Prehospital tranexamic acid shortens the interval to administration by half in Major Trauma Networks: a service evaluation.

INTRODUCTION: Tranexamic acid (TXA) reduces bleeding and mortality. Recent trials have demonstrated improved survival with shorter intervals to TXA administration. The aims of this service evaluation were to assess the interval from injury to TXA administration and describe the characteristics of patients who received TXA pre-hospital and in-hospital. METHODS: We reviewed Trauma and Audit Research Network records and local trauma registries to identify patients of any age that received TXA at all London Major Trauma Centres and Queen's Medical Centre, Nottingham, during 2017. We used the 2016 NICE Guidelines (NG39) which state that TXA should be given within 3 hours of injury. RESULTS: We identified 1018 patients who received TXA, of whom 661 (65%) had sufficient data to assess the time from injury to TXA administration. The median interval was 74 min (IQR: 47-116). 92% of patients received TXA within 3 hours from injury, and 59% within 1 hour. Half of the patients (54%) received prehospital TXA. The median time to TXA administration when given prehospital was 51 min (IQR: 39-72), and 112 min (IQR: 84-160) if given in-hospital (p<0.001). In-hospital TXA patients had less haemodynamic derangement and lower base deficit on admission compared with patients given prehospital TXA. CONCLUSION: Prehospital administration of TXA is associated with a shorter interval from injury to drug delivery. Identifying a proportion of patients at risk of haemorrhage remains a challenge. However, further reinforcement is needed to empower pre-hospital clinicians to administer TXA to trauma patients without overt signs of shock.

Sleep, Cognition and Dementia.

The older patient population is growing rapidly around the world and in the USA. Almost half of seniors over age 65 who live at home are dissatisfied with their sleep, and nearly two-thirds of those residing in nursing home facilities suffer from sleep disorders. Chronic and pervasive sleep complaints and disturbances are frequently associated with excessive daytime sleepiness and may result in impaired cognition, diminished intellect, poor memory, confusion, and psychomotor retardation all of which may be misinterpreted as dementia. The key sleep disorders impacting patients with dementia include insomnia, hypersomnolence, circadian rhythm misalignment, sleep disordered breathing, motor disturbances of sleep such as periodic leg movement disorder of sleep and restless leg syndrome, and parasomnias, mostly in the form of rapid eye movement (REM) sleep behavior disorder (RBD). RBD is a pre-clinical marker for a class of neurodegenerative diseases, the "synucleinopathies", and requires formal polysomnographic evaluation. Untreated sleep disorders may exacerbate cognitive and behavioral symptoms in patients with dementia and are a source of considerable stress for bed partners and family members. When left untreated, sleep disturbances may also increase the risk of injury at night, compromise health-related quality of life, and precipitate and accelerate social and economic burdens for caregivers.

Using CRISPR/Cas9 to identify genes required for mechanosensory neuron development and function.

Tunicates are marine, non-vertebrate chordates that comprise the sister group to the vertebrates. Most tunicates have a biphasic lifecycle that alternates between a swimming larva and a sessile adult. Recent advances have shed light on the neural basis for the tunicate larva's ability to sense a proper substrate for settlement and initiate metamorphosis. Work in the highly tractable laboratory model tunicate Ciona robusta suggests that sensory neurons embedded in the anterior papillae transduce mechanosensory stimuli to trigger larval tail retraction and initiate the process of metamorphosis. Here, we take advantage of the low-cost and simplicity of Ciona by using tissue-specific CRISPR/Cas9-mediated mutagenesis to screen for genes potentially involved in mechanosensation and metamorphosis, in the context of an undergraduate 'capstone' research course. This small screen revealed at least one gene, Vamp1/2/3, which appears crucial for the ability of the papillae to trigger metamorphosis. We also provide step-by-step protocols and tutorials associated with this course, in the hope that it might be replicated in similar CRISPR-based laboratory courses wherever Ciona are available.

Using CRISPR/Cas9 to identify genes required for mechanosensory neuron development and function.

