Surveillance of antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae in children with pneumonia

In order to identify optimal therapy for children with bacterial pneumonia, Pakistan's ARI Program, in collaboration with the National Institute of Health (NIH), Islamabad, undertook a national surveillance of antimicrobial resistance in S. pneumoniae and H. influenzae. The project was carried out at selected urban and peripheral sites in 6 different regions of Pakistan, in 1991–92. Nasopharyngeal (NP) specimens and blood cultures were obtained from children with pneumonia diagnosed in the outpatient clinic of participating facilities. Organisms were isolated by local hospital laboratories and sent to NIH for confirmation, serotyping and antimicrobial susceptibility testing. Following were the aims of the study (i) to determine the antimicrobial resistance patterns of S. pneumoniae and H. influenzae in children aged 2–59 months; (ii) to determine the ability of selected laboratories to identify and effectively transport isolates of S. pneumoniae and H. influenzae cultured from nasopharyngeal and blood specimens; (iii) to validate the comparability of resistance patterns for nasopharyngeal and blood isolates of S. pneumoniae and H. influenzae from children with pneumonia; and (iv) to examine the effect of drug resistance and laboratory error on the cost of effectively treating children with ARI. ^ A total of 1293 children with ARI were included in the study: 969 (75%) from urban areas and 324 (25%) from rural parts of the country. Of 1293, there were 786 (61%) male and 507 (39%) female children. The resistance rate of S. pneumoniae to various antibiotics among the urban children with ARI was: TMP/SMX (62%); chloramphenicol (23%); penicillin (5%); tetracycline (16%); and ampicillin/amoxicillin (0%). The rates of resistance of H. influenzae were higher than S. pneumoniae: TMP/SMX (85%); chloramphenicol (62%); penicillin (59%); ampicillin/amoxicillin (46%); and tetracycline (100%). There were similar rates of resistance to each antimicrobial agent among isolates from the rural children. ^ Of a total 614 specimens that were tested for antimicrobial susceptibility, 432 (70.4%) were resistant to TMP/SMX and 93 (15.2%) were resistant to antimicrobial agents other than TMP/SMX viz. ampicillin/amoxicillin, chloramphenicol, penicillin, and tetracycline. ^ The sensitivity and positive predictive value of peripheral laboratories for H. influenzae were 99% and 65%, respectively. Similarly, the sensitivity and positive predictive value of peripheral laboratory tests compared to gold standard i.e. NIH laboratory, for S. pneumoniae were 99% and 54%, respectively. ^ The sensitivity and positive predictive value of nasopharyngeal specimens compared to blood cultures (gold standard), isolated by the peripheral laboratories, for H. influenzae were 88% and 11%, and for S. pneumoniae 92% and 39%, respectively. (Abstract shortened by UMI.)^

Distribution of human immunodeficiency virus (HIV) in the CNS of children with severe HIV encephalomyelopathy

The presence and distribution of human immunodeficiency virus (HIV) were examined in the CNS of two children with severe HIV encephalitis and myelitis. Using polymerase chain reaction-mediated DNA amplification and subsequent Southern analysis, proviral HIV gag sequences were identified in brain tissue of both patients. In situ hybridization using antisense oligonucleotide probes revealed abundant HIV gag and env/nef RNAs selectively in areas with histopathological evidence for HIV-induced tissue damage. The spinal cord of one patient exhibited a striking subpial accumulation of HIV RNAs strongly suggestive of a liquorigenic spread of the infection. HIV RNAs were typically associated with cells of the monocyte/macrophage lineage, as shown by a combined immunohistochemical and in situ hybridization procedure. The present study supports the view that the pattern and distribution of HIV-induced brain lesions is largely determined by the extent of focal HIV replication within the CNS.

Response Shift and Glycemic Control in Children With Diabetes.

