Emmanouil Galanakis

Variations in prevalence of attention deficit hyperactivity disorder worldwide

Attention deficit hyperactivity disorder (ADHD) is among the most common, intensely investigated, and yet diagnostically controversial neurobehavioral conditions of childhood. The prevalence of ADHD has been reported with great variations among different studies, ranging from 2.2% to 17.8%. The aim of this review was to investigate the variables that influence the prevalence of ADHD and to derive a best estimate for the prevalence of the disorder. We reviewed all the 39 studies on ADHD prevalence appearing in the Pubmed and published since 1992. These studies indicate that ADHD is more common in boys than girls, in younger than older children and adolescents, in one-setting rather than two-setting screening studies, in studies based on DSM-IV rather than DSM-III-R criteria. Additional factors that may well influence prevalence rates include source of information and assessment of clinical impairment. In conclusion, our findings suggest that population characteristics, methodology features, ethnic and cultural differences and diagnostic criteria involved in studies affect the prevalence of ADHD. Standardized designs may lead to firm conclusions on the true prevalence of ADHD, the estimation of which seems impossible to be achieved by reviewing the already existing literature.

Protective effect of exclusive breastfeeding against infections during infancy: a prospective study

Objective To prospectively investigate the effects of breastfeeding on the frequency and severity of infections in a well-defined infant population with adequate vaccination coverage and healthcare standards. Study design In a representative sample of 926 infants, successfully followed up for 12 months, feeding mode and all infectious episodes, including acute otitis media (AOM), acute respiratory infection (ARI), gastroenteritis, urinary tract infection, conjunctivitis and thrush, were recorded at 1, 3, 6, 9 and 12 months of life. Results Infants exclusively breastfed for 6 months, as per WHO recommendations, presented with fewer infectious episodes than their partially breastfed or non-breastfed peers and this protective effect persisted after adjustment for potential confounders for ARI (OR 0.58, 95% CI 0.36 to 0.92), AOM (OR 0.37, 95% CI 0.13 to 1.05) and thrush (OR 0.14, 95% CI 0.02 to 1.02). Prolonged exclusive breastfeeding was associated with fewer infectious episodes (rs=−0.07, p=0.019) and fewer admissions to hospital for infection (rs=−0.06, p=0.037) in the first year of life. Partial breastfeeding was not related to protective effect. Several confounding factors, including parental age and education, ethnicity, presence of other siblings, environmental tobacco smoke exposure and season of birth were demonstrated to have an effect on frequency of infections during infancy. Conclusions Findings from this large-scale prospective study in a well-defined infant population with adequate healthcare standards suggest that exclusive breastfeeding contributes to protection against common infections during infancy regarding and lessens the frequency and severity of infectious episodes. Partial breastfeeding did not seem to provide this protective effect.

Risk factors related to intention to breastfeed, early weaning and suboptimal duration of breastfeeding

Aim: To identify maternal and infantile factors affecting intention to breastfeed, early weaning and duration of breastfeeding.

Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece

INTRODUCTION Association studies of vitamin D receptor (VDR) polymorphisms and risk of type 1 diabetes (T1D) have produced inconsistent results in different populations, pointing to contribution of additional genetic variants and environmental factors. In this study we investigated the association between four VDR polymorphisms and susceptibility to T1D in Crete, an island with homogenous population and considerably low incidence of T1D. RESULTS AND DISCUSSION We genotyped 100 patients with T1D and 96 controls for the FokI (rs10735810), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) single nucleotide polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. In all 4 polymorphisms tested, distribution of VDR genotype frequencies differed significantly between patients and controls. Individuals with T1D presented less commonly with FokI F allele (p=0.008; OR 0.52, 95% CI 0.32 to 0.85) and BsmI B allele (p=0.042; OR 0.65, 95% CI 0.44 to 0.97) and more commonly with ApaI A allele (p=0.024; OR 1.61, 95% CI 1.07 to 2.41) and TaqI T allele (p=0.0001; OR 2.24, 95% CI 1.49 to 3.36). CONCLUSION Our findings derived from a homogenous southern European population with low incidence of T1D suggest that FokI, BsmI, ApaI, and TaqI polymorphisms of the VDR gene are associated with T1D prevalence.

