Successful management with C1-inhibitor concentrate of hereditary angioedema attacks during two successive pregnancies: a case report

Backgroud Hereditary angioedema (HAE) is a rare genetic disorder caused by a deficiency of the plasma protein C1 inhibitor (C1-INH). HAE is characterised by the onset of angioedema, which may develop in one or several organs, and may last from a few hours to several days. Oedema of the upper airway can be life-threatening. As a result of hormonal changes, some women experience more frequent angioedema attacks during pregnancy. During pregnancy, antifibrinolytic agents should only be used with caution, and attenuated androgens are contraindicated; therefore, replacement therapy with C1-INH concentrate represents one of few therapeutic options, but it is not widely documented. Case study We report the first case study of the successful management with regular infusions of C1-INH concentrate, of two successive pregnancies in a patient with HAE. During the second half of the first pregnancy, C1-INH was administered on demand at home. For the second pregnancy, on demand treatment was intensified to prophylactic therapy, with once or twice weekly infusions from the middle of the second trimester in order to efficiently control the frequent attacks. Conclusions This report illustrates that HAE can be successfully managed during pregnancy with C1-INH infusions at home. Since the number of crises may vary between pregnancies, the treatment regimen must be adapted to the patient’s need.     

The effect of learning to drum on behavior and brain function in autistic adolescents

