Ingrida Rumba-Rozenfelde

Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study

Objective To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). Methods CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2–17 years), ERA (12–17 years), or PsA (12–17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. Results 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. Conclusions ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings.

Prevalence of Helicobacter pylori infection and atrophic gastritis in Latvia.

Objectives Helicobacter pylori infection and atrophic gastritis are related to an increased risk for gastric cancer. There is a decrease in global H. pylori prevalence. We analyzed the prevalence of H. pylori infection in Latvia by the plasma IgG test and the presence of atrophy by means of pepsinogen testing. Methods This subanalysis was carried out on a randomly selected cross-sectional sample of a general population of adults to access cardiovascular risk factors. Plasma samples were screened for H. pylori IgG (cutoff value 24 U/ml), and pepsinogens (Pg) I and II. Pg cutoff values of PgI/PgII⩽3 and PgI⩽70 ng/ml were used to assess the prevalence of atrophy of any grade and PgI/PgII⩽2 and PgI⩽30 ng/ml for advanced atrophy. Results Altogether, 3564 serum samples were available for the study (2346 women, 1218 men; median age 54 years). Of the tested individuals, 79.21% were H. pylori positive, with no difference between sexes. The prevalence increased with age (P<0.001). Atrophy of any grade was identified in 1444 individuals (40.52%) and advanced atrophy in 475 individuals (13.33%). Linear association with age was present in both response types (P<0.001). The prevalence of atrophy of any grade was higher in women (41.73%) than in men (38.18%; P=0.04); this difference was lost for advanced atrophy (women 13.98%, men 12.07%; P=0.1). Conclusion The prevalence of H. pylori infection or atrophy remains high in Latvia. Determining the right cutoff value is critically important for pepsinogen-based atrophy detection in Europe in order to objectively stratify gastric cancer risk.

Dissecting the heterogeneity of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

Objective. To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey. Methods. International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course. Results. A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide. Conclusion. The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.

Association of obesity with proteasomal gene polymorphisms in children.

The aim of this study was to ascertain possible associations between childhood obesity, its anthropometric and clinical parameters, and three loci of proteasomal genes rs2277460 (PSMA6 c.-110C>A), rs1048990 (PSMA6 c.-8C>G), and rs2348071 (PSMA3 c. 543+138G>A) implicated in obesity-related diseases. Obese subjects included 94 otherwise healthy children in Latvia. Loci were genotyped and then analyzed using polymerase chain reactions, with results compared to those of 191 nonobese controls. PSMA3 SNP frequency differences between obese children and controls, while not reaching significance, suggested a trend. These differences, however, proved highly significant (P < 0.002) in the subset of children reporting a family history of obesity. Among obese children denying such history, PSMA6 c.-8C>G SNP differences, while being nonsignificant, likewise suggested a trend in comparison to the nonobese controls. No PSMA6 c.-110C>A SNP differences were detected in the obese group or its subsets. Finally, PSMA3 SNP differences were significantly associated (P < 0.05) with circulating low-density lipoprotein cholesterol (LDL) levels. Our results clearly implicate the PSMA3 gene locus as an obesity risk factor in those Latvian children with a family history of obesity. While being speculative, the clinical results are suggestive of altered circulatory LDL levels playing a possible role in the etiology of obesity in the young.

Identification of a novel candidate locus for juvenile idiopathic arthritis at 14q13.2 in the Latvian population by association analysis with microsatellite markers.

To identify novel juvenile idiopathic arthritis (JIA) susceptibility loci, a 270 kb genomic region encompassing FAM177A1, KIAA0391, and PSMA6 genes was genotyped in 97 oligoarthritis (JIoA) and 50 polyarthritis (JIpA) patients and 230 individuals without autoimmune disorders by five microsatellites (MS) previously described as HSMS markers of the 14q13.2 region. Direct sequencing revealed two variable components of the (CAA)(n)(A)(m) motif in HSMS602 marker (FAM177A1 gene). Repeat (AC)(5)AT(AC)(n) of the HSMS701 (KIAA0391 gene) was variable in the Latvian population only in its downstream part. Allele (AC)(5)AT(AC)(15) of HSMS701 was found to be strongly associated with JIA (p = 4.91 x 10(-5), odds ratio [OR] = 18.87) and modestly associated with JIpA (p = 1.64 x 10(-3), OR = 15.69). Alleles (AC)(5)AT(AC)(18) of HSMS701 and (TG)(10) of HSMS702 appear to be JIA and JIoA risk factors (p = 1.09 x 10(-3), OR = 2.64 and p = 2.00 x 10(-3), OR = 7.67, respectively), but allele 168 bp of HSMS602 (p = 9.02 x 10(-4), OR = 0.35) appears to be protective. Two heterozygote genotypes (TG)(20/23) of the HSMS006 and (AC)(22/23) of the HSMS801 showed association with JIA (p < 2 x 10(-3)), but homozygote (TG)(19/19) was found to be protective (p = 5.41 x 10(-4), OR = 0.12). Our results define an additional susceptibility locus for JIA at the 14q13.2 genomic region encompassing KIAA0391 and PSMA6 genes.

