scholarly journals PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Scott L. Weiss ◽  
Fran Balamuth ◽  
Elliot Long ◽  
Graham C. Thompson ◽  
Katie L. Hayes ◽  
...  
Keyword(s):  
Septic Shock ◽  
New Zealand ◽  
Normal Saline ◽  
Therapeutic Window ◽  
Saline Control ◽  
Fluid Type ◽  
Interventional Trial ◽  
Link Type ◽  
Pediatric Trial ◽  
The Usa

Abstract Background/aims Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock. Methods The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under “exception from informed consent” in the USA or “deferred consent” in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed. Discussion PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings. Trial registration PRoMPT BOLUS was first registered at ClinicalTrials.gov (NCT04102371) on September 25, 2019. Enrollment started on August 25, 2020.

An Immigrant Filmmaker Substitutes an Alternative Vision of Adolescence: The Scarecrow (Sam Pillsbury, 1982)

2018 ◽  
Author(s):  
Alistair Fox
Keyword(s):  
New Zealand ◽  
Cinematic Adaptation ◽  
Alternative Vision ◽  
The Face ◽  
The Usa ◽  
Genre Film

By comparing Sam Pillsbury’s cinematic adaptation of Ronald Hugh Morrieson’s The Scarecrow (1963) with the original, this chapter shows how the filmmaker, who was raised in the USA and immigrated to New Zealand in his teens, empties the source novel of the moral ambiguities and transgressive elements that had made the original a genuinely New Zealand work, in so far as it reflected puritan guilt over transgressive impulses in the face of repression, and thus turned the story into a genre film that that is much more anodyne in its vision.

The Influence of the Infomercial in New Zealand

2019 ◽  
pp. 67-80
Author(s):  
Rosser Johnson
Keyword(s):  
New Zealand ◽  
Primary Sources ◽  
Cultural Impact ◽  
Cultural Importance ◽  
The Usa ◽  
The 1950S ◽  
As If

New Zealand television networks introduced infomercials (30 minute advertisements designed to appear as if they are programmes) in late 1993. Although infomercials date from the 1950s in the USA, they were unknown in this country and quickly came to be seen as a peculiarly “intense” form of hyper-commercial broadcasting. This article aims to sketch out the cultural importance of the infomercial by analysing historical published primary sources (from the specialist and general press) as they reflect the views and opinions that resulted from the introduction of the infomercial. Specifically, it outlines the three main areas where that cultural importance was located. It concludes by analysing the significance of the cultural impact of the infomercial, both within broadcasting and within wider society.

scholarly journals Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gernot Marx ◽  
Kai Zacharowski ◽  
Carole Ichai ◽  
Karim Asehnoune ◽  
Vladimír Černý ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Septic Shock ◽  
Severe Sepsis ◽  
Plasma Volume ◽  
Volume Replacement ◽  
Efficacy And Safety ◽  
Volume Responsiveness ◽  
Double Blind ◽  
Link Type ◽  
Icu Discharge

Abstract Background Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime. Methods This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90. Discussion This study aims to generate evidence regarding which regimen—a gelatine-crystalloid regimen or a pure crystalloid regimen—is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload. Trial registration The European clinical trial database EudraCT 2015-000057-20 and the ClinicalTrials.gov Protocol Registration and Results System ClinicalTrials.gov NCT02715466. Registered on 17 March 2016.

scholarly journals The evolution and distribution of phage ST160 within Salmonella enterica serotype Typhimurium

2010 ◽  
Vol 139 (8) ◽  
pp. 1262-1271 ◽  
Author(s):  
M. PRICE-CARTER ◽  
P. ROY-CHOWDHURY ◽  
C. E. POPE ◽  
S. PAINE ◽  
G. W. DE LISLE ◽  
...  
Keyword(s):  
New Zealand ◽  
Salmonella Enterica ◽  
Recent Past ◽  
Major Threat ◽  
Serovar Typhimurium ◽  
The Usa ◽  
Clonal Spread ◽  
Important Disease