Urine Interleukin-8 as a Marker of Vesicoureteral Reflux in Infants

OBJECTIVE. Vesicoureteral reflux (VUR) is a common finding in children presenting with urinary tract infection (UTI) and prenatally diagnosed urinary tract dilatation and in relatives of index patients. Children with VUR are at risk for ongoing renal damage with subsequent infections. Detecting VUR and renal scarring currently depends on imaging modalities with associated problems of radiation, invasiveness, and expense. Noninvasive methods would greatly facilitate diagnosis and would also help in identifying relatives of index cases who should be screened. Interleukin-8 (IL-8) is produced by epithelial cells of the renal tract in response to inflammatory stimuli and has been shown to increase during acute UTI. The objective of this study was to assess the urine levels of IL-8 as a noninvasive marker of VUR in infants in the absence of a recent UTI episode. METHODS. We evaluated urine concentrations of IL-8 in 59 infants aged 1 month to 2 years. All infants were free of UTI for a minimum of 3 weeks before IL-8 evaluation. Infants were divided into 3 groups: group A, subjects with proven VUR (24 infants aged 0.15–1.95 years, median 0.43); group B, subjects with a history of UTI but negative investigation for VUR (14 infants aged 0.32–1.95 years, median 0.57); and group C, subjects without any history of acute or chronic condition that might impair renal function (21 infants aged 0.08–1.92 years, median 0.33). IL-8 concentrations were determined by a commercially available quantitative enzyme-linked immunosorbent assay. To avoid dilution effects, urinary levels of IL-8 were expressed as the ratio of cytokine-to-urinary creatinine. RESULTS. Results were presented as medians and ranges. The Kruskal-Wallis test, the Mann-Whitney rank sum U test, and the Spearman rank order correlation test were performed for the univariate analysis. Two-tailed P values were calculated and the conventional level of significance P < .05 was applied in all cases. Infants in groups A and B had been free of UTI for a period of 3 to 52 weeks (median, 5.0 weeks) and 3 to 78 weeks (median, 4.5 weeks), respectively, before IL-8 determination. No significant difference was noted in the length of the UTI-free period between groups A and B (P = .469). Urine creatinine concentrations did not differ among groups A, B, and C (medians 1.15, 2.25, and 1.15 μmol/mL, respectively; P = .080). The median urine IL-8/creatinine concentrations (pg/μmol) were 40.5 (range, 2.04–3874) in group A, 1.91 (range, 0.001–386) in group B, and 2.47 (range, 0.002–55.6) in group C. Urine IL-8/creatinine concentrations were significantly higher in group A than both in group B (P = .0003) and in group C (P < .0001). No significant difference was observed between groups B and C (P = .749). In group A, no significant correlation was shown between IL-8/creatinine concentrations and the presence of renal parenchymal damage (P = .506), reflux grade (P = .770), or time from UTI (P = .155). A receiver-operator characteristic curve was constructed by plotting the sensitivity versus the specificity for different cutoff concentrations of IL-8/creatinine. With a cutoff concentration of urinary IL-8/creatinine at 5 pg/μmol, the sensitivity of this marker in diagnosing VUR was 88%, the specificity 69%, the positive prognostic value 66%, and the negative prognostic value 89%. In higher cutoff concentrations, specificity of the marker increased but sensitivity rapidly decreased. CONCLUSIONS. We present evidence that urine IL-8 concentrations remain elevated in infants with VUR even in the absence of UTI and that a cutoff of 5 pg/μmol IL-8/creatinine is of high sensitivity and adequate specificity for diagnosing VUR. Elevated urine IL-8 levels in VUR and renal scarring have already been reported; however, the present study is, to our knowledge, the first to confirm significant differences between infants with VUR and infants with a history of UTI alone and healthy controls, and to suggest a reliable cutoff concentration for diagnosing VUR. Our findings additionally suggest that inflammatory process in VUR is ongoing even after UTI has resolved, pointing against the currently held belief that sterile reflux cannot harm kidneys. The chronic inflammatory cell infiltrate associated with reflux nephropathy rather than VUR itself might offer an explanation for the secretion of IL-8, which may well be independent of reflux grade. Using urine IL-8 for diagnosing VUR is not free of limitations, because IL-8 may be elevated as a result of urinary tract manipulation or undetected UTI. In addition, this study focused on infants and not in older children with longstanding VUR. Increased urine IL-8 concentrations after UTI has resolved is a promising noninvasive marker for an initial screening for VUR in infancy with high sensitivity and adequate specificity.