Prevalence of Helicobacter pylori infection among preschool children in Latvia: no significant decrease in prevalence during a ten year period

Aims: Published data show a trend of decreasing prevalence of Helicobacter pylori in Eastern European countries due to socioeconomic changes. The aim of this study was to determine the prevalence of H. pylori infection among children in Latvia and to compare these results with previous studies in the same population. The risk factors associated with infection were also analysed. Methods: Preschool children in kindergartens and primary health care centres were investigated using a stool antigen test. Their parents were asked to fill out a questionnaire about possible risk factors. Statistical analysis included Pearson’s χ2 test and linear regression analysis. Results: The prevalence of H. pylori infection determined by the monoclonal stool antigen test in children aged 1–6 years (median 5 years) was 15.5% (15/101) (95% confidence interval 8.67–23.48%). In the regression analysis, H. pylori positivity was significantly negatively associated with the consumption of imported fruit at least once per week (p=0.02). Conclusions: The prevalence of H. pylori in the studied population has not decreased significantly during the last decade and is still associated with socioeconomic factors. The role of some dietary factors (e.g. the consumption of fruit) in the spread of infection should be studied further.

Pepsinogen testing for evaluation of the success of Helicobacter pylori eradication at 4 weeks after completion of therapy

BACKGROUND AND OBJECTIVE Pepsinogen levels in plasma are increased by inflammation in the gastric mucosa, including inflammation resulting from Helicobacter pylori infection. A decrease in pepsinogen II level has been suggested as a reliable marker to confirm the successful eradication of infection. The aim of our study was to evaluate the potential role of pepsinogens I and II, gastrin-17 and H. pylori antibodies in confirming successful eradication. MATERIAL AND METHODS Altogether 42 patients (25 women, 17 men), mean age 45 years (range 23-74), were enrolled. Pepsinogens I and II, gastrin-17 and H. pylori IgG antibodies were measured in plasma samples using an ELISA test (Biohit, Oyj., Finland) before the eradication and 4 weeks after completing the treatment. The success of eradication was determined by a urea breath test. RESULTS Eradication was successful in 31 patients (74%) and unsuccessful in 11 patients (26%). Pepsinogen II decreased significantly in both the successful (P=0.029) and unsuccessful (P=0.042) eradication groups. Pepsinogen I decreased significantly in the successful (P=0.025) but not the unsuccessful (P=0.29) eradication group. The pepsinogen I/II ratio increased in the successful eradication group (P=0.0018) but not in the group in which treatment failed (P=0.12). There were no differences in gastrin-17 or H. pylori antibody values. CONCLUSIONS A decrease in pepsinogen II levels cannot be used as a reliable marker for the successful eradication of H. pylori 4 weeks after the completion of treatment. The increase in pepsinogen I/II ratio reflects differences in pepsinogen production following the eradication irrespective of improvement in atrophy.

Helicobacter pylori Infection and Risk Factors in Relation to Allergy in Children

Purpose To analyze presence of Helicobacter pylori infection and environmental risk factors among children with and without allergy. Methods Parents of children at primary health care centres/kindergartens and allergologist consultation were asked to answer a questionnaire and to bring a faecal sample. H. pylori infection was detected by monoclonal stool antigen test. Prevalence of H. pylori infection and risk factors were compared between individuals with and without allergy using χ2 test, ANOVA test and parameters and logistic regression. Results Among 220 children (mean age, 4.7 years; ±standard deviation 2.3 years) H. pylori positivity was non-significantly lower among patients with allergy (n=122) compared to individuals without allergy (n=98): 13.9% (17/122) vs. 22.4% (22/98); p=0.106. In logistic regression analysis presence of allergy was significantly associated with family history of allergy (odds ratio [OR], 8.038; 95% confidence interval [CI], 4.067–15.886; p<0.0001), delivery by Caesarean section (OR, 2.980; 95% CI, 1.300–6.831; p=0.009), exclusive breast feeding for five months (OR, 2.601; 95% CI, 1.316–5.142; p=0.006), antibacterial treatment during the previous year (OR, 2.381; 95% CI, 1.186–4.782; p=0.015). Conclusion Prevalence of H. pylori infection did not differ significantly between children with and without allergy. Significant association of allergy with delivery by Caesarean section and antibacterial therapy possibly suggests the role of gastrointestinal flora in the development of allergy, while association with family history of allergy indicates the importance of genetic factors in the arise of allergy.