BACKGROUND: The purpose of this study was to investigate the scale recalibration construct of response shift and its relationship to glycemic control in children with diabetes. METHODS: At year 1, thirty-eight children with type 1 diabetes attending a diabetes summer camp participated. At baseline and post-camp they completed the Problem Areas in Diabetes (PAID) questionnaire. Post-camp, the PAID was also completed using the 'thentest' method, which requires a retrospective judgment about their baseline functioning. At year 2, fifteen of the original participants reported their HbA1c. RESULTS: PAID scores significantly decreased from baseline to post-camp. An even larger difference was found between thentest and post-camp scores, suggesting scale recalibration. There was a significant positive correlation between year 1 HbA1c and thentest scores. Partial correlation analysis between PAID thentest scores and year 2 HbA1c, controlling for year 1 HbA1c, showed that higher PAID thentest scores were associated with higher year 2 HbA1c. CONCLUSION: Results from this small sample suggest that children with diabetes do show scale recalibration, and that it may be related to glycemic control.

Memory and attention problems in children with brain tumors at diagnosis

Purpose: Results from previous studies indicate that children with brain tumors (BT) might present with cognitive problems at diagnosis and thus before the start of any medical treatment. The question remains whether these problems are due to the underlying tumor itself or due to the high level of emotional and physical stress which is involved at diagnosis of a malignant disorder. All children with a de novo oncological diagnosis not involving the central nervous systems (CNS) are usually exposed to a comparable level of distress. However, patients with cancer not involving the CNS are not expected to show disease-related cognitive problems. Thus they serve as a well-balanced control group (CG) to help distinguish between the probable causes of the effect. Method: In a pilot study we analyzed an array of cognitive functions in 16 children with BT and 17 control patients. In both groups, tests were administered in-patient at diagnosis before any therapeutic intervention such as surgery, chemotherapy od irradiation. Results: Performance of children with BT was comparable to that of CG patients in the areas of intelligence, perceptual reasoning, verbal comprehension, working memory, and processing speed. In contrast, however, BT patients performded significantly worse in verbal memory and attention. Conclusion: Memory and attention seem to be the most vulnerable funstions affected by BT, with other functions being preserved at the time of diagnosis. It ist to be expected that this vulnerability might exacerbate the cognitive decline after chemotherapy and radiation treatment - known to impair intellectual performance. The findings highlight the need of early cognitive assessments in children with BT in order to introduce cognitive training as early as possible to minimize or even prevent cognitive long-term sequelae. This might improve long-term academic and professional outcome of these children, but especially helps their return to school after hospitalization.

Neurocognitive deficits in children with brain tumors at diagnosis

Survivors of brain tumors are faced with a high risk for a wide range of cognitive problems and learning difficulties. These problems are caused by the lesion itself and its surgical removal as well as by the treatments to follow (chemo- and/or radiation therapy). A few recent studies have indicated that children with brain tumors (BT) might exhibit cognitive problems already at diagnosis, i.e. before the start of any medical treatment. The aim of the present study was to investigate the "baseline" neuropsychological profile in children with BT in comparison to children with an oncological diagnosis not involving the central nervous system (CNS). 20 children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1 to 16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and its parents completed self-report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy or irradiation. Groups were comparable regarding age, gender and social economic status. Compared to the CG, patients with BTs performed significantly worse in tests of working memory, verbal memory and attention. In contrast the areas of perceptual reasoning, processing speed and verbal comprehension were preserved at this time. Younger children with BT were especially disadvantaged. Compared to aged matched children with malignancies not involving the CNS and older BT patients the young BT patients showed deficits in attention, working memory and verbal memory measures. Our results highlight the need for cognitive assessments and interventions early in the treatment process in order to minimize or even prevent academic difficulties as patients return to school.

Validation of the IMPACT-III quality of life questionnaire in Swiss children with inflammatory bowel disease

BACKGROUND AND AIMS Inflammatory bowel disease (IBD) frequently manifests during childhood and adolescence. For providing and understanding a comprehensive picture of a patients' health status, health-related quality of life (HRQoL) instruments are an essential complement to clinical symptoms and functional limitations. Currently, the IMPACT-III questionnaire is one of the most frequently used disease-specific HRQoL instrument among patients with IBD. However, there is a lack of studies examining the validation and reliability of this instrument. METHODS 146 paediatric IBD patients from the multicenter Swiss IBD paediatric cohort study database were included in the study. Medical and laboratory data were extracted from the hospital records. HRQoL data were assessed by means of standardized questionnaires filled out by the patients in a face-to-face interview. RESULTS The original six IMPACT-III domain scales could not be replicated in the current sample. A principal component analysis with the extraction of four factor scores revealed the most robust solution. The four factors indicated good internal reliability (Cronbach's alpha=.64-.86), good concurrent validity measured by correlations with the generic KIDSCREEN-27 scales and excellent discriminant validity for the dimension of physical functioning measured by HRQoL differences for active and inactive severity groups (p<.001, d=1.04). CONCLUSIONS This study with Swiss children with IBD indicates good validity and reliability for the IMPACT-III questionnaire. However, our findings suggest a slightly different factor structure than originally proposed. The IMPACT-III questionnaire can be recommended for its use in clinical practice. The factor structure should be further examined in other samples.

