Impact of multiplex respiratory virus testing on antimicrobial consumption in adults in acute care: a randomized clinical trial.

OBJECTIVES: Inappropriate use of antibiotics is associated with development of antimicrobial resistance. In respiratory infections it is often difficult to differentiate between viral and bacterial infections, and empirical treatment is common. Enhanced viral testing is expected to clarify clinical decision-making and reduce the prescription of antibacterial agents, but the impact of such information on patient care is unclear. METHODS: We conducted a (1:1) randomized controlled clinical trial involving 998 adults with respiratory symptoms, fever, chest pain or poor general condition in the emergency unit of a tertiary hospital. Multiplex PCR results for 496 patients were available in 24 hours (intervention group) and those for the remaining 502 patients were available in 7 days (control group). Our primary outcome measures were the duration of hospitalization and the consumption of antibiotics within 30 days of enrolment. RESULTS: In all, 841 of 998 (84%) patients had respiratory symptoms at study entry. A respiratory virus was detected in 175 (17.5%). The mean duration of hospitalization was 4.2 days (SD 5.4) in the intervention group and 4.1 days (SD 4.9) in the control group (difference 0.1, 95% CI -0.5 to 0.6, p 0.810). The mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD 11.4) in the control group (difference 0.9, 95% CI -0.6 to 2.4, p 0.235). CONCLUSIONS: Multiplex PCR testing for respiratory viruses with results available within 24 hours did not reduce the consumption of bacterial antibiotics or the length of hospital stay in adults presenting with respiratory symptoms, fever, chest pain or reduced general condition in acute care.

Recurrent acute otitis media detracts from health-related quality of life.

OBJECTIVE: Acute otitis media causes discomfort to children and inconvenience to their parents. This study evaluated the quality of life in children with recurrent acute otitis media aged less than 24 months. METHODS: Quality of life was evaluated in 149 children aged 10 to 24 months who were referred to the Oulu University Hospital on account of recurrent acute otitis media. The children were treated with or without surgery. Age-matched controls were selected randomly from the general child population. Parents completed the Child Health Questionnaire. RESULTS: The children with recurrent acute otitis media had a significantly poorer quality of life than control children. The control children with a history of a few acute otitis media episodes had a significantly poorer quality of life than those without any such history. The quality of life of the children with recurrent acute otitis media improved during the one-year follow up, regardless of the treatment, but did not reach the same level as healthy children. CONCLUSION: Acute otitis media detracted from quality of life when a generic measure was used. The mode of treatment used to prevent further recurrences of acute otitis media did not influence quality of life improvement.

Tonsillar microbiota in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a childhood febrile syndrome of unknown origin that is often cured with tonsillectomy. We aimed to compare the bacterial microbiota of the tonsils removed from PFAPA patients with those of controls. We used next-generation sequencing technology to investigate the bacterial microbiota of the tonsils of 30 PFAPA patients and 24 controls. We found significant differences in the presence and relative abundance of many bacteria between PFAPA cases and controls. For example, cyanobacteria, potential producers of microcystins and other toxins, were more common in the case samples (14/30, 47 %) than in the controls (4/24, 17 %, p = 0.02), and the mean relative abundance of cyanobacteria was higher in the case samples (0.2 %) than in the controls (0.01 %, p = 0.01). Streptococci were present in all samples in both groups, but their mean relative abundance was lower in the case samples (3.7 %) than in the controls (9.6 %, p = 0.01). Typical nasopharyngeal microbes such as fusobacteria, Prevotella, Tannerella, Porphyromonas, and Parvimonas dominated the microbiota of the tonsils in both groups. The microbiota of the tonsils removed from PFAPA patients differed significantly from those of the controls. Tonsillar microbiota may play a role in triggering the inflammatory processes that lead to symptoms of PFAPA.

Initial oxygen saturation values can predict the need to hospitalise children with mild wheezing.

