"The role of L. reuteri DSM17938 in nutritional recovery and treatment of constipation in children and adolescents with anorexia nervosa - a randomized, double blind, placebo controlled study".

BACKGROUND: Anorexia nervosa (AN) carries the risk of potentially irreversible medical complications, especially in children and adolescents. Constipation is frequent and difficult to manage. Due to the symptoms it causes, constipation can further compromise nutritional rehabilitation. OBJECTIVE: To investigate the role of probiotics (Lactobacillus reuteri DSM 17938) in children and adolescent with AN. DESIGN, SETTING AND PARTICIPANTS: Randomized, double blind, placebo controlled study in 31 female pediatric AN patients with constipation, referred to nutritional therapy in Pediatric Gastroenterology Department, Sestre milosrdnice University Hospital Centre in Zagreb. METHODS: At hospitalization, patients were randomly assigned into two groups; one taking L. reuteri, and other placebo for 3 months, along with the conventional nutritional rehabilitation. Patients were followed 3 months after stopping the treatment. The primary outcome was relief of constipation, assessed after 3 months, while secondary outcomes were normalization of body weight, stool frequency and consistency, relief of dyspepsia, weight gain and recovery of malnutrition regarding bone density and vitamin D3 levels. RESULTS: The study showed statistically significant difference between the two groups considering the stool frequency (6.4 vs. 4.2 stools/week; p < 0.05) and normalization of body weight (93 vs. 63%; p = 0.04) after 6 months, but no significant effect on the rate of relief of constipation (87 vs. 64%; p = 0.22) at 3 months. In the L. reuteri group, the normalization of BMD was achieved in 8/15, whereas in the placebo group, in 3/16 patients. However, there was no statistically significant difference compared to the placebo group regarding the BMD recovery as well as the normalization of D3 levels (p = 0.056). CONCLUSIONS: Probiotics may serve as simple and safe adjuvant therapy of constipation in childhood AN and contribute to faster nutritional recovery. Although a statistically significant difference between the two group in relief of constipation could not be shown after 3 months, a benefit from probiotics could be in increasing stool frequency and nutritional recovery in childhood AN after six months. Registered under ClinicalTrials.gov Identifier no. NCT02004288.

The Impact of COVID-19 on Hospital Admissions in Croatia.

Background: The COVID-19 pandemic disrupted hospital care, as hospitals had to deal with a highly infectious virus, while at the same time continuing to fulfill the ongoing health service needs of their communities. This study examines the direct effects of COVID-19 on the delivery of inpatient care in Croatia. Materials and Methods: The research is a retrospective, comparative analysis of the hospital admission rate across all Diagnosis Related Group (DRG) classes before and during the pandemic. It is based on DRG data from all non-specialized acute hospitals in Croatia, which account for 96% of national inpatient activity. The study also used COVID-19 data from the Croatian Institute of Public Health (CIPH). Results: The results show a 21% decrease in the total number of admissions [incident rate ratio (IRR) 0.8, p < 0.0001] across the hospital network during the pandemic in 2020, with the greatest drop occurring in April, when admissions plunged by 51%. The decrease in activity occurred in non-elective DRG classes such as cancers, stroke, major chest procedures, heart failure, and renal failure. Coinciding with this reduction however, there was a 37% increase (IRR 1.39, p < 0.0001) in case activity across six COVID-19 related DRG classes. Conclusions: The reduction in hospital inpatient activity during 2020, can be attributed to a number of factors such as lock-downs and quarantining, reorganization of hospital operations, the rationing of the medical workforce, and the reluctance of people to seek hospital care. Further research is needed to examine the consequences of disruption to hospital care in Croatia. Our recommendation is to invest multidisciplinary effort in reviewing response procedures to emergencies such as COVID-19 with the aim of minimizing their impact on other, and equally important community health care needs.

Antibody response and the clinical presentation of patients with COVID-19 in Croatia: the importance of a two-step testing approach.

