Heart rate variability in children with tricyclic antidepressant intoxication.

The aim of this study was to evaluate HRV in children requiring intensive care unit stays due to TCA poisoning between March 2009 and July 2010. In the time-domain nonspectral evaluation, the SDNN (P < 0.001), SDNNi (P < 0.05), RMSDD (P < 0.01), and pNN50 (P < 0.01) were found to be significantly lower in the TCA intoxication group. The spectral analysis of the data recorded during the first 5 minutes after intensive care unit admission showed that the values of the nLF (P < 0.05) and the LF/HF ratio (P = 0.001) were significantly higher in the TCA intoxication group, while the nHF (P = 0.001) values were significantly lower. The frequency-domain spectral analysis of the data recorded during the last 5 minutes showed a lower nHF (P = 0.001) in the TCA intoxication group than in the controls, and the LF/HF ratio was significantly higher (P < 0.05) in the intoxication group. The LF/HF ratio was higher in the seven children with seizures (P < 0.001). These findings provided us with a starting point for the value of HRV analysis in determining the risk of arrhythmia and convulsion in TCA poisoning patients. HRV can be used as a noninvasive testing method in determining the treatment and prognosis of TCA poisoning patients.

Results of a national study on the awareness of and attitudes toward acute otitis media (AOM) among clinicians and the estimated direct healthcare costs in Turkey (TR-AOM Study).

AIMS: Acute otitis media (AOM) is one of the most frequent diagnoses and reasons for prescribing antibiotics in children. The aims of this prospective study were the following: (1) to assess the continuing education of physicians and the sources of information about AOM; (2) to assess the current knowledge of and attitudes toward AOM as well as the compliance with AOM guidelines; (3) to evaluate opinions about vaccines against AOM; and (4) to estimate the potential costs of AOM on the healthcare system in Turkey. METHODS: This is a web-based cross-sectional survey of a national convenience sample of 600 physicians in Turkey (325 pediatricians (PEDs), 214 family physicians/general practitioners (FP&GPs) and 61 otolaryngologists (ENTs)). RESULTS: Approximately 38.6% of participants (39.4% of PEDs, 44.3% of GP&FPs and 14.7% of ENTs) stated that pneumatic otoscopy is essential for AOM diagnosis. Regarding the most common etiological agents of AOM in children, 54.2% of PEDs, 51.4% of FP&GPs and 57.4% of ENTs stated that the most common causative agents of AOM are Streptococcus pneumoniae and non-typeable Haemophilus influenzae. Nearly 76% of participants indicated they use direct antibiotic therapy when they diagnose AOM in certain situations. The first-line choice of antibiotic therapy is amoxicillin clavulanate, and 67% of participants prefer to use antibiotic therapy for 7-10 days. Approximately 31% of all participants stated that "viruses" are the main cause of AOM; however, 62% of these participants reported using antibiotic therapy. In comparison, 32% participants from private clinics prefer to treat AOM primarily with observation, a rate that is significantly higher than that of other clinical settings. Physicians who prefer to use observation strategy also prefer the combination of paracetamol and NSAIDs. Approximately 41% of participants have undergone postgraduate medical education on the topic of AOM. In total, 73% of all participant physicians believe that otitis media is a vaccine-preventable disease. With the information from all of the participants, the calculated mean cost per case of AOM is 28 ± 4 USD. In Turkey, the estimated incidence of AOM is 24,000-33,000 cases per 10,000 children <5 years of age (1,820,000-2,100,000 cases per year), and the estimated total cost of AOM is 61,152,000 USD (not including acute otitis media-related complications and otitis media-related hospitalizations). CONCLUSION: The medical and economic burden of AOM to the health economics in Turkey is considerable. Specific educational programs and evidence-based national guidelines concerning AOM should be implemented. Improving diagnostic accuracy with education will lead to improved management, judicious use of antibiotics, decreased antibiotic resistance, and potential economic benefits. A more prudent use of antibiotics would also lower the economic burden of this disease. Vaccination seems to be promising for the prevention of AOM.

