Electrocardiographic Abnormalities and Mortality in Epilepsy Patients.

Background and Objectives: People with epilepsy (PWE) have a 2-3 times higher mortality rate than the general population. Sudden unexpected death in epilepsy (SUDEP) comprises a significant proportion of premature deaths, whereas sudden cardiac death (SCD) is among the leading causes of sudden death in the general population. Cardiac pathologies are significantly more prevalent in PWE. Whether electrocardiographic (ECG) parameters are associated with remote death in PWE has yet to be elucidated. The study objective was to assess whether interictal ECG parameters are associated with mortality in the long-term. Materials and Methods: The study involved 471 epilepsy patients who were hospitalized after a bilateral tonic-clonic seizure(s). ECG parameters were obtained on the day of hospitalization (heart rate, PQ interval, QRS complex, QT interval, heart rate corrected QT interval (QTc), ST segment and T wave changes), as well as reported ECG abnormalities. Mortality data were obtained from the Latvian National Cause-of-Death database 3-11, mean 7.0 years after hospitalization. The association between the ECG parameters and the long-term clinical outcome were examined. Results: At the time of assessment, 75.4% of patients were alive and 24.6% were deceased. Short QTc interval (odds ratio (OR) 4.780; 95% confidence interval (CI) 1.668-13.698; p = 0.004) was associated with a remote death. After the exclusion of known comorbidities with high mortality rates, short QTc (OR 4.631) and ECG signs of left ventricular hypertrophy (OR 5.009) were associated with a remote death. Conclusions: The association between routine 12-lead rest ECG parameters-short QTc interval and a pattern of left ventricular hypertrophy-and remote death in epilepsy patients was found. To the best of our knowledge, this is the first study to associate rest ECG parameters with remote death in an epileptic population.

Association between malocclusion and orofacial myofunctional disorders of pre-school children in Latvia.

OBJECTS: Abnormal use of muscles of tongue and lips is called orofacial myofunctional disorders (OMD). In this study, we aimed to investigate the interrelation between occlusal findings and OMD in primary and mixed dentition and to find out the reasons for malocclusions, and the effect modification of these associations by the number of sources that parents used to receive the information on child oral health issues (NSI). SETTING AND SAMPLE POPULATION: Cross-sectional study was performed in one kindergarten in Latvia (cluster sampling). The study sample comprised 141 children-mothers' pairs of pre-school children aged 4-7 years. MATERIALS AND METHODS: Children' myofunctional situation, occlusion and speech defects were assessed during an examination. Children's mothers were interviewed on their socio-demographic situation, feeding and habits of the child, history of diseases and NSI. Multiple logistic regression models adjusted for lip power, swallowing, breathing and speech cases of long respiratory diseases, age and gender were built to investigate associations between the types of occlusion and OMD/health characteristics. Effect modification of these associations by NSI was analysed. RESULTS: Types of occlusion associated with OMD/health characteristics were as follows: normal occlusion with prolonged respiratory diseases (odds ratio, OR = 0.345 [95% confidence interval, CI 0.16; 0.75]); combined type with tongue thrust habits (OR = 3.11 [0.99; 9.90]), lip-closing strength (OR = 0.99 [0.98; 0.99]); and cross-bite with speech (OR = 3.55 [1.07; 11.78]). These associations remained stable when parents used two or less sources of information on children's oral health. CONCLUSIONS: To facilitate occlusal stability, early interdisciplinary examinations should be performed to prevent time-consuming and cost-consuming treatment.

Alcohol-related seizures may be associated with more severe depression, alcohol dependence syndrome, and more pronounced alcohol-related problems.

