Breast and gynecological cancers in Croatia, 1988-2008

Aim

To analyze and interpret incidence and mortality trends of breast and ovarian cancers and incidence trends of cervical and endometrial cancers in Croatia for the period 1988-2008.

Methods

Incidence data were obtained from the Croatian National Cancer Registry. The mortality data were obtained from the World Health Organization (WHO) mortality database. Trends of incidence and mortality were analyzed by joinpoint regression analysis.

Results

Joinpoint analysis showed an increase in the incidence of breast cancer with estimated annual percent of change (EAPC) of 2.6% (95% confidence interval [CI], 1.9 to 3.4). The mortality rate was stable, with the EAPC of 0.3% (95% CI, -0.6 to 0.0). Endometrial cancer showed an increasing incidence trend, with EAPC of 0.8% (95% CI, 0.2 to 1.4), while cervical cancer showed a decreasing incidence trend, with EAPC of -1.0 (95% CI, -1.6 to -0.4). Ovarian cancer incidence showed three trends, but the average annual percent change (AAPC) for the overall period was not significant, with a stable trend of 0.1%. Ovarian cancer mortality was increasing since 1992, with EAPC of 1.2% (95% CI, 0.4 to 1.9), while the trend for overall period was stable with AAPC 0.1%.

Conclusion

Incidence trends of breast, endometrial, and ovarian cancers in Croatia 1988-2008 are similar to the trends observed in most of the European countries, while the modest decline in cervical cancer incidence and lack of decline in breast cancer mortality suggest suboptimal cancer prevention and control.Breast and gynecological cancers are among the seven most common female cancers in Croatia: in 2008 breast cancer was the most common cancer with the proportion of 26% of all cancer sites, endometrial cancer ranked fourth (6%), ovarian cancer (with fallopian tubes cancer) sixth (5%), and cervical cancer seventh (4%) (1).Breast, endometrial, and ovarian cancers share some similar risk factors like early menarche, late menopause, obesity, and low parity (2-5). Also, breast cancer in personal history increases the risk of endometrial and ovarian cancer (6). Delayed childbearing increases the risk of breast cancer but seems to have no impact on the development of ovarian and endometrial cancer (3-5). Diabetes mellitus increases the risk of endometrial and breast cancer (7,8). Use of tamoxifen or other selective estrogen receptor modulators increases the risk of endometrial and ovarian cancer, while the use of combined oral contraceptives is a protective factor (2,9,10). Also, tobacco smoking and alcohol intake reduce the risk of endometrial cancer (2,11,12). Alcohol intake and both oral contraceptives and hormonal replacement therapy are risk factors for breast cancer (2,13,14). Multiparty and physical activity are protective factors for all three cancers (2,4,15,16). Low socioeconomic status, sexually transmitted diseases, promiscuity, unprotected sexual behavior, earlier age of first intercourse, and smoking are risk factors for cervical cancer (2,17-23). Infection with human papillomavirus is considered as a necessary cause of cervical cancer (24).The aim of this study was to report the incidence and mortality of breast and ovarian cancers and incidence of endometrial and cervical cancers, analyze the trends in the period 1988-2008, and compare them to other European countries.     

Trends in lung cancer incidence and mortality in Croatia, 1988-2008

Aim

To describe and interpret lung cancer incidence and mortality trends in Croatia between 1988 and 2008.

Methods

Incidence data on lung cancer for the period 1988-2008 were obtained from the Croatian National Cancer Registry, while mortality data were obtained from the World Health Organization mortality database. Population estimates for Croatia were obtained from the Population Division of the Department of Economic and Social Affairs of the United Nations. We also calculated and analyzed age-standardized incidence and mortality rates. To describe time incidence and mortality trends, we used joinpoint regression analysis.

Results

Lung cancer incidence and mortality rates in men decreased significantly in all age groups younger than 70 years. Age-standardized incidence rates in men decreased significantly by -1.3% annually. Joinpoint analysis of mortality in men identified three trends, and average annual percent change (AAPC) decreased significantly by -1.1%. Lung cancer incidence and mortality rates in women increased significantly in all age groups older than 40 years and decreased in younger women (30-39- years). Age-standardized incidence rates increased significantly by 1.7% annually. Joinpoint analysis of age-standardized mortality rates in women identified two trends, and AAPC increased significantly by 1.9%.

