Psycho-social and health predictors of loneliness in older primary care patients and mediating mechanisms linking comorbidities and loneliness.

BACKGROUND: Aging is associated with many personal, social, and environmental challenges that increase the risk of loneliness. Loneliness is a painful emotional experience associated with a perceived lack of connection and intimacy. Loneliness accelerates health deterioration, but the presence of chronic health conditions (comorbidities) in older individuals may potentiate the feeling of loneliness. The relationships between health status and loneliness in older individuals have not been assessed in an integrated manner, although it is necessary for planning efficient interventions. The aim of this study was to fill in this knowledge gap, by attempting to create an integrated model of loneliness in older individuals. METHODS: The sample consisted of 189 (58% F) older individuals (> 60 years) (mean ± SD, 78.47 ± 6.65), attendees in Primary Health Care. Different factors associated with loneliness in the older population were assessed, and classified as demographic, environmental, physical (health-related), and psychological, in addition to functional abilities. A set of standard questionnaires was used to assess psychological factors and functional abilities. The hierarchical regression model assessed the effect of particular blocks of factors on status loneliness. The second aim was to analyze how psychological factors mediate associations between health status (comorbidity level) and loneliness. RESULTS: Indicated that increasing comorbidity, anxiety, lack of positive moods, not having hobbies/activities, low perception of social support, impaired cognitive function, and suppression of emotion expression, are significant predictors of loneliness. Mediation analysis informed us of how to help patients with comorbidities feel less lonely. Interventions that were suggested were those that can reduce anxiety and depression, improve cognitive abilities and emotional regulation control, and enhance social support. CONCLUSIONS: Results can help understand the pathophysiology loops linking poor health status (comorbidity level) of older individuals and loneliness, and have significant potentials from the translational perspectives, as a decision-support tool.

THE IMPACT OF POSITIVE ANTI-HBC MARKER ON PERMANENT DEFERRAL OF VOLUNTARY BLOOD DONORS IN EASTERN CROATIA AND ESTIMATION OF OCCULT HEPATITIS B VIRUS INFECTION RATE.

Recently an increase has been reported in the number of HBV transmissions from anti-HBc positive blood donors that were repeatedly negative in HBsAg and nucleic acid testing using the most sensitive tests available. The aim of the study was to show the effect of anti-HBc antibody testing performed in 2006 on permanent deferral of voluntary blood donors (VBDs), and to estimate occult hepatitis B infection (OBI) rate in this population after the introduction of mandatory molecular testing in the 2013-2016 period. More than 30,000 blood donations collected during the 2005-2007 period and more than 14,000 VBDs having donated blood during the 2013-2016 period after the introduction of molecular testing from eastern Croatia were included in the study. Serologic testing was performed with HBsAg assay throughout the study period, and anti-HBc assay was only performed in 2006. As part of the confirmatory algorithm testing, all HBsAg positive and unclear results were tested with molecular tests. Anti-HBc prevalence among VBDs in 2006 was 1.5%, with a rate of 1:197, whereas HBsAg prevalence was stable from 2005 to 2007 (0.04%, 0.1% and 0.1%, respectively). The calculated OBI rate from 2013 to 2016 was 1:30,250. Ten of 161 (12.4%) VBDs had serologic anti-HBc-only pattern. Anti-HBc testing in 2006 resulted in statistically more deferrals of VBDs compared to 2005 and 2007, and to the rest of Republic of Croatia. The strategy of universal anti-HBc testing of VBDs in addition to the existing HBsAg and molecular screening could be an additional measure to prevent HBV transmission by blood and blood components.

INTERACTIONS AMONG INTERLEUKIN-6, C-REACTIVE PROTEIN AND INTERLEUKIN-6 (-174) G/C POLYMORPHISM IN THE PATHOGENESIS OF CROHN'S DISEASE AND ULCERATIVE COLITIS.

