Effects of early childhood otitis media and ventilation tubes on psychosocial wellbeing - A prospective cohort study within the Danish National Birth Cohort.

BACKGROUND: Otitis Media (OM) is one of the most common infections among children in developed countries and may result in temporary conductive hearing loss (HL) if accompanied by middle ear effusion (MEE). Ventilation tube insertion (VTI) is recommended as treatment for recurrent acute OM or chronic MEE with HL. HL may lead to impaired development of psychosocial skills. However, evidence for the developmental consequences of OM and the effect of VTI is inconsistent. The objectives of this study were to investigate 1) whether OM in early childhood is associated with long-term consequences of psychosocial development and 2) if VTI prevents the possible negative consequences of OM. METHODS: This study examined prospectively collected data from 52.877 children registered in the Danish National Birth Cohort (DNBC). Information about previous OM-episodes and VTI was obtained through systematic follow-up interviews at seven years, and The Strength and Difficulties Questionnaire (SDQ) containing questions about psychological wellbeing was completed. Five groups were defined based on OM-exposure and the presence of VTI. Baseline characteristics were analysed, and comparison of mean SDQ-scores for the five exposure groups was conducted. Means were adjusted for à priori defined confounding factors. RESULTS: Data from 52,877 children in the DNBC showed an association between OM and poorer SDQ-scores. VTI was associated with an additional increase, i.e. worsening, of the SDQ-score for boys, and only a slight beneficial effect on the girls' outcome. The groups differed in their baseline characteristics in e.g. maternal education, socio-economic status, breastfeeding, and prematurity. CONCLUSION: Significant associations between parent-reported OM in early childhood and later psychosocial health difficulties were found. VTI did not resolve this association.

Associations between otitis media and child behavioural and learning difficulties: Results from a Danish cohort.

OBJECTIVES: Findings from studies investigating early childhood episodes of otitis media (OM) and developmental outcomes are inconclusive. This may in part be because large-scale prospective studies controlling for relevant confounding factors are sparse. The present study investigates associations between OM in early childhood and later behavioural and learning difficulties controlling for relevant confounding factors. METHODS: The study applied data from the Aarhus Birth Cohort's 10-12-year-old follow-up (N=7578). Associations between retrospective parent-reported OM (no OM; 1-3 episodes of OM with/without tympanostomy tubes; 4+ OM episodes without tympanostomy tubes and; 4+ OM episodes with tympanostomy tubes) one the one hand, and parent- and teacher-reported scores on the Strengths and Difficulties Questionnaire (SDQ) and parent-reported academic difficulties on the other hand, were investigated. The following variables were controlled for: parental educational level, maternal and paternal school problems, parental post-natal smoking, breastfeeding, and age at which the child started walking. All analyses were stratified by gender. RESULTS: Large differences in background characteristics were observed for the group of children with 4+ OM episodes with tympanostomy tubes compared to the no OM group. After controlling for relevant confounders, negative associations were consistently observed for the group of children with 4+ episodes of OM with tympanostomy tubes compared to the group of children without OM. This was particularly so for girls. CONCLUSION: The findings suggest an association between 4+ episodes of early OM with tympanostomy tubes and behavioural and learning difficulties later in childhood. The large inter-group differences, i.e. impact of residual and unmeasured confounding factors, may in part explain the observed associations and underline the need to include these in future studies.

Teaching by the nurse: how important is it to patients?

Few studies address patients' perceptions of the importance of education by a nurse and how this relates to their view of quality care. This article reports on a secondary data analysis that examined the influence of demographic and background characteristics and health status on the importance of teaching to patients (n = 239) in ambulatory care. Health education by nurses was important to patients, some more than others. Teaching for health promotion was more important to men than to women (t = 2.51, p = 0.01) and more important to Blacks than to Whites (t = 3.43, p = 0.001). As patients' educational level increased, it was less important to have a nurse in ambulatory care teach them about their illness and treatments and about health promotion. Patient education and being able to call a nurse with questions were significantly more important to patients with lower incomes and lower mental and emotional health scores.

Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2.

BACKGROUND AND OBJECTIVES: Pefloxacin is reported to cause clinically relevant inhibition of theophylline metabolism in vivo, but in vitro pefloxacin was only a weak inhibitor of the cytochrome P450 CYP1A2, mediating main theophylline biotransformation. We therefore further characterized the interaction between pefloxacin and CYP1A2. METHODS: A randomized 3-period change-over study was conducted in 12 healthy young volunteers on the steady-state interactions between pefloxacin or enoxacin (400 mg twice a day) with caffeine (183 mg once daily), a validated marker of CYP1A2. Caffeine pharmacokinetics were estimated after its fifth dose. Studies in human liver microsomes were carried out to measure the effect of pefloxacin and norfloxacin on caffeine 3-demethylation, an in vitro CYP1A2 probe, and to identify the enzyme(s) that mediate pefloxacin N-4'-demethylation with selective inhibitors. RESULTS: For the in vivo study, ANOVA-based point estimates (90% confidence intervals [CI]) for the ratios of caffeine pharmacokinetics with and without pefloxacin coadministration were 1.11 for maximal steadystate plasma concentrations (Cmax,ss; 90% CI, 0.99 to 1.26), 0.53 for total clearance (CLt,ss; 90% CI, 0.49 to 0.58), and 1.04 for the beta-phase distribution volume (Vdbeta; 90% CI, 0.96 to 1.13). The values for enoxacin were 1.99 for Cmax,ss (90% CI, 1.77 to 2.23), 0.17 for CLt,ss (90% CI, 0.16 to 0.19), and 1.01 for Vdbeta (90% CI, 0.90 to 1.13). Thus pefloxacin caused a 2-fold decrease in caffeine clearance, and enoxacin caused a 6-fold decrease in caffeine clearance. In vitro, norfloxacin and pefloxacin competitively inhibited CYP1A2, with inhibition constant (Ki) values of 0.1 and 1 mmol/L, respectively, and CYP1A2 was the only enzyme with a relevant contribution (approximately 50%) to pefloxacin N-4'-demethylation. CONCLUSIONS: Enoxacin and to a lesser extent pefloxacin may cause clinically relevant interactions with further CYP1A2 substrates. The data suggest that the pefloxacin interaction is partly mediated by its major metabolite norfloxacin.

Stereoselective degradation of the fenoprofen acyl glucuronide enantiomers and irreversible binding to plasma protein.

Stereoselective degradation of fenoprofen (FEN) glucuronides and irreversible binding of FEN enantiomers to human serum albumin via their glucuronides were studied. At different pH values, 37 degrees C, and in the absence of albumin, degradation half-lives were diastereomeric, resulting mainly from a combination of hydrolysis and acyl migration. Lower pH enhanced FEN glucuronide stability and reduced the extent of irreversible binding. The degradation rate of R-FEN glucuronide was greater than that of the S-glucuronide (S-FEN). When human serum albumin was added to the medium, stability was decreased as compared to protein-free buffer. FEN glucuronides were readily hydrolyzed to parent drug, indicating an esterase-like activity of the albumin molecule. In vitro irreversible binding was higher for R-FEN (1.22% +/- 0.36) than for S-FEN glucuronide (0.76% +/- 0.12), when a 0.1 mM concentration of each conjugate enantiomer was incubated under physiological conditions (pH 7.4, 37 degrees C). Incubation with unconjugated FEN did not lead to measurable irreversible binding. Analysis of plasma samples from a clinical study showed that enantioselective irreversible binding of FEN to plasma proteins also occurs in vivo. After administration of a single 600-mg dose of racemic FEN to six healthy volunteers, covalent binding of R- and S-FEN to plasma proteins was measured in all subjects. The percentage of S-FEN protein adduct was greater than that of its R-enantiomer adduct. Total amounts of FEN irreversibly bound to plasma protein in vivo were also very low (1.02 +/- 0.32 and 3.23 +/- 0.85 mol/mol protein x 10(-4) for R- and S-FEN, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)