Conclusion

Despite the overall decreasing trend, Croatia is still among the European countries with the highest male lung cancer incidence and mortality. Although the incidence trend in women is increasing, their age standardized incidence rates are still 5-fold lower than in men. These trends follow the observed decrease and increase in the prevalence of male and female smokers, respectively. These findings indicate the need for further introduction of smoking prevention and cessation policies targeting younger population, particularly women.Lung cancer is the most common malignancy worldwide, accounting for one fifth of all cancer-related deaths (1). There are different trends of lung cancer incidence and mortality throughout Europe, mostly reflecting different phases of smoking epidemic in individual countries. In many European countries, the rates in men have recently decreased or stabilized, while the rates in women increased (2-4). Because the majority of lung cancer deaths are attributed to tobacco smoking, any decline or deceleration in the lung cancer death rates could be attributed to the past antismoking interventions (5,6). Early indicators of progress in tobacco-smoking control are lung cancer trends in young adults (6).About 90% of lung cancers in men and 83% in women are caused by smoking (7). The risk of developing lung cancer is affected by the level of consumption and duration of smoking (8), as well as the level of exposure to environmental tobacco smoke (9). The second most important cause of lung cancer is radon, which was estimated to be responsible for 9% of lung cancer deaths in European countries (10). Other risk factors include exposure to asbestos (11), silica (12), nitrogen oxides (13), radiation to the chest as part of the treatment of malignant diseases (14-16), and scarring on the lungs due to tuberculosis or recurrent pneumonia (17).Currently in Croatia, lung cancer is the most common cancer in men and the fifth most common cancer in women, accounting for more than 2000 and 600 deaths per year, respectively (18,19). The aim of this study was to provide an overview of the temporal trends of lung cancer incidence and mortality in Croatia for the period 1988-2008.     

Disparities and relative risk ratio of preterm birth in six Central and Eastern European centers

Aim

To identify characteristic risk factors of preterm birth in Central and Eastern Europe and explore the differences from other developed countries.

Method

Data on 33 794 term and 3867 preterm births (<37 wks.) were extracted in a retrospective study between January 1, 2007 and December 31, 2009. The study took place in 6 centers in 5 countries: Czech Republic, Hungary (two centers), Romania, Slovakia, and Ukraine. Data on historical risk factors, pregnancy complications, and special testing were gathered. Preterm birth frequencies and relevant risk factors were analyzed using Statistical Analysis System (SAS) software.

Results

All the factors selected for study (history of smoking, diabetes, chronic hypertension, current diabetes, preeclampsia, progesterone use, current smoking, body mass index, iron use and anemia during pregnancy), except the history of diabetes were predictive of preterm birth across all participating European centers. Preterm birth was at least 2.4 times more likely with smoking (history or current), three times more likely with preeclampsia, 2.9 times more likely with hypertension after adjusting for other covariates. It had inverse relationship with the significant predictor body mass index, with adjusted risk ratio of 0.8 to 1.0 in three sites. Iron use and anemia, though significant predictors of preterm birth, indicated mixed patterns for relative risk ratio.

Conclusion

Smoking, preeclampsia, hypertension and body mass index seem to be the foremost risk factors of preterm birth. Implications of these factors could be beneficial for design and implementation of interventions and improve the birth outcome.Preterm birth (PTB: spontaneous and indicated), defined as delivery before 37 weeks of gestation, is the most common cause of neonatal mortality in developed countries (1). Worldwide, prematurity complications are the most common cause of neonatal deaths (2), accounting for 80% of the world’s 1.1 million deaths (3,4). Fetal, neonatal, and infant mortality rates vary widely between the countries of Europe. Preterm babies born before 28 weeks of gestational age constitute over one-third of all deaths, but data are not comparable between countries (5).Children born prematurely have a higher incidence of cerebral palsy, sensory deficits, respiratory illnesses, and learning disabilities compared to children born at term. The morbidity associated with preterm birth often extends to later life, resulting in enormous physical, psychological, and economic costs (6,7).In developing countries, accurate and complete population data and medical records often do not exist. Therefore, few international studies regarding preterm birth and neonatal deaths have compared social, economic, or ethnic differences, even though several potential risk factors for preterm birth have been identified, including race, physical environment, nutrition, socioeconomic status, and reproductive age (1,8). Maternal height and weight may also contribute to PTB (9-12), along with cigarette smoking or illicit drug use (13,14). In addition, maternal iron, folic acid, and vitamin D deficiencies may increase the risk for preterm delivery, with nutritional differences among ethnic groups likely contributing to disparities in prematurity (15).The contribution of specific risk factors for PTB in Central and Eastern European counties is unknown. Therefore, the Mother and Child Health Research Network (M&CH RN), as one of the networks of the Association for Regional Cooperation in Health, Science and Technology (RECOOP HST), instituted a retrospective review of delivery records of participating hospitals to identify the risk factors of preterm birth. Its specific aims were to identify the risk factors of preterm birth specific for Central and Eastern Europe (CEE).     

