Mirjana Jarebinski

Lifestyle Factors and Multiple Sclerosis: A Case-Control Study in Belgrade

The aim of this case-control study was to assess the risk of developing multiple sclerosis (MS) associated with certain lifestyle factors (cigarette smoking and coffee and alcohol consumption). The study groups consisted of 210 cases with clinically proven and/or laboratory-confirmed MS (Poser’s criteria) and an identical number of sex- and age-matched hospital controls. In the MS patients, cigarette smoking was significantly more frequent than in the controls (OR = 1.6, p = 0.021). A dose-response relationship between the risk of MS and both duration (years) of smoking (p = 0.027) and number of cigarettes smoked daily (p = 0.021) was observed. Coffee consumption was significantly more frequent in the MS group (OR = 1.7, p = 0.047), with dose-response relationships. The analysis of alcohol drinking showed a significant association between consumption of hard liquor per day and risk of MS (OR = 6.7, p = 0.026). In multivariate logistic regression analysis, smoking was detected to be a significant independent risk factor for MS (OR = 2.4, p = 0.004).

Epidemiological and clinical characteristics of myasthenia gravis in Belgrade, Yugoslavia (1983–1992)

This is the first epidemiological study of myasthenia gravis (MG) in the area of Belgrade. During the survey period (1983–1992), 124 incidental cases of MG were observed, producing an average annual incidence rate of 7.1 per million population (women, 8.3; men, 5.8). Age and sex specific incidence rates for females demonstrated a bimodal pattern, with the first peak in the age group between 20 and 40, and the second peak in the age group 70–80. The age‐specific rates for males showed unimodal pattern, reaching a maximum in the age group between 60 and 80. There was a tendency of more frequent disease appearance in the urban as opposed to the suburban districts. On the prevalence day, December 31, 1992, the point prevalence rate was 121.5 per million (women, 142.5; men, 98.8). Only for incidental cases, the point prevalence rate was 77.1 (women, 83.2; men, 70.4). The average annual mortality rate was 0.47 per million (females, 0.52; males, 0.42), while cumulative lethality was 5.6 (women, 5.6; men, 5.7). Most frequently initial symptoms were ocular, occurring in 58% patients. Through the period of investigation ocular symptoms were generalized in 68%, most frequently in the first 2 years (62.5%). Thymoma was confirmed in 11.3% of patients. In this group there was equal presence of both sexes, older median age at onset, and more severe clinical course of MG. Associated autoimmune disease was found in 17 out of 124 incidental cases (13.7%). The most common were thyroid diseases (7.3%). Family history of MG was recorded in 2 cases belonging to 1 family (1.6%).

Decreased frequency of the tumor necrosis factor α-308 allele in Serbian patients with multiple sclerosis

Tumor necrosis factor (TNF) α has been considered the prototypic cytopathogenic cytokine in multiple sclerosis (MS), but recently this cytokine has been shown to possess significant anti-inflammatory and neuroprotective effects in demyelinating diseases. It has been reported that the TNFα –308 polymorphism influences levels of TNFα production, and that the rare allele, TNF2, is associated with high TNFα production. We investigated the TNFα –308 polymorphism in 143 unrelated Serbian patients with MS and 123 ethnically matched, healthy individuals using the allele-specific restriction fragment length polymorphism polymerase chain reaction technique. The frequency of the TNF2 allele was significantly decreased in MS patients (14%) in comparison with controls (24%; p = 0.044). The TNF2 allele had no influence on disease behavior, since it was not associated with the course and severity of MS in this group of patients. The result suggests that in the Serbian population polymorphism at position –308 of TNFα or at an adjacent locus might have a role in MS susceptibility.

Prevalence of multiple sclerosis in Belgrade, Yugoslavia.