Childhood brucellosis in north-western Greece: A retrospective analysis

Fifty-two cases of childhood brucellosis which occurred in north-western Greece during the 15-year period 1979–1993, are reviewed. It is believed that they represent very closely the total incidence of the disease in the region which has a population of 100,000 children aged 0–14 years old. Brucellosis-affected children were almost exclusively from goat-or shepherd families and of both sexes and all age groups. A broad spectrum of clinical manifestations ranging from malaise only to brain abscess was observed. Fever and arthralgia were the most common manifestations followed by malaise, myalgia, sweating, rash, cough, and gastro-intestinal, cardiac and CNS involvement. Splenomegaly was found more often than hepatomegaly and lymphadenopathy. Laboratory findings included anaemia, leukopenia, neutropenia, lymphocytopenia, monocytosis, eosinophilia, thrombocytopenia and pancytopenia. Leukocytosis and lymphocytosis were extremely rare and ESR and serum C-reactive protein levels were mildly elevated. All patients had positive Rose Bengal slide agglutination tests and standard tube agglutination titres of 1∶60 or more. When performed, blood culture was often diagnostic. The children were treated with streptomycin for 2 weeks plus either tetracyclines or trimethoprim-sulphamethoxazole for 3 weeks. Treatment was well tolerated. Relapse was observed in one case.

Multitarget PCR for Diagnosis of Pertussis and Its Clinical Implications

ABSTRACT PCR has greatly facilitated pertussis diagnosis due to the speed, sensitivity, and specificity of this assay compared to other detection methods. Various single-target PCR assays are currently utilized, but none is universally considered to be the “gold standard.” Our aim was to assess the use of multitarget versus single-target PCR for the diagnosis of pertussis in clinical samples. PCR assays targeting insertion sequence IS481 (IS), pertussis toxin ptxA promoter region (PT), and outer membrane porin (PO), or recA (RA) were evaluated in respiratory specimens collected from 4,442 patients with suspected pertussis. The diagnosis of pertussis was confirmed in 309 (6.96%) patients by the 3-target IS-PT-PO/RA PCR versus 247 (5.56%) by the conventional single-target IS (P = 0.007). Compared to single-target IS, the three-target combination increased the proportion of positive specimens by 1.25-fold, and two-target combinations increased the proportion of positive specimens by 1.10- to 1.24-fold. In addition, nine cases of B. parapertussis infection were also confirmed by using the discriminative features of this multitarget PCR. Of the 89 culture-proven pertussis cases, 17 (19.1%) and 5 of the 16 patients (31.3%) admitted to intensive care unit would have been missed had only the single-target IS PCR been applied. Patients with mild disease (P = 0.004) and shorter hospitalization (P = 0.006) were less likely to have positive cultures. This consensus generating real-time PCR approach permits a sensitive detection, as well as an accurate species identification of the causative Bordetella pathogens for the timely management of patients.

