The pneumococcal conjugate vaccine had a sustained effect on Swedish children 8 years after its introduction.

AIM: The pneumococcal conjugate vaccine, which covered seven serotypes of Streptococcus pneumoniae (PCV7), was introduced in Stockholm, Sweden, in 2007. It was replaced by a 13-valent vaccine (PCV13) in 2011. We previously reported a decreased incidence of pneumonia and sinusitis among young children 4 years after the introduction of the PCV7. This study followed the incidence of pneumonia, sinusitis, mastoiditis and meningitis for four more years. METHODS: We studied validated hospital registry data covering children up to 17 years of age, who were hospitalised in the Stockholm region from 2003 to 2016, when the child population peaked at 485 687. All 11 115 cases diagnosed with pneumonia, coded as bacterial pneumonia, sinusitis, mastoiditis, bacterial meningitis or empyema, were identified. The controls had viral pneumonia or pyelonephritis. RESULTS: The incidence rates for children under 2 years of age hospitalised for sinusitis, mastoiditis and meningitis decreased significantly by 61%-79% during the eight-year post-vaccination period. Hospitalisations for bacterial pneumonia decreased by 19%-25% in the same age group. These changes were probably due to both the vaccines and changes in diagnosis routines. CONCLUSION: The effect of vaccination on children under 2 years of age was sustained 8 years after the introduction of the pneumococcal conjugate vaccines.

Healthcare workers' perceptions of how eHealth applications can support self-care for patients undergoing planned major surgery.

BACKGROUND: In planned major surgery the duration of inpatient hospital care during the last decade has decreased because of a combination of different perioperative interventions. It is expected that patients can manage the needed pre- and postoperative self-care to a large extent on their own. This entails challenges to healthcare system to deliver appropriate information to patients in a safe and efficient manner. The aim of this study was therefore to describe healthcare workers' perceptions of how eHealth applications can support patients' self-care in relation to planned major surgery. METHODS: Semi-structured interviews were performed with sixteen healthcare workers from different disciplines. The interviews were transcribed and analysed using the phenomenography approach. RESULTS: Healthcare workers perceived both positive aspects and challenges with eHealth applications for self-care. eHealth applications can work as an information source, affect patients' understanding of self-care, improve patients' participation in self-care, streamline communication with healthcare professionals and improve patient safety during the pre- and postoperative period. The challenges included perceptions of that eHealth applications may have negative impact on personal interaction in care. eHealth applications may not be useful to all patients because of lack of equipment or knowledge and may increase patients' suffering if physical visits are replaced by digital solutions. CONCLUSIONS: This study improves our understanding of healthcare workers' perceptions of how the use of self-care eHealth applications can support patients in performing pre- and postoperative self-care for major surgery. Access to appropriate and personalized information and instructions can improve patients' understanding of self-care and enhance the participation and safety of those who can afford and handle digital tools. All these aspects must be considered in future digital development of eHealth applications to guarantee a person-centered care.

Nitric Oxide Is Locally Produced in the Human Middle Ear and Is Reduced by Acquired Cholesteatoma.

OBJECTIVE: To find out if nitric oxide (NO) can be locally produced in the middle ear and if chronic otitis media (COM) and acquired cholesteatoma affect the production. DESIGN: Case-control study. SETTING: Two tertiary-referral hospitals. PATIENTS: Gaseous NO from 11 patients with unilateral perforations or grommet openings was measured with chemiluminescence. Middle ear mucosa from 48 patients with COM and 26 patients with cholesteatoma was investigated. MAIN OUTCOME MEASURES: Detection of NO. Expression of nitric oxide synthase (NOS) mRNA, in mucosa from COM, cholesteatoma and healthy controls, quantified using polymerase chain reaction. RESULTS: The gaseous NO from ears with a unilateral tympanic membrane perforation or a grommet was higher (9 ±â€Š3 ppb, n = 11) than among the controls (4 ±â€Š1 ppb, n = 11, p = 0.04). Lower levels of eNOS (2.64 ±â€Š0.86 mol/100,000 mol ACTB) were detected in the pooled samples from the COM group (n = 48), compared with the control group (140.48 ±â€Š92 mol/100,000 mol ACTB, n = 45, p = 0.010). In the cholesteatoma group (n = 26), a lower expression of nNOS (5.78 × 10-6 ±â€Š1.13 × 10-6 ΔCt) was found in comparison with the controls (1.23 × 10-4 ±â€Š3.18 × 10-5 ΔCt, n = 15, p = 0.011). CONCLUSIONS: NO is likely a natural and permanent part of the gas mixture in the human middle ear. The presence of NOS enzymes in the middle ear mucosa indicates an ongoing NO production and the reduction of NOS in ears with cholesteatoma, and pooled samples from ears with COM, suggest a role for locally produced NO in middle ear disease.

