A systematic review of capacity assessment tools in pediatric surgery: Global Assessment in Pediatric Surgery (GAPS) Phase I

Background

The Lancet Commission on Global Surgery highlighted global surgical need but offered little insight into the specific surgical challenges of children in low-resource settings. Efforts to strengthen the quality of global pediatric surgical care have resulted in a proliferation of partnerships between low-and middle-income countries (LMICs) and high-income countries (HICs). Standardized tools able to reliably measure gaps in delivery and quality of care are important aids for these partnerships. We undertook a systematic review (SR) of capacity assessment tools (CATs) focused on needs assessment in pediatric surgery.

Human apolipoprotein B. Evidence for its immunochemical heterogeneity using monoclonal antibodies and an immunoenzymometric assay

Predefined monoclonal antibodies (Mabs) were used in an immunoenzymometric assay to study the immunochemical heterogeneity of lipoproteins and to search for potential epitopes with pathological importance. By measuring apolipoprotein B (apo B) epitopes in patients with and without angiographically documented coronary artery disease and in patients with type IIa hyperlipoproteinemia, we have found that both types of patients have a significant increase in Apo B-containing particles specifically recognized by one Mab (BL3). We have also observed that the effects of fenofibrate on type IIa patients vary greatly depending on the plasma concentrations of various Apo B-containing lipoproteins. The greatest effects occurred in patients with epitopes recognized by BL3. Lastly, by sequential precipitation of specific epitopes by BL3, we have obtained evidence that the residual epitope(s) may be related to one or more lipoprotein particles.     

Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

Postnatal development of the chemosensitivity of rat cerebellar Purkinje cells to excitatory amino acids. An in vitro study

In vitro sagittal slices of immature rat cerebellum were used to study the development of the sensitivity of Purkinje cells (PCs) to L-aspartate (L-Asp), L-glutamate (L-Glu) and related derivatives. As early as postnatal day 0 all PCs already displayed clear excitatory responses to short iontophoretic applications of L-Asp, L-Glu and quisqualate while in the same conditions no effect of N-methyl-D,L-aspartate (NMDLA) was detected. By postnatal day 5, i.e. after the onset of the synaptogenesis, the sensitivity of PCs to L-Asp, L-Glu and quisqualate significantly increased up to values similar to those recorded in adult rat cerebellum and surprisingly nearly all (87%) the recorded cells now also displayed excitatory responses to NMDLA. Although this sensitivity of PCs to NMDLA was significantly lower than that observed with the other drugs, it persisted until the end of the first postnatal month when the adult type of connectivity is already well established but at this stage only 30 per cent of the tested cells were still sensitive to the agonist. During this period, excitatory responses elicited by NMDLA were selectively antagonized by 2-amino-5-phosphonovalerate (2-APV), suggesting that during postnatal development, NMDA receptor types are transiently expressed on PCs membranes since in the adult, NMDLA no longer had an excitatory effect. Instead, this drug now exerted a preferential antagonistic action on the excitatory response elicited by L-Asp. Also in the adult, no major changes occurred in the sensitivity of PCs to L-Asp, L-Glu and quisqualate when these drugs were ejected at a dendritic site whereas, when ejected at the somatic level, the sensitivity of the cell appeared 2-3 times lower.     

Effects of carvedilol on renal function

A randomized, double-blind, placebo-controlled study was conducted to study the effects of acute and chronic administration of carvedilol in essential hypertension, with special emphasis on renal haemodynamics and function. Acute administration of a single dose of 50 mg carvedilol reduced systolic and diastolic blood pressure without inducing reflex tachycardia. Renal blood flow was preserved; accordingly, renal vascular resistance was significantly reduced. A significant reduction in the glomerular filtration rate and filtration fraction was observed. Plasma renin activity (PRA) and plasma aldosterone values were not changed. Chronic carvedilol treatment produced a significant fall in systolic and diastolic blood pressure, heart rate, PRA and plasma aldosterone. Renal blood flow, glomerular filtration rate and filtration fraction also remained unchanged; renal vascular resistance decreased significantly. It is concluded that carvedilol possesses definite antihypertensive and renal vasodilating properties, both acutely and after chronic treatment.     

A screening method for antifungal substances using Saccharomyces cerevisiae strains resistant to polyene macrolides

Strains of Saccharomyces cerevisiae FL200 capable of growing on a solid medium containing a mixture of polyene macrolide antibiotics (nystatin, 40 micrograms/ml, amphotericin B, 40 micrograms/ml, pimaricin, 150 micrograms/ml and RP9971 antibiotic, 10 micrograms/ml) have been isolated after successive selection steps. The mutant strains, PR13 and PRC24, are 10 to 100 times more resistant than the polyene macrolide antibiotics. When 4% Tween 80 is added to the medium, resistance to these antifungal drugs is further increased. In addition, strain PRC24, derived from strain PR13, is resistant to a non-polyene macrolide antifungal antibiotic, cycloheximide. In contrast, PR13 and PRC24 are both highly susceptible to a large range of compounds, including non-polyenic antifungal, antitumor and antibacterial agents. These particular characteristics make these strains useful for the rapid detection of antifungal compounds of the polyene macrolide and cycloheximide types, as well as for the recognition of antimitotic substances.     

Clinical pharmacokinetics of Neoral in pediatric recipients of primary liver transplants

Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i. v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22 % and 21 % for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability. Received: 29 November 1996 Received after revision: 10 April 1997 Accepted: 15 May 1997