Prescription and safety of dimethindene maleate micropellet capsules in Hungary

INTRODUCTION: Dimethindene maleate, the active substance of the extended-release Fenistil 24 capsule, is a first-generation histamine receptor antagonist, which is marketed in 10 European countries. In Hungary approximately 200,000 boxes are sold yearly from this product, which is mainly used for treatment of symptoms associated with allergic diseases (urticaria, itch, hay fever) The aim of the present study was to gather information with the help of medical doctors about the indications, efficacy and primarily the safety of use, observed side effects and frequency of adverse events associated with this product. METHOD: During the study 4574 questionnaires were evaluated out of the 5578 filled by 249 doctors. Responses were included into the evaluation only if the address and type of polyclinic of the doctor filling the questionnaire, indication of the use of the product could be precisely identified and the patient returned for control visit at least once. RESULTS: Based on the study results in Hungary in most cases the product is prescribed according to the indications and dosing schedule given in the SPC. In this study participating doctors found the drug to be effective in 95% of cases. Unexpected, new adverse events were not observed during the study. Approximately 22% of patients reported adverse events, tiredness and sleepiness being the most frequent ones. Occurrence of sedative adverse events was more frequent among those who were prone to tiredness (51 vs. 17%). The adverse events most frequently were reported 10-12 hours after intake. The average length of treatment was 4 weeks or less. The medicine is taken usually at night, before going to sleep. CONCLUSIONS: In Hungary in most cases the product is prescribed according to the indications and dosing schedule given in the current approved Summary of Product Characteristics.     

Trends of premature mortality from cardiovascular diseases in Hungary and the European Union, 1970-1997

It is a well known fact that in Hungary--as in the European Countries, in general--the trends of premature mortality are mainly determined by the trends of mortality caused by cardiovascular diseases. The timeliness of our present study on changes in trends of early cardiovascular mortality in the period of 1970-1997 in Hungary in comparison with trends of EU countries is underlined by the upcoming access of Hungary to the European Union. The evaluation is based on WHO data, the relative risk of premature mortality due to different forms of cardiovascular diseases for different sex and age groups of the Hungarian population is expressed as a ratio between standardized mortality rates of Hungarian groups and that of EU-average and of countries specified. Detailed data demonstrate that the risk of early death caused by cardiovascular--especially ischaemic heart and cerebrovascular--diseases, in contrast with EU countries, is significantly increased in Hungary, most significantly in age groups of 35-44 and 45-64 years for both sexes. The authors' results draw the attention to the possible shortcomings of health care systems and the lack of comprehensive health promotion (including prevention) programs in Hungary.     

Premeditated ecstasy?

The 3-4-methylene-dioxy-methamphetamine, or "Ecstasy" is one of the most preferred, illicite recreational drugs in Hungary also. Its effects are basically the same as of the amphetamine's effects,--i.e., central nervous system's and cardiovascular effects. The most important ones are different disturbances in the serotonin and dopamine metabolism, particularly in the CNS. Moreover, under Ecstasy's effect there can be encountered different toxic signs and symptoms as well, e.g. effect on the temperature regulation,--which may require hospitalization. In spite of the users' tenet,--that the drug is a "safe" one,--it is evident that Ecstasy has late effects as well,--for example a single dose may induce Parkinson's like symptoms. Taking into consideration the above mentioned facts, it can be stated un ambiguously that Ecstasy's use should be banned. It is harmful not only to the individual users but to the whole society as well.     

Role of SPECT scans in the diagnosis of cerebrovascular diseases

With an incidence of 200-250 in 100,000 persons year, cerebrovascular disease (CVD) is the most common neurological disorder. In most countries, CVD is the third most frequent cause of death, exceeded only by heart disease and cancer. There are roughly 5.000 new cases per year in Hungary. Additionally, it should be emphasized that there are facts suggesting a more severe population of patients with CVD compared to the analogue group in more developed countries. There are several causes of stroke, but common to all is a critical reduction in cerebral blood flow, resulting in a focal neurological deficit. Functional imaging, particularly of cerebral perfusion, should therefore have a major role to play in the management of these patients. SPECT methods are of high importance in the diagnosis of CVD and in the patients follow-up.     