SUMMARYSalmonellosis is an internationally important disease of mammals and birds. Unique epidemics in New Zealand in the recent past include two Salmonella serovars: Salmonella enterica subsp. enterica serovar Typhimurium definitive type (DT) 160 (S. Typhimurium DT160) and S. Brandenburg. Although not a major threat internationally, in New Zealand S. Typhimurium DT160 has been the most common serovar isolated from humans, and continues to cause significant losses in wildlife. We have identified DNA differences between the first New Zealand isolate of S. Typhimurium DT160 and the genome-sequenced strain, S. Typhimurium LT2. All the differences could be accounted for in one cryptic phage ST64B, and one novel P22-like phage, ST160. The majority of the ST160 genome is almost identical to phage SE1 but has two regions not found in SE1 which are identical to the P22-like phage ST64T, suggesting that ST160 evolved from SE1 via two recombination events with ST64T. All of the New Zealand isolates of DT160 were identical indicating the clonal spread of this particular Salmonella. Some overseas isolates of S. Typhimurium DT160 differed from the New Zealand strain and contained SE1 phage rather than ST160. ST160 was also identified in New Zealand isolates of S. Typhimurium DT74 and S. Typhimurium RDNC-April06 and in S. Typhimurium DT160 isolates from the USA. The emergence of S. Typhimurium DT160 as a significant pathogen in New Zealand is postulated to have occurred due to the sensitivity of the Salmonella strains to the ST160 phage when S. Typhimurium DT160 first arrived.

scholarly journals 412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A437-A437
Author(s):  
Elena Garralda ◽  
Ravit Geva ◽  
Eytan Ben-Ami ◽  
Corinne Maurice-Dror ◽  
Emiliano Calvo ◽  
...  
Keyword(s):  
T Cells ◽  
Informed Consent ◽  
Antitumor Activity ◽  
Phase I ◽  
Solid Tumors ◽  
Therapeutic Window ◽  
Clinical Activity ◽  
Advanced Solid Tumors ◽  
Link Type ◽  
Dose Levels

BackgroundAgonistic 4-1BB monoclonal antibodies were preclinically validated as promising cancer immunotherapies, both as monotherapy and as potentiators of the activity of PD-(L)1–blocking agents. However, toxicity and a narrow therapeutic window have hampered their clinical development. DuoBody-PD­-L1×4-1BB, a first-in-class, bispecific, next-generation checkpoint immunotherapy, was designed to overcome these limitations by activating T cells through conditional 4-1BB costimulation, while simultaneously blocking the PD-L1 axis. We present preliminary data from the ongoing, first-in-human, open-label, phase I/IIa trial of DuoBody-PD-L1×4-1BB in advanced solid tumors (NCT03917381).MethodsDuring dose escalation, patients with metastatic or unresectable solid tumors not eligible for standard therapy received flat-dose DuoBody-PD-L1×4-1BB (25–1200 mg) intravenously every 3 weeks until disease progression or unacceptable toxicity. Primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Secondary endpoints included pharmacokinetic parameters and antitumor activity (RECIST 1.1). Pharmacodynamic biomarkers and antitumor activity (iRECIST) were assessed as exploratory endpoints.ResultsAs of June 22, 2020, 61 patients were enrolled (median age: 59 years). The most common cancer types were colorectal (19.7%), ovarian (14.8%), pancreatic (9.8%), and NSCLC (9.8%). Patients had previously received a median (range) of 3 (1–11) treatments; 44.2% had prior anti-PD-(L)1 immunotherapy. Patients received a median (range) of 4 (1–15) treatment cycles; Cmax was observed shortly after the end of infusion (mean T½: 2.3–10.3 days). Maximum tolerated dose was not reached; 6 patients experienced DLTs. The most common (=10%) treatment-related AEs (all grades; grades 3–4) were transaminase elevation (24.6%; 9.8%), hypothyroidism (16.4%; 1.6%), and fatigue (13.1%; 1.6%). Treatment-related grade-3 transaminase elevations decreased upon corticosteroid administration; no treatment-related bilirubin increases or grade-4 transaminase elevations occurred. Disease control, including stable disease at first assessment and partial responses in triple-negative breast cancer, ovarian cancer, and immune checkpoint inhibitor (ICI)–pretreated NSCLC, occurred in 40/61 patients (65.6%). Pharmacologic activity, as measured by modulation of adaptive immunity mediators, was observed across a broad range of dose levels. Peripheral proliferating (Ki67+) CD8+ effector memory T cells and serum interferon-gamma levels showed maximum induction relative to baseline (p=0.01) 8 days following treatment.ConclusionsDuoBody-PD-L1×4-1BB demonstrated biologic activity and a manageable safety profile. Encouraging early clinical activity across different dose levels was observed in a heavily pretreated population with advanced solid tumors, including those resistant to prior immunotherapy or typically less sensitive to ICIs. Expansion cohorts of patients for whom DuoBody-PD-L1×4-1BB treatment could be relevant and biologically sound have started enrollment. Updated data will be presented.AcknowledgementsThe authors thank Manish Gupta, Lei Pang, and Thomas Breuer at Genmab A/S; Alice Bexon, Alexander Muik, and Friederike Gieseke at BioNTech SE; and Zuzana Jirakova (formerly at BioNTech SE) for their valuable contributions. This trial was funded by Genmab A/S and BioNTech SE.Trial RegistrationClinicalTrials. gov; trial number: NCT03917381Ethics ApprovalThis trial is undertaken following full approval of the final protocol, amendments, informed consent form, applicable recruiting materials, and subject compensation programs by the Independent Ethics Committee/Institutional Review Board.ConsentWritten informed consent, in accordance with principles that originated in the Declaration of Helsinki 2013, current ICH guidelines including ICH-GCP E6(R2), applicable regulatory requirements, and sponsor policy, was provided by the patients.