AIM: Mild wheezing during respiratory infections is a common cause of paediatric hospital admissions. This study aimed to identify factors predicting this condition in children over six months of age. METHODS: We reviewed the medical records of 539 children, aged 6 months to 16 years, who visited the emergency department because of wheezing during respiratory infection. Mild disease was defined as hospital stays of less than 48 h and severe disease was staying at least 48 h or being treated in intensive care. Patients with an initial oxygen saturation value (SaO2 ) below 90% were analysed separately. RESULTS: Most (87%) of the 539 patients had mild disease, 6% had a severe disease and 7% had an initial SaO2 below 90%. The area under the receiver operating characteristic (ROC) curve for the initial SaO2 predicting mild disease was 0.75 (95% CI 0.53-0.97), and the optimal cut-off value was 93%. An initial SaO2 >93% had a negative predictive value of 93%. Although 270 patients (50%) were hospitalised, only 140 (26%) would have been admitted using an optimal cut-off of SaO2 ≤93%. CONCLUSION: An initial SaO2 >93% reflects a mild course of acute wheezing and using this cut-off point could have almost halved hospital admissions.

Infants under 6 months with bronchiolitis are most likely to need major medical interventions in the 5 days after onset.

AIM: This study examined the need for, and timing of, major medical interventions (MMIs) in infants under 6 months of age with bronchiolitis. METHODS: We reviewed the medical records of 353 children who visited our emergency department with bronchiolitis. MMI was defined as the need for any of the following interventions during admission: supplementary oxygen, intravenous fluids, intravenous antibiotics or admission to the intensive care unit. RESULTS: Altogether 19% of the 353 patients required a MMI and 3% had apnoea. The patients with apnoea were all under 2 months of age, and 90% had a respiratory syncytial virus (RSV) infection and 40% had been born prematurely. The risk of needing a MMI continued for up to 5 days after disease onset. A positive RSV test predicted a MMI with an odds ratio (OR) of 11.5 (95% CI 2.6-50.5), and a fever of over 38°C predicted a MMI with an OR of 3.5 (95% CI 1.4-8.8). Each 1% increase in the initial oxygen saturation value was associated with a decreased risk of MMI (OR 0.7, 95% CI 0.6-0.8). CONCLUSION: Infants under 6 months of age with bronchiolitis were most likely to need MMIs in the first 5 days after disease onset.

Post-discharge follow-up of hospital-associated infections in paediatric patients with conventional questionnaires and electronic surveillance.

BACKGROUND: Viral infections are common causes of hospital-associated infections (HAIs) in paediatric patients, with most of these infections only becoming evident after discharge. AIM: To analyse the benefits and costs of conventional and electronic surveillance methods for conducting HAI follow-ups. METHODS: A comparison was made between response rate, time required per patient and costs to the healthcare system of conventional and electronic surveillance methods (sms, e-mail, telephone call). FINDINGS: Altogether 1927 patients participated in the conventional followed up in 2001-2003, of whom 1175 (61%) returned the questionnaire; during the electronic surveillance period in 2005-2007, 2309 patients were followed-up in hospital, and 1940 of them (84%) returned the post-discharge information to us. The time needed by HCWs was 33 min per patient in the conventional follow-up and 13 min in the electronic follow-up, the total costs per patient being €15.07 and €13.61 respectively. A decrease of 17.1% in annual expenses was achieved with the electronic follow-up. The incidence of HAI was 8.4% in the conventional period and 12.2% in the electronic surveillance period, most cases becoming symptomatic after hospitalization. CONCLUSION: Electronic data collection was a convenient way of implementing a continuous HAI follow-up, achieving both a higher participation rate and lower costs.

Hospital-associated infections in children: a prospective post-discharge follow-up survey in three different paediatric hospitals.