According to anti-SARS-CoV-2 seroresponse in patients with COVID-19 from Croatia, we emphasised the issue of different serological tests and need for combining diagnostic methods for COVID-19 diagnosis. Anti-SARS-CoV-2 IgA and IgG ELISA and IgM/IgG immunochromatographic assay (ICA) were used for testing 60 sera from 21 patients (6 with severe, 10 moderate, and 5 with mild disease). The main clinical, demographic, and haemato-biochemical data were analysed. The most common symptoms were cough (95.2%), fever (90.5%), and fatigue and shortness of breath (42.9%). Pulmonary opacities showed 76.2% of patients. Within the first 7 days of illness, seropositivity for ELISA IgA and IgG was 42.9% and 7.1%, and for ICA IgM and IgG 25% and 10.7%, respectively. From day 8 after onset, ELISA IgA and IgG seropositivity was 90.6% and 68.8%, and for ICA IgM and IgG 84.4% and 75%, respectively. In general, sensitivity for ELISA IgA and IgG was 68.3% and 40%, and for ICA IgM and IgG 56.7% and 45.0%, respectively. The anti-SARS-CoV-2 antibody distributions by each method were statistically different (ICA IgM vs. IgG, p = 0.016; ELISA IgG vs. IgA, p < 0.001). Antibody response in COVID-19 varies and depends on the time the serum is taken, on the severity of disease, and on the type of test used. IgM and IgA antibodies as early-stage disease markers are comparable, although they cannot replace each other. Simultaneous IgM/IgG/IgA anti-SARS-CoV-2 antibody testing followed by the confirmation of positive findings with another test in a two-tier testing is recommended.

Correlation of UGT1A1 TATA-box polymorphism and jaundice in breastfed newborns-early presentation of Gilbert's syndrome.

OBJECTIVE: The etiology of jaundice in otherwise healthy breastfed newborns that can present as early-onset exaggerated physiologic jaundice, or late breast milk jaundice (BMJ), is not yet entirely understood. This study tested the hypothesis that molecular marker for Gilbert's syndrome (GS), UGT1A1 TATA-box polymorphism, is associated with this disorders. METHODS: We have investigated the UGT1A1 polymorphism frequency and its relation to severity of hyperbilirubinemia and jaundice duration among 220 exclusively breastfed term newborns; 57 of them with non-physiologic hyperbilirubinemia (NH), and 163 with BMJ, and in 187 healthy controls. RESULTS: Significant differences in TA7/7 genotype frequency were established. The highest frequency was observed among the newborns with BMJ (42.0%), intermediate in the NH group (24.6%), while the controls had the lowest TA7/7 frequency (12.8%). Linear increase in TA7/7 frequency was observed depending on the duration of jaundice, peaking at 42.4% in newborns with the longest jaundice duration. Positive correlation between the serum bilirubin levels and the TATA-box length was established in all groups. CONCLUSION: This study provides evidence that UGT1A1 TATA-box polymorphism is an important risk factor for developing jaundice in term breastfed newborns, presented as either early non-physiologic hyperbilirubinemia or breast milk jaundice. These results further support the original Odell's idea of neonatal jaundice as an early presentation of GS.

Croatian dental students' educational experiences and knowledge in regard to child abuse and neglect.

The purpose of this study was to investigate the educational experiences of a group of Croatian dental students and to assess their knowledge about child abuse and neglect. In the study, 544 respondents (153 male and 391 female) from all six years at the University of Zagreb School of Dental Medicine completed questionnaires, with a response rate of 74.9 percent. A chi-square test was applied to test the differences among students' answers. Values of p<0.05 were considered statistically significant. Out of the total number of respondents, 33.6 percent had encountered the topic of child abuse and neglect during their lectures. The results show a lack of knowledge of the signs pointing to physical and sexual abuse of children. Students from more senior teaching years showed a greater amount of knowledge related to child abuse and neglect in contrast to students from more junior teaching years. In conclusion, dental students should be better educated and prepared for the important role of helping protect children from abuse and neglect.

Growth charts for Croatian school children and secular trends in past twenty years.

The aim of this study was to construct new Croatian growth charts for body height and weight of boys and girls aged 6.5 to 18.5 years and to investigate differences between our and pre-existing studies. Analysis was based on a multistage stratified sample representative for school children aged 6.5 to 18.5, 6046 boys and 5656 girls. Growth reference was constructed using LMS method. Present results demonstrated an increment of body height and weight during the last two decades. Highest increase of body height is in boys aged 13-14 years 6.5 cm, in girls aged 12 years is 5.0 cm. Highest increase of body weight is in 16 year age group of boys 8.7 kg and in 11-12 year age group of girls 5.2 kg. In conclusion, regarding presence of secular trend because previously used growth charts in Croatia are obsolete.

Clinical characteristics at presentation of type 1 diabetes mellitus in children younger than 15 years in Croatia.

