Assessment of acute asthma in children: do parents and healthcare providers speak the same language?

OBJECTIVE: Education and self-management plans enhance parents' self-efficacy in managing their child's asthma symptoms. By understanding how parents recognize and interpret acute asthma symptoms, we can compile patient information using terms that are familiar to parents. METHOD: Semi-structured interviews were carried out with 27 parents of children with asthma aged 2-12 years. The interviewees were selected from three groups: parents of children admitted for acute asthma, parents of children receiving outpatient asthma care, and parents who had access to a self-management plan. Parents were invited to report symptoms they would associate with acute asthma. Subsequently, parents were queried about their recognition of symptoms from a predefined list and asked to explain how they would assess these symptoms in case their child would experience an attack of acute asthma. RESULTS: The most frequently reported symptoms for acute asthma were shortness of breath (77.8%) and coughing (63%). Other signs such as retractions, nasal flaring, and wheezing were reported by less than 25% of the parents. All parents recognized shortness of breath, wheezing and gasping for breath from a predefined list of medical terms. Retractions and nasal flaring were recognized by 81.5% and 66.7% of the parents, respectively. Recognizing the medical terms did not necessarily translate into parents being able to explain how to assess these symptoms. CONCLUSION: Parents and healthcare professionals do not always speak the same language concerning symptoms of acute asthma. This may hamper timely recognition and adequate self-management, highlighting the necessity to adjust current medical information about acute asthma.

Education and self-management plans enhance parents' self-efficacy in managing their child's asthma symptoms.Parents may identify symptoms of acute asthma differently than healthcare providersInformation material about acute asthma should be adjusted to empower parents to decide when to commence treatment and when to seek medical attention.

Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the Netherlands.

OBJECTIVE: To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA). DESIGN: A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9% confidence intervals (CI). RESULTS: The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR < 1 was found, other comorbidities showed no association with exposure to knee OA. For 26 comorbidities, exposure to hip OA showed a HR larger than 1. The largest were found for polymyalgia rheumatica 1.81 (1.41-2.32) and fibromyalgia 1.70 (1.10-2.63). All other comorbidities showed no associations with hip OA. CONCLUSION: This study showed that many comorbidities were diagnosed more often in patients with knee or hip OA. This suggests that the management of OA should consider the risk of other long-term-conditions.

Medical students' perception of general practice: a cross-sectional survey.

BACKGROUND: An increase in the demand for general practitioners is expected in many countries, but only a minority of medical students consider a career in general practice. More detailed and up-to-date knowledge about medical student's perception of general practice would be helpful for efforts to encourage medical students to consider a career in general practice. METHODS: We performed a cross-sectional single center survey among Dutch medical students to evaluate their perception of general practice at three different stages in their study: Ba1: first-year bachelor students; Ba3: third-year bachelor students; Ma3: third-year master students. The impact of different factors on their attitudes and perceptions was quantified. A multivariate logistic regression was performed with 'interest in general practice' as the outcome variable. RESULTS: The median age for Ba1 was 18 (IQR: 18-19) and 71.5% were female, for Ba3 the median age was 20 (IQR: 20-21) and 70.6% were female and for Ma3 the median age was 25 years (IQR: 24-26) and 73.3% were female. On average, 31.2% of the respondents had a migration background. The mean response rate for this study was 77.1%. Of the participating Ba1 students (n = 340) only 22.4% considered working as a GP after medical school; for Ba3 students (n = 231) this percentage was 33.8%, and for Ma3 students (n = 210) it was significantly higher at 70.5%; in the final multivariate model this corresponded to an odds ratio (OR) of 4.3 (95%-CI:2.6-6.9) compared to Ba1 students. The strongest predictor in the final model was the opinion that general practice provides a pleasant working environment (OR 9.5; 95%-CI: 6.2-14.5). CONCLUSION: This study showed that multiple factors are significantly related to medical students' interest in general practice. Although students believed that general practice does not have a high status within the medical profession, they acknowledged the social importance and the pleasant working environment of general practice. Knowledge obtained in this study can be used when designing a medical curriculum or a general practice course.

Asthma control is not associated with physical activity level in children with asthma during regular follow-up.