A Swedish population-based study of complications due to acute rhinosinusitis in children 5-18 years old.

BACKGROUND: There are few population-based studies of complications due to acute rhinosinusitis in children. The aim was to clarify the admission and complication rate and analyze bacterial cultures in children five to 18 years old in Stockholm, Sweden. METHODS: This was a population-based observational cohort study with retrospectively collected data from individual medical records, from 1 July 2003 to 30 June 2016 in Stockholm, Sweden. Hospital admissions of children with a discharge diagnosis of rhinosinusitis and related complications were reviewed. RESULTS: Incidence of admission due to acute rhinosinusitis was 7.8 per 100 000 children per year (boys 9.2, girls 6.2) and 61% of the admitted children were boys. A severe - postseptal orbital, intracranial or osseous - complication, was present in 34% of admissions (postseptal orbital 28%, intracranial 6%, osseous 4%), resulting in an incidence of 2.6 severe complications per 100 000 children per year (boys 3.6, girls 1.6). Orbital preseptal cellulitis was present in 88% of admissions. Incidence of surgery was 1.3 per 100 000 per year (boys 1.8, girls 0.8) and the percentage of admitted children that had surgery increased with age. S. pyogenes was the most common pathogen found in the whole cohort (29 admissions), while S. milleri was the most common pathogen found among the children with severe complication and surgery. CONCLUSIONS: There is a relative high risk of severe complications in children between five to 18 years that are admitted due to acute rhinosinusitis. There is a need for prospective studies to further analyze the pathogens involved in complications due to acute rhinosinusitis.

A case study where pharmaceutical salts were used to address the issue of low in vivo exposure.

The present active pharmaceutical ingredient (API) is a lipophilic compound with a significant risk of not achieving therapeutic plasma concentrations due to solubility-limited absorption. The aim of the presented studies was to investigate whether three novel salts of a new selected candidate in the cardiovascular therapy area could be applied to improve intestinal absorption and the subsequent in vivo exposure. Three salts (chloride, hydrogen sulfate, and hemi-1.5-naphtalenedisulphonate) of the compound were manufactured and investigated regarding solubility, dissolution rate, and in vivo exposure in rats. The chemical and physical stability of the salt forms (and the crystalline parent compound) were followed in solid state, when dissolved and when formulated as microsuspensions. All salts showed improved solubility in investigated media, increased dissolution rate, and elevated in vivo exposures compared to a nanocrystal formulation (top-down) of the parent free base of the compound. The chloride- and the hydrogen sulfate salts of the API showed similar patterns regarding the chemical stability in solid state as the crystalline free base, while the salt formed of the hemi-1.5-naphtalenedisulphonic acid showed significantly improved stability. In conclusion, this study showed that three salts of a new selected candidate drug could be used to improve solubility, increase dissolution rate, and enhance oral absorption compared with a more commonly used nanocrystal formulation of the API. However, the identity of the counter ion appeared to be of less importance. On the other hand, only the salt of the hemi-1.5-naphtalenedisulphonic acid seemed to improve chemical stability compared with the API.

Antibiotic use and bacterial complications following upper respiratory tract infections: a population-based study.

