7 results
Characteristics of pivotal clinical trials of FDA-approved endovascular devices between 2000 and 2018: An interrupted time series analysis
- John T. Moon, Menelaos Konstantinidis, Nevon Song, Nariman Nezami, Bill S. Majdalany, Allen Herr, Gary Siskin
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 03 February 2023, e67
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- Article
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Background:
The Food and Drug Administration (FDA) reviews safety, efficacy, and the quality of medical devices through its regulatory process. The FDA Safety and Innovation Act (FDASIA) of 2012 was aimed at accelerating the regulatory process for medical devices.
Objectives:The purpose of our study was to (1) quantify characteristics of pivotal clinical trials (PCTs) supporting the premarket approval of endovascular medical devices and (2) analyze trends over the last two decades in light of the FDASIA.
Methods:We surveyed the study designs of endovascular devices with PCTs from the US FDA pre-market approval medical devices database. The effect of FDASIA on key design parameters (e.g., randomization, masking, and number of enrolled patients) was estimated using an interrupted time series analysis (segmented regression).
Results:We identified 117 devices between 2000–2018. FDASIA was associated with a decrease in double blinding (p < 0.0001) and a decrease in historical comparators (p < 0.0001).
Discussion:Our results reveal an overall trend of decreased regulatory requirements as it relates to clinical trial characteristics, but a compensatory increased rate of post-approval across device classes. Furthermore, there was an emphasis on proving equivalence or non-inferiority rather than more use of active comparators in clinical trials. Medical device stakeholders, notably clinicians, must be aware of the shifting regulatory landscape in order to play an active role in promoting patient safety.
Best Clinical Practice With Ziprasidone IM: Update After 2 Years of Experience
- Dan L. Zimbroff, Michael H. Allen, John Battaglia, Leslie Citrome, Avrim Fishkind, Andrew Francis, Daniel L. Herr, Douglas Hughes, Marc Martel, Horacio Preval, Ruth Ross
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- Journal:
- CNS Spectrums / Volume 10 / Issue S11 / 2005
- Published online by Cambridge University Press:
- 07 November 2014, pp. 1-15
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Acute agitation is a common psychiatric emergency often treated with intramuscular (IM) medication when rapid control is necessary or the patient refuses to take an oral agent. Conventional IM antipsychotics are associated with side effects, particularly movement disorders, that may alarm patients and render them unreceptive to taking these medications again. Ziprasidone (Geodon®) is the first second-generation, or atypical, antipsychotic to become available in an IM formulation. Ziprasidone IM was approved by the Food and Drug Administration in 2002 for the treatment of agitation in patients with schizophrenia. In October 2004, a roundtable panel of physicians with extensive experience in the management of acutely agitated patients met to review the first 2 years of experience with this agent. This monograph, a product of that meeting, discusses clinical experience to date with ziprasidone IM and offers recommendations on its use in various settings.
In clinical trials, patients treated with ziprasidone IM demonstrated significant and rapid (within 15-30 minutes) reduction in agitation and improvement in psychotic symptoms, agitation, and hostility to an extent greater than or equal to that attained with haloperidol IM. Tolerability of ziprasidone IM was superior to that of haloperidol IM, with a lower burden of movement disorders. Clinical trials have also shown that ziprasidone IM can be administered with benzodiazepines without adverse consequences. Transition from IM to oral ziprasidone has been well tolerated, with maintenance of symptom control. The most common adverse events associated with ziprasidone IM were insomnia, headache, and dizziness in fixed-dose trials and insomnia and hypertension in flexible-dose trials. No consistent pattern of escalating incidence of adverse events with escalating ziprasidone doses has been observed. Changes in QTc interval associated with ziprasidone at peak serum concentrations are modest and comparable to those seen with haloperidol IM. Results of randomized clinical trials of ziprasidone IM have been corroborated in studies in real-world treatment settings involving patients with extreme agitation or a recent history of alcohol or substance abuse. In these circumstances, clinically significant improvement was seen within 30 minutes of ziprasidone IM administration, without regard to the suspected underlying etiology of agitation. Agents with a good safety/tolerability profile, such as ziprasidone IM, may be more cost effective long term than older agents, due to reduced incidence of acute adverse effects (eg, acute dystonia) that often require extended periods of observation. Additional trials of ziprasidone IM in agitated patients in a variety of clinical settings are warranted to generate comparative risk/benefit data with conventional agents and other second-generation antipsychotics.