Coping is excellent in Swiss Children with inflammatory bowel disease: results from the Swiss IBD cohort study

BACKGROUND Inflammatory bowel disease (IBD) starting during childhood has been assumed to impair quality of life (QoL) of affected children. As this aspect is crucial for further personality development, the health-related quality of life (HRQOL) was assessed in a Swiss nationwide cohort to obtain detailed information on the fields of impairment. METHODS Data were prospectively acquired from pediatric patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by PCDAI and PUCAI. The age adapted KIDSCREEN questionnaire was evaluated for 110 children with IBD (64 with Crohn's disease 46 with ulcerative colitis). Data were analyzed with respect to established reference values of healthy controls. RESULTS In the KIDSCREEN index a moderate impairment was only found for physical wellbeing due to disease activity. In contrast, mental well-being and social support were even better as compared to control values. A subgroup analysis revealed that this observation was restricted to the children in the German speaking part of Switzerland, whereas there was no difference compared to controls in the French part of Switzerland. Furthermore, autonomy and school variables were significantly higher in the IBD patients as compared to controls. CONCLUSIONS The social support for children with IBD is excellent in this cohort. Only physical well-being was impaired due to disease activity, whereas all other KIDSCREEN parameters were better as compared to controls. This indicates that effective coping and support strategies may be able to compensate the burden of disease in pediatric IBD patients.

Alternative outcomes for the multiple breath washout in children with CF

BACKGROUND The lung clearance index (LCI) measured by multiple-breath washout (MBW) has been proposed as an outcome for clinical trials; however, MBW is time consuming and LCI can be affected by breathing pattern. We aimed to evaluate moment ratios and abbreviated LCI in school-aged children with mild-to-moderate CF lung disease. METHODS Using existing data from three studies we assessed the sensitivity of moment ratios and abbreviated LCIs to (i) detect mild-to-moderate CF lung disease and (ii) detect treatment effects after 4weeks of hypertonic saline or dornase alfa inhalation. MBW was measured by respiratory mass spectrometry using 4% "sulphur hexafluoride as a tracer gas. RESULTS Compared to the traditional LCI, moment ratios and abbreviated LCIs were similarly sensitive to detect CF lung disease. Moment ratios consistently demonstrated treatment effects, whereas abbreviated LCIs were less sensitive. CONCLUSIONS Both moment ratios and abbreviated LCI are suitable to differentiate health from disease. Sensitivity is decreased for abbreviated LCIs in interventional studies in mild CF lung disease.

Multiple breath washout is feasible in the clinical setting and detects abnormal lung function in infants and young children with cystic fibrosis.

BACKGROUND Cystic fibrosis (CF) lung disease starts in the first months of life often before the onset of clinical symptoms. Multiple breath washout (MBW) detects abnormal lung function in infants and young children in the laboratory setting. OBJECTIVE The aim of this study was to determine the feasibility of MBW in 0- to 4-year-old children with CF and non-CF controls in the clinical setting. METHODS Fourteen children with CF (mean age 1.3 ± 1.0 years) and 26 age-matched non-CF controls were sedated with chloral hydrate and MBW was performed with sulfur hexafluoride. RESULTS MBW measurements were successful in 27 of 40 children (67.5%). The mean lung clearance index (LCI) was significantly higher in CF patients compared to non-CF controls (p = 0.006). Further, the frequency of elevated LCI (z-score >1.96) was significantly increased in CF patients compared to controls (p = 0.0003). CONCLUSIONS We conclude that MBW is feasible and sensitive to detect abnormal lung function in infants and young children with CF in the clinical setting.