scholarly journals Pharmacokinetic and Pharmacodynamic Analysis of Alfaxalone Administered as a Bolus Intravenous Injection of Phaxan in a Phase 1 Randomized Trial

2020 ◽  
Vol 130 (3) ◽  
pp. 704-714
Author(s):  
Colin S. Goodchild ◽  
Juliet M. Serrao ◽  
John W. Sear ◽  
Brian J. Anderson
Keyword(s):  
Randomized Trial ◽  
Intravenous Injection ◽  
Phase 1 ◽  
Pharmacodynamic Analysis ◽  
Bolus Intravenous Injection

Bolus Intravenous Injection of Phosphorothioate Oligonucleotides Causes Hypotension by Acting as α1-Adrenergic Receptor Antagonists

1999 ◽  
Vol 160 (3) ◽  
pp. 289-296 ◽  
Author(s):  
Patrick L. Iversen ◽  
Kurtis G. Cornish ◽  
Laurie J. Iversen ◽  
John E. Mata ◽  
David B. Bylund
Keyword(s):  
Intravenous Injection ◽  
Adrenergic Receptor ◽  
Receptor Antagonists ◽  
Bolus Intravenous Injection

The vagus nerve in the thermoregulatory response to systemic inflammation

1997 ◽  
Vol 273 (1) ◽  
pp. R407-R413 ◽  
Author(s):  
A. A. Romanovsky ◽  
C. T. Simons ◽  
M. Szekely ◽  
V. A. Kulchitsky
Keyword(s):  
Intravenous Injection ◽  
Systemic Inflammation ◽  
Second Phase ◽  
Thermoregulatory Response ◽  
Cool Environment ◽  
Bolus Intravenous Injection ◽  
High Doses ◽  
Colonic Temperature ◽  
Dose Dependent ◽  
Higher Doses

Experimentally, systemic inflammation induced by a bolus intravenous injection of lipopolysaccharide (LPS) may be accompanied by three different thermoregulatory responses: monophasic fever (the typical response to low doses of LPS), biphasic fever (medium doses), and hypothermia (high doses). In our recent study [Romanovsky, A. A., V. A. Kulchitsky, C. T. Simons, N. Sugimoto, and M. Szekely. Am. J. Physiol. (Regulatory Integrative Comp. Physiol.). In press], monophasic fever did not occur in subdiaphragmatically vagotomized rats. In the present work, we asked whether vagotomy affects the two other types of thermoregulatory response. Adult Wistar rats were vagotomized (or sham operated) and had an intravenous catheter implanted. On day 28 postvagotomy, the thermal responses to the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000 micrograms/kg) were tested in either a neutral (30 degrees C) or slightly cool (25 degrees C) environment. Three major results were obtained. 1) In the sham-operated rats, the 1 microgram/kg dose of LPS caused at 30 degrees C a monophasic fever with a maximal colonic temperature (Tc) rise of approximately 0.6 degree C; this response was abated (no Tc changes) in the vagotomized rats. 2) At 30 degrees C, all responses to higher doses of LPS (10-1,000 micrograms/kg) were represented by biphasic fevers (the higher the dose, the less pronounced the first and the more pronounced the second phase was); none of these biphasic fevers was altered in the vagotomized animals. 3) In response to the 1,000 micrograms/kg dose at 25 degrees C, hypothermia occurred: Tc changed by -0.5 +/- 0.1 degree C (nadir); this hypothermia was exaggerated (-1.1 +/- 0.1 degrees C) in the vagotomized rats. It is concluded that vagal afferentation may be important in the mediation of the response to minor amounts of circulating LPS, whereas the response to larger amounts is brought about mostly (if not exclusively) by nonvagal mechanisms. This difference may be explained by the dose-dependent mechanisms of the processing of exogenous pyrogens. Vagotomized animals also appear to be more sensitive to the hypothermizing action of LPS in a cool environment; the mechanisms of this phenomenon remain speculative.

scholarly journals Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel) in sexually active young women (MTN-004)

AIDS ◽  
2011 ◽  
Vol 25 (8) ◽  
pp. 1057-1064 ◽  
Author(s):  
Ian McGowan ◽  
Kailazarid Gomez ◽  
Karen Bruder ◽  
Irma Febo ◽  
Beatrice A Chen ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Young Women ◽  
Phase 1 ◽  
Sexually Active