OBJECTIVE: Engagement in physical activity (PA) is one of the important aims of long-term asthma treatment. The objective of this study is to evaluate whether improvement of asthma control is associated with enhanced PA during regular follow-up in children with asthma. METHODS: Children, 6-18 years, with asthma were eligible for inclusion when their asthma was uncontrolled at a regular follow-up visit. Participants completed a seven-day recall questionnaire to assess engagement in different physical activities (Physical Activity Questionnaires for Children) at baseline and at the time asthma control was achieved according to predefined criteria. They were also instructed to wear an accelerometer (ActigraphTM GT1M) for seven consecutive days at these timepoints. RESULTS: Thirty children (21 boys), aged 10.5 (2.9) years, with uncontrolled asthma were included. After a median (IQR) follow up time of 163 (94-253) days PA was assessed again. Accelerometer obtained moderate vigorous PA (median (IQR) 56 (43-66) versus 53 (35-63) minutes) as well as self-reported PA (median (IQR) PAQ score 7.4 (5.9-10.1) versus 7.2 (6.5-11.0)) were not significantly different at the time of uncontrolled and controlled asthma. Moderate vigorous PA increased in 46.2%, was comparable in 23.1%, and decreased in 30.7% of patients, respectively. Self-reported PA increased in 19.0%, was comparable in 52.4%, and decreased in 28.6% of patients, respectively. CONCLUSIONS: Based on the results of this study we conclude that asthma control is not associated with self-reported and accelerometer obtained level of physical activity during regular follow-up in children with asthma.

Practice variation among Dutch paediatricians in palivizumab prescription rates: the importance of parental counselling approach.

AIM: To investigate differences in palivizumab prescription rates between Dutch paediatricians, and the role of parent counselling in this practice variation. METHODS: A retrospective chart review of premature infants <32 weeks of gestation, aged less than six months at the start of the winter season, born between January 2012 and July 2014, in three secondary hospital-based paediatric practices in the Netherlands. RESULTS: We included 208 patients, 133 (64%) of whom received palivizumab. Prescription rates varied considerably between the three hospitals: 8% (6/64), 89% (32/36) and 99% (97/98). A noticeable difference in the way parents were counselled about palivizumab was the use of the number needed to treat (NNT). In the hospital with the lowest prescription rate (8%), an NNT of 20 to prevent one hospitalisation was explicitly discussed with parents. Bronchiolitis-related hospital admissions occurred in 11.3% of patients receiving palivizumab compared to 20.0% in nonimmunised infants (p = 0.086). CONCLUSION: Considerable practice variation exists among Dutch paediatricians regarding palivizumab prescription rates. The counselling method seems to play an important role. Presenting palivizumab prophylaxis as a preference-sensitive decision, combined with the explicit use and explanation of an NNT, leads many parents to refrain from respiratory syncytial virus immunisation.

[Treatment of asthma in children: revised international guidelines not suitable for use in the Netherlands]. / Behandeling van astma bij kinderen: herziene internationale richtlijnen niet geschikt voor gebruik in Nederland.

The most recent revision of the Global Initiative for Asthma (GINA) guidelines for the treatment of asthma propose to classify and monitor the disease based on asthma control. This concept is attractive but not evidence based. Based on methodological shortcomings the revised GINA guidelines fail to meet the standards for evidence-based guidelines. Inhaled corticosteroids are and remain the cornerstone of asthma management in children. Extensive explanation to children and their parents, intensive followup, and instruction of and adherence to a correct inhalation technique are key factors in effective treatment of asthma in children.

The Ch14.18-GM-CSF fusion protein is effective at mediating antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro.

Granulocyte/macrophage-colony stimulating factor (GM-CSF) is very effective at enhancing antibody-dependent cellular cytotoxicity (ADCC) mediated by granulocytes and monocytes. Recently, a fusion protein consisting of GM-CSF and chimeric human/mouse anti-ganglioside G(D2) antibody Ch14.18 (Ch14.18-GM-CSF) has been generated to improve the effectiveness of immunotherapy by directing GM-CSF to the tumor microenvironment and prolonging its relatively short half-life. In this study, we examined the ability of this fusion protein to enhance the in vitro killing of G(D2)-expressing human neuroblastoma cells by granulocytes and mononuclear cells, as well as by complement. The Ch14.18-GM-CSF fusion protein was equally effective as the combination of equivalent amounts of free Ch14.18 and GM-CSF in mediating the killing of NMB7 neuroblastoma cells by granulocytes from seven of eight neuroblastoma patients. The fusion protein was also equally effective as the combination of Ch14.18 and GM-CSF in mediating ADCC by neuroblastoma patients' mononuclear cells. In addition, the fusion protein was as effective as Ch14.18 alone in directing complement-dependent cytotoxicity against NMB7 cells. Our results demonstrate that the biological activities expressed by ADCC and complement-dependent cytotoxicity of both monoclonal antibody Ch14.18 and GM-CSF are retained by the Ch14.18-GM-CSF fusion protein and lend further support for future clinical trials of this fusion protein in patients with neuroblastoma.