The Latvian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Latvian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 100 JIA patients (2% systemic, 56% oligoarticular, 17% RF negative polyarthritis, 25% other categories) and 204 healthy children, were enrolled at the paediatric rheumatology centre. The JAMAR components discriminated healthy subjects from JIA patients, except for the paediatric rheumatology quality of life (HRQoL), psychosocial health (PsH) subscales, the HRQoL total score and for the school-related problems variable. All JAMAR components revealed good psychometric performances. In conclusion, the Latvian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

FEEDING INFANTS WITH COW'S MILK AND SOY ALLERGY: SOCIAL AND ECONOMIC ASPECTS OF EFFICACY

Abstract Allergy to cow’s milk protein and/or soy is common among allergic diseases in infants. They appear at an early infant stage and remain important in clinical practice from one up to three years. According to clinical research, cow’s milk allergy affects about 1.9-4.9% of babies and infants, respectively, and in addition some of them also suffer from soy protein allergy. Dietary prevention of allergic protein by its elimination in food is a significant part of treatment, and allows adequate development of babies and restricts the risk of progressive allergic diseases. Securing exclusive breastfeeding is one of the basic principles in successful therapy treatment. However, there are cases when breastfeeding does not prevent the development of cross milk protein allergy. Only adequate special feeding formulas can provide both energy needs and sufficient quantity of proteins (8.9-11.5%) in food when breastfeeding is not possible. Knowledge of effective compensation mechanisms become apparent by analysing the situation in Europe and USA in the area of different available feeding formulas using both the medical insurance system and randomised formula providing tolerance of the mixture at about 90-95%. The goal of research was to determine the correlation between the availability of a special mixture, parental adherence and treatment outcomes. Applying special formulas is a routine part of treatment, and there is no doubt about its efficacy. No compensation mechanisms exist in present-day Latvia, and the current complicated economic situation in Latvia reduces the ability of parents to choose and buy appropriate formula food. Therefore, a substantial part of therapy treatment is unavailable to infants. Dietary prevention of allergic diseases in infants and small children in Latvia needs special consideration also because of poor knowledge of parents regarding the real situation. Abstrakt Govs piena olbaltuma alerģija un/vai sojas aleiģija ir viena no pirmajām alerģisko slimību izpausmēm, kas sākas jau agrīni zīdaiņa vecumā un ir klīniski nozīmīga Bdz 1-3 gadu vecumam. Saskaņā ar kBnisko pētījumu datiem govs piena olbaltuma alerģijas izplatība ir no 1.9 Bdz 4.9% zīdaiņu un mazu hēmu vidū. daļai no šiem hēmiem ir arī sojas olbaltuma alerģija. Ār-iešanas nozīmīga daļa ir izraisošā olbaltuma alergēna eliminēšanai no uztura, lai nodrošinātu adekvātu bčma attīaību un mazinātu risku tālākai alerģisko slimību attīaībai. Ekskluzīvas zīdīšanas nodrošināšana ir viei* pamatnosacījumiem veiksmīgai uztura terapijai Gadījumos, kad tas nav iespējams, tikai a&kvāta ārstnieciskā maisījuma lietošana mākslīgi ēdinātiem bērniem spēj nodrošināt enerģētiskās vajadzības un pietiekamu olbaltuma daudzumu no8.9 līdz 11.5% uzturā. Eiropas un ASV situācijas analīze par maisījumu pieejamību vecākiem parāda efektīva kompensācijas mehānisma darbību, gan izmantojot veselības apdrošināšanas sistēmu. gan receptūru, kas pierādītas alerģijas gadījumā nodrošina maisījumu toleranci par 90-95%. Ārstniecisko maisījumu lietošana ir ikdienas terapijas daļa. tās lietderība netiek apšaubīta. Latvijā kompensācijas mehānisms neeksistē, un valsti esošā ekonomiskā situācija ierobežo vecāku iespēju iegādāties maisījumus, līdz ar to bērnam nav iespēju saņemt nepieciešamo terapijas daļu.