OBJECTIVES: To investigate if use of antibiotics was associated with bacterial complications following upper respiratory tract infections (URTIs). DESIGN: Ecological time-trend analysis and a prospective cohort study. SETTING: Primary, outpatient specialist and inpatient care in Stockholm County, Sweden. All analyses were based on administrative healthcare data on consultations, diagnoses and dispensed antibiotics from January 2006 to January 2016. MAIN OUTCOME MEASURES: Ecological time-trend analysis: 10-year trend analyses of the incidence of URTIs, bacterial infections/complications and respiratory antibiotic use. Prospective cohort study: Incidence of bacterial complications following URTIs in antibiotic-exposed and non-exposed patients. RESULTS: The utilisation of respiratory tract antibiotics decreased by 22% from 2006 to 2015, but no increased trend for mastoiditis (p=0.0933), peritonsillar abscess (p=0.0544), invasive group A streptococcal disease (p=0.3991), orbital abscess (p=0.9637), extradural and subdural abscesses (p=0.4790) and pansinusitis (p=0.3971) was observed. For meningitis and acute ethmoidal sinusitis, a decrease in the numbers of infections from 2006 to 2015 was observed (p=0.0038 and p=0.0003, respectively), and for retropharyngeal and parapharyngeal abscesses, an increase was observed (p=0.0214). Bacterial complications following URTIs were uncommon in both antibiotic-exposed (less than 1.5 per 10 000 episodes) and non-exposed patients (less than 1.3 per 10 000 episodes) with the exception of peritonsillar abscess after tonsillitis (risk per 10 000 tonsillitis episodes: 32.4 and 41.1 in patients with no antibiotic treatment and patients treated with antibiotics, respectively). CONCLUSIONS: Bacterial complications following URTIs are rare, and antibiotics may lack protective effect in preventing bacterial complications. Analyses of routinely collected administrative healthcare data can provide valuable information on the number of URTIs, antibiotic use and bacterial complications to patients, prescribers and policy-makers.

Long-term hearing outcomes after recurrent acute otitis media during early childhood.

OBJECTIVE: To survey long-term hearing outcomes and middle ear pathology in a 30-year follow-up in individuals with onset of recurrent acute otitis media (rAOM) before three years of age. METHODS: 28 adults, aged 30.1-31.8 years, who originally - at the age of 12-32 months - participated in a study on rAOM between 1979 and 1983, were re-examined regarding self-reported ear problems, current tympanic membrane changes and audiology. Thirteen subjects had suffered from rAOM during early childhood and 15 subjects served as a control group. RESULTS: Recurrent acute otitis media subjects reported hearing problems comparable to those of the controls. Pure tone audiometry, at 125-8000 Hz, did not differ between groups. The rAOM group had a trend for impaired high-frequency (9000-14,000 Hz) threshold levels (9000-14,000 Hz); implying that their cochlear function seemed to have deteriorated. CONCLUSIONS: Adults, who suffered from recurrent acute otitis media as infants, did not show any clinically significant hearing loss for pure tone audiometry when compared to controls, but there was a trend for impaired results regarding extended high frequency audiometry (9-14 kHz). Children suffering from rAOM will be at low risk of developing hearing loss and severe middle ear disease.

Recurrent Acute Otitis Media: What Are the Options for Treatment and Prevention?

PURPOSE OF REVIEW: To survey current strategies for treatment and prevention of recurrent acute otitis media (rAOM). RECENT FINDINGS: Treatment with systemic antibiotics is required in recurrent episodes of acute otitis media. A cautious attitude is recommended due to antibiotic resistance. Antibiotics also provide effective prophylaxis for rAOM. Topical treatment with ear drops is recommended in rAOM with otorrhea from tympanostomy tubes. Pneumococcal conjugated vaccines seem to have a moderate reductive effect on overall otitis media. The effect on rAOM is still unclear. Different administrations of immunoglobulins have not been effective against rAOM. Breastfeeding had a protective effect against rAOM. A recommendation against cigarette smoke exposure as a measure to prevent otitis seems warranted. An effect for adenoidectomy in children <2 years old with rAOM has been suggested. There is a strong genetic connection with rAOM. Probiotics and nasal spray with Streptococci might offer future opportunities as prophylaxis. Too little is known about complimentary treatments to give any recommendations. SUMMARY: Systemic antibiotics are still needed as treatment against episodes of AOM in rAOM children. There are several preventive measures that can be taken to reduce the burden of AOM but they all have a small-moderate effect. Systemic antibiotics provide effective prophylaxis in rAOM, but must be used with extreme caution due to the emerging antibiotic resistance.

Preformulation investigation and challenges; salt formation, salt disproportionation and hepatic recirculation.