8 - An overview of arbuscular mycorrhizal fungal composition, distribution and host effects from a tropical moist forest
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- By Edward Allen Herre, Smithsonian Tropical Research Institute, Damond Kyllo, Smithsonian Tropical Research Institute, Scott Mangan, Smithsonian Tropical Research Institute and Indiana University, Rebecca Husband, Smithsonian Tropical Research Institute and University of York, Luis C. Mejia, Smithsonian Tropical Research Institute, Ahn-Heum Eom, Smithsonian Tropical Research Institute and Korea National University of Education
- Edited by David Burslem, University of Aberdeen, Michelle Pinard, University of Aberdeen, Sue Hartley, University of Sussex
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- Book:
- Biotic Interactions in the Tropics
- Published online:
- 25 August 2009
- Print publication:
- 08 September 2005, pp 204-225
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Summary
Introduction
Arbuscular mycorrhizal fungi (AMF) (Zygomycetes) are an ancient group, dating back to the invasion of land surfaces by plants. Currently, they are perhaps the most abundant soil fungi, and they form intimate relationships with the roots of the vast majority of terrestrial plant species across the planet. These fungal symbionts generally play a mutualistic role, aiding the host plant primarily by enhancing the acquisition of soil nutrients, particularly phosphorus (P). In addition, AMF species often affect plant hormone production/induction (Allen et al. 1980), resistance to root pathogens (Newsham et al. 1995); water uptake (Kyllo et al. 2003) and soil structure (Andrade et al. 1998; Rillig & Allen 1999). In return, all AMF species obligately depend on the host plant for photosynthetically fixed carbon. Given their obligate dependence, AMF are influenced by their hosts at essentially every phase in their life history – hyphal development, sporulation and spore germination (Hetrick & Bloom 1986; Sanders & Fitter 1992; Bever et al. 1996). On the other hand, the degree of mycorrhizal dependence often varies widely among the host plant species in a community (Janos 1980a; Azcon & Ocampo 1981; Hetrick et al. 1992; Kiers et al. 2000).
A central and still largely unanswered question is the degree to which host plant and AMF species influence each other's community composition in natural systems. Fundamentally, for community effects to occur, different combinations of host and AMF species must produce different outcomes of survival and growth.
9 - Tropical plants as chimera: some implications of foliar endophytic fungi for the study of host-plant defence, physiology and genetics
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- By Edward Allen Herre, Smithsonian Tropical Research Institute, Sunshine A. Van Bael, Smithsonian Tropical Research Institute, Zuleyka Maynard, Smithsonian Tropical Research Institute, Nancy Robbins, Smithsonian Tropical Research Institute, Joseph Bischoff, Rutgers University, Anne E. Arnold, Smithsonian Tropical Research Institute and Duke University, Enith Rojas, Smithsonian Tropical Research Institute, Luis C. Mejia, Smithsonian Tropical Research Institute, Roberto A. Cordero, Smithsonian Tropical Research Institute, Catherine Woodward, Smithsonian Tropical Research Institute, Damond A. Kyllo, Smithsonian Tropical Research Institute
- Edited by David Burslem, University of Aberdeen, Michelle Pinard, University of Aberdeen, Sue Hartley, University of Sussex
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- Book:
- Biotic Interactions in the Tropics
- Published online:
- 25 August 2009
- Print publication:
- 08 September 2005, pp 226-238
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Summary
Introduction
Fungal endophytes are defined as those fungi that live inside plant tissues (e.g. roots, stems, leaves) without causing apparent harm to their host (see Wilson 1995). Although we will also mention stem-associated endophytes (see Evans et al. 2003) and endophytes associated with roots (mycorrhizae; see Herre et al., this volume), throughout this chapter, we will focus primarily on the implications of recent studies of the endophytic fungi that live inside plant leaf tissue. These foliar endophytes are extremely diverse phylogenetically and have been documented in nearly all plants sampled (e.g. mosses, liverworts, ferns, conifers and angiosperms; Carroll 1988; Clay 1988; Petrini 1991; Schultess & Faeth 1998; Frohlich & Hyde 1999; Stone et al. 2000; Arnold et al. 2000; Arnold 2002; Arnold et al. 2003; Davis et al. 2003). Despite the growing recognition of their wide distribution across plant taxa, basic attributes of their biology are still poorly understood. Specifically, endophyte diversity, distributions, life cycles, interactions with hosts and other fungi, and their net chemical, physiological and ecological influences are only beginning to be appreciated and studied. This is particularly true in the extremely diverse tropics.
The best-studied endophytes are ascomycetes belonging to the family Clavicipitaceae. These fungi grow throughout the aboveground tissues of some temperate grass species (e.g. Festuca arundinacea, see Clay & Schardl 2002). Typically, in infected individuals, a single fungal genotype infects a single plant individual.
Chapter 20 - Using sex ratios: why bother?