The aim of the study was to determine the clinical and biochemical characteristics of type 1 diabetes mellitus (DM) at presentation in children younger than 15 years in Croatia during a 9-year period, with special attention to diabetic ketoacidosis (DKA) incidence. The registered data set comprised blood glucose, pH, serum bicarbonate levels, and clinical symptoms at disease manifestation. During the study period, 692 children were diagnosed with type 1 DM. Polydipsia (96.7%), polyuria (96.05%), and weight loss (82.7%) were the most frequent symptoms anticipating disease detection. Enuresis was recorded in 11.55%. A total of 36.41% patients had DKA (pH < 7.3) at disease onset. During the 9-year period, the percentage of children presenting with DKA at time of diagnosis decreased from 41.67% to 33.33% (z = 1.68, p = 0.046). A positive family history of DM, the only factor with an impact on the DKA incidence rate in our population, lowers the probability of the development of ketoacidosis. This study confirms the importance of the detection of the classic symptoms of polyuria, polydipsia, and weight loss in patients with new-onset type 1 DM. The percentage of patients with DKA at diabetes onset decreased during the observed period but is still high and includes one-third of all patients. This is why in every acutely ill child, especially at a younger age, one should evaluate the possibility of type 1 DM to avoid the development of ketoacidosis.

Prognostic value of computed tomography morphologic characteristics in stage I non-small-cell lung cancer.

BACKGROUND: In this study, we describe the prognostic value of NSCLC morphologic characteristics obtainable by computed tomography (CT) in the preoperative staging. Starting with the initial hypothesis that CT morphologic characteristics of NSCLC have a prognostic value, we conducted a retrospective study that included 194 patients. PATIENTS AND METHODS: All patients underwent surgery because of stage IA or IB non-small-cell lung carcinoma (NSCLC). Surgical procedures were performed in our clinic over the period of 9 years and 8 months starting in June 1996 and ending in February 2006. Preoperative CT scans and clinical data available for each patient were analyzed retrospectively. RESULTS: Over the study period, 93 patients died. The mean survival time was 78.6 months (95% confidence interval was 72.63-84.57 months). After a 2-year follow-up, 85.57% of patients were alive, but this decreased to 63.9% living patients after 5 years. Morphologic tumor characteristics were obtained by analyzing CT images available for each patient. These CT morphologic characteristics were divided into 5 categories: size, tumor edges, structure, and periphery of the tumor, as well as its relation to visceral pleura. We correlated each of these characteristics to the survival of patients. CONCLUSION: We conclude that, within stage I NSCLC, patient survival and disease prognosis vary significantly depending on such morphologic characteristics. This fact is one of the weakest points of the current tumor-node-metastasis (TNM) classification. Along with already-established tumor prognostic attributes such as size and TNM grade, we identified CT morphologic characteristics as powerful additional prognostic factors for NSCLC.

Correlation of histopathology and symptoms in allergic and non-allergic patients with chronic rhinosinusitis.

The aim of this study was to estimate and compare some histopathologic predictors of efficacy of endoscopic sinus surgery (ESS) in allergic and non-allergic patients with chronic rhinosinusitis (CRS). Symptomatology was rated in 50 allergic and 50 non-allergic patients prior to as well as 12 and 24 months after surgery. Specimens taken during the procedure were scored for goblet cells, subepithelial thickening, mast cells and eosinophils. The correlation between histopathology and symptoms was evaluated. Goblet cells and subepithelial thickening were the best predictors in both groups of patients. These parameters are significant global outcome predictors for allergic, but not for non-allergic patients. It is concluded that certain histopathologic parameters in CRS correlate with certain symptoms. Certain histopathologic changes are predictable for persistence of some bothersome symptoms after ESS. Pathologic evaluation might give prediction of response to ESS in allergic and non-allegic patients with CRS.

Ovarian follicular concentration of IL-12, IL-15, IL-18 and p40 subunit of IL-12 and IL-23.

BACKGROUND: The aim of the study was to determine the presence of interleukin (IL)-12, IL-15, IL-18 and p40 subunit of IL-12/IL-23 in follicular fluid from spontaneous cycles and the relation between the concentration of selected cytokines and IVF-embryo transfer outcome. METHODS: IVF-embryo transfer and enzyme immunoassay (EIA) (R&D Systems, Minneapolis, MN, USA and MBL, Nagoya, Japan) were used. RESULTS: Follicular fluid of women included in the IVF-embryo transfer procedure contained common p40 subunit of IL-12/IL-23 (median 70.1 pg/ml), IL-15 (median 1.3 pg/ml) and IL-18 (median 38.2 pg/ml). There was a significant negative correlation between follicular fluid concentrations of IL-15 and IL-18 (R=-0.392, P=0.003). Significantly higher concentrations of common p40 subunit of IL-12/IL-23 (median 79.8 pg/ml) were found in the follicular fluid taken from follicles containing oocytes, when compared with those without an oocyte (median 44.5 pg/ml, P=0.006). Patients who achieved clinical pregnancy had significantly decreased concentration of IL-15 (median 0.8 pg/ml) compared with patients without successful IVF-embryo transfer outcome (median 1.4 pg/ml, P=0.047). CONCLUSION: Follicular fluid collected from spontaneous cycles contains detectable levels of p40 subunit of IL-12/IL-23, IL-15 and IL-18. Increased concentrations of p40 subunit of IL-12/IL-23 in follicles containing oocytes suggest an important role of this cytokine in reproduction. Possible negative value of IL-15 as a predictor of IVF-embryo transfer success remains to be determined.