Effectiveness and safety of Saccharomyces boulardii for acute infectious diarrhea.

INTRODUCTION: Acute diarrhea continues to be a leading cause of morbidity, hospitalization and mortality worldwide and probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. Regarding the treatment of acute diarrhea, a few probiotics including Saccharomyces boulardii seem to be promising therapeutic agents. AREAS COVERED: We performed a systematic review and meta-analysis regarding the use of S. boulardii in the treatment of acute infectious diarrhea with relevant studies that searched with the PubMed, Embase, Scopus, Google Scholar, the Cochrane Controlled Trials Library, and the Cochrane Database of Systematic Reviews through October 2011. This review describes the effects of S. boulardii on the duration of diarrhea, the risk of diarrhea during the treatment (especially at the third day) and duration of hospitalization in patients with acute infectious diarrhea. This review also focused on the potential effects of S. boulardii for acute infectious diarrhea due to different etiological causes. EXPERT OPINION: S. boulardii significantly reduced the duration of diarrhea approximately 24 h and that of hospitalization approximately 20 h. S. boulardii shortened the initial phase of watery stools; mean number of stools started to decrease at day 2; moreover, a significant reduction was reported at days 3 and 4. This systematic review and meta-analysis of the efficacy of S. boulardii in the treatment of acute infectious diarrhea show that there is strong evidence that this probiotic has a clinically significant benefit, whatever the cause, including in developing countries. Therefore, with S. boulardii, the shortened duration of diarrhea and the reduction in hospital stay result in social and economic benefits.

The epidemiology and economic impact of varicella-related hospitalizations in Turkey from 2008 to 2010: a nationwide survey during the pre-vaccine era (VARICOMP study).

Varicella can cause complications that are potentially serious and require hospitalization. Our current understanding of the causes and incidence of varicella-related hospitalization in Turkey is limited and sufficiently accurate epidemiological and economical information is lacking. The aim of this study was to estimate the annual incidence of varicella-related hospitalizations, describe the complications, and estimate the annual mortality and cost of varicella in children. VARICOMP is a multi-center study that was performed to provide epidemiological and economic data on hospitalization for varicella in children between 0 and 15 years of age from October 2008 to September 2010 in Turkey. According to medical records from 27 health care centers in 14 cities (representing 49.3% of the childhood population in Turkey), 824 children (73% previously healthy) were hospitalized for varicella over the 2-year period. Most cases occurred in the spring and early summer months. Most cases were in children under 5 years of age, and 29.5% were in children under 1 year of age. The estimated incidence of varicella-related hospitalization was 5.29-6.89 per 100,000 in all children between 0-15 years of age in Turkey, 21.7 to 28 per 100,000 children under 1 year of age, 9.8-13.8 per 100,000 children under 5 years of age, 3.96-6.52 per 100,000 children between 5 and 10 years of age and 0.42 to 0.71 per 100,000 children between 10 and 15 years of age. Among the 824 children, 212 (25.7%) were hospitalized because of primary varicella infection. The most common complications in children were secondary bacterial infection (23%), neurological (19.1%), and respiratory (17.5%) complications. Secondary bacterial infections (p < 0.001) and neurological complications (p < 0.001) were significantly more common in previously healthy children, whereas hematological complications (p < 0.001) were more commonly observed in children with underlying conditions. The median length of the hospital stay was 6 days, and it was longer in children with underlying conditions (<0.001). The median cost of hospitalization per patient was $338 and was significantly higher in children with underlying conditions (p < 0.001). The estimated direct annual cost (not including the loss of parental work time and school absence) of varicella-related hospitalization in children under the age of 15 years in Turkey was $856,190 to $1,407,006. According to our estimates, 882 to 1,450 children are hospitalized for varicella each year, reflecting a population-wide occurrence of 466-768 varicella cases per 100,000 children. In conclusion, this study confirms that varicella-related hospitalizations are not uncommon in children, and two thirds of these children are otherwise healthy. The annual cost of hospitalization for varicella reflects only a small part of the overall cost of this disease, as only a very few cases require hospital admission. The incidence of this disease was higher in children <1 year of age, and there are no prevention strategies for these children other than population-wide vaccination. Universal vaccination is therefore the only realistic option for the prevention of severe complications and deaths. The surveillance of varicella-associated complications is essential for monitoring of the impact of varicella immunization.