A compound, which is a selective peroxisome proliferator activated receptor (PPAR) agonist, was investigated. The aim of the presented studies was to evaluate the potential of the further development of the compound. Fundamental physicochemical properties and stability of the compound were characterized in solution by liquid chromatography and NMR and in solid-state by various techniques. The drug itself is a lipophilic acid with tendency to form aggregates in solution. The neutral form was only obtained in amorphous form with a glass-transition temperature of approximately 0°C. The intrinsic solubility at room temperature was determined to 0.03mg/mL. Chemical stability studies of the compound in aqueous solutions showed good stability for at least two weeks at room temperature, except at pH1, where a slight degradation was already observed after one day. The chemical stability in the amorphous solid-state was investigated during a period of three months. At 25°C/60% relative humidity (RH) and 40°C/75% RH no significant degradation was observed. At 80°C, however, some degradation was observed after four weeks and approximately 3% after three months. In an accelerated photostability study, degradation of approximately 4% was observed. Attempts to identify a crystalline form of the neutral compound were unsuccessful, however, salt formation with tert-butylamine, resulted in crystalline material. Results from stability tests of the presented crystalline salt form indicated improved chemical stability at conditions whereas the amorphous neutral form degraded. However, the salt form of the drug dissociated under certain conditions. The drug was administered both per oral and intravenously, as amorphous nanoparticles, to conscious dogs. Plasma profiles showed curves with secondary absorption peaks, indicating hepatic recirculation following both administration routes. A similar behavior was observed in rats after oral administration of a pH-adjusted solution. The observed double peaks in plasma exposure and the dissociation tendency of the salt form, were properties that contributed to make further development of the candidate drug challenging. Options for development of solid dosage forms of both amorphous and crystalline material of the compound are discussed.

Panel 8: Report on Recent Advances in Molecular and Cellular Biochemistry.

Objectives To update the medical literature on recent cellular and molecular advances in otitis media disease models with a principal focus on developments in the past 5 years. We also aim to explain recent translational advances in cellular and molecular biology that have influenced our understanding and management of otitis media. Data Sources PubMed-indexed peer-reviewed articles. Review Methods A comprehensive review of the literature was conducted with the term otitis media and the following search terms: molecular biology, cell biology, innate immunity, oxidative stress, mucins, molecular diagnostics. Included articles were published in the English language from January 1, 2010, to July 31, 2015. Implications for Practice The molecular understanding of otitis media disease progression has rapidly advanced over the last 5 years. The roles of inflammation, mucins, and cell signaling mechanisms have been elucidated and defined. Advances in the field provide a plethora of opportunities for innovative molecular targeting in the development of novel therapeutic strategies for otitis media.

Evaluation of preclinical formulations for a poorly water-soluble compound.

One central aim of the present work was to find a robust oral formulation approach for Compound A, both to achieve reliable pharmacodynamic read outs but also for long time safety assessment studies. The compound has low aqueous solubility (0.4µM at 37°C), is highly lipophilic and has high Caco-2 permeability, i.e. a typical BCS II compound. A nanocrystal formulation, some oil approaches and a fat diet approach were evaluated in vivo in rats. The two latter strategies resulted in significantly higher in vivo exposures after oral administration compared to the nanocrystal approach. For simplicity, and due to the project development program, a food pellet formulation was selected. In addition, tentative data from a subcutaneous study in mice using nanocrystals of the compound are presented, showing extended profiles on the cost of Cmax. Exposure data in monkeys after administration of nanocrystals both intravenously and per oral are presented. When switched from nanocrystals to an oil formulation, the observed oral exposure behavior was similar as observed in rats.

Arginine and Caries Prevention: A Systematic Review.