Treatment of menopausal symptoms--review of the current literature

Although the expected mean age of women increased significantly in the 20th century, the time of menopause has not changed (age of 50-51 years). Women's life span in Hungary is 77.2 years, which means, that one third of their lives is lived in menopause. Aging and the consequent lack of estrogen means a more and more serious problem on social level as well. In Hungary there are approximately 1.8 million women above the age of 50. Only an insignificant part of them is treated, which is about 5%, compared to other European countries, where this ratio is between 5 and 25%. Menopause-related symptoms can be divided into the following groups: vasomotor symptoms (sweating, hot flashes, palpitation), decreased psychic and physical functions (fatigue, depression, panic disease, cognitive problems, decreased libido), cardiovascular diseases (ischaemic heart disease), endometrial atrophy, bone and articular alterations (osteoporosis) and urogenital symptoms (vaginal dryness, incontinence, cystitis). The most frequent symptom is hot flashes, which is characteristic of more than 60% of women in menopause. Osteoporosis after the cardiovascular diseases is the second most serious problem on public health level. Approximately 9% of the Hungarian population suffers from osteoporotic problems, which concretely means 600.000 women and 300.000 men. The most frequent fractures are the hip and vertebral fractures. In 1999, 15.100 hip and 51.000 peripheric fractures occurred in Hungary. The above mentioned symptoms, even separately, may decrease the quality of life, therefore their treatment and the knowledge of all of the therapeutic possibilities are essential.     

Increase of homocysteine in cardiovascular diseases in Hungary

There are only very few epidemiological data about homocysteine levels in patients suffering from cardiovascular (CV) disease in Hungary, however, homocysteine is a newly recognized, independent risk factor of CV diseases. AIM OF THE STUDY: Therefore, in the present study, data of 1010 East-Hungarian patients with signs of CV disease were analyzed retrospectively for correlation between the level of homocysteine and CV diseases, laboratory parameters, as well as genetic differences. PATIENTS AND METHODS: From the studied patient population a control ("healthy") group has been selected according to the following criteria: lack of previous stroke or stenosis of the carotid arteries or the lower extremities, lack of coronary artery stenosis more than 50%, no previous coronary intervention or an angiography diagnosed progression of the coronary atherosclerosis. RESULTS: The level of homocysteine showed statistically significant negative linear correlation with HDL-cholesterol and the anti-atherogenic ApoAI, and showed a positive correlation with CRP and FXIII activities in the entire patient population. When compared to the control group, homocysteine level was significantly higher in patients with previous stroke or acute myocardial infarction, coronary stenosis, progressive coronary disease, physical inactivity, MTHFR gene polymorphism, low folate or vitamin B12 level in both men and women. In patients with type II diabetes the level of homocysteine was significantly higher only in women. CONCLUSIONS: It can be concluded that the level of homocysteine in patients suffering from various CV diseases is high in Hungary. This may have a prognostic value, and shows that reduction of homocysteine level in these patients may be beneficial.     

Somatostatin receptor endoradiotherapy of neuroendocrine tumors: experience in Hungarian patients

