Impact of PKU on the reproductive patterns in collaborative study families

Factors that relate to reproductive patterns in 129 families after the birth of a child with phenylketonuria (PKU) include birth order of the index child, age of the parents at the birth of the index child, and expressed intentions of the parents whether or not to have additional children. Factors that do not correlate with reproductive histories include knowledge of the genetic and metabolic nature of PKU, the relationship of PKU to mental retardation and special diet, parental upset about the diagnosis, sex of the affected child, parental IQ, religion, education, and social class. Correlations found related to the question, "Is PKU the reason you don't want more children?" include stress factors in family functioning, mother's upset with the diagnosis, father's concerns about being a carrier, sex of the child with PKU, and degree of knowledge about PKU. Many of the Collaborative Study clinics tend to be more concerned about the consequences of PKU on the family than on society, and feel that families should receive genetic counseling to determine their reproductive risks and future plans. Upon self-report, many clinics declare their counseling to be either "completely nondirective" or making a "conscious effort to be nondirective."     

Evaluating denoising strategies in resting‐state functional magnetic resonance in traumatic brain injury (EpiBioS4Rx)

Resting‐state functional MRI is increasingly used in the clinical setting and is now included in some diagnostic guidelines for severe brain injury patients. However, to ensure high‐quality data, one should mitigate fMRI‐related noise typical of this population. Therefore, we aimed to evaluate the ability of different preprocessing strategies to mitigate noise‐related signal (i.e., in‐scanner movement and physiological noise) in functional connectivity (FC) of traumatic brain injury (TBI) patients. We applied nine commonly used denoising strategies, combined into 17 pipelines, to 88 TBI patients from the Epilepsy Bioinformatics Study for Anti‐epileptogenic Therapy clinical trial. Pipelines were evaluated by three quality control (QC) metrics across three exclusion regimes based on the participant''s head movement profile. While no pipeline eliminated noise effects on FC, some pipelines exhibited relatively high effectiveness depending on the exclusion regime. Once high‐motion participants were excluded, the choice of denoising pipeline becomes secondary ‐ although this strategy leads to substantial data loss. Pipelines combining spike regression with physiological regressors were the best performers, whereas pipelines that used automated data‐driven methods performed comparatively worse. In this study, we report the first large‐scale evaluation of denoising pipelines aimed at reducing noise‐related FC in a clinical population known to be highly susceptible to in‐scanner motion and significant anatomical abnormalities. If resting‐state functional magnetic resonance is to be a successful clinical technique, it is crucial that procedures mitigating the effect of noise be systematically evaluated in the most challenging populations, such as TBI datasets.     

Neuroprotection in acute brain injury: an up-to-date review

Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.     

Treatment of Status Epilepticus: An International Survey of Experts

Background

As part of the development of the Neurocritical Care Society (NCS) Status Epilepticus (SE) Guidelines, the NCS SE Writing Committee conducted an international survey of SE experts.

Methods

The survey consisted of three patient vignettes (case 1, an adult; case 2, an adolescent; case 3, a child) and questions regarding treatment. The questions for each case focused on initial and sequential therapy as well as when to use continuous intravenous (cIV) therapy and for what duration. Responses were obtained from 60/120 (50%) of those surveyed.

Results

This survey reveals that there is expert consensus for using intravenous lorazepam for the emergent (first-line) therapy of SE in children and adults. For urgent (second-line) therapy, the most common agents chosen were phenytoin/fosphenytoin, valproate sodium, and levetiracetam; these choices varied by the patient age in the case scenarios. Physicians who care for adult patients chose cIV therapy for RSE, especially midazolam and propofol, rather than a standard AED sooner than those who care for children; and in children, there is a reluctance to choose propofol. Pentobarbital was chosen later in the therapy for all ages.

Conclusion

There is close agreement between the recently published NCS guideline for SE and this survey of experts in the treatment of SE.     