Tunicates are marine, non-vertebrate chordates that comprise the sister group to the vertebrates. Most tunicates have a biphasic lifecycle that alternates between a swimming larva and a sessile adult. Recent advances have shed light on the neural basis for the tunicate larva's ability to sense a proper substrate for settlement and initiate metamorphosis. Work in the highly tractable laboratory model tunicate Ciona robusta suggests that sensory neurons embedded in the anterior papillae of transduce mechanosensory stimuli to trigger larval tail retraction and initiate the process of metamorphosis. Here, we take advantage of the low-cost and simplicity of Ciona by using tissue-specific CRISPR/Cas9-mediated mutagenesis to screen for genes potentially involved in mechanosensation and metamorphosis, in the context of an undergraduate "capstone" research course. This small screen revealed at least one gene, Vamp1/2/3 , that appears crucial for the ability of the papillae to trigger metamorphosis. We also provide step-by-step protocols and tutorials associated with this course, in the hope that it might be replicated in similar CRISPR-based laboratory courses wherever Ciona are available.

Tapia's Syndrome (Concurrent Unilateral Recurrent Laryngeal and Hypoglossal Nerve Palsy) Following Left Retrosigmoid Craniotomy for Schwannoma Resection.

Tapia's syndrome, a unilateral, extracranial combined lesion to the hypoglossal nerve (cranial nerve [CN] XII) and the recurrent laryngeal branch of the vagal nerve (CN X), has been observed to occur after general anesthesia for a variety of surgical procedures. Surgical intraoperative neck positioning and airway management are hypothesized as causative factors. The condition presents with ipsilateral motor paralysis of the tongue and vocal cords. Postoperatively, patients often present with dysphonia, dysphagia, and difficulty swallowing. We discuss a unique case of Tapia's syndrome occurring after retrosigmoid craniotomy for left vestibular schwannoma resection in a 42-year-old male. General anesthesia was uneventful with an atraumatic, grade 2a intubation and a normal endotracheal tube cuff pressure of 30 cm of water. The patient was positioned laterally, even though the exact head position was not documented. Institutional practice in these cases is for the head to be maintained neutral or with a slight turn. An uneventful subtotal resection of the tumor was performed after retrosigmoid exposure. Postoperatively, the patient complained of left-sided mouth tingling, a hoarse voice, and tongue weakness which impacted his ability to chew and swallow. He had mild left-sided facial weakness and decreased sensation in the V1 and V2 distribution of the trigeminal nerve. Postoperative brain MRI showed postsurgical changes without evidence of neurological or vascular involvement. Fiberoptic endoscopy performed in the otolaryngology clinic showed immobility of the right vocal cord. Consequently, Tapia's syndrome was diagnosed. He later underwent a right vocal fold injection with Prolaryn gel (Merz North America, Inc, Greensboro, NC, USA) via flexible laryngoscopy with a slight improvement in his dysphonia. At his last visit, he declined further interventions based on acceptable voice quality. Tapia's syndrome can occur due to the close anatomical proximity of the hypoglossal and recurrent laryngeal nerves as they pass lateral to the oropharynx and hypopharynx. This predisposes the nerves to anesthetic and surgical insults such as over-stretching of the nerves during head manipulation and trauma to the nerve fibers following laryngoscopy. Our case report highlights this potential rare complication to anesthetic and surgical teams. Awareness of this concurrent paralysis can assist practitioners to rapidly diagnose and treat patients who present in this way postoperatively. It can also enable avoidance of causative factors and remind practitioners of the importance of meticulous perioperative documentation.

Prognostic benefit of transcatheter aortic valve implantation compared with medical therapy in patients with inoperable aortic stenosis.

OBJECTIVES: To compare survival in patients with inoperable aortic stenosis who undergo transcatheter aortic valve implantation against those managed medically. BACKGROUND: Without surgical correction, survival of patients with severe symptomatic aortic stenosis is poor. It is unknown whether patients undergoing transcatheter aortic valve implantation (TAVI) have a better prognosis than similar patients who are treated with medical management. METHODS: Survival rates were compared in consecutive patients with severe symptomatic aortic stenosis who either underwent TAVI or continued on medical management following multidisciplinary team assessment. All patients had been turned down, or considered at unacceptably high risk, for conventional aortic valve surgery. Patients were reviewed in clinic or by telephone six monthly. Mortality data was obtained from the United Kingdom Office of National Statistics. RESULTS: The study group included 85 patients aged 81 +/- 7 years (range 62-94), of whom 48 were male. Thirty eight patients underwent TAVI while 47 patients were deemed unsuitable based on echocardiographic, angiographic, or clinical criteria and remained on medical therapy. The calculated EuroSCORE for the TAVI group was 11 +/- 2 and for the medical group 9 +/- 2 (P < 0.001). TAVI-related procedural mortality was 2.6%, and 30-day mortality was 5.2%. Among the medically-treated patients, 14 (30%) underwent palliative balloon aortic valvuloplasty, with a trend toward improved survival (P = 0.06). During overall follow-up of 215 +/- 115 days there were a total of 18 deaths; TAVI N = 5 (13%); Medical N = 13 (28%) (P = 0.04). CONCLUSIONS: Patients with severe aortic valve disease who are not suitable for surgical aortic valve replacement have an improved prognosis if treated with transcatheter aortic valve implantation rather than continuing on medical management alone.