A randomized trial of a palliative care intervention for patients on phase I studies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12001-12001
Author(s):  
Thomas J. Smith ◽  
Vincent Chung ◽  
Mark T. Hughes ◽  
Marianna Koczywas ◽  
Nilofer Saba Azad ◽  
...  
Keyword(s):  
Palliative Care ◽  
Supportive Care ◽  
Phase I ◽  
Usual Care ◽  
Randomized Trial ◽  
Phase 1 ◽  
Quality Care ◽  
Care Plan ◽  
Phase I Clinical Trials ◽  
Care Intervention

12001 Background: The purpose of this study was to test a Palliative Care Intervention for patients with solid tumors enrolled in phase I therapeutic trials. Methods: This randomized trial compared patients accrued to phase I Clinical Trials in groups of Usual Care compared to a Palliative Care Intervention (PCI) in two comprehensive cancer centers. The PCI included assessment of quality of life (QOL) and symptoms, an interdisciplinary meeting to discuss the care plan, including goals of care, and two nurse-delivered teaching sessions. Subjects (n=479) were followed for 24 weeks, with 12 weeks as the primary outcome point. Results: Outcomes revealed that relative to Usual Care, PCI subjects showed less Psychological Distress (1.9 in Intervention and 1.2 in Control pts, p=0.03) and a trend toward improved QOL (3.7 versus 1.6, p=0.07), with differences between sites. We observed high rates of symptom-management admissions (41.3%) and low rates of Advance Directive completion (39%), and use of supportive care services including hospice (30.7%, for only1.2 months duration), despite a median survival for all patients in both groups of 10.1 months from initiating a phase 1 study until death. Patient satisfaction with oncology care was already high at baseline, and we did not see clinically significant changes in those scores by week 12. Conclusions: Palliative care interventions can improve QOL outcomes and distress for patients participating in phase 1 trials. Greater integration of PC is needed to provide quality care to these patients and to support transitions from treatment to supportive care, especially at the end of life. Clinical trial information: NCT01828775 .

scholarly journals A cluster randomized trial of strategies to increase uptake amongst young women invited for their first cervical screen: The STRATEGIC trial

2017 ◽  
Vol 25 (2) ◽  
pp. 88-98 ◽  
Author(s):  
H Kitchener ◽  
M Gittins ◽  
M Cruickshank ◽  
C Moseley ◽  
S Fletcher ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Randomized Trial ◽  
Young Women ◽  
Phase 1 ◽  
Cervical Screening ◽  
Cluster Randomized Trial ◽  
Phase 2 ◽  
Screening Uptake ◽  
Nurse Navigator ◽  
Cluster Randomized

Objectives To measure the feasibility and effectiveness of interventions to increase cervical screening uptake amongst young women. Methods A two-phase cluster randomized trial conducted in general practices in the NHS Cervical Screening Programme. In Phase 1, women in practices randomized to intervention due for their first invitation to cervical screening received a pre-invitation leaflet and, separately, access to online booking. In Phase 2, non-attenders at six months were randomized to one of: vaginal self-sample kits sent unrequested or offered; timed appointments; nurse navigator; or the choice between nurse navigator or self-sample kits. Primary outcome was uplift in intervention vs. control practices, at 3 and 12 months post invitation. Results Phase 1 randomized 20,879 women. Neither pre-invitation leaflet nor online booking increased screening uptake by three months (18.8% pre-invitation leaflet vs. 19.2% control and 17.8% online booking vs. 17.2% control). Uptake was higher amongst human papillomavirus vaccinees at three months (OR 2.07, 95% CI 1.69–2.53, p < 0.001). Phase 2 randomized 10,126 non-attenders, with 32–34 clusters for each intervention and 100 clusters as controls. Sending self-sample kits increased uptake at 12 months (OR 1.51, 95% CI 1.20–1.91, p = 0.001), as did timed appointments (OR 1.41, 95% CI 1.14–1.74, p = 0.001). The offer of a nurse navigator, a self-sample kits on request, and choice between timed appointments and nurse navigator were ineffective. Conclusions Amongst non-attenders, self-sample kits sent and timed appointments achieved an uplift in screening over the short term; longer term impact is less certain. Prior human papillomavirus vaccination was associated with increased screening uptake.

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