Topical nitroglycerin ointment as salvage therapy for peripheral tissue ischemia in newborns: a systematic review.

BACKGROUND: Topical nitroglycerin (TNG) ointment has been used for almost 3 decades to treat neonatal peripheral tissue ischemia, but this product is now no longer being produced by its Canadian manufacturer. Our aim was to investigate the efficacy and safety of TNG products in newborns in neonatal intensive care units. METHODS: In this systematic review we searched Embase, CINAHL, MEDLINE, PubMed and Web of Science from inception to April 2020 for studies on the use of TNG products (TNG ointment, TNG spray, glyceryl trinitrate [GTN] patch) for the treatment of neonatal tissue ischemia. We did not apply language or study design limitations. Animal studies and duplicate records were excluded. Two reviewers screened and extracted data. The Tool for Evaluating the Methodological Quality of Case Reports and Case Series was used to assess the risk of bias of individual studies. RESULTS: We included 23 articles (20 case reports, 2 case series and 1 retrospective audit) describing the use of TNG ointment, TNG spray or GTN patch in the treatment of 39 tissue ischemia events in 37 newborns. Twenty-three (62.2%), 12 (32.4%), 1 (2.7%) and 1 (2.7%) infants received TNG ointment, GTN patch, both TNG ointment and GTN patch, and TNG spray, respectively. Nineteen (76.0%) and 7 (53.8%) injuries treated with TNG ointment and GTN patch showed complete recovery, respectively. Two (16.7%) infants treated with GTN patch experienced adverse events (i.e., methemoglobinemia) requiring treatment discontinuation. INTERPRETATION: TNG ointment presents a safe therapeutic modality for salvage therapy of neonatal tissue ischemia. Engagement of stakeholders is essential to address its recent commercial inaccessibility in Canada.

Tolerability of Vidaza (azacitidine) subcutaneous administration using a maximum volume of 3 ml per injection.

The azacitidine (Vidaza®) product monograph indicates that doses greater than 4 ml should be divided equally into two syringes and injected into different sites. Although 2 ml is a more commonly used maximum volume for subcutaneous injections, there is a lack of evidence to support the use of any given maximum volume with azacitidine. Applying the status quo of 2 ml to azacitidine results in patients receiving 3-4 injections per visit. This prospective study evaluated the frequency and type of injection site reactions when the maximum subcutaneous injection volume was increased from 2 to 3 ml per injection site. Among 30 patients, 309 doses were administered, and injection site reactions were noted in 92.9% of all doses, with the majority (82.2%) being grade 1; only 10.7% of doses resulted in grade 2 reactions, and there were no grade 3 or 4 reactions. There was no increase in frequency or severity of injection site reactions when the maximum volume was increased to 3 ml. The median number of injections that patients received per visit decreased from 3 to 2 after the volume was increased, and there was a statistically significant reduction in the incidence of pain. Decreasing the number of injections also facilitates ease of rotation of injection sites and decreases pharmacy preparation time. This is the first time that injection site reaction data relating to injection volume have been reported for azacitidine.

Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation.

Characterizing new drugs and chemical probes of biological systems is hindered by difficulties in identifying the mechanism of action (MOA) of biologically active molecules. Here we present a metabolite suppression approach to explore the MOA of antibacterial compounds under nutrient restriction. We assembled an array of metabolites that can be screened for suppressors of inhibitory molecules. Further, we identified inhibitors of Escherichia coli growth under nutrient limitation and charted their interactions with our metabolite array. This strategy led to the discovery and characterization of three new antibacterial compounds, MAC168425, MAC173979 and MAC13772. We showed that MAC168425 interferes with glycine metabolism, MAC173979 is a time-dependent inhibitor of p-aminobenzoic acid biosynthesis and MAC13772 inhibits biotin biosynthesis. We conclude that metabolite suppression profiling is an effective approach to focus MOA studies on compounds impairing metabolic capabilities. Such bioactives can serve as chemical probes of bacterial physiology and as leads for antibacterial drug development.