Cloning and expression of the dermonecrotic toxin gene of Pasteurella multocida ssp. multocida in Escherichia coli.

A DNA library of Pasteurella multocida ssp. multocida strain CVI 47459 was constructed in the Lambda GEM-11 vector. Recombinant clones that encoded dermonecrotic toxin (DNT) were identified immunologically with antiserum raised against purified DNT. By comparing the DNA restriction maps of the immunoreactive recombinants, we located the DNT gene. Hybridization studies with 10 strains of P. multocida ssp. multocida suggested that strains that do not produce the DNT do not contain sequences homologous to the DNT gene.

Poor inhalation technique, even after inhalation instructions, in children with asthma.

The aim of this study was to evaluate the effect of instructions to children with asthma (given by general practitioners or by pharmacy assistants) on how to inhale from metered dose inhalers with spacers (MDI/s) or dry powder inhalers (DPI). We scored inhalation technique of asthmatic children according to criteria defined by the Netherlands Asthma Foundation, and related the performance to the inhalation instructions given. For each inhaler, a number of steps were considered essential for reliable drug delivery. Patients newly referred for asthma were asked to demonstrate their inhalation technique and to fill out a questionnaire on the inhalation instruction received prior to referral. Children participating in a clinical trial, who had received repeated comprehensive inhalation instructions, served as a control group. Sixty-six newly referred patients (1-14 years of age, median age 5 years; 37 boys) and 29 control patients (5-10 years of age, median age 7 years; 21 boys) completed the study. Sixty patients (91%) had received inhalation instruction prior to referral. Only 29% of these patients, using a dry powder inhaler, performed all essential steps correctly, compared to 67% of children using a metered dose inhaler/spacer combination (P < 0.01). Children who had received comprehensive inhalation instructions with repeated checks of proper inhalation technique at the pharmacy or in the clinical trial setting were more likely to perform all essential steps correctly (79% and 93%, respectively) than children who had received a single instruction by a general practitioner (39%, P < 0.01). Many asthmatic children use their inhalers devices too poorly to result in reliable drug delivery, even after inhalation instruction. Comprehensive inhalation instruction and repeated check-ups are needed to assure reliable inhalation technique.

Role of macrophage colony-stimulating factor in the differentiation and expansion of monocytes and dendritic cells from CD34+ progenitor cells.

The present study focused on whether it is possible to expand monocytic cells from CD34+ progenitor cells by using macrophage colony-stimulating factor (M-CSF) in the absence and presence of mast cell growth factor (MGF) and IL-6. It was demonstrated that CD34+ cells differentiate without expansion to functional mature monocytic cells in the presence of M-CSF or combinations of M-CSF plus IL-6 and MGF. A different response pattern was observed for the number of clonogenic cells. The addition of IL-6 or both IL-6 and MGF to M-CSF containing cultures resulted in significant higher numbers of colony-forming unit-macrophage (CFU-M) as tested in clonogenic and 3H-thymidine assays. Furthermore, M-CSF plus both IL-6 and MGF appeared to be the most potent combination to preserve the monocytic precursor in cell suspension culture assays. These results indicate that IL-6 and MGF in conjunction with M-CSF affect CD34+ cells especially at precursor level without distinct effect on the more mature stages. Secondly we studied whether M-CSF is only critical for the monocytic lineage or also affects dendritic cell (DC) development. Indeed, we were able to culture CD83+ DC from CD34+ progenitor cells in the presence of M-CSF in conjunction with TNF-alpha, IL-4, and MGF although their absolute number is almost threefold lower than the number of CD83+ cells yielded from GM-CSF plus TNF-alpha, IL-4, and MGF stimulated CD34+ cells.

[The peak flow meter: limited role in the diagnosis and follow-up of children with asthma]. / De piekstroommeter: beperkte rol in de diagnostiek en follow-up bij kinderen met astma.