Inflammatory bowel diseases are multifactorial disorders the clinical manifestation of which depends on the interaction among immune response, genetic and environmental factors. There is growing evidence that cytokines and gene polymorphisms have an important role in disease pathogenesis in various populations although molecular mechanism of their signaling and interactions is not fully understood yet. The present study aimed at exploring the effects of interleukin-6, C-reactive protein and interleukin-6 rs1800795 polymorphism on the development of Crohn's disease, ulcerative colitis and inflammatory bowel diseases overall and at determining differences between inflammatory bowel disease patients and healthy controls. A total of 132 inflammatory bowel disease patients and 71 healthy blood donors were investigated. In order to assess the clinical relevance of interleukin-6 and C-reactive protein serum concentration and interleukin-6 rs1800795 single nucleotide polymorphism in patients with Crohn's disease and ulcerative colitis, we performed a cross-sectional, case-control study. Quantitative assessment of serum interleukin-6 and C-reactive protein was performed with solid-phase, enzyme-labeled, chemiluminescent sequential immunometric and immunoturbidimetric assay, respectively. A real-time fluorescence resonance energy transfer-based method on a LightCyclerTM PCR 1.2 was used for genotyping of IL-6 rs1800795 polymorphism. Both interleukin-6 and C-reactive protein serum levels were elevated in Crohn's disease and ulcerative colitis patients. Positive correlations were observed between C-reactive protein and interleukin-6 serum concentration and ulcerative colitis activity index as measured by modified Truelove-Witt's severity index scale. C-reactive protein serum level was higher in Crohn's disease patients without intestinal resection than in Crohn's disease patients with prior intestinal resection. In ulcerative colitis patients, interleukin-6 and C-reactive protein serum levels were statistically significantly higher in CC interleukin-6 genotype in comparison to GG+GC genotype. Analysis of the promoter region of the interleukin-6 rs1800795 gene polymorphism showed no statistically significant difference in allele frequency either between inflammatory bowel disease patients and healthy controls or between the two inflammatory bowel disease phenotypes and healthy controls. Associations presented in this study give a potentially important insight into the role of interleukin-6 and C-reactive protein signaling and interleukin-6 polymorphism in the pathogenesis of Crohn's disease and ulcerative colitis disease.

Association Between Interleukin-10 Gene (-1082g/A) Polymorphism and Type 2 Diabetes, Diabetes-Related Traits, and Microvascular Complications in the Croatian Population.

Interleukin (IL)-10 is an anti-inflammatory cytokine, and a decrease in its secretion is associated with obesity, metabolic syndrome and type 2 diabetes. However, it has not been established whether the intensity of the immune response during diabetes-associated chronic inflammation affects the development and/or progression of type 2 diabetes and its microvascular complications. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP)-1082G/A for IL-10 gene in development of diabetes type 2 and its complications. DNA was extracted from blood cells of 240 overweight/obese subjects for IL-10 genotyping. Based on the presence of diabetes type 2, patients were divided in two groups: experimental group of 144 patients with diabetes type 2 and control group of 96 age- and gender-matched subjects without diabetes. Compared to control group, diabetic group had higher levels of leukocytes (p=0.012), fibrinogen (p=0.049) and plasminogen activator inhibitor-1 (PAI-1) (p=0.009), and lower levels of albumin (p=0.001). There were no differences in the frequency of SNP-1082G/A for IL-10 gene between the two groups (p=0.654). When considering diabetes related traits in all subjects in relation to specific genotype, a group with homozygous (AA) genotype had higher values of the mean fasting glucose (p<0.000001), HbA1c (p<0.000001) and HOMA-IR (p=0.003632), while the mean HOMA-B value (p=0.000178) was lower when compared to the groups with GG and GA genotypes. There was no difference in devel-opment of diabetic nephropathy, retinopathy and polyneuropathy between the IL-10 polymorphism genotypes. In conclusion, obese diabetes type 2 patients had an increased inflammation activity com-pared to obese non-diabetic individuals. There was no association of the investigated polymorphisms and development of type 2 diabetes and its microvascular complications. However, diabetes related traits clearly depended on the presence of specific IL-10 genotype.