Beside conventional therapies for the treatment of neuroendocrine tumors, a new therapeutical approach, peptide receptor radionuclide therapy has been developed recently. There are two important features which make this therapy feasible: somatostatin receptors are strongly over-expressed in most neuroendocrine tumors resulting in a high tumor-to-background ratio and internalization of the somatostatin-receptor complex in neuroendocrine cells. Due to these features, neuroendocrine tumors can be treated with radiolabelled somatostatin analogues. For peptide receptor radionuclide therapy, somatostatin analogues are conjugated to a chelator that can bind a radionuclide. The most frequently used radionuclides for neuroendocrine tumor treatment are the β-emitter Yttrium-90 (??Y) and the β+γ emitter Lutetium-177 (1??Lu). Candidates for somatostatin receptor endoradiotherapy are patients with progressive, metastatic, somatostatin-receptor positive neuroendocrine tumors. Many patients have been successively treated with this approach: according to international results major remission can be achieved in 25% of the cases. Although this therapy is still unavailable in Hungary, Hungarian patients can be treated with somatostatin receptor endoradiotherapy with financial support from the National Health Fund in a co-operation with the University of Basel since 2005. During the past 5 years, 51 Hungarian patients have been treated with this therapy. This review briefly summarizes the theoretical background, indications, effectiveness and side effects of somatostatin receptor endoradiotherapy and the authors present the first data obtained from Hungarian patients.     

Epidemiology of hypertension in adolescence and factors influencing blood pressure

The authors summarize the determining and influencing factors of adolescent hypertension. An overview of the definition and prevalence of hypertension in adolescence is given and the predictive role of the adolescent hypertension on the incidence of adult cardiovascular diseases is pointed out. According to the previous literature data, adult hypertension is more frequent in those people who have had hypertension in their adolescence. There are no widely used, population-based nomograms of adolescent hypertensives available. According to the opinion of the authors, a population-based hypertension screening program would help in delineating the factors influencing adolescent blood pressure, and the most frequent risk factors for hypertension in Hungary. With the follow-up and appropriate treatment of the hypertensives the reduction of target-organ damages may be possible.     

The role of biological agents in the treatment of psoriatic arthritis, literature review

INTRODUCTION: The recognition of the key pathogenetic role of TNF-alpha in psoriatic arthritis has made it possible to introduce new drugs in the treatment. TNF-alpha inhibitors available in Hungary (infliximab, etanercept, adalimumab) are potential therapies for patients who have not adequately responded to traditional disease-modifying antirheumatic drugs. OBJECTIVE: The aim of the study was to present the epidemiology and progression of psoriatic arthritis in Hungary based on national and international data, to assess the target population for biological therapy and to analyze their effectiveness, reviewing the available literature of randomized controlled trials. METHODS: The prevalence of psoriatic arthritis in Hungary was estimated using international data. Characteristics of psoriatic arthritis population were studied using the database of a rheumatology ward. A systematic literature search was performed to identify each relevant trial. A synthesis and comparison of the results from the 5 identified trials was performed and the average effect of biological agents was calculated. Both the fixed and the random effect model were used for the data synthesis; the results were probed with Mantel-Haenzel test. RESULTS: The prevalence of psoriatic arthritis is about 10.000-20.000 in Hungary. Average disease-duration was 10 years in the sample (n = 189), the most frequent was polyarticular form (51%). Regarding functional status the mean HAQ score was 1.46, with an average progression of 0.05 points/year. The trial data confirmed that biological agents are superior to placebo in improving symptoms (achieving ACR20); risk difference between biological treatments and placebo is 47% (RD = 0.47, 95% CI: 0.42-0.53). The biological treatment of 2 patients improves the status of 1 patient (NNT = 2.1 95% CI 1.9-2.4). There is no significant difference in efficacy between the three biological agents. CONCLUSIONS: TNF-alpha inhibitors are effective treatments of psoriatic arthritis and are safe under strict medical control. The principles of indications, contraindications, administration and control have been worked out by the Rheumatology and Physical Medicine Board.     

Rheumatic diseases as risk factors for cardiovascular disease

Cardiovascular disease is the leading cause of death in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE). In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Prospective intervention trials aimed at the modification of cardiovascular risk factors are needed to determine the impact of cardiovascular risk reduction in patients with rheumatic disease. In addition to SLE, RA and AS should be acknowledged as new risk factors for cardiovascular disease.     