Severe alcohol abuse and related medical and social functioning risks, as well as clinically significant depression, are common in patients who are admitted to hospital with alcohol-related seizures (ARS) and significantly affect the quality of life of the patient. Compared with studies involving patients with alcohol dependence, no large-scale studies with the aim of finding the prevalence and severity of depression and its most commonly affected aspects for patients with ARS have been carried out in Latvia yet. The habits and frequency of alcohol use in correlation to depression and its severity are also not known. One hundred ten patients were included in the study - 60 patients with ARS and 50 patients with alcohol use disorder (AUD) - without ARS. The research population consists mainly of working-age adults; however, most patients with ARS have significantly impaired daily activity and social life. Compared with patients who only have alcohol dependence, a more common problem in patients with ARS is having an alcohol dependence level that requires additional clinical examinations and consultations by a narcologist using the Alcohol Use Disorder Identification Test (AUDIT) scale, and this level is more often related to depression particularly characterized by pronounced suicidal thoughts (exhibited by almost 1 out of every 4 patients). According to the Hamilton Depression Rating Scale (HAM-D), depression has affected 81.7% of patients with ARS and 96% of patients with AUD. Seizures negatively affect patients' physical and emotional well-being in over 80% of cases; moreover, it is common for most patients to feel depressed after the seizures. Over half of the patients with ARS scored 20-40 points according to the AUDIT scale, indicating serious alcohol abuse disorder. Our research data can help bring awareness of the need to more carefully evaluate patients with ARS for an early detection of alcohol abuse disorder and depression with a risk of self-harm and unintentional harm to others as well as to decrease the burden on social care and healthcare. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays.

BACKGROUND: Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy. METHODS: We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs histological diagnosis were calculated using both the manufacturers' and optimized cutoffs. RESULTS: Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all P-values<.01). Based on manufacturers' cutoffs, sensitivities, specificities and areas under the ROC curve for detecting moderate to severe histological corpus atrophy by PgI/PgII were 44%/91%/0.70, 56%/84%/0.76, and 52%/90%/0.77 for Biohit, Vector Best and Eiken, respectively. Cutoffs optimized by ROC or data mining analyses did not substantially improve test performance. CONCLUSIONS: Commercial assays for pepsinogen have good relative agreement but are imperfect tests for clinical diagnosis of gastric atrophy. IMPACT: Pepsinogen testing alone does not provide sufficient information for gastric cancer risk stratification. Future investigations should focus on other potential markers, in combination with pepsinogens.

The Association between the Dental Status and Tongue Thrust Habits of Latvian Preschool Children and Their Mothers' Oral Health Knowledge.

OBJECTIVES: The aim of this study was to describe the factors that affect the normal dental development of preschool children in Latvia, and to investigate sources that mothers use to get information on children's oral health. MATERIALS AND METHODS: A cross-sectional study was performed in two kindergartens in Latvia (cluster sampling). The study sample comprised 141 child-mother pairs of preschool children aged 4-7 years. The dental situation of all children was assessed including evaluation by an orthodontist and a speech therapist, and mothers of children filled out the survey on oral health-related habits and information about it. STATISTICAL ANALYSIS: We described individually factors related to orthodontal situations, children's speech problems, and factors that can affect tongue thrust. We investigated relationships between sources of mothers' information and oral health-related behaviors using univariate (Kruskal-Wallis test, a chi-squared test, a Fisher test, or Cramer's V test) and multivariate analyses. We built a multiple logistic regression model adjusted for the demographic and oral health-related factors to investigate the factors associated with tongue thrust. Results of multiple logistic regression were presented with odds ratio (OR) and 95% confidence intervals (CI). RESULTS: In total, 36.9% of children grazed vegetables several times a week, and 61.0% cleaned their teeth twice a day. Of mothers, 12% did not receive any information about child dental care from their general physician, and 23.4% found the received information insufficient. A total of 43.3% of mothers received oral health-related information from friends, and it was significantly related to less carbonated water (p < 0.01), more help during teeth cleaning (p = 0.03), starting cleaning teeth in earlier age (p = 0.03), and more frequent visits to a child dentist (p = 0.03). CONCLUSIONS: A lack of knowledge was found to be prominent in mothers of kindergarten children in Latvia, and most of them received information not from official sources such as their general physician. This can be related to some problems in oral health behaviors and oral health-related diseases. Communication among dental health specialists, state authorities, and families is crucial for the improvement of children's dental situation.