Malignant neoplasms of respiratory and intrathoracic organs (C30-C39) in the Osijek-Baranja County, Croatia.

The Institute of Public Health of the Osijek-Baranja County in collaborate with different county institutes provide updated information on the cancer occurrence and trends in the Osijek-Baranja County (OBC). The cancers were defined according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), codes of malignant neoplasms of respiratory and intrathoracic organs (C30-C39). The aim of this article was to show the size of cancer problem with the C30-C39 cancer group in the Osijek-Baranja County (OBC). This article processes data on cancer incidence and mortality, appertaining age distribution, median age, cancer survival and length of stay in hospital collected in period 2001-2009. Out of all patients diagnosed with C30-C39 cancers, there were 18.2% of females and 81.8% of males. The total incidence rate in males (119.5/100,000) decreases while the total mortality rate (110.9/100,000) does not change in 9-year period. In the same period, the total mortality rate in females (15.7/100,000) increase moderately. The age-standardized incidence rate was six times higher in males than in females. The overall median age at diagnosis of C30-C39 cancers of both genders was 64.5 years, which exceeds the average age at diagnosis of cancer in general in the OBC by 4.8 years. Five-year relative survival rate was 14.8%, 19.7% for females and 13.7% for males. Male lung and bronchus cancer patients (C34) were 1 year younger at diagnosis of cancer than the respective female patients. An average C30-C39 cancer patient was hospitalized 2.0 times during the course of their illness while the median length of stay in hospital amounted to 16.1 days. The number of hospital admissions in both genders decreased over the 2001-2009 period. In both genders, the total length of stay in hospitals was slightly reduced. Females spent 0.4 days more in hospital than males. The overall incidence and mortality rate in the OBC were among the highest in Europe. However, these rates in females reached neither the Croatian nor the EU average. Other data are similar to those in Europe.

Importance of interleukin 6 in pathogenesis of inflammatory bowel disease.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is an uncontrolled chronic inflammation of the gastrointestinal tract caused by an interaction of diverse genes and environmental factors. There is growing evidence that cytokine production plays an important role in IBD. One of the key roles in signaling pathway in development of IBD is performed by interleukin 6 (IL-6), although molecular mechanism of this pathway is not yet fully understood. In order to assess the clinical relevance of IL-6 serum concentration in patients with CD and UC we performed cross-sectional, case-control study of IL-6 levels in patients' and healthy blood donors' sera. A total of 100 CD and UC patients and 71 healthy blood donors were investigated. Clinical activity of CD and UC was evaluated using the Crohn's disease activity index and Truelove-Witt's criteria, respectively. Quantitative assessment of serum IL-6 was performed with solid-phase, enzyme-labeled, chemiluminescent sequential immunometric assay. Our results indicate that serum IL-6 is a clinically relevant parameter for CD and UC that strongly correlates with inflammatory activity of disease. We confirmed and extended the role of cytokine production patterns for IBD presentation in Croatian population.

Malignant neoplasms of digestive organs (C15-C26) in the Osijek-Baranja County, Croatia.

