI, 12.2-73.8%) vs 0%; P = 0.03). CONCLUSION: This study demonstrates no benefit of ED of fetuses with gastroschisis when postnatal gastroschisis management is similar to that used in routine care. Rather, the data suggest that ED is detrimental to infants with gastroschisis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Parto inducido a las 34 semanas versus atención obstétrica rutinaria en la gastrosquisis fetal: ensayo controlado aleatorizado OBJETIVO: Evaluar si el parto pretérmino inducido (PI) a las 34 semanas es beneficioso para los recién nacidos con gastrosquisis aislada en comparación con la atención obstétrica rutinaria (AR). MÉTODOS: Entre mayo de 2013 y septiembre de 2015, se invitó a participar en este estudio a todas las mujeres con diagnóstico ecográfico de gastrosquisis fetal remitidas a un mismo centro terciario, antes de las 34 semanas de gestación. Las pacientes elegibles fueron asignadas al azar al PI (inducción del parto a las 34 semanas) o a la AR (parto espontáneo a las 37-38 semanas, en función de los indicios obstétricos estándar). La medida de resultado primaria fue la duración de la nutrición parenteral total (NPT). Las medidas de resultado secundarias fueron el tiempo hasta el cierre de la gastrosquisis y la duración de la estancia hospitalaria. Las variables de resultado se compararon mediante métodos estadísticos apropiados. El análisis se basó en la intención de tratar. RESULTADOS: Se evaluó la elegibilidad de 25 mujeres, de las cuales 21 (84%; IC 95%, 63,9-95,5%) aceptaron participar en el estudio; de ellas, 10 fueron asignadas al azar al PI y 11 a la AR. El ensayo se detuvo después del primer análisis provisional planificado debido a preocupaciones sobre la seguridad de las pacientes y por su intrascendencia; por lo tanto, sólo se reclutaron 21 de las 86 pacientes esperadas (24,4%; IC 95%, 15,8-34,9%). La mediana de la edad gestacional en el momento del parto fue de 34,3 (rango: 34-36) semanas en el grupo de PI y 36,7 (rango: 27-38) semanas en el grupo de AR. Una paciente del grupo de PI tuvo un parto a las 36 semanas, después de una inducción infructuosa a las 34 semanas. Los neonatos de las mujeres que se sometieron a PI, comparados con los del grupo de AR, no mostraron diferencias en la mediana del número de días de NPT (54 (rango: 17-248) vs 21 (rango: 9-465) días; P=0,08), número de días hasta el cierre de la gastrosquisis (7 (rango: 0-15) vs 5 (rango: 0-8) días; P=0,28) y duración de la estancia hospitalaria (70,5 (rango: 22-137) vs 31 (rango: 19-186) días; P=0,15). Sin embargo, la probabilidad de experimentar sepsis de inicio tardío fue mayor en los neonatos del grupo de PI en comparación el grupo de AR (40% (IC 95%, 12,2-73,8%) vs 0%; P=0,03). CONCLUSIÓN: Este estudio demuestra que el PI no presenta ningún beneficio para los fetos con gastrosquisis cuando el tratamiento de la gastrosquisis postnatal es similar al utilizado en la atención rutinaria. Más bien, los datos sugieren que el PI es perjudicial para los lactantes con gastrosquisis.

Outcomes of early carotid stenting and angioplasty in large-vessel anterior circulation strokes treated with mechanical thrombectomy and intravenous thrombolytics.