Clinical efficacy of Saccharomyces boulardii or metronidazole in symptomatic children with Blastocystis hominis infection.

Although many Blastocystis infections remain asymptomatic, recent data suggest it also causes frequent symptoms. Therapy should be limited to patients with persistent symptoms and a complete workup for alternative etiologies. The goal of this study was to compare the natural evolution (no treatment) to the efficacy of Saccharomyces boulardii (S. boulardii) or metronidazole for the duration of diarrhea and the duration of colonization in children with gastrointestinal symptoms and positive stool examination for Blastocystis hominis. This randomized single-blinded clinical trial included children presenting with gastrointestinal symptoms (abdominal pain, diarrhea, nausea-vomiting, flatulence) more than 2 weeks and confirmed B. hominis by stool examination (B. hominis cysts in the stool with microscopic examination of the fresh stool). The primary end points were clinical evaluation and result of microscopic stool examination at day 15. Secondary end points were the same end points at day 30. Randomization was performed by alternating inclusion: group A, S. boulardii (250 mg twice a day, Reflor®) during 10 days; group B, metronidazole (30 mg/kg twice daily) for 10 days; group C, no treatment. At day 15 and 30 after inclusion, the patients were re-evaluated, and stool samples were examined microscopically. On day 15, children that were still symptomatic and/or were still B. hominis-infected in group C were treated with metronidazole for 10 days. There was no statistically significant difference between the three study groups for age, gender, and the presence of diarrhea and abdominal pain. On day 15, clinical cure was observed in 77.7% in group A (n, 18); in 66.6% in group B (n, 15); and 40% in group C (n:15) (p < 0.031, between groups A and C). Disappearance of the cysts from the stools on day 15 was 80% in group B, 72.2% in group A, and 26.6% in group C (p = 0.011, between group B and group C; p = 0.013, between group A and group C). At the end of the first month after inclusion, clinical cure rate was 94.4% in group A and 73.3% in group B (p = 0.11). Parasitological cure rate for B. hominis was very comparable between both groups (94.4% vs. 93.3%, p = 0.43). Metronidazole or S. boulardii has potential beneficial effects in B. hominis infection (symptoms, presence of parasites). These findings challenge the actual guidelines.

Tigecycline treatment of multi-drug-resistant Corynebacterium jeikeium infection in a child with relapsing and refractory acute lymphoblastic leukemia.

Corynebacterium jeikeium has been recognized as an important cause of infection, particularly among neutropenic patients who have central venous catheter (CVC). Routine use of tigecycline in children is not yet approved. Here in we present a child with relapsed-refractory lymphoblastic leukemia who was successfully treated with tigecyline due to multi-drug-resistant C. jeikeium sepsis without removal of CVC. Our case highlights the use of tigecycline where there are no alternatives. Further studies regarding the efficacy and safety of tigecycline in pediatric patients are needed.

Pneumococcal conjugated vaccine: PHiD-CV.