The Institute of Public Health for the Osjek-Baranja County (OBC) has processed the data on cancer patients that were collected from mandatory county hospitals data reports, county bureaus of statistics and the County Register of Deaths. The cancers were defined according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), codes of malignant neoplasms of digestive organs (C15-C26). The aim of this article is to show the size of the problem and the burden of the health care system caused by cancers of the digestive system (C15-C26) in the OBC in the period 2001-2006. This article deals with cancer incidence and mortality data, appertaining age distribution, cancer survival, median age at diagnosis and at death and length of stay in hospitals. The overall incidence and mortality rate from cancer group C15-C26 (101.1 and 80/100,000, respectively, EU standard population) declined in all age groups, comparing the data originating from the 2001-2003 period to the data referring to the 2004-2006 period. The median age at diagnosis of cancer was 67.8 years with a shift of 0.91 year up in second period (the median age in the first period was 67.3 years and in the second one 68.2 years). The median age at diagnosis of cancer in females was 69.7 years while in males was 66.3 years, which represents a difference of 2.9 years in favour of females. The overall relative survival rate of all ages was 23.6%. This figure was slightly bigger for females (24.3%) than for males (23.1%). Concerning all age groups, the number of hospital admissions of males increased during the observation period while the number of hospital admissions of women decreased at the same time. The average length of stay over the six years did not changed significantly. Group of cancer C15-C26 was the most common group of cancers regarding both genders. The five-year relative survival as one of the reliable benchmarks of the quality of the health care system needs to be raised to a great extent in order to come nearer to the EU average within a short period of time.

Pilot study of variants of the IL-23R and STAT3 genes reveals no association with Hashimoto's thyroiditis in the Croatian population.

Interleukin-23 receptor (IL-23R) and signal transducer and activator of transcription 3 (STAT3) polymorphisms are common risk factors for a number of T helper (Th) 17-mediated autoimmune diseases. However, the importance of genetic variations in Th17 pathways to thyroid autoimmunity, and particularly Hashimoto's thyroiditis (HT), is not fully understood. In this study, we genotyped three single nucleotide polymorphisms (SNPs) within the IL-23R (rs11209026/p.Arg381Gln, rs7530511) and STAT3 (rs744166) genes in 217 Croatian patients with HT and 161 healthy controls using fluorescence resonance energy transfer technology and melting curve analysis of polymerase chain reaction products. None of the tested SNPs or IL-23R haplotypes was associated with HT susceptibility or disease severity. These results suggest that the studied IL-23R/STAT3 polymorphisms affecting Th17 signaling efficiency are not major determinants of HT risk in the Croatian population. Further work is necessary to determine if these loci contribute modestly or conditionally to the risk of HT.

First six years of implementing colorectal cancer screening in the Osijek-Baranja County, Croatia--can we do better?

The primary goal of this paper is to evaluate the efficiency of the Colorectal Cancer Screening Program in the Osijek-Baranja County. The screening method for early detection of colorectal cancer was the guaiac Faecal Occult Blood Test (gFOBT) and colonoscopy for gFOBT positive finding. The target population were asymptomatic subjects at average risk, aged 50-74. The responding rate was 20.3% (14.9% of men and 19.3% of women). The percentage of gFOBT positive tests was 8.5% (11.2% of men and 6.6% of women). From the 1,657 individuals who were invited to further assessment (884 men and 773 women), 1,157 underwent a colonoscopy exam (649 men and 508 women). We can conclude that the response to FOBT in our county was extremely poor. 83 carcinomas were found, with almost double findings among men than among women. Our population has a significantly higher number of men with malignant and premalignant changes when compared with women. Considering the higher incidence among men, as well as an increase in incidence in the entire population, we have to take care that our public health programmes are being created with this taken into account, as to increase the response rate, especially among those with a higher risk of developing a disease.

[Croatian consensus on the treatment of inflammatory bowel diseases with biologic therapy]. / Hrvatski konsenzus o lijecenju upalnih bolesti crijeva bioloskom terapijom.

Introduction of biologic therapy in clinical practice represented significant progress in the treatment of inflammatory bowel diseases (IBD) because of its proven efficacy and due to the fact that biologics are the first drugs used in the treatment of IBD that can change the natural course of this diseases. At the same time, biologics are very expensive drugs with complex mechanism of action and important side effects and their use requires evidence-based clinical guidelines. These were the reasons that Referral Center of the Croatian Ministry of Health for IBD and the IBD Section of the Croatian Society of Gastroenterology organised Croatian consensus conference that defined guidelines for the treatment of IBD with anti-TNF drugs. The text below includes definitions of IBD, general principles of IBD therapy, comments on the importance of mucosal healing, analysis of reasons for nonresponse and loss of response to anti-TNF drugs, recommendation for the duration of anti-TNF therapy, rules of screening for opportunistic infections prior to anti-TNF therapy, comments on the problems with reproduction in IBD and finally guidelines for the treatment of various phenotypes of IBD including extraintestinal manifestations with anti-TNF therapy.