BACKGROUND: Reported viral hospital-associated infection (HAI) frequencies have ranged from 1% to 24% between paediatric wards and hospitals. Reasons for this variation remain unclear. AIM: To evaluate the rate of viral HAIs and risk factors in three different paediatric hospitals. METHODS: Data were collected prospectively for two years in one infectious disease ward and three general paediatric wards in Finland and Switzerland. Infections were recorded during the hospitalization and one week after discharge. Ward-specific risk factors for HAIs within each ward were searched by using multivariate logistic regression analysis. FINDINGS: Altogether 5119 patients were hospitalized. Total HAI frequency was 12.2%, with 2.4% of the patients developing HAI in hospital, most often gastroenteritis, and 9.8% [95% confidence interval (CI): 8.9-10.8%] within 72 h of discharge. HAI rates varied from 5.8% to 17.1% between the wards, the highest rate being in a general paediatric ward where shared rooms were common and active cohorting according to viral aetiology was not done. Shared room (OR: 5.45; 95% CI: 2.44-12.2 in a general ward treating infants), longer hospitalization (OR: 1.42 per day; 95% CI: 1.20-1.67 in an infectious disease ward) and young age (OR: 0.71 per year; 95% CI: 0.51-0.98 in general paediatric ward for children aged >1 year) increased risk of HAI in hospital. CONCLUSION: Most viral HAIs in paediatric wards become evident after discharge. Single room bedding appears to be effective in preventing HAIs, especially the spread of respiratory viruses. It also appears that caring for patients with contagious diseases in a separate unit is advantageous.

Occurrence of vesicoureteral reflux in children.

AIM: The reported low occurrence of vesicoureteral reflux in the general population seems implausible. We wanted to test the hypothesis that reflux is more common and more independent of urinary-tract infection than has previously been thought. METHODS: We tested our hypothesis by analysing the characteristics of 406 consecutive children aged <5years who had been referred for consultation because of urinary-tract infection. Using data on their urine samples, we evaluated the reliability of the urinary-tract infection diagnosis and analysed the frequencies of vesicoureteral reflux and abnormal ultrasound findings in three reliability groups (A: certain urinary-tract infection, B: possible and C: improbable). RESULTS: The occurrence of reflux was the same irrespective of the diagnostic reliability of urinary-tract infection (A: 98/276 [36%] versus B: 13/46 [28%] versus C: 9/25 [36%]). Most of the abnormal ultrasound findings (58/71, 80%) were found among patients with a certain diagnosis (Group A). CONCLUSION: We suggest that vesicoureteral reflux is more common in children even without urinary-tract infection than has been thought previously. The guidelines recommending a search for reflux by means of voiding cystourethrography should be reconsidered.

Cardiac troponin-I as a screening tool for myocarditis in children hospitalized for viral infection.

AIM: The incidence of myocarditis in children is uncertain because patients with minor symptoms can remain undiagnosed. We hypothesized that screening all children who are hospitalized for an acute infection with troponin-I (TnI) would reveal myocarditis cases and performed a prospective screening study. METHODS: Between October 2005 and July 2008, a blood sample for TnI measurement was taken every time a sample for C-reactive protein measurement was drawn. If TnI value was above the screening limit (0.06 microg/L), electrocardiogram (ECG) and cardiac ultrasound were performed. TnI measurements were repeated until at normal level. RESULTS: Altogether, 1009 children were screened during the 33 months. TnI was above the screening limit (0.06 microg/L) in six children. None of them had any signs of myocarditis in ECG or cardiac ultrasound. Five of those six children were younger than 30 days. All had a respiratory infection as a cause for hospitalization, three of which was caused by RSV. In four children, all younger than 30 days, TnI levels remained high (>0.37 microg/L) for two months, but decreased after that to normal levels. CONCLUSION: The incidence of myocarditis during viral infections is low and a routine TnI screening for asymptomatic myocarditis is not useful.

Finland introduces rotavirus vaccine into the national vaccination programme in September 2009.