At the beginning of a new century, we have gained significant achievements against pneumococcal infections by using conjugated pneumococcal vaccines. In January 2009, the EMEA issued a positive opinion about, and recommended the approval of, GlaxoSmithKline's pediatric pneumococcal candidate vaccine, which is indicated for active immunization against invasive pneumococcal disease (IPD) and acute otitis media caused by Streptococcus pneumoniae in infants and children from 6 weeks up to 2 years of age. The approved 10-valent pneumococcal vaccine (PHiD-CV) contains all serotypes in 7-valent pneumococcal conjugate vaccine (PCV-7) plus serotypes 1, 5 and 7F. Protein D from nontypeable Haemophilus influenzae is the carrier protein for eight serotypes, while tetanus and diphtheria toxins are in the carrier proteins for the remaining two serotypes. It has also been proved that PHiD-CV is immunogenic, safe and well-tolerated in children. This vaccine can be coadministered with routinely used pediatric vaccines. Noninferiority criteria of PHiD-CV compared with PCV-7 were established in shared serotypes, except for serotypes 6B and 23F, and PHiD-CV is immunogenic for additional serotypes as assessed by the percentage of subjects with antibody concentrations. PHiD-CV is also immunogenic for ten serotypes as assessed by post-primary and post-booster dose opsonophagocytic activity responses. Vaccine efficacy against IPD and other conditions should be monitored for shared serotypes and also additional serotypes during the postmarketing period. Optimal scheduling, safety and immunogenicity data in children with different risk factors for IPD, or whether it will provide herd immunity, are the questions waiting for answers in the postmarketing period. Further studies are needed to assess the potential advantages of protein D as a carrier and the potential efficacy of this new vaccine against H. influenzae. The potential public health efficacy of PHiD-CV in low-income countries, where IPD and pneumonia are a major public health problem, is a major concern.

27th Annual Meeting of the European Society for Pediatric Infectious Disease.

The 27th Annual Meeting of the European Society for Pediatric Infectious Disease (ESPID) was held in Brussels, Belgium, on 8-13 June 2009. Europe's largest pediatric infectious disease congress brought international pediatricians and experts on pediatric infectious disease and vaccine together. Owing to the numerous pediatric infectious topics and issues that were discussed, in this report we summarize the current knowledge about pneumococcal disease and pneumococcal conjugate vaccines (PCVs). The main topics covered are current pneumococcal seroepidemiology after the introduction of the 7-valent conjugated pneumococcal vaccine (PCV7), the efficacy and immunogenicity of a reduced-dose schedule of PCV7, and the effectiveness of PCV7 against invasive pneumococcal disease, otitis media and related conditions, pneumonia, and nasopharyngeal carriage. New studies, including that on the cost-effectiveness of the currently licensed 10-valent pneumococcal vaccine, which uses protein D from the nontypeable Haemophilus influenzae protein (PHiD-CV) and investigational PCVs (investigational 13-valent PCV [PCV13] and 11-valent PCV [PCV11]), were also presented. Next year, the 28th ESPID meeting will be held in Nice, France, on 4-8 June 2010. We will have a chance to see and evaluate, after the PCV7 and PHiD-CV era, current efficacy studies about new vaccines and investigational vaccines. With the 2015 key millennium development goalonly 5 years away, we need to accelerate the introduction of current vaccines and also evaluate newcomer vaccines in order to reduce the mortality rate among children younger than 5 years of age by two-thirds.

Current knowledge regarding the investigational 13-valent pneumococcal conjugate vaccine.

The introduction of a 7-valent pneumococcal conjugate vaccine (PCV-7) into the routine childhood vaccination schedule has been shown to be effective in preventing invasive pneumococcal disease (IPD), pneumonia, otitis media and meningitis in infants and young children as determined by epidemiological surveillance studies. There has been a rise in IPD due to nonvaccine serotypes; however, this rise is small compared with the overall reduction in IPD. Non-PCV-7 serotypes and vaccine-related serotypes, such as serotypes 1, 5, 7F, 6A and 19A, have also been reported to cause IPD in some parts of the world where morbidity and mortality from pneumococcal disease are higher. An investigational 13-valent pneumococcal conjugate vaccine (PCV-13) uses CRM(197) as a carrier, similar to the current PCV-7, and covers serotypes 1, 3, 5, 6A, 7F and 19A, in addition to the serotypes of PCV-7 (serotype 4, 6B, 9V, 14, 18C, 19F and 23F). PCV-13 is safe and well tolerated with other pediatric vaccines in infants according to clinical trials. IgG anticapsular polysaccharide-binding concentrations and opsonophagocytic assay responses are similar and noninferior between PCV-13 and PCV-7 and, according to immunogenicity studies, PCV-13 has more potential to protect against pneumococcal diseases with the additional six serotypes. With the addition of these new serotypes, it could be possible to cover potential pneumococcal serotypes causing IPD throughout the world. The cost of the vaccine, its length of duration, optimal scheduling, combination and boosting with PCV-7 are still unresolved issues. Assessment of the vaccine's effectiveness and efficacy following potential licensure will require carefully designed cohort and case-control studies that can assess the indirect effects of PCV-13.