Omega-3 fatty acids and cardiovascular disease

PURPOSE OF REVIEW: Omega-3 fatty acids are gaining acceptance in the cardiovascular field. The present review describes the most recent studies and developments in the field. RECENT FINDINGS: Marine omega-3 fatty acids, that is eicosapentaenoic and docosahexaenoic acids, prevent fatal myocardial infarction and sudden cardiac death by their antiarrhythmic effects and presumably also by their effect on infarct size, the latter mediated by plaque stabilization, improvements in endothelial function and other mechanisms. In contrast, a cardioprotective effect of alpha-linolenic acid, a plant-derived omega-3 fatty acid, remains to be clearly demonstrated in adequate intervention trials. Other forms of applications, like parenteral use or other indications, like in the psychiatric field, are currently being actively investigated. SUMMARY: Eicosapentaenoic and docosahexaenoic acids, but not alpha-linolenic acid, prevent sudden death and other cardiovascular catastrophies, and have therefore been recently incorporated into the pertinent guidelines of European and American cardiologic societies.     

Consumer perception of the use of high-pressure processing and pulsed electric field technologies in food production

The success of new food processing technologies is highly dependent on consumers' acceptance. The purpose of this paper is to study consumers' perceptions of two new processing technologies and food products produced by means of these novel technologies. To accomplish this, a qualitative study on consumer attitudes towards high-pressure processing (HPP) and pulsed electric field (PEF) processing of food was carried out. In all 97 adults between 20 and 71 years of age participated in 12 focus groups conducted in Slovenia, Hungary, Serbia, Slovakia, Norway and Denmark using a common guideline. Participants were introduced to the HPP and PEF technologies and then to the effect of the two new technologies on two specific product categories: juice and baby food. The transcribed data was content analysed and the coded data was transformed into diagrams using UCINET 5 and NETDRAW. The results show that consumers perceived the main advantages of HPP and PEF products to be the products' naturalness, improved taste and their high nutritional value, whereas the main disadvantage was the lack of information about the PEF and HPP products. The results of the participants' evaluation of the PEF and HPP processes showed that environmental friendliness and the more natural products were seen as the main advantages, while they were concerned about body and health, the higher price of the products, the lack of information about the technologies and a general scepticism. The study also shows that North European participants were a bit more sceptical towards PEF and HPP products than the East European participants.     

Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of rheumatoid arthritis in six Central and Eastern European countries

The first biosimilar monoclonal antibody (infliximab, CT-P13) was registered by the European Medicines Agency in 2013 for the treatment of several inflammatory conditions including rheumatoid arthritis (RA). Biosimilar infliximab is first being marketed in the Central and Eastern European countries. This paper presents the estimated budget impact of the introduction of biosimilar infliximab in RA over a 3-year time period in six selected countries, namely Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. A prevalence-based model was constructed for budget impact analysis. Two scenarios were compared to the reference scenario (RSc) where no biosimilar infliximab is available: biosimilar scenario 1 (BSc1), where interchanging the originator infliximab with biosimilar infliximab is disallowed, and only patients who start new biological therapy are allowed to use biosimilar infliximab; as well as biosimilar scenario 2 (BSc2), where interchanging the originator infliximab with biosimilar infliximab is allowed, and 80 % of patients treated with originator infliximab are interchanged to biosimilar infliximab. Compared to the RSc, the net savings are estimated to be €15.3 or €20.8 M in BSc1 and BSc2, respectively, over the 3 years. If budget savings were spent on reimbursement of additional biosimilar infliximab treatment, approximately 1,200 or 1,800 more patients could be treated in the six countries within 3 years in the two biosimilar scenarios, respectively. The actual saving is most sensitive to the assumption of the acquisition cost of the biosimilar drug and to the initial number of patients treated with biological therapy. The study focused on one indication (RA) and demonstrated that the introduction of biosimilar infliximab can lead to substantial budget savings in health care budgets. Further savings are expected for other indications where biosimilar medicines are implemented.     

