EAN guideline on palliative care of people with severe, progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. METHODS: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score > 6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. RESULTS: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. CONCLUSIONS: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs.

Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis.

BACKGROUND AND PURPOSE: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. METHODS: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. RESULTS: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre-specified topics (from 89% for 'advance care planning' to 98% for 'multidisciplinary rehabilitation'), and <5% replied 'I prefer not to answer' to any topic. There were 569 free comments: 182 (32%) on the pre-specified topics, 227 (40%) on additional topics (16 guideline-pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient-important outcomes and of taxing issues. CONCLUSIONS: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient-important outcomes.

Transcranial sonography in dopa-responsive dystonia.

BACKGROUND AND PURPOSE: Mutations in the GCH1 gene, encoding GTP cyclohydrolase 1, the enzyme critically important for dopamine production in nigrostriatal neurons, are the most common cause of dopa-responsive dystonia (DRD), characterized predominantly by limb dystonia, although parkinsonian features may also be present. It has been suggested that DRD is a neurochemical rather than neurodegenerative disorder. METHODS: Transcranial brain sonography, which might be a risk marker for nigral injury, was obtained from 141 subjects divided into four groups: (i) 11 patients with genetically confirmed DRD; (ii) 55 consecutive patients with Parkinson's disease (PD); (iii) 30 patients diagnosed as isolated adult-onset focal dystonia; and (iv) 45 healthy controls (HCs). RESULTS: Substantia nigra hyperechogenicity was present in 63.6% of patients with DRD, which was significantly different in comparison to patients with dystonia (20%) and HCs (6.7%), but not in comparison to the PD group (87.3%). Also, values of the maximal areas of substantia nigra hyperechogenicity in patients with DRD were higher in comparison to HCs, but significantly lower than among the PD group. CONCLUSIONS: We suggested that the observed transcranial brain sonography features in patients with DRD might primarily be risk markers for particular clinical features (parkinsonism, dystonia) occurring in the specific genetic context (i.e. GCH1 mutations), or might reflect compensated neurodegenerative processes triggered by the long-lasting dopamine deficiency due to the profound delay in levodopa treatment in our patients with DRD.

Epidemiological study of adult-onset myasthenia gravis in the area of Belgrade (Serbia) in the period 1979-2008.

BACKGROUND: The aim of this study was to analyze the prevalence and incidence of adult-onset myasthenia gravis (MG) in the Belgrade population from 1979 to 2008. METHODS: Data on the number of MG patients and their basic demographic and clinical characteristics were collected from hospital records (1979-1992) and the Belgrade MG Registry (1993-2008). Incidence and prevalence were standardized by the direct method (using the world standard population). A time-trend analysis of MG incidence was performed using a linear regression model. RESULTS: During the study period 562 cases (316 women, 246 men) were registered. On December 31st, 2008, the standardized prevalence (according to the world standard population) was 188.3/1,000,000 (women: 237.8/1,000,000; men: 139.4/1,000,000). The average annual standardized incidence rate was 13.3/1,000,000 (women: 14.1/1,000,000; men: 12.2/1,000,000). The incidence rates tended to increase significantly in both sexes during the study period (y = 3.299 + 14.363x, p = 0.002). Age-specific incidence rates for women demonstrated a bimodal pattern, with the first peak in the 20- to 29-year age group and the second one in the ≥70-year group. For both genders, an increase in age-specific incidence rates was registered for all age groups, although this was significant (p = 0.001) only for an MG onset of ≥60 years of age. CONCLUSIONS: The study confirms an increase in the incidence of MG in the area of Belgrade during the study period, especially for those with MG onset after 60 years of age.

Prevalence of multiple sclerosis in the Serbian district Sumadija.