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- By Stuart A. West, Institute of Cell, Animal and Population Biology, University of Edinburgh, United Kingdom, Edward Allen Herre, Smithsonian Tropical Research Institute, USA, and, Smithsonian Tropical Research Institute, Republic of Panama
- Edited by Ian C. W. Hardy, University of Nottingham
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- Book:
- Sex Ratios
- Published online:
- 06 August 2009
- Print publication:
- 13 June 2002, pp 399-413
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Summary
Many see research into sex allocation as the jewel in the crown of evolutionary ecology. There is a very rich experimental literature providing qualitative, and in some cases quantitative, support for the predictions of numerous theoretical models. Consequently, it might be argued that future work will primarily be concerned with dotting i's and crossing t's. Given that there are still so many relatively untamed areas in evolutionary biology, we should therefore ask – why bother with more sex-allocation studies? Our aim in this chapter is to address this question (why?), complementing the more methodological (how?) parts of this book. We argue that sex allocation is an excellent model trait for examining general questions in evolutionary biology.
The usefulness of sex allocation
The strength of sex-allocation research arises for both theoretical and empirical reasons. Sex allocation has a direct and potentially large influence on fitness, and the relevant trade-offs are easy to quantify. Consequently, optimality models are able to make clear theoretical predictions in many specified cases. Empirically, sex allocation can be a relatively easy trait to measure. This is especially true in cases where males and females are equally costly to produce, and so we can concern ourselves simply with the sex ratio (defined as proportion males, i.e. males/(males+females)). In this case, all we must do is count the number of male and female offspring that are produced.
6 - Selective Regime and Fig Wasp Sex Ratios: Toward Sorting Rigor from Pseudo-Rigor in Tests of Adaptation
- Edited by Steven Hecht Orzack, The Fresh Pond Research Institute, Cambridge, MA, Elliott Sober, University of Wisconsin, Madison
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- Book:
- Adaptationism and Optimality
- Published online:
- 06 January 2010
- Print publication:
- 04 June 2001, pp 191-218
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Summary
We use a detailed case study to identify considerations that are likely to be important in constructing and interpreting tests of the optimality of adaptations. Specifically, we consider the sex ratio responses in natural populations of 15 fig-pollinating wasp species and the predictions of local mate competition theory. The mean sex ratios exhibited by fig wasps show qualitative and often quantitative agreement to a wide range of predictions of these models. However, we also find (1) deviations of mean responses from theoretical optima, (2) variation among individuals in their responses to given situations, and (3) unresolved doubts concerning the parameterization and applicability of the models used to predict optimal brood sex ratios. A fundamental question in interpretation arises: Are we using the theory to test the precision of adaptation, or are we using the responses to test the precision of the models? A partial solution to this problem is offered by the fact that within and across these fig wasp species, the frequency with which any particular situation occurs (i.e., selective regime) can be estimated. Across species, the deviations from the predicted optima are fewest in the situations most frequently encountered by the organisms. Similarly, variance in the responses of individuals is lowest for those situations most commonly encountered. Furthermore, phylogenetic relationships of the wasps have little or no relationship with means, deviations, or variance of their sex ratios, suggesting that these characters evolve very rapidly with respect to speciation and are not correlated with other characters that are themselves closely correlated with phylogenetic relationships.
13 - Fig–associated wasps: pollinators and parasites, sex–ratio adjustment and male polymorphism, population structure and its consequences
- Edited by Jae C. Choe, Seoul National University, Bernard J. Crespi, Simon Fraser University, British Columbia
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- Book:
- The Evolution of Mating Systems in Insects and Arachnids
- Published online:
- 03 May 2010
- Print publication:
- 12 June 1997, pp 226-239
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ABSTRACT
Fig–pollinating and fig–parasitizing wasps are integral parts of one of the most fascinating plant–insect interactions known. Moreover, studies of these wasps have been instrumental in developing and refining ideas concerning the influence of population structure and inbreeding on shaping the outcome of kin selection. We present data compiled from six studies spanning five continents that relate brood sex ratios with foundress number in 24 pollinator species. All predictions of local mate competition (LMC) and inbreeding theory are at least qualitatively supported. Additionally, the sex ratios produced by single foundresses of any given species appear to be influenced by brood size and the frequency of multiple foundress broods in that species. We then consider the assumptions underlying the testing of the specific LMC model and consider the relative merits of observational and experimental tests of the theory. Furthermore, we discuss the existing studies of the parasitic wasp species that have addressed the unusual morphological and behavioral polymorphisms for flightlessness and lethal combat that are found in the males of these species. These differences appear to be influenced by the parasites' population structure and density, although other factors are also implicated. Finally, we compare the nature of the support for LMC theory from fig–pollinating wasps with that from the parasitoid wasp Nasonia vitripennis, and suggest future lines of research.