Prenatal ultrasound screening and congenital anomalies at birth by region: Pattern and distribution in Latvia.

Objective: The objective was to compare the ultrasound scan frequency and rate of congenital malformations between urban and rural areas. Study design: We conducted a population-based retrospective study using linked data from administrative data sources and register data. All singleton live births in 2018 that could be linked (n = 18,759) were included in the data analysis. Place of residence was categorized into three groups: Riga (capital city), other big cities and rural areas (including regional cities). Adjusted ORs were calculated. The multiple regression model was adjusted for maternal age, living area and prenatal screenings. Results: Overall, 3% (n = 536) of the live-born infants were reported to have congenital malformations at birth. The proportion of congenital anomalies was, on average, 2% higher (p < 0.001) in Riga (4%, n = 334) than in the rural regions (2%, n = 93) and other cities (1%, n = 109). Women whose infants had congenital anomalies at birth had higher and statistically significant odds of having abnormal findings on ultrasound (US) screening (OR=2.3; 95% CI 1.5-3.4; p < 0.001) and undergoing invasive diagnostic tests during pregnancy (OR=2.2; 95% CI 1.4-3.5; p < 0.001). The median number of ultrasound scans during pregnancy was 3 (IQR 2) in Riga and 4 (IQR 2) in the other cities and rural regions. The top 3 types of congenital anomalies at birth were deformations of the musculoskeletal system and congenital malformations of the circulatory system and genital organs. Conclusions: The findings of this study showed a statistically significant association between the rate of foetal anomalies and the frequency of prenatal examinations. A higher average number of US examinations per pregnancy was observed in the rural regions. Regional variations exist in the rates of specific congenital anomalies. Further studies are recommended in this field for better understanding. Surveillance systems that are able to analyse the efficiency of US examinations need to be developed for the early prenatal detection of congenital anomalies.

Assessing the utility of pepsinogens and gastrin-17 in gastric cancer detection.

OBJECTIVES: The aim of the study was to determine the proportion of gastric cancer patients with decreased levels of pepsinogen and gastrin-17 in plasma, with the goal of providing indirect evidence of the sensitivity of these biomarkers when applied in a cancer screening setting. METHODS: The levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori immunoglobulin antibodies in plasma samples of gastric cancer patients were evaluated using the GastroPanel test system (Biohit Oyj, Helsinki, Finland). A decreased level of the pepsinogen I/II ratio was defined as less than three, while a decrease in gastrin-17 was defined as less than 1 pmol/L. Univariate analysis using non-parametric tests was used to investigate differences between normal and low concentrations of biomarkers. RESULTS: In total, 481 plasma samples from patients (59.9% male) with a median age of 64 years (ranging from 27 to 88 years) were analyzed. Out of the 400 cases of gastric cancer (83.2% of the total), 182 were categorized as the intestinal type, 141 as the diffuse type, 60 as the mixed type, and 17 as indeterminate according to the Lauren classification system. The H. pylori immunoglobulin test was positive in 74.0% of the patients. Pepsinogen I/II ratio was decreased in 32.4% (36.8% of the intestinal type); gastrin-17 in 12.3% (10.1% of the antral region) of all cases. CONCLUSION: The majority of gastric cancer patients had normal levels of pepsinogen and gastrin-17, suggesting that these biomarkers have limited application as screening tools in the Caucasian population.

Breath Volatile Organic Compounds in Surveillance of Gastric Cancer Patients following Radical Surgical Management.