BACKGROUND: The aim of this study was to estimate the prevalence of multiple sclerosis (MS) in the district of Sumadija (central part of Serbia). METHODS: All persons suffering from MS, with permanent residence in the region, were recruited. Prevalence was calculated on December 31, 2006, according to a standard procedure. RESULTS: On December 31, 2006, one hundred ninety-four patients (72 males and 122 females) were found to have MS. We found a crude MS prevalence of 64.9/100,000 (49.3/100,000 for males and 79.9/ 100,000 for females). The highest prevalence rates were registered in the age group of 30-39 years for females and 40-49 years for males, although the age-specific rates were higher in females in all age groups. The mean age at onset was 34.2 ± 9.3 years. The average duration of MS was 8.9 ± 6.2 years. The median EDSS score was 3.9 ± 2.0. The course of MS was relapsing-remitting in 63.9% of patients, secondary progressive in 32.5%, and primary progressive in 3.6%. At MS onset, motor symptoms were present in 70.1% of patients, sensory in 40.7%, cerebellar in 21.1%, brainstem in 15.5%, visual in 22.2%, and bowel/bladder disturbances in 22.2%. CONCLUSIONS: Our results demonstrate that the MS prevalence registered in the Serbian district Sumadija is similar to that of other surrounding areas in Southeastern Europe.

Epidemiology of Charcot-Marie-Tooth disease in the population of Belgrade, Serbia.

BACKGROUND: The aim of this study was to determine prevalence and 15-year survival in Charcot-Marie-Tooth disease (CMT). METHODS: The study covers the period from 1 January 1988 to 31 December 2007 in the territory of Belgrade. Data on a number of CMT-affected persons and their basic demographic characteristics as well as data on the disease were collected from medical records. Data on the course and outcome of the disease were obtained through direct contact with patients, their families and their physicians. RESULTS: We registered 161 patients with CMT in the population of Belgrade. The most frequent type was CMT1. The crude prevalence of CMT disease in the Belgrade population on 31 December 2007 was 9.7/100,000 for all subtypes, 7.1/100,000 for CMT1, and 2.3/100,000 for CMT2. Gender-specific prevalence was 11.2/100,000 for males and 8.3/100,000 for females. The highest age-specific prevalence was registered in the oldest age group (75+ years; 19.1/100,000), and the lowest one in patients aged 5-14 years (5.0/100,000). The cumulative probability of 15-year survival for CMT patients in Belgrade was 85.6 ± 7.8% (44.9 ± 31.8% for males and 98.2 ± 1.8% for females). CONCLUSIONS: The prevalence of CMT found in Belgrade is similar to the prevalence registered in Southern European countries.

Outcome of childhood brain tumors in Serbia.

PURPOSE: To present the results of treatment for childhood brain tumors in Serbia. METHODS: The medical records of patients with brain tumors diagnosed and operated at the Institute of Neurosurgery, Clinical Center of Serbia and treated with postoperative radiotherapy and chemotherapy at the Institute of Oncology and Radiology of Serbia, Belgrade, between January 1995 and December 2004, were reviewed. Of the 247 patients who were identified, 212 formed the basis of this study. Overall survival (OS) was determined by the Kaplan-Maier method, using log-rank test for comparisons. RESULTS: With a mean follow up of 46.9-33.6 months (range 7-120), the 5-and 8-year OS rates were 70.0% and 61.5%, respectively. At the time of evaluation 119 (60.1%) patients had no evidence of disease. Among 79 patients who failed therapy, most of them (n=61; 77.2%) had local failure only. According to histologic tumor type most of them (n=27; 34.2%) were in the group of malignant medulloblastoma. Girls had better survival than boys, but without statistical significance (p=0.185). Also, no significant difference in survival in relation to age was seen (p=0.291). Patients with supratentorial tumors had significantly better survival than those with infratentorial localizations (p=0.036). Patients with low grade astrocytomas had significantly better survival than malignant gliomas, ependymomas and primitive neuroectodermal tumors (PNETs) (p=0.0001). CONCLUSION: OS rates were concordant with the results of other modern series. Although the survival rates were encouraging, there is still significant room for improvement in the management of childhood brain tumors.