This current study aimed to investigate the impact of drum training on behavior and brain function in autistic adolescents with no prior drumming experience. Thirty-six autistic adolescents were recruited and randomly assigned to one of two groups. The drum group received individual drum tuition (two lessons per week over an 8-wk period), while the control group did not. All participants attended a testing session before and after the 8-wk period. Each session included a drumming assessment, an MRI scan, and a parent completing questionnaires relating to the participants’ behavioral difficulties. Results showed that improvements in drumming performance were associated with a significant reduction in hyperactivity and inattention difficulties in drummers compared to controls. The fMRI results demonstrated increased functional connectivity in brain areas responsible for inhibitory control, action outcomes monitoring, and self-regulation. In particular, seed-to-voxel analyses revealed an increased functional connectivity in the right inferior frontal gyrus and the right dorsolateral prefrontal cortex. A multivariate pattern analysis demonstrated significant changes in the medial frontal cortex, the left and right paracingulate cortex, the subcallosal cortex, the left frontal pole, the caudate, and the left nucleus accumbens. In conclusion, this study investigates the impact of a drum-based intervention on neural and behavioral outcomes in autistic adolescents. We hope that these findings will inform further research and trials into the potential use of drum-based interventions in benefitting clinical populations with inhibition-related disorders and emotional and behavioral difficulties.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder characterized by deficits in social communication and social interactions as well as a range of restricted, repetitive interests, activities, and behaviors (1). Over recent decades, incidence estimates for ASD have increased (2), with a prevalence of 1 in 59 children in the United States (3) and over 600,000 people in the United Kingdom, which is equivalent to a population prevalence of ∼1% (4, 5). In this context of increased autism prevalence, there is an existing need to develop interventions that offer new insights and perspectives and help address the specifically high demand for services for autistic adolescents and young adults (6). [The term “autistic” is used throughout this paper because of a large percentage of the UK autism community’s preference for the identity-first construction (e.g., “autistic person”) over the person-first phrase (e.g., “person with autism”) (7).] Indeed, autistic young people often face discontinuity in care provision in the transitionary period from child and adolescent services to adult services, just when their care needs are most pressing, making their transition into adulthood particularly difficult (8). In particular, mismatches across services, such as differences in eligibility criteria or age cutoffs, mean that many autistic young adults fall through the care gap after exiting high school (8). Autistic individuals are particularly vulnerable during this period because they often face high unemployment rates, increased levels of comorbid psychiatric diagnoses such as anxiety and depression, and, more broadly, greater reliance on assistance from others when it comes to carrying out adulthood-related daily activities (9–11).A growing body of research suggests that key social domains of the ASD symptomatology may be related to atypical executive functioning (12, 13). Inhibitory control, one of the core executive functions (EFs), corresponds to the ability to delay the onset of behavioral responses, or withhold behaviors that are prepotent but contextually inappropriate (14, 15). It works in concert with other EFs, such as cognitive flexibility and working memory, to exert top-down control on behavioral responses, enable self-regulation, and help navigate social relationships, therefore supporting transition into adulthood and independent living (16, 17). More specifically, it is thought that atypical inhibitory control in autism may underlie significant strengths but may also exacerbate key features of the ASD symptomatology, such as struggling with change and uncertainty, or having difficulty interpreting social cues (18–21). Impaired performance on inhibitory control tasks is frequent in autistic individuals (12, 13, 22, 23). In particular, it has been associated with severe restricted and repetitive behaviors (19, 24, 25), as well as a deficit in proactive response slowing [the ability to slow the initiation of a behavioral response in preparation for stopping during conditions of uncertainty (19)]. At the neuroimaging level, prior studies have revealed atypical recruitment of frontal regions in autistic adolescents (20), and impaired functional connectivity (FC) of the inferior frontal junction, key regions for inhibitory control, in autistic children (26).Autistic individuals often report being preoccupied with certain topics (27) and struggling with anxiety and anger management (28, 29). In a study by Van Hees et al. (30), higher-education autistic students described feeling overwhelmed by the demands placed on them while facing significant difficulties with planning, information processing, time management, organizational skills, and sensory overload. These difficulties may reflect impaired attention and inhibition abilities, complementary processes that allow individuals to pursue the achievement of a particular goal while remaining flexibly responsive to environmental demands (21, 31). A research study on a population-based twin sample of 17,000 children (9 y to 12 y old) concluded that the vast majority of children with ASD traits also exhibit cooccurring attention deficit and hyperactivity disorder (ADHD) traits (32). More specifically, the authors demonstrated that 82% of the boys and 95% of the girls with high ASD traits on all three ASD domains (social impairments, communication impairments, and restricted repetitive behaviors and interests) exhibited difficulties on at least one of the three ADHD domains (attentional difficulties, hyperactivity, and impulsivity). Additionally, they reported that repetitive and restricted behaviors in ASD correlated with ADHD domains, particularly with impulsivity and attentional difficulties. This is in line with a previous twin study in adults, which reported the highest phenotypic and genetic overlap between ADHD traits and “nonsocial” autistic-like traits such as attention switching difficulties (33).Music has long been known to promote cognitive and emotional wellbeing in both clinical and healthy populations (34, 35). Rhythm-based musical training, in particular, has been shown to enhance higher-order cognition and motor control (31). There is growing evidence that activities designed to improve beat synchronization skills may provide an effective approach to developing neurological processes that underpin self-regulation and EF skills (36). Indeed, EF deficits have been linked with poor rhythm perception in children (37) and poor sensorimotor synchronization in young adults (38). Using the Integrated Visual and Auditory Plus Continuous Performance Test (39), Slater et al. (31) highlighted that drumming practice is associated with better scores in inhibitory control and selective attention in adult percussionists compared to nonmusicians.More specifically, learning to drum requires error monitoring and temporal accuracy and therefore both attentional and inhibitory control (31, 40). In a recent study, Lowry et al. (40) used a mixed-methods analysis to investigate behavioral changes in children with emotional and behavioral difficulties, after learning to drum. Following drum training, the participants displayed enhanced attentional focus and reduced hyperactivity and peer problems (40). These results concur with Draper et al.’s (41) recent findings showing that drumming improves motor control and attentional focus and reduces emotional and peer problems in autistic children. It is important to note that motor control is particularly relevant in the context of ASD. Indeed, recent studies have consistently demonstrated motor impairments across the autism spectrum (42, 43), including gross and fine motor difficulties (44, 45) and delays with motor planning (46). Sokhadze et al. (47) showed that ∼80% of autistic individuals also present with clumsiness or motor dyspraxia, which can manifest as having difficulty with motor coordination as well as concentration, planning, and organization. These difficulties may impact the individual’s ability to carry out daily activities, which, in turn, can lead to rejection from peers and social isolation (48). Similarly, motor impairments in balance, motor accuracy, and object manipulation scores have been reported to be predictive of social dysfunction in young autistic boys (49). In this context, learning to drum could be regarded as particularly beneficial because it involves not only musicality but also the development of multimodal skills such as body coordination, sensorimotor integration, and cardiovascular exercise processes (50). Additionally, it is appealing and accessible to everyone regardless of age, gender, ethnicity, or musical background (51, 52).In our proof-of-concept study, Amad et al. (53) showed that the brain is capable of neuroplastic modifications through drum-based practice in neurotypical adolescents. In particular, changes in FC were observed post drum training in brain regions known to exhibit atypical functioning in autism, such as areas associated with motor skills and the mirror neuron system.In the present study, we investigated the impact of drum training on brain function in 36 autistic adolescents who were split into two age- and gender-matched groups: a drum group (n = 19), who were evaluated before and after learning to drum, and a control group (n = 17), who were also evaluated longitudinally but with no intervention. We explored behavioral outcomes related to drum practice in this clinical population and examined their association with changes in FC between the two groups (i.e., drum group vs. control group) over time (i.e., before vs. after drum training).We hypothesized that drumming performance would improve in the drum group over time, while no improvement would be observed in the control group. Furthermore, we hypothesized that changes in hyperactivity, attentional difficulties, problem behaviors, and repetitive and restricted behaviors would be observed in the drum group. We also hypothesized that cooccurring changes in FC in brain areas responsible for attentional focus and inhibitory control would be identified following drum training.     