OBJECTIVES: To evaluate the available evidence that the use of arginine-containing dental care products prevents the development of new caries lesions and the progression of existing lesions. SEARCH METHODS: We performed a systematic literature search of databases including PubMed, the Cochrane Library and EMBASE. SELECTION CRITERIA: We selected randomized controlled trials of treatment with arginine in fluoride-containing dental products measuring dental caries incidence or progression in children, adults and elderly subjects. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for risk of bias and evaluated overall study quality using the GRADE classification. MAIN RESULTS: Due to conflicts of interest and weak transferability to Swedish conditions, no conclusions can be drawn from studies on the effects of arginine-fluoride toothpaste in children. Arginine-containing toothpaste costs about 40% more than basic fluoride toothpaste; to determine whether it is more cost-effective, the higher cost must be considered in relation to any additional caries-preventive effect. The literature review also disclosed some questionable research ethics: in several of the studies, the children in the control group used non-fluoride toothpaste. Toothpaste without fluoride is not as effective against dental caries as the standard treatment - fluoride toothpaste - which has a well-documented effect. This contravenes the fundamental principles of research ethics. CONCLUSION: At present there is insufficient evidence in support of a caries-preventive effect for the inclusion of arginine in toothpastes. More rigorous studies, and studies which are less dependent on commercial interests, are required.

Thrombin generation test in children and adolescents with chronic liver disease.

INTRODUCTION: The aim of this study was to evaluate if real-time thrombin generation assay provides additional information to assess the hemostatic balance in children with liver disease as compared to routine coagulation tests. PATIENTS AND METHODS: Sixty-three children with chronic liver disease were enrolled at our tertiary referral center for pediatric hepatology, eight whose routine coagulation tests gave abnormal results (Group A) and 55 whose test results were normal (Group B). Abnormal routine coagulation test was defined as at least one of the following: international normalized ratio≥1.4, activated partial thromboplastin time>44 sec., fibrinogen<1.5 g/L. Platelet-poor plasma was analyzed with the fluorogenic Calibrated Automated Thrombogram to test for thrombin generation, including endogenous thrombin potential. Further, routine coagulation tests and plasma levels of pro- and anticoagulant factors were measured. Twenty age-matched children without liver disease served as controls. RESULTS: The endogenous thrombin potential in the 55 patients with normal routine coagulation tests was not significantly different from that in controls. Group A had significantly lower levels not only of procoagulant factors (II, V, VII, X) but simultaneously also of the anticoagulant factors antithrombin, protein S free, and protein C. These patients had a reduced endogenous thrombin potential compared to Group B, in agreement with their routine coagulation test results. CONCLUSION: Thrombin generation analysis seems to give information on the hemostatic balance consistent with routine coagulation test results in children with liver disease. Further development and clinical evaluation of the method are warranted.

Normalized immunoglobulin patterns in adults with recurrent acute otitis media and low IgG2 levels during early childhood.

OBJECTIVES: Children who suffer from recurrent acute otitis media (rAOM) sometimes display low immunoglobulin levels. It is not known whether the differences in immunoglobulin levels remain during adulthood or if rAOM-patients have more episodes of AOM and airway infections as adults. METHODS: A study on adults, with a history of rAOM during childhood, was performed. The immunologic status and individual disposition for upper airway infections were evaluated in 28 subjects who originally participated in a study on rAOM between 1979 and 1983. 13 subjects had suffered from rAOM during early childhood and 15 subjects without rAOM served as a control group. The study included analysis of immunoglobulins in serum and self evaluation regarding susceptibility to infections of the upper airway. RESULTS: There was no difference between the groups neither regarding IgG2 concentrations nor specific antibody levels. No episodes of AOM were reported after 20 years of age in any of the study subjects. The history of airway infections was similar in both groups. CONCLUSIONS: Study subjects who had rAOM combined with low IgG2 levels during childhood had a normalized immunoglobulin pattern as adults.

Reduced iNOS expression in adenoids from children with otitis media with effusion.

Nitric oxide (NO) is a key mediator in the local immune response of human airways. Inducible NO-synthases (iNOS), and endothelial NO-synthases (eNOS) are two enzymes known to regulate its production. The role of NO in middle ear disease is not fully known. Previous studies suggest that NO might have a dual role, both promoting and suppressing middle ear inflammation. The aim of the present study was to compare the eNOS and iNOS expression in adenoids obtained from children with otitis media with effusion (OME) with the expression seen in adenoids derived from children without middle ear disease. In addition, the expression of IL-1ß and TNF-α were analyzed, because of their role in the iNOS-induction pathway. The iNOS and eNOS expression were analyzed with real-time PCR in 8 OME and 11 control adenoids. The corresponding proteins were demonstrated by immunohistochemical staining of adenoid tissue. A Luminex(®) assay was performed to analyze IL-1ß and TNF-α in nasopharyngeal secretion in 10 OME and 8 controls, and immunohistochemistry was performed on adenoid tissue and imprints from the adenoid surface. Children with OME exhibited lower levels of iNOS than controls without middle ear disease. No such difference was seen for eNOS. The corresponding proteins were found mainly in conjunction with surface epithelium. No significant changes were seen among the cytokines tested. The present results indicate that local induction of iNOS in adenoids might be of importance for preventing development of OME.