Validation of Serbian version of the disease-specific myasthenia gravis questionnaire.

AIM: The aim of this study was to validate translated and cross-cultural adapted Italian version of myasthenia gravis-specific questionnaire (MGQ) in Serbian MG patients. MATERIALS AND METHODS: The questionnaire was validated in 140 consecutive MG patients from Belgrade. In each patient association between the total MGQ score and form and severity of the disease was determined. Also, correlation between regional domain scores of MGQ and main clinical findings according to Besinger's clinical score was analyzed. RESULTS: Patients' participation in the assessment was satisfactory with excellent internal consistency and reproducibility. Total MGQ score, as well as domain scores, correlated with highly significant inverse relationship with the disease severity and clinical status of patients at the moment of completing the questionnaire. Furthermore, the bulbar domain of the questionnaire appeared more specific and sensitive than clinical history and examination. CONCLUSION: We concluded that the Serbian version of the MGQ may be useful as a measure of clinical outcome in patients with MG.

Psychological well-being in advanced NSCLC patients in Serbia: impact of sociodemographic and clinical factors.

UNLABELLED: Patients with advanced non-small cell lung cancer (NSCLC) usually undergo toxic treatment (chemotherapy and/or radiotherapy). They can experience devastating effects of illness and therapies on their psychological and emotional well-being. On the other hand, untreated psychological distress is associated with reduced quality of life and inadequate palliation of physical symptoms.
In order to estimate frequency of anxiety and depressive symptoms and influence of demographic, socioeconomic and clinical factors on psychological well-being, we performed this cross-sectional study in group of 100 patients with advanced stage of disease. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating scale (HDRS). Health-related quality of life data are obtained by EORTC QLC C30 and SF 36.
Patients with poor performance status (PS) experienced significantly more anxiety and depressive symptoms (p=0.001) and worse emotional (p=0.001) and mental functioning (p=0.001). Treated patients had significantly better mental (p=0.011) and emotional (p=0.001) functioning in compared to newly diagnosed ones. Somewhat unusual, unemployed participants reported significantly less anxiety (p=0.029) and depressive (p=0.002) symptoms, better mental (p=0.030) and emotional functioning (p=0.007). Additionally, nausea and vomiting adversely affected mental health and emotional functioning and correlated significantly positively with HARS and HDRS scores.
Our findings suggest significant impact of some disease-related factors (PS, active treatment) and treatment-related factors (chemotherapy -induced nausea and vomiting) on psychological well-being of patients with advanced NSCLC. This should be taking an account when appropriate interventions are planned. KEYWORDS: lung cancer, anxiety, depression, quality of life, chemotherapy, chemotherapy-induced nausea and vomiting.

Health-related quality of life in lung cancer patients in Serbia: correlation with socio-economic and clinical parameters.

The objective of this study was to assess health-related quality of life (HRQoL) in patients with advanced non-small cell lung cancer (NSCLC). In Serbia, there is the lack of available data on HRQoL in lung cancer patients. The special attention in our study has been paid on relationships between socio-economic factors and HRQoL. This cross-sectional study was undertaken in group of 100 NSCLC patients with advanced stage diseases. HRQoL was measured using three standard instruments: 36-item Short Form Health Survey, EORTC QLQ-C30 and its Lung Cancer module (EORTC QLQ-LC13). Unexpected, highly educated patients reported significantly worse social functioning (P=0.044), and higher degree of financial difficulties (P=0.047), in comparison with less-educated. Also unusual, unemployed patients had significantly better HRQoL in all domains and significantly lower symptom distress. Significantly better overall HRQoL (P=0.043), social (P=0.024), emotional (P=0.001) and mental functioning (P=0.011) were observed in patients treated with chemotherapy in comparison with newly diagnosed ones. In addition, the most prominent side effects of chemotherapy were nausea and vomiting, and all QoL domains correlated significantly with them. Patients who undergo active treatment improve their HRQoL but chemotherapy-induced emesis adversely affects many HRQoL domains. Additionally, HRQoL is highly dependent on patient's socio-economic characteristic.