Introduction Proximal cervical internal carotid artery stenosis greater than 50% merits revascularization to mitigate the risk of stroke recurrence among large-vessel anterior circulation strokes undergoing mechanical thrombectomy. Carotid artery stenting necessitates the use of antiplatelets, and there is a theoretical increased risk of hemorrhagic transformation given that such patients may already have received intravenous thrombolytics and have a significant infarct burden. We investigate the outcomes of large-vessel anterior circulation stroke patients treated with intravenous thrombolytics receiving same-day carotid stenting or selective angioplasty compared to no carotid intervention. Materials and methods The study cohort was obtained from the National (Nationwide) Inpatient Sample database between 2006 and 2014, using International Statistical Classification of Diseases, ninth revision discharge diagnosis and procedure codes. A total of 11,825 patients with large-vessel anterior circulation stroke treated with intravenous thrombolytic and mechanical thrombectomy on the same day were identified. The study population was subdivided into three subgroups: no carotid intervention, same-day carotid angioplasty without carotid stenting, and same-day carotid stenting. Outcomes were assessed with respect to mortality, significant disability at discharge, hemorrhagic transformation, and requirement of percutaneous endoscopic gastronomy tube placement, prolonged mechanical ventilation, or craniotomy. Results This study found no statistically significant difference in patient outcomes in those treated with concurrent carotid stenting compared to no carotid intervention in terms of morbidity or mortality. Conclusions If indicated, it is reasonable to consider concurrent carotid stenting and/or angioplasty for large-vessel anterior circulation stroke patients treated with mechanical thrombectomy who also receive intravenous thrombolytics.

RESPONDING PROFESSIONALLY TO REQUESTS FOR CESAREAN DELIVERY.

Patients' requests for non-indicated cesarean delivery challenge the professionalism of obstetricians. This is because physicians should not provide clinical management in the absence of an evidence-based indication for it. The ethics of responding professionally to requests for non-indicated cesarean delivery would appear to be simple: just say "No." This paper presents an ethically and clinically more nuanced approach, on the basis of the professional responsibility model of obstetric ethics, emphasizinga preventive ethics approach. Preventive ethics deploys the informed consent process to minimize ethical conflict in clinical practice. This process should focus on when to recommend against cesarean delivery - rather than simply saying no. There is no evidence of net clinical benefit for pregnant, fetal, and neonatal patients from non-indicated cesarean delivery. Obstetricians should therefore respond to such requests by recommending against cesarean delivery, recommending vaginal delivery, and explaining the evidence base for these recommendations.

Three decades after Baby Doe: how neonatologists and bioethicists conceptualize the Best Interests Standard.

OBJECTIVE: The objective of this study is to determine how neonatologists and bioethicists conceptualize and apply the Best Interests Standard (BIS). STUDY DESIGN: Members of the American Society for Bioethics and Humanities and the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine were surveyed to determine how they conceptualized the BIS and ranked the appropriateness of forgoing life-sustaining therapy (LST). RESULTS: Neonatologists' median response supported an infant-specific BIS conceptualization that linked the infant's and family's interests. They did not support allowing limitations on the family's obligations. Ethicists' supported a conceptualization that linked the infant's and family's interests and limitations on the family's obligations, a less infant-specific conceptualization. Ethicists were less or equally likely to agree with forgoing LST in seven of eight cases. CONCLUSIONS: Ethicists endorsed a conceptualization of the BIS that includes the effects on the family and rejected an infant-specific one. Neonatologists split between these two and rejected limiting the family's obligations. Critical appraisal of the BIS is needed in neonatal ethics.

Femoral vein injury from a trochanteric hip fracture.

A case of a comminuted trochanteric fracture where the lesser trochanteric fragment had displaced significantly injuring and becoming lodged within the common femoral vein.

Social interaction plays a critical role in neurogenesis and recovery after stroke.

Stroke survivors often experience social isolation. Social interaction improves quality of life and decreases mortality after stroke. Male mice (20-25 g; C57BL/6N), all initially pair housed, were subjected to middle cerebral artery occlusion (MCAO). Mice were subsequently assigned into one of three housing conditions: (1) Isolated (SI); (2) Paired with their original cage mate who was also subjected to stroke (stroke partner (PH-SP)); or (3) Paired with their original cage mate who underwent sham surgery (healthy partner (PH-HP)). Infarct analysis was performed 72 h after stroke and chronic survival was assessed at day 30. Immediate post-stroke isolation led to a significant increase in infarct size and mortality. Interestingly, mice paired with a healthy partner had significantly lower mortality than mice paired with a stroke partner, despite equivalent infarct damage. To control for changes in infarct size induced by immediate post-stroke isolation, additional cohorts were assessed that remained pair housed for three days after stroke prior to randomization. Levels of brain-derived neurotrophic factor (BDNF) were assessed at 90 days and cell proliferation (in cohorts injected with 5-bromo-2'-deoxyuridine, BrdU) was evaluated at 8 and 90 days after stroke. All mice in the delayed housing protocol had equivalent infarct volumes (SI, PH-HP and PH-SP). Mice paired with a healthy partner showed enhanced behavioral recovery compared with either isolated mice or mice paired with a stroke partner. Behavioral improvements paralleled changes in BDNF levels and neurogenesis. These findings suggest that the social environment has an important role in recovery after ischemic brain injury.