Predictors of influenza severity among hospitalized adults with laboratory confirmed influenza: Analysis of nine influenza seasons from the Valencia region,Spain

PurposeInfluenza hospitalizations contribute substantially to healthcare disruption. We explored the impact of ageing, comorbidities and other risk factors to better understand associations with severe clinical outcomes in adults hospitalized with influenza.MethodsWe analysed multi‐season data from adults ≥18 years, hospitalized with laboratory‐confirmed influenza in Valencia, Spain. Severity was defined as intensive care unit (ICU) admission, assisted ventilation and/or death. Generalized estimating equations were used to estimate associations between risk factors and severity. Rate of hospital discharge was analysed with a cumulative incidence function.ResultsOnly 26% of influenza patients had their primary discharge diagnosis coded as influenza. Comorbidities were associated with severity among adults aged 50–79 years, with the highest odds ratio (OR) in patients with ≥3 comorbidities aged 50–64 years (OR = 6.7; 95% CI: 1.0–44.6). Morbid obesity and functional dependencies were also identified risk factors (ORs varying from 3 to 5 depending on age). The presence of increasing numbers of comorbidities was associated with prolonged hospital stay.ConclusionsInfluenza clinical outcomes are aggravated by the presence of comorbidities and ageing. Increased awareness of influenza among hospitalized patients could prompt clinical and public health interventions to reduce associated burden.     

A DISCOURSE ANALYSIS OF THE CONSTRUCTION OF MENTAL ILLNESS IN TWO UK NEWSPAPERS FROM 1985–2000

This study explored the discourse of mental illness contained within two UK newspapers over a 15-year period, excluding those stories that mentioned any reference to a diagnosis. Using frame analysis, a form of discourse analysis, ten distinct frames were identified and classified into “stories.” These ten stories were categorized as: foreign, legal, drug, feature, trauma, tragedy, community care tragedy, social policy, inquiry report, and sports/celebrity stories. Each frame is described and the potential influence of such frames on both social policy and nursing practice is discussed.     