Long-term outcome in Serbian patients with Wilson disease.

BACKGROUND AND PURPOSE: To investigate survival rates, prognostic factors, and causes of death in Wilson disease (WD). METHODS: In the years 1980-2007, a cohort of 142 patients with WD was prospectively registered (54 presented with neurologic symptoms, 49 with hepatic symptoms, 33 had mixed form, and data were missing for six patients). The duration of follow-up for patients alive was 11.1 +/- 8.8 years. RESULTS: After initiation of treatment (d-penicillamine and zinc salts), 79% of patients had a stable or improved course of disease. Despite early diagnosis and appropriate therapy, 15 patients still had a relentlessly progressive course. Thirty patients died. The cumulative probability of survival in a 15-year period for the whole group was 76.7 +/- 4.9%. Better prognosis of WD was associated with male sex, younger age at onset, neurologic form of the disease, and treatment continuity. Causes of death were predominantly related to hepatic failure (16 patients), but also suicide (four patients) and cancer (three patients). CONCLUSION: Despite the relatively early diagnosis and treatment of our patients with WD, mortality was still considerably high.

Identification of mutations in the PARK2 gene in Serbian patients with Parkinson's disease.

Mutations in the PARK2 (PRKN) gene are the most common cause of autosomal-recessive (AR) juvenile parkinsonism and young-onset Parkinson's disease (YOPD). >100 different variants have been reported, including point mutations, small indels and single or multiple exon copy number variations. Mutation screening of PARK2 was performed in 225 Serbian PD patients (143 males and 82 females) with disease onset before 50 years and/or positive family history with apparent AR inheritance. All coding regions and their flanking intronic sequences were amplified and directly sequenced. Whole exon multiplications or deletions were detected using Multiple Ligation Probe Amplification (MLPA) method. We identified 12 PD patients with PARK2 mutations (5.3%). Five patients (2.2%) had biallelic mutations and seven (3.1%) were single mutation carriers. Patients with compound heterozygous mutations had earlier onset of the disease compared to non-carriers (p = 0.005) or heterozygotes (p = 0.001). Other clinical features in mutation carriers were not different compared to non-carriers. In our cohort, sequence and dosage variants were equally represented in patients, inducing their first symptoms mainly before the age of 30. For efficient genetic testing strategy, patients with early, especially juvenile onset of PD were strong candidates for both dosage and sequence variants screening of PARK2 gene.

Acute and Late Genitourinary Toxicity after 72 Gy of Conventionally Fractionated Conformal Radiotherapy for Localised Prostate Cancer: Impact of Individual and Clinical Parameters.

AIM: Our aim was to estimate the incidence of acute and late genitourinary toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for localised prostate cancer and to estimate the possible influence of individual and clinical characteristics. MATERIALS AND METHODS: Between September 2009 and September 2013, 225 patients with localised prostate cancer were treated with 3DCRT. Ninety-four patients with an estimated risk of lymph node involvement ≤15%, according to the Roach formula, were evaluated in this study. All patients received a total dose of 72 Gy in 36 fractions. Acute and late genitourinary toxicity were graded according to the European Organization for Research and Treatment of Cancer radiation morbidity scoring scale. Characteristics such as age, smoking status, previous abdominal or pelvic surgery (PAPS), diabetes mellitus and the use of diuretics were analysed as possible predictive factors of toxicity. The median follow-up was 27 months. RESULTS: Grade ≥2 acute toxicity during 3DCRT developed in 25 of 94 patients (26.5%). Predictive factors of acute genitourinary toxicity grade ≥2 in the multivariate logistic regression analysis (MVA) were current smoking status (P = 0.003), PAPS (P = 0.012) and the use of diuretics (P = 0.017). The 2 and 3 year cumulative risk of late genitourinary toxicity grade ≥1 was 25.3% and 30.2%, respectively. In the MVA, acute genitourinary toxicity was significantly associated with late genitourinary toxicity (P = 0.024). CONCLUSION: Current smoking status, PAPS and the use of diuretics have a significant effect on the occurrence of acute genitourinary toxicity grade ≥2. The occurrence of any grade of acute genitourinary toxicity has a significant influence on the development of any grade of late genitourinary toxicity.