Supported by an economic evaluation, rotavirus vaccine is introduced into the national immunisation schedule in Finland. The vaccination programme has been estimated to be reasonably cost-effective. Given at the age of two, three and five months, the vaccine is expected to prevent annually in Finland among children under the age of five years approximately 2,000 rotavirus diarrhoea episodes needing hospitalisation, and over 10,000 outpatient visits. The impact of the programme will be evaluated in 2011 by repeating the economic analysis and carefully monitoring adverse events.

Hospital-associated infections during and after care in a paediatric infectious disease ward.

Viruses are important causes of paediatric hospital-associated infections (HAIs). We evaluated the frequency of viral HAIs during hospitalisation and after discharge in a paediatric infection ward. Data were collected prospectively for two years with follow-up questionnaires in which parents reported symptoms of new infections. Infections occurring >72 h after admission to hospital or <72 h after discharge were regarded as hospital-associated. The mean age of patients was 3.0 years and the mean hospitalisation time 3.0 days. Twenty-one out of the 1927 patients [1.1%, 95% confidence interval (CI): 0.7-1.7] developed an HAI during hospitalisation, in every case diarrhoea. A total of 1175 (61%) questionnaires were returned. In all, 86 children (7.3%, 95% CI: 5.9-9.0) had new symptoms within 72 h of discharge, most often diarrhoea (49%). Older age protected against HAI [odds ratio (OR, per year in age): 0.92; 95% CI: 0.85-0.99; P=0.02]. Among the patients hospitalised for respiratory infections, a shared room increased the risk of HAI (OR: 2.3; 95% CI: 1.1-4.8; P=0.03). Eight percent of the patients in our ward, where alcohol hand gel is actively used and single rooms are common, developed an HAI. Eighty percent of the HAIs appeared at home, which emphasises the importance of post-discharge follow-up.

A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

OBJECTIVE: We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. STUDY DESIGN: Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred. RESULTS: Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy. CONCLUSION: Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA.

Nasopharyngeal dimensions in magnetic resonance imaging and the risk of acute otitis media.

BACKGROUND: We have previously found by lateral cephalometry an association between nasopharyngeal anatomy and the risk of acute otitis media (AOM). We evaluate here the association of nasopharyngeal dimensions in magnetic resonance imaging (MRI) with the occurrence of AOM in otherwise healthy children. METHODS: Sixty-one healthy children (mean age 5.7 years, range 3.9-6.9) were recruited from child care centres. The parents filled in a questionnaire on the child's history of ear infections and adenoidectomy. MRI was performed with a 4 mm slice thickness during an upper respiratory infection. Five dimensions and two angles expressing the structure of the bony nasopharynx were measured in sagittal images. RESULTS: The dimension from the caudal edge of the septum to the midpoint of the sella, reflecting the height of the nasopharynx, was on average 2.2 mm smaller in the children who had had AOM attacks during the last 12 months than those without attacks (95% confidence interval (CI) 0.9 to 3.4, p=0.001) and the nasal base angle was on average 2.1 degrees smaller (95% CI 0.7 to 3.5, p=0.004). These differences remained significant after adjustment for age, sex and previous adenoidectomy in the logistic modelling. A history of adenoidectomy did not have any effect on the dimensions. CONCLUSIONS: The nasopharynx was smaller in the children with AOM attacks during the last year. The value of this finding for predicting susceptibility to recurrent AOM and directing preventive procedures should be evaluated.