As of today, there is a lack of a perfect non-invasive test for the surveillance of patients for potential relapse following curative treatment. Breath volatile organic compounds (VOCs) have been demonstrated to be an accurate diagnostic tool for gastric cancer (GC) detection; here, we aimed to prove the yield of the markers in surveillance, i.e., following curative surgical management. Patients were sampled in regular intervals before and within 3 years following curative surgery for GC; gas chromatography-mass spectrometry (GC-MS) and nanosensor technologies were used for the VOC assessment. GC-MS measurements revealed a single VOC (14b-Pregnane) that significantly decreased at 12 months, and three VOCs (Isochiapin B, Dotriacontane, Threitol, 2-O-octyl-) that decreased at 18 months following surgery. The nanomaterial-based sensors S9 and S14 revealed changes in the breath VOC content 9 months after surgery. Our study results confirm the cancer origin of the particular VOCs, as well as suggest the value of breath VOC testing for cancer patient surveillance, either during the treatment phase or thereafter, for potential relapse.

Clinicopathological Significance of Exosomal Proteins CD9 and CD63 and DNA Mismatch Repair Proteins in Prostate Adenocarcinoma and Benign Hyperplasia.

INTRODUCTION: Recently, it has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. The gold standard for prostate carcinoma (PCa) diagnosis is biopsy and histopathological examination. Thus, the complex evaluation of exosomal and MMR proteins could be beneficial for prostate cancer risk stratification and diagnostics. The aim of the current study was to evaluate and compare the expression of exosomal proteins CD9 and CD63 and MMR proteins in the tissue of patients with prostate benign hyperplasia (BPH) and PCa. METHODS: The study was retrospective. Altogether, 92 patients with PCa and 20 patients with BPH (control group) were enrolled in the study. Exosomal and MMR protein expression was analyzed by immunohistochemistry (IHC). The follow-up for each PCa patient in our study lasted till disease progression and/or a maximum of 5 years. RESULTS: Low-grade PCa was observed in 56 patients and high-grade PCa in 36 patients. CD63 expression was significantly higher in patients with high-grade PCa compared to those with low-grade PCa. CD9 expression was significantly downregulated in PCa patients compared to the control group. MMR protein expression deficiency was observed in 10 PCa patients. MMR proteins were maintained in all cases of BPH. The study found a negative correlation between MMR protein loss and PCa ISUP grade groups. Progression-free survival (PFS) in patients with MMR deficiency was significantly shorter than in patients with maintained MMR expression. CONCLUSIONS: CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa.

Mortality of children under five and prevalence of newborn congenital anomalies in relation to macroeconomic and socioeconomic factors in Latvia.

BACKGROUND: Mortality of infants and children younger than 5 years is a globally recognized and broad national welfare indicator. Scientific literature has data on the correlation of mortality indicators with macroeconomic indicators. It is important to study the associations between prevalence and mortality indicators and socioeconomic factors, since deaths from congenital anomalies account for approximately 25%-30% of all deaths in infancy. The aim of the study was to analyze the overall trend in mortality of infants and young children aged 0 to 4 years in relation to macroeconomic factors in Latvia and prevalence of congenital anomalies in newborns in relation to socioeconomic factors. MATERIAL AND METHODS: The Newborns' Register and Causes of Death Register were used as data sources; data on specific socioeconomic factors were retrieved from the Central Statistics Office. RESULTS: The results of the study show a strong correlation between mortality in children younger than 5 years and gross domestic product, as well as health budget in LVL per capita and the national unemployment level. The average decrease in infant mortality from congenital anomalies in Latvia was found to be 6.8 cases per 100,000 live births. CONCLUSIONS: There is a strong correlation between child mortality and socioeconomic situation in the country. There is a need to analyze the data on child mortality in a transnational context on a regular basis and studying the correlations between child mortality indicators and socioeconomic indicators and health care management parameters.

Association between Anxiety, Quality of Life and Academic Performance of the Final-Year-Students in Latvia.