ß-Blockers associated with no class-specific survival benefit in acute intracerebral hemorrhage.

OBJECTIVES: Despite the high mortality, there is currently no specific treatment for intracerebral hemorrhage (ICH). Research investigating optimum degree of blood pressure control in patients presenting with ICH and hypertension is ongoing. However, there is limited understanding of the potential benefits of specific classes of antihypertensive therapy. ß-Adrenergic antagonists may provide neuroprotection from inflammation-induced injury by inhibiting sympathetic nervous system mediated immune activation. We examined mortality in ICH patients receiving ß-adrenergic antagonists to determine whether this class of antihypertensive therapy was associated with improved survival. METHODS: A retrospective analysis of a large, prospectively collected database of patients presenting with acute ICH was performed. Patients were grouped by inpatient ß-blocker treatment to determine an effect on mortality during the inpatient stay and at 3 months of follow-up. Additional analysis was conducted comparing ß-blocker therapy to any other antihypertensive treatment to determine a class-specific association of ß-blocker treatment with mortality. RESULTS: The study population included 426 patients with acute, spontaneous ICH. Inpatient ß-blocker use was independently associated with decreased rates of inpatient death and mortality at 3 months of follow-up. However, univariate and multivariable analyses comparing ß-blocker use to other antihypertensives failed to show any class-specific reduction in mortality at either time point. DISCUSSION: Our study demonstrates that the improvement seen in patients treated with ß-adrenergic antagonists is not an effect unique to this class. This supports ongoing trials to determine optimum levels of blood pressure control using multiple classes of antihypertensives.

NAD+ and nicotinamide: sex differences in cerebral ischemia.

BACKGROUND: Previous literature suggests that cell death pathways activated after cerebral ischemia differ between the sexes. While caspase-dependent mechanisms predominate in the female brain, caspase-independent cell death induced by the activation of poly(ADP-ribose) polymerase (PARP) predominates in the male brain. PARP-1 gene deletion decreases infarction volume in the male brain, but paradoxically increases damage in PARP-1 knockout females. PURPOSE: This study examined stroke-induced changes in NAD+, a key energy molecule involved in PARP-1 activation in both sexes. METHODS: Mice were subjected to middle cerebral artery occlusion and NAD+ levels were assessed. Caspase-3 activity and nuclear translocation were assessed 6h after ischemia. In additional cohorts, Nicotinamide (500 mg/kg i.p.) a precursor of NAD+ or vehicle was administered and infarction volume was measured 24h after ischemia. RESULTS: Males have higher baseline NAD+ levels than females. Significant stroke-induced NAD+ depletion occurred in males and ovariectomized females but not in intact females. PARP-1 deletion prevented the stroke-induced loss in NAD+ in males, but worsened NAD+ loss in PARP-1 deficient females. Preventing NAD+ loss with nicotinamide reduced infarct in wild-type males and PARP-1 knockout mice of both sexes, with no effect in WT females. Caspase-3 activity was significantly increased in PARP-1 knockout females compared to males and wild-type females, this was reversed with nicotinamide. CONCLUSIONS: Sex differences exist in baseline and stroke-induced NAD+ levels. Nicotinamide protected males and PARP knockout mice, but had minimal effects in the wild-type female brain. This may be secondary to differences in energy metabolism between the sexes.

[Planned non-hospital births in industrialized countries: bureaucratic dream vs. professional responsibility]. / Die geplante Hausgeburt in industrialisierten Ländern: Bürokratische Traumvorstellung vs. professionelle Verantwortlichkeit.