Pneumococcal conjugated vaccines: impact of PCV-7 and new achievements in the postvaccine era.

Pneumococcal disease is a major health problem worldwide. Large, rapid declines in overall invasive pneumococcal disease and mucosal disease in children, reductions in vaccine-type disease in unvaccinated children and adults (indirect effects) and significant drops in antibiotic-resistant infections were observed after the introduction of a safe, available and immunogenic seven-valent pneumococcal vaccine. The determination of vaccine efficacy is a complex process, which includes efficacy, immunogenicity, safety, cross-reactivity, indirect effects and substantial geographic variation in serotype coverage. In this report, we perform an overview of the literature on current, investigational and potential candidate pneumococcal conjugated vaccines (PCVs). Every country should have its own strong and sustained surveillance system implemented to monitor the effects of vaccination on the frequency of vaccine and nonvaccine serotypes for invasive or mucosal disease, nasopharyngeal carriage and the indirect effects before and after introduction of PCV. New PCVs (PHiD-CV and PCV-13) may provide even greater coverage worldwide, especially in developing countries. Vaccine experts' efforts are currently focused on developing alternative vaccine strategies against pneumococcal infections, especially the development of vaccines based on pneumococcal proteins.

In vitro activity of ertapenem and other carbapenems against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae clinical isolates in a tertiary care center in Turkey.

OBJECTIVE: To evaluate the in vitro effect of ertapenem, imipenem and meropenem in clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing strains of Escherichia coli and Klebsiella pneumoniae. DESIGN/METHODS: We studied 82 consecutive clinical isolates of ESBL-producing E. coli (n = 49) and K. pneumonia (n = 33) between February 2006 and September 2007. The minimum inhibitory concentration for each carbapenem was determined using the agar dilution method. RESULTS: Eighty two consecutive microorganisms from sterile sites were evaluated. A total of 48.8% of patients had a history of surgical intervention, 78.0% needed urinary catheterization, 57.3% required vascular access and 40.3% mechanical ventilation; and 70.7% had a history of ICU stay. High resistance rates were shown for both E. coli and K. pneumoniae against cefepime (81.7%), ciprofloxacin (50.9%), tetracycline (75.0%), co-trimoxazole (47.4%), and gentamicin (48.7%). In addition, most K. pneumoniae and E. coli isolates were susceptible to amikacin (78.3%) and piperacilline-tazobactam (91.5%). Meropenem and imipenem showed activity against 100% of the isolates. Ertapenem showed activity against 100% of K. pneumoniae isolates, against 95.9% of E. coli isolates and against 97.5% of the 82 ESBL-producing microorganisms. Two E. coli isolates showed ertapenem resistance. CONCLUSION: In recent literature, carbapenems were the most active antimicrobial agents against ESBL-producing Enterobacteriaceae, as in our study. This is the first study on the in vitro activity of ertapenem against ESBL-producing E. coli and K. pneumoniae conducted in Turkey. In view of the serious infections caused by ESBL-producing microorganisms, therapeutic interventions are still problematic in serious clinical conditions. Ertapenem may be a good choice for treatment, with the additional advantage of being a once a day regimen.