The peak flow meter is commonly used to diagnose and follow up asthma in children and adults. This practice, however, is not supported by evidence from the literature. The amount of overlap in peak flow level and variation between healthy and asthmatic subjects precludes the use of peak flow diaries as a reliable tool in diagnosing asthma. It has also become clear that the correlation between peak flow variation and other indices of asthma severity is inconsistent. Moreover, children and adults have been shown to be unreliable in keeping peak flow diaries: 20-40% of all recorded values in a peak flow diary are invented, and another 25% are recorded inaccurately. Finally, self-management programmes for asthma have been shown to be effective, whether they incorporate peak flow monitoring or not. Therefore, peak flow registration cannot be recommended for the routine diagnosis and follow-up of asthma. In isolated cases however, such as patients who poorly perceive a deterioration of their asthma, or when it is unclear what triggers asthmatic symptoms, the peak flow meter can be useful.

Education, self-management and home peak flow monitoring in childhood asthma.

Current asthma guidelines focus on self-management by the patient, in which monitoring of peak flow plays an important role. To be able to participate in self-management, the patient must be educated rigorously on pathophysiological mechanisms of the disease, principles of treatment, correct inhalation technique, treatment goals and the action to take when symptoms or peak flow worsen. This is a time-consuming but important and worthwhile task. The pivotal role of home peak flow monitoring in asthma self-management is based on the assumptions that peak flow variation is a useful measure of disease activity and that peak flow diaries are kept reliably by patients. There is now evidence that neither of these assumptions are true. Self-management plans based on education alone are just as effective as those incorporating peak flow monitoring. Education, therefore, is the most important component of asthma self-management, and home peak flow monitoring is not needed in the majority of asthmatic children.

Peak flow diaries in childhood asthma are unreliable.

BACKGROUND: A study was undertaken to investigate the compliance with and accuracy of peak flow diaries in childhood asthma. METHODS: Forty asthmatic children (5-16 years) were asked to perform peak flow measurements twice daily for 4 weeks by means of an electronic peak flow meter and to record values in a written diary. Patients and parents were unaware that the device stored the peak flow values on a microchip. In random order, half of the patients were only told that the device allowed for more accurate assessment of peak flow while the other half were told that accurate recording of peak flow was important because the results would be used in guiding adjustments to treatment. Data in the written diary (reported data) were compared with those from the electronic diary (actual data). RESULTS: In the entire study population the mean (SD) actual compliance (77.1 (20.5)%) was much lower than the mean reported compliance (95.7 (9.1)%) (95% CI for difference 12.7% to 24.4%) The percentage of correct peak flow entries decreased from 56% to <50% from the first to the last study week (p<0.04), mainly as a result of an increase in self-invented peak flow entries. Results were comparable for both groups. For incorrect peak flow entries the mean difference between written and electronically recorded entries ranged from -72 to 34 l/min per patient. CONCLUSIONS: Peak flow diaries kept by asthmatic children are unreliable. Electronic peak flow meters should be used if peak flow monitoring is required in children with asthma.

The nitrate reductase and nitrite reductase operons and the narT gene of Staphylococcus carnosus are positively controlled by the novel two-component system NreBC.

In Staphylococcus carnosus, the nreABC (for nitrogen regulation) genes were identified and shown to link the nitrate reductase operon (narGHJI) and the putative nitrate transporter gene narT. An nreABC deletion mutant, m1, was dramatically affected in nitrate and nitrite reduction and growth. Transcription of narT, narGHJI, and the nitrite reductase (nir) operon was severely reduced even when cells were cultivated anaerobically without nitrate or nitrite. nreABC transcripts were detected when cells were grown aerobically or anaerobically with or without nitrate or nitrite. NreA is a GAF domain-containing protein of unknown function. In vivo and in vitro studies showed that NreC is phosphorylated by NreB and that phospho-NreC specifically binds to a GC-rich palindromic sequence to enhance transcription initiation. This binding motif was found at the narGHJI, nir, and narT promoters but not at the moeB promoter. NreB is a cytosolic protein with four N-terminal cysteine residues. The second cysteine residue was shown to be important for NreB function. In vitro autophosphorylation of NreB was not affected by nitrate, nitrite, or molybdate. The nir promoter activity was iron dependent. The data provide evidence for a global regulatory system important for aerobic and anaerobic metabolism, with NreB and NreC forming a classical two-component system and NreB acting as a sensor protein with oxygen as the effector molecule.