Tuberculosis trends in Central Serbia in the period 1956-1996.

OBJECTIVE: To estimate tuberculosis incidence and mortality trends in Central Serbia (excluding Kosovo and Vojvodina provinces) in the period 1956-1996. DESIGN: The incidence and mortality data of tuberculosis in Central Serbia in the period 1956-1996 were analysed based on the annual reports of the Institute for Lung Diseases and Tuberculosis in Belgrade and the official data of the Republic Health Institute. RESULTS: During the period under observation, tuberculosis incidence decreased from 324.0 to 34.8/100 000 population, fitting the exponential model (y = 389.066e-(0.0689); F = 847.60; P = 0.000). Mortality rates decreased from 76.0 in 1956 to 0.9/100000 in 1982. Over the whole period (1956-1996) the decrease in mortality rates fitted the exponential model (y = 66.83e-(0.0922); F = 150.95; P = 0.000). The increase in mortality rates in the period 1982-1996 fitted cubic model (y = 7.647 - 2.674x + 0.359x(2)-0.013x(3); F = 12.17; P = 0.001). CONCLUSION: Decreasing trends in tuberculosis incidence are the result of good control programmes. Changes in mortality trends are related to migration from war zones and poor economic conditions which hinder the detection and treatment of tuberculosis.

The pattern of lung cancer mortality in Montenegro.

The aim of the study was to examine recent lung cancer mortality trends in Montenegro in the period 1976-2000, with special emphasis on correlation with tobacco consumption. A population-based study analysing lung cancer mortality in Montenegro in the period 1976-2000 was carried out. Mortality rates were adjusted by direct method. A cohort analysis of age-specific death rates was performed. The analysis of tobacco consumption (cigarettes consumption per capita) was based on the official data for the period 1965-1990. Linear regression coefficients in a time trends analysis of mortality rates and tobacco consumption were assessed using Fisher's test. The highest average standardized lung cancer mortality rates in Montenegro increased in each successive five-year period for both sexes from 1976 to 2000, with highest values in the last five years (1996-2000). In males the death rate has almost doubled, and in females it was nearly three-fold higher. In the cohort analysis of age-specific death rates, all age groups in the birth cohort born before 1911 had a higher lung cancer mortality risk than those in the birth cohort comprising those born between 1912 and 1931. The rates showed an increasing tendency in all age groups irrespective of sex, except in males in the 25-44 age group. The time analysis of lung cancer mortality rates for the period 1976-2000, revealed annual changes of 3% for males and 6.6% for females, respectively. During the period observed the consumption of cigarettes increased by 98.2% (from 1.064 kg per capita in 1965 to 2.109 kg per capita in 1990). The significant increasing tendency in cigarette consumption was registered (y=1.10+0.05x, P=0.001). A significant correlation between lung cancer mortality rates and cigarette consumption is also observed (r=0.427, P=0.037). Smoking trends up to the 1990s in Montenegro, indicate that one can expect lung cancer mortality rates to continue to increase in males but even more so in females.

Infectious diseases mortality in central Serbia.

