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Aim: Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality of both young adults and the elderly, and is a key contributing factor in about 30% of all injury‐associated deaths occurring within the United States of America. Albeit substantial impact has been made to improve our comprehension of the mechanisms that underpin the primary and secondary injury stages initiated by a TBI incident, this knowledge has yet to successfully translate into the development of an effective TBI pharmacological treatment. Developing consent suggests that a TBI can concomitantly trigger multiple TBI‐linked cascades that then progress in parallel and, if correct, the multifactorial nature of TBI would make the discovery of a single effective mechanism‐targeted drug unlikely. Discussion: We review recent data indicating that the small molecular weight drug (−)‐phenserine tartrate (PhenT), originally developed for Alzheimer's disease (AD), effectively inhibits a broad range of mechanisms pertinent to mild (m) and moderate (mod)TBI, which in combination underpin the ensuing cognitive and motor impairments. In cellular and animal models at clinically translatable doses, PhenT mitigated mTBI‐ and modTBI‐induced programmed neuronal cell death (PNCD), oxidative stress, glutamate excitotoxicity, neuroinflammation, and effectively reversed injury‐induced gene pathways leading to chronic neurodegeneration. In addition to proving efficacious in well‐characterized animal TBI models, significantly mitigating cognitive and motor impairments, the drug also has demonstrated neuroprotective actions against ischemic stroke and the organophosphorus nerve agent and chemical weapon, soman. Conclusion: In the light of its tolerability in AD clinical trials, PhenT is an agent that can be fast‐tracked for evaluation in not only civilian TBI, but also as a potentially protective agent in battlefield conditions where TBI and chemical weapon exposure are increasingly jointly occurring. [ABSTRACT FROM AUTHOR]

Of the estimated 5.3 million people with Alzheimer's disease in the United States, more than half would be classified as having moderate or severe disease. Alzheimer's disease is a progressive disorder with the moderate to severe stages generally characterized by significant cognitive, functional, and behavioral dysfunction. Unsurprisingly, these advanced stages are often the most challenging for both patients and their caregivers/families. Symptomatic treatments for moderate to severe Alzheimer's disease are approved in the United States and include the acetylcholinesterase inhibitor donepezil and the glutamate receptor antagonist memantine. Progressive symptomatic decline is nevertheless inevitable even with the available therapies, and therefore additional treatment options are urgently needed for this segment of the Alzheimer's disease population. An immediaterelease formulation of donepezil has been available at an approved dose of 5-10 mg/d for the past decade. Recently, the United States Food and Drug Administration approved a higher-dose (23 mg/d) donepezil formulation, which provides more gradual systemic absorption, a longer time to maximum concentration (8 hours) versus the immediate-release formulation (3 hours), and higher daily concentrations. Herein, we review (1) the scientific data on the importance of cholinergic deficits in Alzheimer's disease treatment strategies, (2) the rationale for the use of higher-dose acetylcholinesterase inhibitors in patients with advanced disease, and (3) recent clinical evidence supporting the use of higher-dose donepezil in patients with moderate to severe Alzheimer's disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acquisition of competence in performing a variety of procedures is essential during Internal Medicine (TM) residency training. PURPOSES: Determine the rate of procedural complications by TM residents; determine whether there was a correlation between having 1 or more complications and institutional procedural certification status or attending ratings of resident procedural skill competence on the American Board of Internal Medicine (ABIM) monthly evaluation form (ABIM-MEF). Assess if an association exists between procedural complications and in-training examination and ABIM board certification scores. METHODS: We retrospectively reviewed all procedure log sheets, procedural certification status, ABIM-MEF procedural skills ratings, in-training exam and certifying examination (ABIM-CE) scores from the period 1990-1999 for TM residency program graduates from a training program. RESULTS: Among 69 graduates, 2,212 monthly procedure log sheets and 2,475 ABIM-MEFs were reviewed. The overall complication rate was 2.3/1,000 procedures (95% CI: 1.4-3.1/1,000 procedure). With the exception of procedural certification status as judged by institutional faculty, there was no association between our resident measurements arid procedural complications. CONCLUSIONS: Our findings support the need for a resident procedural competence certification system based on direct observation. Our data support the ABIM's action to remove resident procedural competence from the monthly ABIM-MEF ratings. [ABSTRACT FROM AUTHOR]