In-hospital initiation of secondary prevention is associated with improved vascular outcomes at 3 months.

BACKGROUND: Although various in-hospital stroke quality improvement programs have been associated with high treatment rates at hospital discharge, there are few data on the impact of these programs on clinical outcomes. We evaluated the impact of the PROTECT (Preventing Recurrence Of Thromboembolic Events through Coordinated Treatment) program on short-term vascular risk. METHODS: Prospective data collected after discharge for ischemic stroke or transient ischemic attack caused by presumed atherosclerotic mechanism from a PROTECT intervention hospital and a comparison community hospital, which used conventional care, were compared. The 3-month follow-up clinical outcome data were then evaluated and differences in outcome frequency data between the two hospital groups were analyzed using Fisher's exact test. Covariate adjusted comparisons of percent with a vascular event was computed via logistic regression methods. RESULTS: A total of 224 patients met study criteria: 126 patients at a PROTECT hospital and 98 patients at a comparator hospital. The 3-month postdischarge data were available for 78 patients at PROTECT hospital versus 65 control patients. Patients at a PROTECT hospital were more likely to be younger, be current smokers, and not have a history of atrial fibrillation. At 3 months, there was a covariate-adjusted difference in the intervention-hospital group versus the control-hospital group with regard to the incidence of a vascular event (transient ischemic attack, stroke, or myocardial infarction), 8.4% versus 22% (P = .036). CONCLUSIONS: Compared with conventional care, PROTECT was associated with better 3-month vascular outcomes after stroke hospitalization. Further study is needed to confirm the potential favorable impact of stroke quality improvement programs on clinical outcomes.

Electromyography and nerve conduction studies of the lower extremity: uses and limitations.

Electrodiagnostic testing (EDX), the combination of electromyography and nerve conduction studies, is a useful extension of the physical exam. In the proper clinical context, it can help distinguish between the various nerve processes that may contribute to foot pain. This article discusses those processes, their clinical presentation, and the relative usefulness of EDX for each.

Gendered policies and practices that increase older men's risk of elder mistreatment.

We aim to detail some of the ways that social policy and gendered practices put older men at risk of elder mistreatment. Research on the abuse and neglect that older adults experience has often focused on the characteristics of the victims and the dynamics within families, emphasizing factors such as the likelihood of an intergenerational cycle of violence, substance abuse and dependency, and older men's financial status as key risks in elder abuse. The effect on men from this type of analysis is that elder mistreatment remains an individual or family problem rather than being viewed as a larger societal concern. This article challenges the individualistic focus by outlining the importance of societal forces affecting older men's risk of mistreatment.

Frequency and characteristics of anxiety among patients with Alzheimer's disease and related dementias.

The purpose of this study was to assess the cross-sectional prevalence and characteristics of anxiety among patients with Alzheimer's disease (AD), as compared with patients with frontotemporal dementia (FTD), patients with vascular dementia (VaD), and normal control subjects. The authors used the anxiety subscale of the Neuropsychiatric Inventory (NPI), an instrument with established reliability and validity, to compare patients. Patients were identified in a query of the UCLA Alzheimer's Disease Center database and included 115 patients with probable AD, 43 patients with VaD, 33 patients with FTD, and 40 normal, elderly control subjects. Descriptive statistics were generated, and partial correlations, controlling for Mini-Mental State Examination (MMSE) score, were performed between the anxiety subscale and other behavioral features as measured by the NPI and the Functional Activities Questionnaire (FAQ). Relationships between cognitive status (as indicated by MMSE score) and anxiety were explored. Anxiety was reported more commonly in patients with VaD and FTD than in patients with AD. These differences remained significant (P<0.01) in an analysis of variance (ANOVA) after adjusting for age, age at onset, educational level, and MMSE score. In AD, anxiety was inversely related to MMSE score (i.e., worse with more severe dementia), was more prevalent among patients with a younger age at onset (under age 65), and correlated with disability as measured by the FAQ score. These data suggest that anxiety is common among patients with diverse forms of dementia. In AD, anxiety is most common in those with more severe cognitive deterioration and an earlier age at onset.