Frequency of tuberculosis at autopsies in a large hospital in Zagreb, Croatia: a 10-year retrospective study

Aim

To assess the frequency and forms of pulmonary tuberculosis at autopsy in a high-traffic hospital in the capital city of a country with a low tuberculosis incidence.

Methods

We performed a retrospective search of autopsy data from the period 2000 to 2009 at Sestre Milosrdnice University Hospital Center, Zagreb, Croatia. We also examined patients’ records and histological slides.

Results

Of 3479 autopsies, we identified 61 tuberculosis cases, corresponding to a frequency of 1.8%. Active tuberculosis was found in 33 cases (54%), 23 of which (70%) were male. Of the 33 active cases, 25 (76%) were clinically unrecognized and 19 (76%) of these were male.

Conclusion

Clinically undiagnosed tuberculosis accounted for a substantial proportion of active tuberculosis cases diagnosed at autopsy. Autopsy data may be an important complement to epidemiological data on tuberculosis frequency.Each year, there are nearly 9 million new tuberculosis cases globally and nearly 2 million tuberculosis-related deaths (1,2). Tuberculosis occurs throughout the world, but its incidence varies greatly (3). Preventing infection through contact between healthy individuals and patients is the best measure to fight tuberculosis. The new World Health Organization strategy to fight tuberculosis, Stop TB Strategy (2006-2015), deals with the human immunodeficiency virus epidemic that has increased the incidence of tuberculosis (4). The European Centre for Disease Prevention and Control in 2008 created a strategy against tuberculosis called the “Framework Action Plan to Fight Tuberculosis in the European Union” (5). The long-term goal of the Stop TB Strategy and TB Framework Action Plan is to control and ultimately eliminate tuberculosis in the world based on four basic principles: ensure prompt and quality care for all; strengthen the capacity of health systems; develop new tools; and build partnerships and collaboration with countries and stakeholders (4,5).Croatia has a low incidence of tuberculosis, which has been steadily decreasing for the last five decades (6). The peak of the epidemic was at the turn of the 19th and 20th century, when more than 400 deaths per 100 000 people occurred as a direct result of tuberculosis (6). In the mid-20th century, the incidence of new tuberculosis cases was 20 000 per 100 000 people (6). In 2009, the incidence of new tuberculosis cases was 20 per 100 000 people (7) and in 2006 nearly all reported cases showed low levels of multidrug resistance (2,6,7). In accordance with international and European efforts, Croatia has its own guidelines for the fight against tuberculosis, with the following goals: to cure at least 85% of cases; to detect at least 70% of tuberculosis patients, and to decrease the incidence of the disease to 10 per 100 000 people (6-8).Although tuberculosis can affect any organ, 70%-80% of cases suffer from pulmonary tuberculosis (2). Generally, it is possible to detect tuberculosis infection 8-10 weeks after exposure based on a positive tuberculin skin test or an interferon-gamma release assay (9). The rest of the cases have latent tuberculosis infection (LTBI), which is an asymptomatic condition, and cannot transmit the disease (1,2). However, transmission becomes possible under certain conditions such as stress or immune suppression (6,10,11). It is believed that individuals with LTBI account for most infections in low-incidence countries like Croatia, and that this problem is compounded by migration and increasing numbers of homeless persons, alcoholics, and drug addicts (6,10,12).Statistics about tuberculosis prevalence may underestimate the number of infected people, since as many as half of the cases of pulmonary tuberculosis seen at autopsy were previously undiagnosed (12,13). In fact, few studies have examined the relationship between tuberculosis diagnoses at autopsy and reported tuberculosis prevalence in the population (14). This information may help assess whether clinically unrecognized tuberculosis poses a significant public health threat. The present study examined 3479 autopsies performed from 2000 through 2009, to assess the frequency and forms of pulmonary tuberculosis in a country with a low tuberculosis incidence. The results were compared with the number of tuberculosis patients in Croatia recorded in the Croatian Health Service Yearbook for the same period (7,8).     