3,4-methylene-dioxy-pyrovalerone (MDPV) epidemic?

Little is known about 3,4-methylene-dioxy-pyrovalerone (MDPV), a new designer drug that has become popular in Hungary in the last couple of months. At the same time, its consumption, as a consequence of its low street-price, rises so fast that the event can be considered an epidemic. This paper reviews the chemistry, biochemistry and metabolism of MDPV. Then, on the basis of a few international reports and the author's own clinical observations, it discusses MDPV intoxication and withdrawal. In the metabolism of MDPV, the most important catalyst is the CYP2C19 isoenzyme, but the CYP1A2 and the CYP2D6 isoenzymes also play a crucial role. The formed catechols are conjugated with either glucuronic acid or sulfate. It is important to note that MDPV is consumed either together or in a sequence with other illicit drugs of abuse. As far as it can be established, MDPV use increases the activity and vigilance, decreases appetite and claim to sleep, but it can also provoke cardiac sensations and disturbance of perception. In the course of coming down, withdrawal after MDPV use, bone and muscle pain, hypersomnia, disturbance of vision are experienced, but panic attack may also occur. The appearance of new designer drugs on the market draws attention to a need of paradigm changing in spiritual field. Unless it happens these negative trends likely will speed up.     

基于综合评价体系的农村卫生适宜技术筛选研究：以河南省为例

目的:筛选适合于在河南省推广应用的农村卫生适宜技术,建立可持续性卫生技术筛选体系和方法。方法:采用现场评分的方法,利用综合评价体系对卫生部"十年百项计划"第5~7批卫生适宜技术进行评价筛选。结果:参加评分的233名专家性别年龄比、学历、职称和从医年限等指标均基本与全国水平一致或高于全国水平;27项卫生适宜技术按照不同的专业领域进行评分,评分结果合理,与当地卫生需求一致,根据评分值进行排序,可确定进一步推广应用的具体卫生技术。结论 :河南省长葛市和新密市卫生机构人员构成合理,水平较高,有利于卫生适宜技术的进一步推广。筛选出的卫生适宜技术与当地卫生需求一致,评分分布合理,可为进一步推广应用提供理论依据。     

Public health control of hyperhomocysteinemia and its consequences

The etiological role of hyperhomocysteinemia in the origin of neural-tube defects was proved, therefore a mandatory flour folic acid fortification program was introduced in the USA since January 1, 1998. In Hungary one kind of breads was fortified with folic acid, vitamin B12 and vitamin B6. The Hungarian randomised controlled trials of periconceptional folic acid containing micronutrient-combination supplementation also indicated a reduction in the occurrence of congenital cardiovascular malformations, urinary tract's defects and congenital limb deficiencies and these findings were confirmed by US teams. Recent studies showed a positive association between cardiovascular diseases and hyperhomocysteinemia as well, thus it is considered as an independent etiological factor in the pathogenesis of ischemic heart diseases, stroke, deep vein thrombosis, in addition of vascular diseases in the placenta during pregnancy. Other studies showed that hyperhomocysteinemia is more prevalent in demented patients and in persons with impaired cognitive performance. Some association was also found between hyperhomocysteinemia and cancers (e.g. colon). There is strong evidence that four vitamins B, such as vitamin B11 (folate-folic acid), vitamin B12, B2 and B6 can reduce the level of serum homocysteine and subsequently neural-tube defects. In addition the results of intervention studies indicated a protective effect of folic acid and other vitamins B for some other congenital abnormalities, cardiovascular diseases, senile dementia and cancers. The flour fortification with these water-soluble vitamins B is appropriate for an effective public health program for the primary prevention of these hyperhomocysteinemia-related disorders. There is no real risk for side effects on the basis of available US, Canadian and Hungarian experiences. In conclusion an urgent task is to introduce a mandatory flour fortification program in Hungary.     