The International Multi-disciplinary Consensus Conference on Multimodality Monitoring: Future Directions and Emerging Technologies

Introduction

Propofol is used extensively in neurocritical care (NCC) due to its pharmacologic properties allowing for facilitation of serial neurologic examinations. Despite widespread use, few studies have identified risk factors for hypotension in these patients. We aimed to determine predictors of hypotension in NCC patients sedated with propofol.

Methods

This retrospective, multicenter study evaluated 237 patients at two academic medical centers, both with dedicated NCC teams led by board-certified neurointensivists. Univariate analyses were performed to determine risk factors associated with severe hypotension during sedation with propofol. Multivariable analysis was performed to determine variables independently associated with hypotension, defined as a mean arterial pressure (MAP) less than 60 mmHg.

Results

There was an average maximum reduction in MAP of 28.8 % after propofol initiation in the entire cohort. Severe hypotension developed in 62 (26.2 %) patients to a median nadir MAP of 56 mmHg. Those who developed severe hypotension had a longer median duration of mechanical ventilation (5.0 vs. 3.6 days; p = 0.01) and an increased in-hospital mortality (38.7 vs. 24.0 %; p = 0.03). Multivariable logistic regression analysis identified increasing number of changes to the propofol infusion rate, baseline MAP 60–70 mmHg, and need for renal replacement therapy (RRT) as factors independently associated with hypotension.

Conclusions

Multiple factors predicted hypotension in NCC patients receiving propofol. Clinicians should use propofol cautiously in patients with a lower baseline MAP or receiving RRT. Development of protocols related to the frequency of dose titrations is also recommended to prevent this avoidable complication.     

Intracranial Pressure Monitoring: Fundamental Considerations and Rationale for Monitoring

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In large part critical care for TBI is focused on the identification and management of secondary brain injury. This requires effective neuromonitoring that traditionally has centered on intracranial pressure (ICP). The purpose of this paper is to review the fundamental literature relative to the clinical application of ICP monitoring in TBI critical care and to provide recommendations on how the technique maybe applied to help patient management and enhance outcome. A PubMed search between 1980 and September 2013 identified 2,253 articles; 244 of which were reviewed in detail to prepare this report and the evidentiary tables. Several important concepts emerge from this review. ICP monitoring is safe and is best performed using a parenchymal monitor or ventricular catheter. While the indications for ICP monitoring are well established, there remains great variability in its use. Increased ICP, particularly the pattern of the increase and ICP refractory to treatment is associated with increased mortality. Class I evidence is lacking on how monitoring and management of ICP influences outcome. However, a large body of observational data suggests that ICP management has the potential to influence outcome, particularly when care is targeted and individualized and supplemented with data from other monitors including the clinical examination and imaging.     

Monitoring Nutrition and Glucose in Acute Brain Injury

The metabolic response to injury is well described; however, very little is understood about optimal markers to measure this response. This summary will address the current evidence about monitoring nutritional status including blood glucose after acute brain injury (ABI). An electronic literature search was conducted for English language articles describing the testing, utility, and optimal methods to measure nutritional status and blood glucose levels in the neurocritical care population. A total of 45 articles were included in this review. Providing adequate and timely nutritional support can help improve outcome after ABI. However, the optimal content and total nutrition requirements remain unclear. In addition, how best to monitor the nutritional status in ABI is still being elucidated, and at present, there is no validated optimal method to monitor the global response to nutritional support on a day-to-day basis in ABI patients. Nitrogen balance may be monitored to assess the adequacy of caloric intake as it relates to protein energy metabolism, but indirect calorimetry, anthropometric measurement, or serum biomarker requires further validation. The adverse effects of hyperglycemia in ABI are well described, and data indicate that blood glucose should be carefully controlled in critically ill patients. However, the optimal frequency or duration for blood glucose monitoring after ABI remains poorly defined. There are significant knowledge gaps about monitoring nutritional status and response to nutritional interventions in ABI; these need to be addressed and hence few recommendations can be made. The optimal frequency and duration of blood glucose monitoring need further study.     