[Pharmacology of biologic medications]. / Farmakologija bioloskih lijekova.

Two major types of inflammatory bowel diseases (IBD) are Crohn's disease (CD) and ulcerative colitis (UC). Insights into their pathophysiology and inflammatory cascade have lead to the discovery of medications that can have a selective effect on a particular molecule or signal pathway and correct an imbalance in pro- and anti-inflammatory mediators. The first to be developed were the TNF-alpha antagonists, soluble receptors like etanercept and monoclonal antibodies. Infliximab has been approved worldwide for treatment of moderate to severe and active fistulizing forms of Crohn's disease, as well as for severe forms of ulcerative colitis in adults who do not react to full and adequate corticosteroid and/or immunosuppressive therapy, i.e. for patients who have problems with or medical contraindications to such therapy and for treatments of severe forms of active disease in children. Adalimumab can be applied in cases when antibodies develop as a reaction to infliximab, leading to reduced drug efficacy and allergic reactions. According to the available data from preclinical tests and earlier phases of clinical tests, potential candidates for new biological medications in treating IBDs are another TNF-alpha antagonist (certolizumab), inhibitors of Th1 polarisation (fontolizumab, ustekinumab) and selective adhesion-molecule inhibitors (natalizumab).

Polymorphisms of interleukin-23 receptor in patients with inflammatory bowel disease in a Croatian tertiary center.

The Interleukin-23 signalling pathway is important for the differentiation of TH17 lymphocytes and is involved in the pathogenesis of Inflammatory bowel disease. Polymorphisms in the IL-23 receptor gene were previously found to be associated with Inflammatory bowel disease in various populations. The aim of this study was to determine whether the specific rs11209026 and rs7530511 single-nucleotide polymorphisms in the Interleukin-23 receptor gene are associated with Crohn's disease and ulcerative colitis in a Croatian patient population. A total of 50 patients with Crohn's disease and 93 patients with ulcerative colitis, as well as 99 healthy control subjects were included in the study. The results determined a significantly higher occurrence of rs11209026 in control group compared to patients with inflammatory bowel disease, suggesting a protective effect of this polymorphism. The rs11209026 variant was strongly associated with Crohn's disease, but it was absent in ulcerative colitis. However, there was no significant association between the rs7530511 polymorphism with either ulcerative colitis or Crohn's disease. Associations presented in this study give potentially important insight into the roles of specific Interleukin-23 receptor polymorphisms in Crohn's disease pathogenesis in the Croatian population.

The influence of the different morphological changes on gastric mucosa on somatostatin cell number in antrum mucosa and serum somatostatin.

The aim of our paper was to investigate the influence of the different morphological changes on gastric mucosa on somatostatin D-cell number in antral mucosa and serum Somatostatin. We analyzed according to Sydney classification to what extent the severity of gastritis affect the observed hormonal values. somatostatin D-cell number in antral mucosa and serum Somatostatin values were compared between three groups of patients; mild, moderate and severe chronic gastritis. The average number of somatostatin cell in biopsy sample of antrum mucosa was 30.41 +/- 35.38 (N = 17) in the case of middle form, 18.69 +/- 26.65 (N = 56) in moderate and in severe case of chronic gastritis 5.23 +/- 5.93 (N = 7) cells in mm2 of mucosa. The level of somatostatin in the serum of middle form gastritis were 26.43 +/- 28.76, moderate 19.95 +/- 35.93 and severe 17.88 +/- 17.66 pg/mL. In order to determine the number of somatostatin cells in antrum mucosa and serum somatostatin with present morphological changes of mucosa, it might helpful to exclude the patients with non-ulcer dyspepsia, but with the higher risk of premalignant and malignant changes.