The main objective of this study was to investigate the association between final-year students' anxiety level and quality of life (QOL) with their academic achievements. A longitudinal study was performed in regular schools and in high-rated gymnasiums at the beginning and at the end of the school year. Multiple linear regression models were built for the association between level of anxiety/QOL with academic achievements. Type of school and gender-but not the level of anxiety-were the main predictors of academic achievements of 287 adolescents (e.g., for mathematics, the effect estimates were: ß = -1.71 [95% confidence interval -2.21; -1.21]; ß = -0.50 [-0.95; -0.06], ß = 0.09 [-0.02; 0.20] for the type of school, gender, and changes in level of anxiety, respectively). To conclude, particular efforts should be made to reduce the level of anxiety in girls, especially those that study in high-rated schools.

Maternal and Neonatal Characteristics for Late Foetal Death in Latvia between 2001 and 2014: Population-Based Study.

INTRODUCTION: Stillbirth is one of the most common adverse pregnancy outcomes worldwide. Late foetal death (LFD) rates are mostly used for international comparisons because of the large variations in stillbirth rates between countries. OBJECTIVE: To examine trends in LFD (including antepartum and intrapartum) by multiple births, birth weight, and maternal age in two time periods. METHODS: A retrospective cohort study was used to analyse data from the Medical Birth Register (2001-2014), divided into 2 periods of 7 years each. In total, data on 1,340 singletons were analysed. This study calculated LFD rates and rate ratios (RR). RESULTS: The overall LFD rate showed a slight statistically significant reduction (p < 0.001) of 18% between 2001-2007 and 2008-2014. There was a slight increase in the mortality rate from multiple pregnancies (RR 1.1/1000; 95% CI 0.6-1.9). There were no major differences in the LFD rate by maternal age during the time periods. CONCLUSIONS: LFD decreased (RR 0.8/1000 births), as well as intrapartum LFD (RR 0.6/1000 births). Older maternal age influenced pregnancy outcomes, and higher LFD rates were observed in the age group ≥35 years. Substantial intrapartum stillbirths rates indicate problems with quality of intrapartum care and emergency obstetric care. Further research is needed to evaluate the strategies necessary to substantially reduce the number of stillbirths in the country.

Associations of Epstein-Barr Virus-Positive Gastric Adenocarcinoma with Circulating Mediators of Inflammation and Immune Response.

Epstein-Barr virus (EBV)-positive gastric adenocarcinoma exhibits locally intense inflammation but systemic manifestations are uncertain. Our study examined whether circulating mediators of inflammation and immune response differ by tumor EBV status. From a Latvian series of 302 gastric cancer cases, we measured plasma levels of 92 immune-related proteins in the 28 patients with EBV-positive tumors and 34 patients with EBV-negative tumors. Eight markers were statistically significantly higher with tumor EBV positivity: chemokine C-C motif ligand (CCL) 20 (Odds Ratio (OR) = 3.6; p-trend = 0.001), chemokine C-X-C motif ligand 9 (OR = 3.6; p-trend = 0.003), programmed death-ligand 1 (PD-L1; OR = 3.4; p-trend = 0.004), interleukin (IL)-10 (OR = 2.4; p-trend = 0.019), CCL19 (OR = 2.3; p-trend = 0.019), CCL11 (OR = 2.2; p-trend = 0.026), IL-17A (OR = 2.0; p-trend = 0.038) and CCL8 (OR = 1.9; p-trend = 0.049). Systemic responses to EBV-positive gastric cancer are characterized by alterations in chemokines and PD-L1. Profiling of these molecules may enable non-invasive diagnosis of EBV status when tumor tissue is unavailable. Our findings provide theoretical justification for clinical evaluations of immune checkpoint therapy for EBV-positive gastric cancer.

Multicentric randomised study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study.

INTRODUCTION: Population-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40-64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome. METHODS AND ANALYSIS: Individuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase. ETHICS AND DISSEMINATION: The study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT02047994.