Serum concentrations of interferon-gamma and intercellular adhesion molecule-1 eight years after an early respiratory syncytial virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) infection may influence the development of recurrent wheezing and atopy, but the mechanisms are unclear. OBJECTIVE: The purpose was to evaluate serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), CD14, IgE, IL-5 and IFN-gamma in children 6-10 years after an RSV infection and their correlation with subsequent asthma and atopy. METHODS: Fifty-one subjects admitted to hospital for RSV infection during the first year of life and controls matched for birth date and sex underwent clinical examinations including lung function, skin prick and blood tests. RESULTS: The RSV subjects had significantly higher serum concentrations of IFN-gamma and sICAM-1 than the controls (for IFN-gamma 224.9 pg/mL (standard deviation (SD) 271.3) vs. 187.1 pg/mL (372.9), difference 37.8 pg/mL, 95% confidence interval (CI) -90.3 to 166.0, P = 0.05; for sICAM-1 170.2 ng/mL (SD 63) vs. 147.8 ng/mL (SD 57), difference 22.4 ng/mL, 95% CI -1.4 to 46.1, P = 0.04). The RSV subjects with asthma had significantly higher concentrations of IFN-gamma than the controls with asthma, and the RSV subjects with wheezing during the previous 12 months had significantly higher concentrations of both IFN-gamma and sICAM-1 than the controls with wheezing. CONCLUSIONS: Children hospitalized for RSV infection in infancy still differ in IFN-gamma and sICAM-1 production 6-10 years after the infection. The data suggest that the pathomechanism of asthma and wheezing after an early RSV infection may be different from that of children without an early RSV infection.

Association of an early respiratory syncytial virus infection and atopic allergy.

BACKGROUND: Respiratory syncytial virus (RSV) causes postbronchiolitic wheezing but its role in allergic sensitization is controversial. The purpose of the study was to examine the effect of an early RSV infection on allergic sensitization. METHODS: Seventy-six subjects were examined 6-10 years after hospitalization for RSV infection during the first year of life. Fifty-one subjects (68%) attended clinical studies and 25 filled in a questionnaire. The study protocol included lung function, skin-prick and blood tests. The controls were matched for birth date and sex. RESULTS: Eight per cent of the subjects and 37% of the controls had at least one positive skin-prick test (SPT) (difference -35%, 95% CI -50 to -19%, P < 0.0001). Allergic rhinitis, atopic dermatitis and asthma occurred as often in both groups, but asthma had been diagnosed significantly earlier in the subjects than in the controls [mean age 3.0 years (SD 2.6) and 5.6 years (SD 3.0), difference 2.6 years, 95% CI 0.57-4.65, P = 0.014]. In a logistic regression analysis, RSV infection was associated with negative SPTs. CONCLUSIONS: An early RSV infection results in reduction of SPT positivity but not of occurrence of atopic diseases. This finding might explain why there is less atopic sensitization in countries with a greater probability of acquiring RSV infection at an early age.

Xylitol concentrations in the saliva of children after chewing xylitol gum or consuming a xylitol mixture.

Xylitol prevents otitis media when given to children regularly five times per day. To find a more convenient dosing schedule, an enzymatic assay was used to measure xylitol concentrations in the saliva of 65 children after giving them xylitol chewing gum or syrup in doses equal to those used in clinical trials. Although concentrations high enough to have an antimicrobial effect were attained, the xylitol disappeared from the saliva within 15 min. This finding indicates that high peak concentrations are more important for efficacy than the amount of time the xylitol concentration exceeds that needed to produce an antimicrobial effect. A schedule with the same single doses given less frequently could be clinically effective in preventing otitis media.

Comparison of nasal swab culture, quantitative culture of nasal mucosal tissue and PCR in detecting Streptococcus pneumoniae carriage in rats.

It is not known how well nasopharyngeal swab culture represents pneumococcal carriage status. We tested this by comparing swab culture to quantitative culture and quantitative PCR of mucosal tissue in a rat model of pneumococcal carriage. Quantitative culture and quantitative PCR identified significantly more carriers compared to swab culture (differences 15% and 33%, 95% CI 1-28% and 16-47%, p=0.04 and 0.001, respectively). The sensitivity and specificity of swab culture was 75/92% and 63/100% compared to quantitative tissue culture and quantitative PCR, respectively. The quantitative estimates of culture and PCR were very similar (Pearson correlation coefficient 0.79, p<0.001). In conclusion, even a well-controlled swab sampling markedly underestimates pneumococcal carriage rate, and simultaneous use of quantitative culture and PCR increases the number of positive samples by about one third.