Objectives – To estimate the distribution of multiple sclerosis in the Belgrade population. Methods– All persons who were affected and/or died from multiple sclerosis (Posers criteria), with residence in the Belgrade region had been collected from January 1, 1985 to December 31, 1996. Prevalence was adjusted by direct method, using world population. Results– From 1985 to 1996, 823 patients were suffering from multiple sclerosis. Sex ratio was 1:1.9. The mean age at onset was 32.2±9.8 years. A relapsing–remitting course of multiple sclerosis was reported in 50.7% patients, secondary progressive in 36.4% patients, and primary progressive in 12.9% patients. On December 31, 1996, age‐adjusted prevalence of multiple sclerosis in Belgrade was 41.5/100,000, 28.2/100,000 for males, and 54.1/100,000 for females. During the period studied, statistically highly significant increasing trend of multiple sclerosis prevalence was observed (P=0.0001). Conclusions– According to findings presented in this study, Belgrade is an area with high prevalence of multiple sclerosis.

Survival of Multiple Sclerosis Patients in the Belgrade Population

The aim of this study was to estimate survival rates of multiple sclerosis (MS) patients in the Belgrade population, Yugoslavia, and furthermore, to determine the prognostic value of some demographic and clinical variables for survival. The cumulative survival probability was calculated by the Kaplan-Meier method. The prognostic value of different variables was assessed by univariate and multivariate analyses using the Cox regression model. In the Belgrade population, the cumulative 25-year survival probability of MS patients and the mean survival time from MS onset were 73.2% and 38 years, respectively. The univariate analysis showed that survival was significantly related to sex, age at onset, course of disease and monoregional initial symptoms. A multivariate model demonstrated that a relapsing-remitting course of MS and monoregional onset were predictors of a better prognosis. The presence of motor symptoms at the onset was found to be an independent predictor of a poorer outcome of MS.

Mortality trends of malignant tumours of digestive organs in Belgrade, Yugoslavia, 1975–1997

AIM To analyse mortality trends of malignant digestive tract tumours. MATERIAL AND METHODS Population of Belgrade (Yugoslavia) in the period 1975-1997. Mortality rates were standardized by direct method using world population as the standard. For time series, exponential trends were calculated by the use of three-year moving average rates. RESULTS In males, the highest mortality rate was for stomach cancer: 14. 6 per 100,000 (average for the period 1975-1997), followed by cancer of liver and cancer of colon: 8.4/100,000, cancer of rectum: 8.1/100,000, cancer of pancreas: 7.3/100,000, oesophageal cancer: 2.8/100,000 and gallbladder cancer: 2.0/100,000. In males, upward mortality trends for carcinomas of colon, rectum, pancreas, oesophagus, gallbladder and bile ducts were observed. The mortality rates series for stomach cancer and liver cancer did not fit any usual trend function. In females, the highest mortality rate was also for stomach cancer 7.7 per 100,000, then for cancer of colon: 6.0/100,000, cancer of rectum: 5.3/100,000, cancer of liver: 4.4/100,000, cancer of pancreas: 4.4/100,000, gallbladder cancer 3.4/100,000 and oesophageal cancer: 0.8/100,000. In females, upward mortality trends were observed for colon and rectal cancer, cancer of pancreas, and gallbladder and bile duct cancer. Downward mortality trends were present for stomach cancer and liver cancer. Mortality rates series for oesophageal cancer did not fit any usual trend function. CONCLUSIONS In the majority of digestive tracts cancers, an upward mortality trend was observed which is in keeping with the mortality trends of these malignant tumours in many other countries.

Childhood Infections as Risk Factors for Multiple Sclerosis: Belgrade Case-Control Study

The aim of this case-control study was to analyze the role of childhood infections and vaccinations in patients with MS in the Belgrade population. The study group comprised 110 cases with definite MS according to Poser’s criteria, in whom onset symptoms occurred up to 2 years prior to the interview. An equal number of controls, individually matched by sex, age and area of residence, was recruited from patients with various nonautoimmune neurological disorders. Measles (OR = 2.6, 95%CI 1.4–5.0), chickenpox (OR = 3.0, 95%CI 1.5–6.0), rubella (OR = 2.4, 95%CI 1.2–4.7), whooping cough (OR = 1.9, 95%CI 0.8–4.4), and mumps (OR = 1.8, 95%CI 0.8–4.5), at age ≤7 years, were more frequently reported by MS cases. The total number of childhood viral infections (including measles, rubella, chickenpox, and mumps) at age ≤7 years was significantly higher in MS cases than in controls (OR = 1.8, 95%CI 1.4–2.5). Concerning vaccinations, no statistically significant differences were found between groups. According to multivariate analysis, rubella (OR = 2.5, 95%CI 1.4–4.4, p = 0.001) and measles (OR = 2.4, 95%CI 1.3–4.3, p = 0.003) at age ≤7 years were significantly related to MS.