Maternal microchimerism in juvenile tonsils and adenoids.

During pregnancy small amounts of cells pass between the mother and the fetus, and this transfer may give rise to a chimeric state that persist for years in both individuals. Both fetal and maternal microchimerism (MMc) have been associated with different autoimmune disorders. Information about MMc in tissues of healthy individuals is sparse but is important when looking for maternal cells within affected tissues of certain diseases. The aim of this study was to investigate the occurrence of maternal cells in tonsils and adenoids of 20 healthy children between the ages of 2 and 15 years. All the children underwent surgery because of recurrent tonsillitis or respiratory obstruction. MMc was detected using an RT-PCR assay based on differences in gene polymorphisms between mother and child. We found maternal cells in the tonsils and/or adenoids in four of 20 children. This frequency is less than the frequency of maternal cells found in the peripheral blood of healthy adults but in agreement with the previously reported frequency of maternal chimerism in control tissues

Increased TLR7 expression in the adenoids among children with otitis media with effusion.

CONCLUSION: Toll-like receptor 7 (TLR7) is present in the adenoids in young children and might play a role in the immunological response behind the development of otitis media with effusion (OME). OBJECTIVES: To investigate the expression of the TLRs TLR4 and TLR7 in adenoids from children with OME and to compare the results with data obtained from healthy controls. SUBJECTS AND METHODS: This was a controlled, prospective study. Eleven young children with long-standing OME and 10 controls with healthy middle ears were recruited consecutively when scheduled for adenoidectomy. mRNA was quantified using real-time polymerase chain reaction (PCR) and the localization of the corresponding proteins was assessed by immunohistochemistry. RESULTS: mRNA for TLR4 and TLR7 could be obtained from all samples tested along with their corresponding proteins. The mRNA levels for TLR7 were increased among the children with a history of OME. No such increase was found for TLR4.

Compartmentalization of immune responses in human tuberculosis: few CD8+ effector T cells but elevated levels of FoxP3+ regulatory t cells in the granulomatous lesions.

Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-gamma, tumor necrosis factor-alpha, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-beta and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-beta and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control.

Tube associated otorrhea in children with recurrent acute otitis media; results of a prospective randomized study on bacteriology and topical treatment with or without systemic antibiotics.

OBJECTIVE: To establish if otorrhea associated to tympanostomy tubes in infants suffering from recurrent acute otitis media is similar to acute otitis media, and if topical treatment alone is sufficient or if addition of systemic antibiotics is required. METHODS: Children under 3 years of age with tympanostomy tubes due to recurrent acute otitis media were recruited to the study. The study design was open label randomized and prospective. Fifty patients were allocated to either of two treatment groups and were monitored for 6 months. Group I received only topical treatment (commercially available ear drops and saline solution) in case of otorrhea. Group II was treated with topical treatment together with systemic antibiotics. All episodes of acute otorrhea were registered. Main outcome measure was duration of otorrhea in days. Bacterial samples from the ear discharge were taken. RESULTS: Forty-one episodes were treated according to protocol. The bacteriological testing mainly showed bacteria typical of acute otitis media. A majority of episodes were cured within 7 days in both groups, and statistical analysis showed no significant difference between the treatment groups in duration of otorrhea. In Group I systemic antibiotics were added in one-third (7/21) of the episodes due to signs of affected general condition such as high fever and severe earache. CONCLUSIONS: The otorrhea episodes in the study were similar to acute otitis media based on the bacteriological results. Topical treatment alone might be used as first treatment of choice. Although systemic antibiotics were added in several cases in the topical treatment group, the findings of the study do not support use of systemic antibiotics for tube associated otorrhea in RAOM children in general.