Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Sep 2014
ReviewThe evolution of the regulatory framework for antibacterial agents.
The rising tide of antibacterial resistance and the lack of a diverse, vibrant pipeline of novel antibacterial agents is a global crisis that impairs our ability to treat life-threatening infections. The recent introduction of a tiered approach to the regulatory framework in this area offers one path to resolving some of the challenges. ⋯ There are limitations to these pathways, and they are not easy to implement, but making reliable noninferiority-based approaches available is critical to reinvigorating the global antibiotic pipeline. With the recognition of these ideas by key regulatory authorities in recent guidance, the next challenges in this area will focus on interpretive breakpoints, the extent of data in the prescribing information, ensuring that multiple agents can be progressed, and the challenge of the antibiotic business model.
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Discovery of the neuromuscular effects of botulinum toxin began in the early 19th century and has continued to evolve. Currently, onabotulinumtoxinA is approved by the U. S. ⋯ OnabotulinumtoxinA significantly reduced the number of headache days per 28-day cycle relative to placebo at week 24 (change from baseline: -8.4 days for onabotulinumtoxinA versus -6.6 days for placebo; P < 0.001, pooled data). OnabotulinumtoxinA improved health-related quality of life and had an acceptable safety profile. OnabotulinumtoxinA is the only approved treatment specifically for CM prevention and represents a safe and effective therapeutic for chronic migraineurs.
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Ann. N. Y. Acad. Sci. · Jan 2014
Randomized Controlled TrialIntegrating nutrition and early child-development interventions among infants and preschoolers in rural India.
This article describes the development, design, and implementation of an integrated randomized double-masked placebo-controlled trial (Project Grow Smart) that examines how home/preschool fortification with multiple micronutrient powder (MNP) combined with an early child-development intervention affects child development, growth, and micronutrient status among infants and preschoolers in rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months) and a preschool phase (enrollment age: 36-48 months). Infants are individually randomized into one of four groups: placebo, placebo plus early learning, MNP alone, and MNP plus early learning (integrated intervention), conducted through home visits. ⋯ The evaluation examines whether the effects of the MNP intervention vary by the quality of the early learning opportunities and communication within the AWCs. Study outcomes include child development, growth, and micronutrient status. Lessons learned during the development, design, and implementation of the integrated trial can be used to guide large-scale policy and programs designed to promote the developmental, educational, and economic potential of children in developing countries.
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Ann. N. Y. Acad. Sci. · May 2015
What is wrong with the tenets underpinning current management of severe traumatic brain injury?
The results of a recent randomized controlled trial comparing intracranial pressure (ICP) monitor-based treatment of severe traumatic brain injury (sTBI) to management without ICP monitoring prompt this skeptical reconsideration of the scientific foundation underlying current sTBI management. Much of current practice arises from research performed under conditions that are no longer relevant today. The definition of an episode of intracranial hypertension is incomplete, and the application of a fixed, universal ICP treatment threshold is poorly founded. ⋯ Similar concerns also apply to manipulation of cerebral perfusion with respect to maintaining universal thresholds for contrived variables rather than tailoring treatment to monitored processes. As such, there is a failure to either optimize management approaches or minimize associated treatment risks for individual sTBI patients. The clinical and research TBI communities need to reassess many of the sTBI management concepts that are currently considered well established.
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Ann. N. Y. Acad. Sci. · May 2015
Hypertonic saline for the management of raised intracranial pressure after severe traumatic brain injury.
Hyperosmolar agents are commonly used as an initial treatment for the management of raised intracranial pressure (ICP) after severe traumatic brain injury (TBI). They have an excellent adverse-effect profile compared to other therapies, such as hyperventilation and barbiturates, which carry the risk of reducing cerebral perfusion. The hyperosmolar agent mannitol has been used for several decades to reduce raised ICP, and there is accumulating evidence from pilot studies suggesting beneficial effects of hypertonic saline (HTS) for similar purposes. ⋯ To date, no large clinical trial has been performed to directly compare the two agents. The best current evidence suggests that mannitol is effective in reducing ICP in the management of traumatic intracranial hypertension and carries mortality benefit compared to barbiturates. Current evidence regarding the use of HTS in severe TBI is limited to smaller studies, which illustrate a benefit in ICP reduction and perhaps mortality.