Ethics of mandatory vaccination for healthcare workers

Healthcare workers (HCWs) are at increased risk of contracting infections at work and further transmitting them to colleagues and patients. Immune HCWs would be protected themselves and act as a barrier against the spread of infections and maintain healthcare delivery during outbreaks, but vaccine uptake rates in HCWs have often been low. In order to achieve adequate immunisation rates in HCWs, mandatory vaccination policies are occasionally implemented by healthcare authorities, but such policies have raised considerable controversy. Here we review the background of this debate, analyse arguments for and against mandatory vaccination policies, and consider the principles and virtues of clinical, professional, institutional and public health ethics. We conclude that there is a moral imperative for HCWs to be immune and for healthcare institutions to ensure HCW vaccination, in particular for those working in settings with high-risk groups of patients. If voluntary uptake of vaccination by HCWs is not optimal, patients’ welfare, public health and also the HCW’s own health interests should outweigh concerns about individual autonomy: fair mandatory vaccination policies for HCWs might be acceptable. Differences in diseases, patient and HCW groups at risk and available vaccines should be taken into consideration when adopting the optimal policy.

Carnitine deficiency in children and adolescents with type 1 diabetes

Carnitine is essential for the lipid and carbohydrate metabolism, and proper metabolic control in type 1 diabetes has potential impact on long-term complications. The plasma total, free, and acylcarnitine levels in 47 children and adolescents with type 1 diabetes were determined by a radioisotopic assay and compared to the values of a series of anthropometric measurements and metabolic parameters, including blood glycosylated hemoglobin Alc, serum cholesterol and triglycerides, and urine microalbumin levels. Plasma values for total, free, and acylcarnitine were 30.1+/-7.26, 20.0+/-4.50, and 10.2+/-6.47 micromol/l, respectively. Acyl/free carnitine ratio was 0.544+/-0.369. Individuals with type 1 diabetes had significantly lower total and free carnitine levels and significantly higher acyl/free carnitine ratios than controls (P<.001). Plasma total and free carnitine levels were inversely correlated to the duration of diabetes (P=.036 and P=.071, respectively). No statistical relationship was documented between carnitine levels and the remaining anthropometric and metabolic variables. In conclusion, total and free carnitine levels are decreased in children and adolescents with type 1 diabetes. This reduction is time related and may have potential interactions with the long-term complications of type 1 diabetes. Larger studies are required for final conclusions to be drawn on the precise role of carnitine and the possible benefit, if any, of carnitine supplementation in diabetic patients.

Four-Year Experience of Use of the Cobas Amplicor System for Rapid Detection of Mycobacterium tuberculosis Complex in Respiratory and Nonrespiratory Specimens in Greece

To evaluate the experience of a clinical microbiology laboratory with a DNA amplification assay for routine detection of Mycobacterium tuberculosis, the Cobas Amplicor Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) assay (Roche Diagnostics Systems, USA) was performed on 7,722 respiratory and 1,451 nonrespiratory specimens collected from 3,321 patients. The results were compared with those of culture in conventional Lowenstein-Jensen medium, culture in the MB/BacT system (Organon Teknika, France), and clinical investigations. A total of 240 of the 254 respiratory specimens culture positive for Mycobacterium tuberculosis were also positive in the PCR assay. Of the 7,300 culture-negative specimens, 45 (0.6%) were positive in the PCR. After detailed interpretation, the overall sensitivity, specificity, and positive and negative predictive values of the PCR assay were 84.5, 99.8, 94.1, and 99.4%, respectively, for respiratory specimens. The PCR assay was more sensitive for smear-positive respiratory specimens (97.1%) than for smear-negative respiratory specimens (48.6%). Of the 18 culture-positive (smear-negative) nonrespiratory specimens, 9 were positive in the PCR. None of the 1,384 culture-negative nonrespiratory specimens were positive in the PCR. The inhibition rates detected by the internal control of the test were 2.2% for respiratory specimens and 3.4% for nonrespiratory specimens. After resolving the discrepancies, the overall sensitivity, specificity, and positive and negative predictive values of the PCR assay were 82.5, 99.8, 94.3, and 99.4%, respectively, when compared to the results of diagnostic culture. In conclusion, the use of the Cobas Amplicor MTB-PCR assay might enable clinical microbiology laboratories with considerable previous experience in molecular biology testing to perform PCR and confirm tuberculosis infection immediately, leading to improved patient management.