STUDY OBJECTIVE: To determine the influence and the effect of the war in the former Yugoslavia and of the United Nations economic sanctions on mortality from infectious diseases. DESIGN: This was a descriptive study analysing mortality data time series. SETTING: Central Serbia, Yugoslavia. PARTICIPANTS: The population of central Serbia was the subject of the study (about six million inhabitants). MEASUREMENTS: Mortality rates were standardised directly, using the "European population" as the standard. Regression analysis and analysis of covariance were undertaken. MAIN RESULTS: During the period 1973-93, mortality from infectious diseases showed a decreasing trend. From 1987-90, and infectious diseases was significantly higher than expected on the basis of the trend for the preceding period (p = 0.020 and p = 0.00). In addition, there was a statistically significant departure from the preceding trend (p = 0.036) in men between 1991 and 1993 (the period of the war and UN sanctions)--the main effect being in younger age groups. CONCLUSION: The economic crisis in the former Yugoslavia during the 1980s followed by the outbreak of the war and the damaging effects of UN economic sanctions had a distinctly adverse effect on mortality from infectious diseases.

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.

Radiotherapy plus fifth day carboplatin in locally advanced bladder cancer.

The goal of our prospective nonrandom study was to improve treatment results in advanced bladder cancer and possibility of cure with acceptable toxicity and reduced rate of late complications. Fifty-three patients with locally advanced bladder cancer (clinical stage T3a and b) treated by radical radiotherapy (65 Gy, conventional fractionation) and concomitant carboplatin (150 mg in bolus infusion, once a week, every fifth day an hour prior to the irradiation, up to total dose of 900 mg, during the treatment course. Out of 53 evaluable patients, complete response was achieved in 47/53 (88.7%) and partial response in 2/53 patients (3.8%). Hematological toxicity grade I and II occurred in the majority of patients. Mean follow-up was 16 months (range 4-24), 2-year overall survival has been achieved in 85% and disease free survival of 49 responding patients in 84%.

Case-control study of multiple myeloma with special reference to diet as risk factor.

The case-control study was conducted in Belgrade (Yugoslavia) during the period 1994-1998. The objective of the study was to investigate factors related to the occurrence of multiple myeloma (MM). The study group consisted of 100 newly diagnosed MM patients and the same number of matched hospital controls. In the analysis conditional univariate and multivariate logistic regression were applied. According to multivariate analysis the following factors were significantly related to MM: smoking > or =25 cigarettes per day (Odds ratio--OR=6.7, 95% confidence interval--95% CI=1.3-34.3); having more than two brothers (OR=2.7, 95% CI=1.3-5.3), rheumatoid arthritis in personal history (OR=4.2, 95% CI=1.2-14.8), and frequent (4-7 times per week vs. lower frequency) consumption of yogurt (OR=3.1, 95% CI=1.6-6.0) and vegetables (OR=0.4, 95% CI=0.1-1.0).

Extrathymic malignancies in a defined cohort of patients with myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) may be associated with extrathymic malignancies, especially in patients with thymoma. AIM: To determine the frequency and type of extrathymic malignancies in MG patients from the Belgrade area, and to identify potential risk factors associated with tumors. PATIENTS AND METHOD: The study comprised 390 patients with MG. Different sociodemographic and clinical variables potentially associated with extrathymic neoplasms were analyzed. RESULTS: Extrathymic malignancies were present in 42 (10.8%) MG patients - 22 (52.4%) males and 20 (47.6%) females. The most frequently detected were breast (40%) and lung (40%) neoplasms. The tumors appeared with similar frequency before (45.2%) and after the onset of MG (42.9%). Significant predictors for the development of extrathymic malignancies were current age (p = 0.001) and immunoglobulin (IVIg) therapy (p = 0.021). On the other hand, current age (p=0.001), longer MG duration (p = 0.001) and generalized form of MG (p = 0.002) were significant predictors of malignancy occurring after the MG onset. CONCLUSION: Our study revealed that older MG patients, as well as those with longer duration of the disease, and those who received IVIg therapy had a higher oncogenic risk for the development of extrathymic malignancies.