Tissue Damage Caused by the Intramuscular Injection of Long-Acting Penicillin

PEDIATRICS ◽  
1985 ◽  
Vol 75 (4) ◽  
pp. 741-744
Author(s):  
Harry Schanzer ◽  
Julius H. Jacobson
Keyword(s):  
New Zealand ◽  
Femoral Artery ◽  
Normal Saline ◽  
Tissue Damage ◽  
Intramuscular Injection ◽  
Penicillin G ◽  
Left Femoral Artery ◽  
New Zealand White Rabbits ◽  
Long Acting ◽  
The Right

In order to elucidate whether tissue damage produced on occasion by intramuscular injection of longacting penicillin is due to accidental intra-arterial injection or vasospasm, two types of experiments were carried out in rabbits. In the first set of experiments, six New Zealand White rabbits were given intra-arterial injections of 0.4 mL of a mixture containing 300,000 U of penicillin G benzathine and 300,000 units of penicillin procaine per milliliter (Bicillin C-R) into the left femoral artery and 0.4 mL of normal saline into the right femoral artery as autocontrol. In a second set of experiments, 0.4 mL of the same penicillin preparation was injected in the space surrounding the left femoral artery in five New Zealand rabbits, and 0.4 mL of normal saline was injected in a similar fashion around the right femotal artery as control. The legs of the rabbits that received the intra-arterial injection of penicillin invariably developed ischemic manifestations. None of the legs of rabbits given intra-arterial injections of normal saline had pathologic manifestations. None of the rabbits that received the periarterial penicillin preparation or normal saline developed abnormalities. These results strongly suggest that the tissue damage produced by penicillin is secondary to the intra-arterial administration of the drug.

Century plus journeys: using career crafting to explore the career success of pioneer women accountants

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Mohini P. Vidwans ◽  
Rosalind H. Whiting
Keyword(s):  
New Zealand ◽  
Great Britain ◽  
Organizational Support ◽  
Career Success ◽  
Design Methodology ◽  
Content Type ◽  
The Usa ◽  
Political Economic ◽  
Pioneer Women ◽  
Insight Into

PurposeThe purpose of this study is to explore the struggle for entry and career success of the early pioneer women accountants in Great Britain and its former colonies the USA, Canada, Australia and New Zealand.Design/methodology/approachA career crafting matrix guides the analysis of historical information available on five pioneer women accountants in order to understand their success in gaining entry into the profession and their subsequent careers.FindingsDespite an exclusionary environment, career crafting efforts coupled with family and organizational support enabled these women to become one of the first female accountants in their respective countries. Their struggles were not personal but much broader—seeking social, political, economic and professional empowerment for women.Originality/valueThis is the first paper to utilize the career crafting matrix developed from current female accountants' careers to explore careers of pioneering female accountants. It adds to the limited literature on women actors in accounting and may provide insight into approaching current forms of difference and discrimination.

Chrysomyxa abietis (needle rust of fir).

2021 ◽  
Author(s):  
Keyword(s):  
Life Cycle ◽  
New Zealand ◽  
North America ◽  
Rust Fungus ◽  
Significant Problem ◽  
Northern Europe ◽  
Native Range ◽  
Obligate Parasite ◽  
The Usa ◽  
Accidental Introduction

Abstract C. abietis is a microcyclic rust fungus; an obligate parasite completing its life cycle on species of Picea (spruce). Only the current year's needles of Picea are infected and those needles are shed early. Reported from northern Europe and Asia, the fungus is a Regulated Pest for the USA. It is absent from North America, where susceptible species are native, and Australia and New Zealand, where they are introduced. Although usually not a significant problem in its native range, because conditions are not favourable for heavy infections every year (Smith et al., 1988; Hansen, 1997), this rust could be more damaging as an invasive in other temperate areas. Due to the fact that small amounts of infection may be overlooked, accidental introduction could occur through importation of infected seedlings or young trees.

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