Physiologic mechanism and preoperative prediction of new-onset dysphagia after laparoscopic Nissen fundoplication

The aim of this study was to determine whether preoperative physiologic factors can account for and be used to predict the development of postoperative dysphagia after laparoscopic Nissen fundoplication. One hundred sixty-three patients with gastroesophageal reflux disease underwent laparoscopic Nissen fundoplication with a median follow-up of 14 months (range 6 to 81 months). Preoperative dysphagia was present in 37% (60 of 163) and was relieved in all but five patients (92%). Female sex (P = 0.01) and the presence of a stricture (P = 0.02) were the only preoperative variables associated with the presence of preoperative dysphagia. Eight percent (8 of 103) of patients without preoperative dysphagia developed new-onset dysphagia, and of these 63% (5 of 8) had a normal lower esophageal sphincter (LES) (pressure >6 mm Hg; length >2 cm; abdominal length >1 cm). New-onset dysphagia was significantly more common in patients with a normal LES (22% [5 of 23] vs. 4% [3 of 80], P = 001). Patients with a normal LES had almost a sixfold increase in the risk of developing dysphagia as those with an abnormal LES (relative risk = 5.8). Only a preoperative normal LES (P = 0.02) or mean LES pressures (P = 0.04) were positively associated with the development of postoperative dysphagia. The severity of this dysphagia also showed a strong positive trend of increasing with mean preoperative LES pressures (P = 0.07). Finally, preoperative LES pressure significantly correlated with postoperative LES pressure (r = 0.48, P = 0.01) and with mean residual LES (nadir) pressure (r = 0.33, P = 0.05) offering insight into the mechanism of this dysphagia. In conclusion, preoperative LES parameters play a role in the development of dysphagia after laparoscopic Nissen fundoplication. Patients with a normal LES or high mean LES pressures are at increased risk for developing this complication and should be informed of this before laparoscopic Nissen fundoplication. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Ga., May 20–23, 2001.     

The Cotton osteotomy: indications and techniques

Stage II posterior tibial tendon dysfunction (PTTD) is characterized by an incompetent posterior tibial tendon that results in a flexible pes planovalgus deformity. As the hindfoot drifts into valgus, compensatory varus develops in the forefoot. Alternatively, in some cases medial column instability can result in primary forefoot varus that drives the hindfoot into valgus. Recently, there has been increasing awareness of the importance of forefoot varus in PTTD.     

Bioprotection of tendon repair: adjunctive use of botulinum toxin A in Achilles tendon repair in the rat

BACKGROUND: Tendon-repair techniques have evolved to increase the construct strength of the repair site in order to permit early active range of motion without tendon gap or rupture. The present study evaluated the hypothesis that the injection of botulinum neurotoxin type-A (BoNT-A) into the gastrocnemius muscle will reduce the active force production of that muscle below the force required to rupture the associated, repaired Achilles tendon. METHODS: Seventy-nine rat Achilles tendons were surgically bisected and were repaired with use of a two-strand core suture with a running epitenon repair. After the repair, the animals were treated with unilateral intramuscular (gastrocnemius) injections of either BoNT-A (6 U/kg body weight) (thirty-seven rats) or saline solution (forty-two rats). Operatively treated ankles were fixed in the neutral position with a percutaneous pin for the first two days after surgery. Unrestricted ankle motion and weight-bearing were allowed after the second postoperative day. An assessment of gap formation or rupture at the repair site, electrophysiologic measurements of force applied to the tendon, and an assessment of the strength of the repaired tendon were performed. RESULTS: Intramuscular BoNT-A injections produced a significant, reversible reduction in active muscle force (p < 0.007). Twitch and tetanus contractions decreased to approximately 25% of the values for the control side within one week, remained at <50% of the values for the control side at one month, and returned to normal levels by six months. The tetanic force capability of the muscles that had been injected with BoNT-A was fivefold to tenfold less than the force required to rupture the associated Achilles tendon for as long as four weeks after tendon repair. The spontaneous Achilles tendon rupture rate of repaired tendons in the BoNT-A group was three times lower than that in the saline solution group at one week, and the tendon rupture force was significantly higher in the BoNT-A group between one and three weeks after repair (p < 0.007). There was no significant difference in tendon rupture force between the two groups after three weeks. CONCLUSIONS: Intramuscular gastrocnemius BoNT-A injections were associated with a significant reduction in force-generating potential, such that the muscle was incapable of actively producing enough force to rupture the repaired Achilles tendon in this rat model of tendon repair.