This article addresses in how far planned non-hospital births should be an alternative to planned hospital births. Advocates of planned non-hospital deliveries have emphasised patient safety, patient satisfaction, cost effectiveness, and respect for women's rights. We provide a critical evaluation of each of these claims and have doubts that the information available for the pregnant women and the public is in accord with professional responsibility. We understand that the increasing rates of interventions and operative deliveries in hospital births demand an answer, but we doubt that planned home birth is the appropriate professional solution. Complications during non-hospital births inevitably demand a transport of mother and child to a perinatal centre. The time delay by itself is an unnecessary risk for both and this cannot be abolished by bureaucratic quality criteria as introduced for non-hospital births in Germany. Evidence-based studies have shown that modern knowledge of the course of delivery including ultrasound as well as intensive care during the delivery all reduce the rate of operative deliveries. Unfortunately, this is not well-known and only rarely considered during any delivery. All these facts, however, are the best arguments to find a cooperative model within perinatal centres to combine the art of midwifery with modern science, reduction of pain and perinatal care of the pregnant women before, during and after birth. We therefore call on obstetricians, midwifes and health-care providers as well as health politicians to carefully analyse the studies from Western countries showing increasing risks if the model of intention-to-treat is considered and accoordingly not to support planned non-hospital births nor to include these models into prospective trials. Alternatively, we recommend the introduction of a home-like climate within hospitals and perinatal centres, to avoid unnecessary invasive measures and to really care for the pregnant mother before, during and after delivery within a cooperative model without the lack of patient safety for both mother and child in case of impending or acute emergencies.

Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet.

UNLABELLED: Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy. INTRODUCTION: We report the results of a randomized, controlled, clinical study assessing the efficacy and safety of a delayed-release (DR) 35 mg weekly oral formulation of risedronate that allows patients to take their weekly risedronate dose before or immediately after breakfast. METHODS: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg immediate-release (IR) daily (n = 307) at least 30 min before breakfast, or risedronate 35 mg DR weekly, either at least 30 min before breakfast (BB, n = 308) or immediately following breakfast (FB, n = 307). Bone mineral density (BMD), bone turnover markers (BTMs), fractures, and adverse events were evaluated. The primary efficacy variable was percent change from baseline in lumbar spine BMD at Endpoint. RESULTS: Two hundred fifty-seven subjects (83.7%) in the IR daily group, 252 subjects (82.1%) in the DR FB weekly group, and 258 subjects (83.8%) in the DR BB weekly group completed 1 year. Both DR weekly groups were determined to be non-inferior to the IR daily regimen. Mean percent changes in hip BMD were similar across groups. The magnitude of BTM response was similar across groups; some statistical differences were seen that were small and deemed by investigators to have no major clinical importance. The incidence of adverse events leading to withdrawal and serious adverse events were similar across treatment groups. All three regimens were well tolerated. CONCLUSIONS: Risedronate 35 mg DR weekly is similar in efficacy and safety to risedronate 5 mg IR daily, and will allow patients to take their weekly risedronate dose immediately after breakfast.

Biopsychosocial risks of parental care for high-risk neonates: implications for evidence-based parental counseling.

OBJECTIVE: Provide an evidence base for counseling parents of high-risk neonates about the biopsychosocial impact of providing long-term care. STUDY DESIGN: A review of the effects of long-term care on families of high-risk neonates. Our search was limited to 1993-2010. We used the terms 'long-term care,' 'family,' 'neonate' and 'technology dependence.' Results were organized based on Engel's biopsychosocial model. RESULT: Physical-parental caregivers reported more health problems, had fewer health-promoting behaviors and lower vitality.Psychological-parental caregivers had higher rates of post-traumatic stress disorder and depressive symptoms, although some improved with time. Siblings reported greater stress and depression. Social-parental caregivers achieved fewer years of education, higher unemployment and lower incomes. Couples reported greater family strain. The effect on divorce was mixed. Siblings reported disruption in their academic and social lives. CONCLUSION: Providing long-term care involves biopsychosocial risks. Counseling of parents should identify them and advocate strategies for prevention.