Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness,research, and response

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely – and at times uniquely – affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group – a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy – in consultation with a variety of external experts and stakeholders.     

The peril and promise of sensitivity in eating disorders

Differential susceptibility, a reconceptualization of the diathesis-stress model of psychopathology, describes gene–environment interactions that reflect individual differences in responsiveness to environmental influences, both detrimental and beneficial. This model has been described metaphorically by the classification of orchids, which thrive under optimal care but wither under adverse conditions, and dandelions, which weather broad environmental circumstances but are less responsive to careful cultivation. Etiological research in the field of eating disorders has largely focused on the identification of specific behavioral phenotypes, temperamental traits, genotypes and neurobiological processes that confer risk. In this article, we propose that these putative vulnerability factors represent phenotypes and endophenotypes of a genetic predisposition towards environmental sensitivity. We assert that this sensitivity not only transmits eating disorder risk but also confers resilience, depending on the circumstances. In particular, we propose that differential susceptibility can be used as a framework to organize disparate temperamental and neurobiological findings and their complex interplay with various developmental, environmental and sociocultural influences to increase eating disorder risk and treatment responsiveness. Finally, we assert that viewed through the lens of differential susceptibility, sensitivity can be leveraged to refine our interventions and develop novel treatment and prevention strategies to support favorable outcomes for individuals with eating disorders.     

Succinylcholine and vecuronium blockade of the diaphragm,laryngeal and limb muscles in the anaesthetized goat

The purpose of the study was to compare the response of the cricoarytenoideus dorsalis muscle (CD) to neuromuscular blocking drugs with those of the thyroarytenoideus (TA), diaphragm (DI) and ulnaris lateralis (UL) muscles. Evoked electromyographic response to indirect supramaximal stimulation at 1 Hz was monitored in ten adult goats under thiopentone-halothane anaesthesia. The onset time and duration of neuromuscular blockade after intravenous administration of 500 μg · kg^?1 of succinylcholine or 4 μg · kg^?1 of vecuronium were determined. Times to 100% paralysis in CD, TA, DI and UL after succinylcholine were (mean ± SD) 39 ± 11, 39 ± 11, 42 ± 8 and 57 ± 8 seconds, respectively; the corresponding times for vecuronium were 5.6 ± 2.3, 4.6 ± 1.7, 6.0 ± 1.9 and 9.6 ± 1.7 min. The order of recovery to 25% spontaneous EMG activity was TA, CD, DI and UL after succinylcholine (durations: 9.7 ± 3.6, 11.0 ± 3.0, 15.3 ± 1.3 and 22.0 ± 1.2 min, respectively) but DI, CD, TA and UL after vecuronium (durations: 31.9 ± 18.6, 35.2 ± 19.5, 47.1 ± 19.9 and 71.7 ± 16.1 minutes, respectively). Thus, as in the diaphragm and thyroarytenoideus muscles, onset time and duration of succinylcholine or vecuronium blockade were shorter in the abductor muscle of the glottis, cricoarytenoideus dorsalis, than in the limb muscle.     

Oral ondansetron decreases vomiting after tonsillectomy in children

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our doubleblind, placebocontrolled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2–14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg · kg^?1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N₂O. Vecuronium 0.1 mg · kg^?1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N₂O, 50 μg · kg^?1 midazolam iv and 1–1.5 mg · kg^?1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of inhospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg · kg^?1 dimenhydrinate ivfor vomiting × 2 and 50 μg · kg^?1 droperidol iv for vomiting × 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic inhospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.     

Wound cleansing by irrigation for implant surgery

Wound irrigation is an adjunct to all implant surgeries involving surgical incisions or arthroplasties. An understanding of the physics of wound irrigation provides a scientific basis for recommending wound irrigation systems for implant surgery. When inserting implants through surgical incisions, a low-pressure irrigation system is recommended for removing blood from the wound surface. In contrast, high-pressure irrigation systems are indicated to cleanse the intramedullary canal before cemented arthroplasty. With the advent of static and dynamic pressure transducers, irrigation systems can now be specifically designed to achieve these goals.     

The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium

Contraceptive use often leads to disrupted endometrial bleeding patterns in women. In this study, two different contraceptive regimes (Mircette, a monophasic oral contraceptive and Implanon, a long-acting gestagen) were used and their effects on the immunoreactivity of vascular endothelial growth factor (VEGF), oestrogen receptor (ER), progesterone receptor (PR) and endothelial cell number were determined. During the untreated normal cycle, there was a significant increase (P = 0.005) in glandular VEGF immunoreactivity and a significant decrease (P < 0.05) in PR immunoreactivity in the mid- and late secretory phases compared with the proliferative phase. There was a significant positive correlation (gamma = 0.38, P = 0.046) between stromal VEGF immunoreactivity and endothelial cell number. This correlation was also apparent during treatment with Implanon, but not with Mircette. Disrupted bleeding patterns were associated with Implanon and, to a lesser extent, with Mircette. Both contraceptives significantly reduced glandular VEGF immunoreactivity. Implanon significantly increased (P = 0.016) glandular PR staining, but Mircette significantly reduced (P = 0.027) stromal PR staining when compared with secretory before-treatment biopsies. There were no changes in endothelial cell number or glandular or stromal ER during the normal cycle, or with use of either contraceptive. There was no association between the parameters measured with bleeding patterns and histological category.     

Plexiform neurofibroma of the small bowel infiltrated with metastatic adenocarcinoma

Neurofibromatosis Type 1 (NF1) is not classically associated with gastrointestinal manifestations although these patients are at increased risk of several GI complications. We describe the ultrasound, CT and barium findings in a patient with NF1 who had a huge benign plexiform neurofibroma of the ileum that was infiltrated with metastatic adenocarcinoma.