Plasma homocysteine concentration in healthy middle-aged men and its presumed association with cardiovascular mortality]

It has recently become clear that hyperhomocysteinemia is an independent risk factor for vascular diseases. The plasma homocysteine concentrations of 71 healthy men (aged 40-49) living in Hungary were compared with those of randomly selected healthy age-matched men (n = 260) living in 11 different countries. The association between the mean plasma homocysteine concentration and reported cardiovascular mortality was analyzed in the respective countries. In Hungary the mean (+/- SD) plasma homocysteine concentration was 10.6 +/- 4.3 mumol/l. In the 11 other countries the mean (+/- SD) plasma homocysteine concentration ranged from 7.1 +/- 1.4 mumol/l (Schleiz, Germany, n = 20) to 10.7 +/- 2.1 mumol/l (Kuopio, Finland, n = 20). There was a significant correlation (r = 0.71, p < 0.005) between the plasma homocysteine concentration and male cardiovascular mortality in there countries. The strength of the correlation between the male plasma homocysteine concentration and cardiovascular mortality suggests that homocysteine may be an important factor in the variation of cardiovascular mortality between populations. The mean plasma homocysteine concentrations were the highest in the Hungarian (Budapest and Pest county) and the Finnish (Kuopio) groups but cardiovascular mortality is higher in Hungary than in Finland, referring to the pivotal role of other cardiovascular risk factors for the Hungarian population.     

The role of control technologies in preventing occupational disease

There has been little past emphasis on determining the impact of control technologies on health. Compliance with legally mandated standards has received the greatest emphasis, certainly since passage of the OSHA of 1970. Risk assessment focuses on needed data to estimate risk and can be used for estimates of workplace impacts before and after adoption of control technologies. Two possible approaches to workplace improvements are suggested for estimating impacts on worker health. Persons removed from risk can be used where workers' exposures to hazardous agents are reduced from above to below a TLV. Second, for carcinogens the percent reduction in exposure can be used as a surrogate for reduction in future cancer incidence. Both measures suffer from a host of assumptions required by the user. There may be better measures for estimating today the reductions in chronic disease which control technologies will bring about. These measures are desperately needed to establish priorities and to guide installation of control technologies. Finally, research in control technologies is needed to improve effectiveness and to lower costs. However, it is widely accepted by engineers in this field that while improved methods are always welcome, current available technologies are under-utilized in practice.     

Nutritional health aspects of mycotoxins

Mycotoxins produced by mould fungi can enter into the human food chain directly through foods of plant origin (cereal grains), consumer goods (coffee and bear) and indirectly through foods of animal origin (kidney, liver, milk and eggs). Mycotoxins occur in small amount in the foods; however their continuous intake even in microdoses can result in accumulation in the organism. Synergic effects of the mycotoxins as well as their possible additive multi-toxic effects seem to be especially dangerous. Mycotoxin problems are very important in Hungary because these natural toxins occur mainly in those cereals (e.g. wheat, maize) that amount to high proportion of the sowing area in Hungary and provide the main foods to the inhabitants. Public health risks of the toxins accumulating in the human and animal bodies during the long term consumption of the mycotoxins containing foods--even in small doses--have not been evaluated yet as thoroughly as their importance would require. However, there are more and more direct and indirect expressions of the danger resulting from the toxins. The most frequently observed human health effects are carcinogen effects (aflatoxin, ochratoxin A, fumonisins, patulin); effects causing developmental abnormalities (zearalenon, ochratoxin); effects harmful to the reproduction (zearalenon, and trichotecenes), effects decreasing the resistance; immunosuppressive effects (trichotecenes), and effects causing injury of the nervous system (ochratoxin A, fumonisins). Prevention of the injury of the health caused by mycotoxins can be completed by joint and integrated activity of the various disciplines only and requires a comprehensive interdisciplinary cooperation. This paper gives a discussion on health injuring effects of the most frequently occurring mycotoxins that are very important from human health aspects in Hungary; on their occurrence in the foods and on their human risk.