Interlocked RNA circle formation by a self-splicing yeast mitochondrial group I intron.

RNA containing the aI3 group I intron of the yeast mitochondrial gene encoding cytochrome oxidase subunit I shows self-splicing in vitro. The excised intron, comprising 1514 nucleotides, is partially split into an upstream portion, containing the intronic reading frame, and a downstream portion, containing the typical group I conserved sequence elements. Full-length intron RNA and intron parts occur in linear and circular form. In the transesterification reactions leading to circle formation, only the guanosine nucleotide added during splicing is removed. Reincubation of isolated, complete circular intron RNA under self-splicing conditions leads to formation of free subintronic RNA circles. Under similar conditions, purified linear intron RNA gives rise to a number of circular and linear products, one of which consists of interlocked subintronic RNA circles. These observations suggest that the intron RNA possesses a dynamic structure in which subtle alterations in folding result in the formation of RNA products with different topology.

Morphometric analysis of the corneal endothelium with three different specular microscopes.

The morphometry of the central corneal endothelium of 10 eyes in 10 subjects was analyzed with three different specular microscopes. Computer-assisted analysis was performed with only two microscopes (Zeiss and Keeler Konan sp 3300) because the third microscope (Topcon sp 1000) could not be adapted to our computerized system. With this Topcon microscope a grid with standard densities was used to compare the images with, in addition, we also performed manual cell counting on the same Topcon images. The coefficient of variation of the cell analysis of three different images per cornea with the four methods varied between 3.4 and 4.7 percent. One-way analysis of variance showed a significant difference between the Zeiss and the other microscopes. So only the Keeler Konan and the Topcon microscopes could be used interchangeably. The computerized image analysis permitted also an evaluation of the hexagonality. The results of polygonality were not significantly different between the Zeiss and the Keeler Konan. For clinical purposes the Topcon specular microscope is more advantageous than the other two methods, since it is the most rapid way to record and analyze specular images. But for more precise measurements an image processing system is indispensable.

Specificity of DNA probes for the detection of toxigenic Pasteurella multocida subsp. multocida strains.

Five DNA probes directed against different regions of the gene that encodes the dermonecrotic toxin of Pasteurella multocida subsp. multocida were examined for their ability to identify toxigenic P. multocida subsp. multocida strains. The specificities of the probes were studied with 96 strains of P. multocida subsp. multocida and 22 strains of 11 other bacterial species. Results of colony hybridization assays using these probes indicated that two of the five probes have potential diagnostic value.

Effect of bacterial filters on spirometry measurements.

Lung function measurements with and without a disposable bacterial filter were compared in 60 children. Although statistically significant, the reduction of lung function measurements caused by using bacterial filters was small and clinically irrelevant (2-4% of predicted for forced expiratory volume in one second and vital capacity).

Determinants of correct inhalation technique in children attending a hospital-based asthma clinic.

UNLABELLED: Many children with asthma use their inhaler device incorrectly even after comprehensive inhalation instruction. The aim of this study was to identify factors associated with correct inhalation technique. Two hundred children with asthma demonstrated their inhalation technique. Patient characteristics and the components of inhalation instructions they had received were compared for children demonstrating a correct or incorrect inhalation technique. In addition, the inhalation technique of 47 newly referred patients was followed-up prospectively after repeated comprehensive instruction sessions. Seventy-eight percent of all patients demonstrated a correct inhalation technique. Patients who had received repeated instruction sessions and patients who had previously been asked to demonstrate the use of their inhaler during an instruction session were more likely than other children to demonstrate a correct inhalation technique (p < 0.001 and p = 0.03, respectively). Multiple logistic regression analysis showed that repetition of instructions was significantly associated with a correct inhalation technique (odds ratio (OR) 8.2, 95% CI 3.2-21.5; p < 0.0001) irrespective of type of inhaler used. Demonstration of the inhaler use by the patient was significantly associated with a correct inhalation technique for patients using a metered dose inhaler plus spacer device (OR 3.5, 95% CI 1.0-12.6; p = 0.05). but not for patients using a dry powder inhaler (OR 1.6, 95% CI 0.4-6.4; p = 0.54). The number of newly referred patients demonstrating a correct inhalation technique improved from 57.4% to 97.9% after three comprehensive instruction sessions. CONCLUSION: Inhalation instruction should be given repeatedly to achieve and maintain correct inhalation technique in asthmatic children.