[Comparison of two or more samples of quantitative data]. / Usporedba dviju ili vise skupina kvantitativnih podataka.

In the study of the difference between the two or more data groups, first a scientific hypothesis is to be presented involving guessing, questing, and hypothesizing that motivate research. Statistical hypothesis is drawn from the scientific hypothesis, namely, the hypothesis of the researcher (which, as a rule, is affirmative). The mode of statistical hypothesis is presented so as to be valued by statistical and analytical procedures. Testing of the hypothesis is a statistical procedure that can determine whether and how reliably the available data support the given hypothesis. Testing of hypotheses, namely, testing of the significance is basically the procedure of the quantification of impressions regarding the specific hypothesis. The sequence of actions in the testing of the hypothesis: stating a null and an alternative hypothesis; the choice of the significance level (alpha); collection of relevant data based on the adequate sample of subjects; evaluation of the value of results of the statistical test specific for the null hypothesis (Ho); comparison of results of the statistical test with the values from the known value distribution specific for the given test; interpretation of the statistical test results in the probability terms (P-value). The Ho is a supposition of the absence of effect, i.e. that there is no difference between the samples in the population of interest (for example, that there is no difference in arithmetical means). This is a hypothesis of no difference. It is (mostly) made with the aim of rejection. It is either rejected or accepted. The choice of the corresponding statistical test depends on the researcher's design (dependent or independent study design of two or more data samples) as well as on the nature of data (distribution normality and variance homogeneity). Parametric tests carry more strength (the power to detect the difference if in reality it really exists) than nonparametric or distribution free tests. The latter are practical for smaller samples and situations in which the conditions for conducting parametric tests have not been satisfied.

[Clinical and radiographic characteristics of patients with osteoarthritis of knees]. / Klinicka i radioloska obiljezja bolesnika s osteoartritisom koljena.

The study of 60 outpatients with clinical diagnosis of the osteoarthritis (OA) of the knees is performed. Measured parameters were: general demographic data, clinical data and standard radiographic x-ray of knees in standing position, graduated by Kellgren and Lawrence clasificiation from 0-4. The aim of this study was to establish clinical and radiographic features of OA of knees and to compare those characteristiscs in the two subgroups of patients according to radiographic stages: a group of an early disease (stages 0 or 1) and a group of late disease (stages from 2 to 4). The mean age was 60 years with range from 39 to 85 years. 85% of patients were female. Distribution of patients according to Kellgren and Lawrence radiographic stages was as follows: 13 patients (21,7%) in grade 0, 17 (28,3%) in grade 1, 10 (16,7%) in grade 2, 11 (18,3%) in grade 3, and nine patients (15%) in grade 4. Crepitus on movement was registered in aproximatelly 80% of all patients, with no difference between early and late disease. Instability of the knee was present in eleven patients (18%), with more than a half of them (56%) in a radiographic grade 4 of OA of knees. There were no difference between functional parameters comparing original group of patients and two sub-groupes. Crepitus on movement was not related to any specific radiographic stage of disease, but instability of knee was frequently registered in late disease.

Smoking habits, signs of chronic diseases and survival in inland and coastal regions of Croatia: a follow-up study.

Aim of the study was to estimate, the relationship between survival, smoking habits, and the results of medical examinations in inland and coastal regions of Croatia. Age and sex stratified sample of general population (1,571 men and 1,793 women, 37-56 years old in 1972; followed in 1982: N = 1,090 men; 1,325 women and/or 1972-1999 controlling vital status). Relative risks and 95% confidence limits were estimated using Cox regression in the model with time dependent covariates, separately by sex. In all regions, the proportion of male smokers decreased between 1972 and 1982. The proportion of female smokers increased, differently in urban and rural regions. During the follow-up between 1972 and 1999, 568 deaths were recorded among men and 382 among women. In men, in addition to age, significant hazards of death were the number of smoked cigarettes per day, body mass index, sedative intake, vital lung capacity (FVC), 100FEV1/VC, systolic blood pressure, electrocardiogram, history of heart attack, and region. In women, in addition to age, significant predictors were the number of smoked cigarettes per day, systolic blood pressure, electrocardiogram, history of heart disease (excluding coronary diseases), and region. Survival relative risk increased with each additional smoked pack of cigarettes by 2.4% in women and 1.3% in men. Regional differences vs. smoking habit were observed. These data emphasize the need for prevention of smoking.