Evaluating palatability in young children: a mini-review of relevant physiology and assessment techniques.

The palatability of pediatric pharmaceutical products plays a crucial role of influencing medication compliance. Rejection of unpalatable medications can potentially lead to treatment failure which can have immediate and delayed consequences. With advances in both the food and pharmaceutical industries, the systematic assessment of palatability has gained importance. Various methods such as visual analogue scales, facial hedonic scales, and facial recognition software, have been employed to assess palatability. While proven to be useful, these methods have significant limitations and may not be workable for young children. Despite these advancements, a universally accepted "gold standard" for assessing pediatric mediation palatability, recognized by drug regulatory agencies, is yet to be established.

Targeted liquid chromatography-mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children.

AIM: Long-chain acylcarnitines have been postulated to be sensitive biomarkers of acetaminophen (APAP)-induced hepatotoxicity in mouse models. In the following study, the relationship of acylcarnitines with other known indicators of APAP toxicity was examined in children receiving low-dose (therapeutic) and high-dose ('overdose' or toxic ingestion) exposure to APAP. MATERIALS & METHODS: The study included three subject groups: group A (therapeutic dose, n = 187); group B (healthy controls, n = 23); and group C (overdose, n = 62). Demographic, clinical and laboratory data were collected for each subject. Serum samples were used for measurement of APAP protein adducts, a biomarker of the oxidative metabolism of APAP and for targeted metabolomics analysis of serum acylcarnitines using ultra performance liquid chromatography-triple-quadrupole mass spectrometry. RESULTS: Significant increases in oleoyl- and palmitoyl-carnitines were observed with APAP exposure (low dose and overdose) compared with controls. Significant increases in serum ALT, APAP protein adducts and acylcarnitines were observed in overdose children that received delayed treatment (time to treatment from overdose >24 h) with the antidote N-acetylcysteine. Time to peak APAP protein adducts in serum was shorter than that of the acylcarnitines and serum ALT. CONCLUSION: Perturbations in long-chain acylcarnitines in children with APAP toxicity suggest that mitochrondrial injury and associated impairment in the ß-oxidation of fatty acids are clinically relevant as biomarkers of APAP toxicity.

The influence of research compensation options on Practice-based Research Network (PBRN) physician participation: a North Texas (NorTex) PBRN study.

OBJECTIVE: To study the effect of two compensation approaches, continuing medical education (CME) credits (5 hours) or monetary ($150), on the participation rate of a physician needs assessment study. METHODS: Physicians representing family medicine, internal medicine, pediatric, and geriatrics specialties, and practicing in ambulatory primary care clinics affiliated with the North Texas Primary Care (NorTex) PBRN clinics, were recruited to complete a survey relevant to their subspecialty and to conduct a self-audit/abstraction of five medical records. Physicians were recruited from four health care systems, and the recruiting methods varied by system. Study outcome was the rate of study completion by type of incentive. RESULTS: One hundred five of 211 (49.8%) physicians approached to participate gave consent and 84 (39.8%) completed the study. There was no difference in the number of physicians randomly assigned to monetary compared with CME compensation for giving consent to participate (adjusted odds ratio = 1.42, confidence interval = 0.69, 2.93). However, physicians in the monetary compensation group were more likely to complete the study after giving consent (adjusted odds ratio = 4.70, confidence interval = 1.25, 17.58). This monetary effect was also significant from the perspective of all physicians approached initially (adjusted odds ratio = 2.78, confidence interval = 1.16, 6.67). DISCUSSION: This study suggests that future PBRN investigators should receive monetary compensation for the opportunity cost of adding research activities to their already busy practices. This compensation may be especially vital for PBRNs to complete more ambitious projects requiring a significant time commitment from the participating physicians.

Recruiting Practice-based Research Network (PBRN) physicians to be research participants: lessons learned from the North Texas (NorTex) needs assessment study.

INTRODUCTION: The purpose of this study was to examine strategies for recruiting physician subjects in a practice-based research network continuing education research study, using different recruitment methods at four systems, or health plan arrangements. METHODS: The North Texas Primary Care Practice-based Research Network Needs Assessment Study consisted of a survey and five self-directed medical record abstractions. Physicians were recruited to be research subjects from four systems, using different recruitment strategies. χ(2) was used to determine differences in physicians consenting and completing the study between systems. Kruskal-Wallis was used to determine differences in time from first contact to consent and number of contacts required before consent between systems. RESULTS: One hundred five of 211 physicians (49.8%) consented to participate, of which 90 (85.7%) completed the survey. There was a significant difference by system in the number of physicians who consented (P = .04) and number of contacts required pre-consent (P < .001) but not in the number of physicians completing the study or time from first contact to consent. DISCUSSION/CONCLUSIONS: Success of recruiting physicians to be research subjects varied between systems using different recruitment methods. Lessons learned include using clinician champions to make initial contact, establishing a relationship with clinic personnel, distinguishing the research team from a pharmaceutical representative, establishing a preferred contact method, and collecting study materials on a set timeline.

Pharmacokinetics of famotidine in infants.

BACKGROUND: Although famotidine pharmacokinetics are similar in adults and children older than 1 year of age, they differ in neonates owing to developmental immaturity in renal function. Little is currently known about the pharmacokinetics of famotidine in infants aged between 1 month and 1 year, a period when renal function is maturing. OBJECTIVE: To characterise the pharmacokinetics of famotidine in infants. DESIGN: This was a two-part multicentre study with both single dose (Part I, open-label) and multiple dose (Part II, randomised) arms. PATIENTS: Thirty-six infants (20 females and 16 males) who required treatment with famotidine and who had an indwelling arterial or venous catheter for reasons unrelated to the study. METHODS: Infants in Part I were administered a single dose of famotidine 0.5 mg/kg; the dose was intravenous or oral according to the judgement of the attending physician. Infants receiving 0.5 mg/kg intravenously were divided into two groups by age, and pharmacokinetic parameters in infants 0-3 months and >3 to 12 months of age were compared. Infants in Part II were randomised to one of the following treatments: 0.25 mg/kg/dose intravenously or 0.5 mg/kg/dose orally on day 1 and subsequent days, or 0.25 mg/kg/dose intravenously or 0.5 mg/kg/dose orally on day 1 followed by doses of either 0.5 mg/kg/dose intravenously or 1 mg/kg/dose orally on subsequent days. From day 2 onwards, age-adjusted dose administration regimens (once daily in infants <3 months of age and every 12 hours in infants >3 months of age) were used; the total number of famotidine doses ranged from 3 to 11 and the total number of days of dose administration ranged from two to eight. RESULTS: In infants <3 months of age, plasma and renal clearance of famotidine were decreased compared with infants >3 months of age. Pharmacokinetic parameters for the older infants (i.e. those >3 months) were similar to those previously reported for children and adults. Approximate dose-proportionality, no accumulation on multiple dosing and an estimated bioavailability similar to adult values were also observed. CONCLUSION: A short course of famotidine therapy in infants appears generally well tolerated, and the characteristics of famotidine pharmacokinetics during the first year of life are explained to a great degree by the development of renal function, the primary route of elimination for this drug.