[Hormonal regulation of gastric secretion and Helicobacter pylori]. / Hormonska regulacija zelucane sekrecije i Helicobacter pylori.

Helicobacter pylori has been recognized as one of the most important factors that lead to chronic changes in the gastric mucosa. These changes have either direct or indirect impact on various intestinal hormones (gastrin, somatostatin, bombensin, cholecystokinin...) which regulate gastric secretion. Gastric secretion enhancement is mostly caused by higher concentration of serum gastrin. The mechanism in which the Helicobacter pylori infection influences the regulation of gastrin and other intestinal hormones is yet to be discovered. It is known that eradication of the Helicobacter pylori infection decreases serum gastrin concentration, thus decreasing gastric secretion and inflammatory changes of the gastric mucosa.

[Duodenal ulcer and Helicobacter pylori infection]. / Ulkus na dvanaesniku i infekcija Helicobacterom pylori.

The research accomplishment of Australian investigators Marshall and Warren, published in 1983, has entirely changed our understanding of ulcer genesis and proposed a new strategy in diagnostics and therapy of peptic ulcer disease. The key etiopathogenetic role of Helicobacter pylori has been recognised. Marshall confirmed on himself that Helicobacter pylori, as an infectious agent, fulfilled all Koch's postulates. The bacterial infection caused the mucosal inflammatory changes in his stomach which were rapidly resolved by antibiotics. During later clinical and experimental investigations the association of Helicobacter pylori and peptic ulcer has also been proved. Etiopathogenetic influence of Helicobacter pylori infection on duodenal ulcer development is nowadays very well known. Diagnostic guidelines, the modes of treatment and clinical management of these patients are mostly precisely defined. In this article, besides the general review of modern knowledge about Helicobacter pylori infection concerning epidemiology, etiopathogenesis, diagnostics and duodenal ulcer therapy, we are going to present also our results in the management of the large group of patients with duodenal peptic ulcer or ulcer scars.

[Helicobacter pylori--overview of therapy]. / Helicobacter pylori--pregled terapijskih mogucnosti.

The clinical significance of Helicobacter pylori infection in the etiopathogenesis of many gastroduodenal disorders, especially peptic ulcer disease and current awareness of the benefits of its eradication has entirely changed the current treatment of these diseases. Eradication was already defined as the disappearance of Helicobacter pylori from the gastric mucosa (finding negativization) confirmed at least 4 weeks (or later) after completed antibiotic eradication therapy. The regimen has to be simple, cheap and tolerable so that the patient could carry it out completely and as easy as possible (good compliance is required). The success of Helicobacter pylori eradication, evaluated by the strict "intention-to-treat" criteria, has to be higher than 80%. Current modern therapy should be triple and not longer than 7 days. One of three proton pump inhibitors is recommended as the antisecretory component (omeprazole, pantoprazole or lansoprazole). Two of three following antibiotis is added to this therapy: metronidazole/tinidazole, clarithromycin or amoxicillin. Treatment failure and growing number of antimicrobial resistant Helicobacter pylori strains require new ways of therapy and more effective drugs. Our results of 7-, 10- and 14-day therapy consisting of omeprazole, amoxicillin and metronidazole are poorer than those of drug combination including clarithromycin instead of amoxicillin. The results of Clinical Hospital "Merkur" showed that combination of amoxicillin, metronidazole and pantoprazole was more effective than the same combination with omeprazole, and the opposite was true for metronidazole and azithromycin combined with omeprazole and pantoprazole, respectively. The results of other medical centers prescribing the same eradication protocols were completely different. The differences are probably caused by poor patient compliance.