Early and persistent impaired percent alpha variability on continuous electroencephalography monitoring as predictive of poor outcome after traumatic brain injury

OBJECT: Early prediction of outcomes in patients after they suffer traumatic brain injury (TBI) is often nonspecific and based on initial imaging and clinical findings alone, without direct physiological testing. Improved outcome prediction is desirable for ethical, social, and financial reasons. The goal of this study was to determine the usefulness of continuous electroencephalography (EEG) monitoring in determining prognosis early after TBI, while the patient is in the intensive care unit. METHODS: The authors hypothesized that the reduced percentage of alpha variability (PAV) in continuous EEG tracings indicates a poor prognosis. Prospective continuous EEG monitoring was performed in 89 consecutive patients with moderate to severe TBI (Glasgow Coma Scale [GCS] Scores 3-12) from 0 to 10 days after injury. The PAV was calculated daily, and the time course and trends of the PAV were analyzed in comparison with the patient's Glasgow Outcome Scale (GOS) score at the time of discharge. In patients with GCS scores of 8 or lower, a PAV value of 0.1 or lower is highly predictive of a poor outcome or death (positive predictive value 86%). The determinant PAV value was obtained by Day 3 after injury. Persistent PAV values of 0.1 or lower over several days or worsening of the PAV to a value of 0.1 or lower indicated a high likelihood of poor outcome (GOS Scores 1 and 2). In comparison with the combination of traditional initial clinical indicators of outcome (GCS score, pupillary response to light, patient age, results of computerized tomography scanning, and early hypotension or hypoxemia), the early PAV value during the initial 3 days after injury independently improved prognostic ability (p < 0.01). CONCLUSIONS: Continuous EEG monitoring performed with particular attention paid to the PAV is a sensitive and specific method of prognosis that can indicate outcomes in patients with moderate to severe TBI within 3 days postinjury.     

Impact of influenza vaccination on civilian aircrew illness and absenteeism

BACKGROUND: Approximately 10% of the general population worldwide acquires influenza infection every year. Airline crews run a particularly high risk of contracting influenza and influenza-like viruses because they come in contact with hundreds of potentially infected individuals every day. Respiratory diseases are the most frequent cause of absenteeism among flight crews in airline companies. Several studies have shown the efficacy of influenza vaccination in the workplace of healthy, working adults leading to increased productivity and lower absenteeism. We conducted a double blind, randomized, placebo-controlled study on flight crews of an airline company in order to determine the safety and efficacy of a trivalent inactivated influenza vaccine in reducing illness and absences from work. METHODS: The 813 healthy members of a Brazilian airline company were randomly assigned to receive injections of either an influenza vaccine or a placebo, with a follow-up period of 7 mo after vaccination. Primary outcomes included influenza-like illness episodes and absenteeism from work due to such episodes. RESULTS: Demographic characteristics were similar in the two groups. No significant side-effects occurred in either group. Compared to the placebo group, individuals receiving the vaccine showed 39.5% fewer episodes of flu-like illness (p < 0.001) and 26% fewer days of work lost (p = 0.03).The vaccinated group developed 33% fewer episodes of any severe flu-like illness (p < 0.01). CONCLUSION: The data indicates that influenza vaccination is safe in airline flight crews and may produce health-related benefits including reduced absenteeism.     

Continuous EEG monitoring for the detection of seizures in traumatic brain injury, infarction, and intracerebral hemorrhage: "to detect and protect".

Brain injury results in a primary pathophysiologic response that enables the brain to have seizures. Seizures occur frequently after traumatic and nontraumatic intracerebral bleeding. These seizures can be nonconvulsive, and if one does not monitor for seizures, one will not know they are occurring. The use of continuous EEG monitoring (cEEG) to detect brain arrhythmias after a primary insult, much in way that cardiac arrhythmias are detected after myocardial infarction, can influence treatment decisions and mitigate some of the pathophysiologic natural history of brain injuries. Seizures after brain injury worsen clinical outcome and need to be treated. In summary, cEEG is a valuable clinical instrument "to detect and protect," i.e., to detect seizures and protect the brain from seizure-related injury in critically ill patients, whose brains are often in a particularly vulnerable state.