Trends in mortality from different subtypes of stroke in the population of Belgrade (Serbia)

OBJECTIVE To estimate trends in mortality due to different stroke subtypes in the population of Belgrade during the period 1989-2003. PATIENTS AND METHODS Mortality data for stroke were compiled from material of the Municipal Institute of Statistics. Stroke mortality rates were standardized by world standard population. Linear regression coefficient in time trend analysis of mortality rates was assessed by Fishers test. RESULTS In Belgrade, 1989-2003, the highest values of mortality rates were for ischemic stroke in both sexes: 50.1/100,000-men, and 39.9/100,000-women. The mortality rate from subarachnoid hemorrhage (SAH) was lower in men (3.9/100,000) compared to women (5.3/100,000). For intracerebral hemorrhage (ICH), the death rate was 3.1 times higher than that for SAH. Stroke due to hemorrhage was a more common cause of death than ischemic stroke for both sexes in all age groups up to 59. In older age, ischemic stroke became the more frequent cause of death. The time trends of stroke mortality rates in the Belgrade population during the period 1989-2003 showed that the most excessive statistically significant increase in death rates was related to ICH in both sexes. The death rates from SAH had increasing tendency in both sexes, especially in women (p=0.017). Upward trends were observed for ischemic stroke mortality rates too, with statistical significance in men (p=0.048). CONCLUSION Further research is needed to explain the causes of the increasing burden of stroke in Serbia. Since different profiles of risk factors play a role in the etiology of different stroke subtypes, these facts should be taken into account in the creation of both prevention and management strategies.

INCIDENCE OF PRIMARY CENTRAL NERVOUS SYSTEM TUMORS AMONG CHILDREN IN BELGRADE (SERBIA), 1991–2004

The aim of this survey was to estimate the incidence of primary CNS tumors among children aged 0–14 in Belgrade during the period 1991–2004. Incidence rates were age-adjusted according to the world standard population. The average age-adjusted incidence rates were 3.4/100,000 for boys, 2.4/100,000 for girls, and 2.9/100,000 for both genders. There was a nonsignificant tendency toward increased CNS tumor incidence (y = 2.547 + 0.052x, p =. 549). The age-specific incidence rates were 3.0/100,000 (0–4 years), 2.2/100,000 (5–9 years), and 3.8/100,000 (10–14 years). Among the population aged between 0 and 14, the cumulative probability of acquiring primary CNS tumors was 1 per 1961 for boys and 1 per 2778 for girls. Astrocytoma was the most common pathohistological type of primary CNS tumors accounting for 41.5% of cases.

Stroke Mortality in Belgrade, Serbia: Age, Period, and Cohort Analyses

Objective: To assess the age, period, and cohort effects on stroke mortality in Belgrade, Serbia, between 1989 and 2003. Methods: Mortality data for stroke events were obtained from the Municipal Institute of Statistics. The age- and gender-specific mortality rates were calculated for the cohorts of individuals born between 1904–1908 and 1964–1968. Results: In males, the average mortality rate increased from 80.9/100,000 in 1989–1993 to 111.3/100,000 in 1994–1998, and decreased slightly to 101.8/100,000 in 1999–2003. A similar pattern was observed among females. Stroke mortality risk was strongly related to age in both genders. This age effect was present for both genders, independent of the cohort or time period. The majority of the successive generations in Belgrade had an increased risk of death from stroke in the recent cohorts especially among females. Conclusions: Our results suggest the need to improve efforts in the primary and secondary prevention of stroke.