An estimate of asthma prevalence in Africa: a systematic analysis

Aim

To estimate and compare asthma prevalence in Africa in 1990, 2000, and 2010 in order to provide information that will help inform the planning of the public health response to the disease.

Methods

We conducted a systematic search of Medline, EMBASE, and Global Health for studies on asthma published between 1990 and 2012. We included cross-sectional population based studies providing numerical estimates on the prevalence of asthma. We calculated weighted mean prevalence and applied an epidemiological model linking age with the prevalence of asthma. The UN population figures for Africa for 1990, 2000, and 2010 were used to estimate the cases of asthma, each for the respective year.

Results

Our search returned 790 studies. We retained 45 studies that met our selection criteria. In Africa in 1990, we estimated 34.1 million asthma cases (12.1%; 95% confidence interval [CI] 7.2-16.9) among children <15 years, 64.9 million (11.8%; 95% CI 7.9-15.8) among people aged <45 years, and 74.4 million (11.7%; 95% CI 8.2-15.3) in the total population. In 2000, we estimated 41.3 million cases (12.9%; 95% CI 8.7-17.0) among children <15 years, 82.4 million (12.5%; 95% CI 5.9-19.1) among people aged <45 years, and 94.8 million (12.0%; 95% CI 5.0-18.8) in the total population. This increased to 49.7 million (13.9%; 95% CI 9.6-18.3) among children <15 years, 102.9 million (13.8%; 95% CI 6.2-21.4) among people aged <45 years, and 119.3 million (12.8%; 95% CI 8.2-17.1) in the total population in 2010. There were no significant differences between asthma prevalence in studies which ascertained cases by written and video questionnaires. Crude prevalences of asthma were, however, consistently higher among urban than rural dwellers.

Conclusion

Our findings suggest an increasing prevalence of asthma in Africa over the past two decades. Due to the paucity of data, we believe that the true prevalence of asthma may still be under-estimated. There is a need for national governments in Africa to consider the implications of this increasing disease burden and to investigate the relative importance of underlying risk factors such as rising urbanization and population aging in their policy and health planning responses to this challenge.Chronic respiratory diseases (CRDs) are among the leading causes of death worldwide, with asthma rated the most common chronic disease affecting children (1). Globally, about 300 million people have asthma, and current trends suggest that an additional 100 million people may be living with asthma by 2025 (1,2). The World Health Organization (WHO) estimates about 250 000 deaths from asthma every year, mainly in low- and middle-income countries (LMIC) (3,4). Just like with many other chronic diseases in Africa, the fast rate of urbanization has been linked to the increase in the burden of asthma and other allergic diseases (3,5,6). The prevalence of these conditions may, in theory, have the potential to reach levels higher than those observed in high-income countries (HIC) due to priming effects of parasitic helminthic infections on the immune system, as these infections are common in many African settings (5). The International Study of Asthma and Allergies (ISAAC) reported that asthma prevalence among children was increasing in Africa and has contributed most to the burden of disease through its effects on quality of life (3). In-patient admissions and purchase of medications account for most of the direct costs on government, while loss of productivity, due to absenteeism from work and school, are responsible for most of the indirect costs (7,8).Asthma is widely known as a multifactorial respiratory disorder with both genetic and environmental underlying risk factors (3). Exposure to common allergens (including pollens, dust mites, and animal furs) and indoor and outdoor air pollution from various sources (eg, traffic pollution, combustion of fossils and biomass fuels, workplace dust) have all been implicated as triggers of the disease (9). Second hand tobacco smoking is a confirmed risk factor in pediatric patients (5,10). Viral infections, a major cause of upper respiratory tract infections and “common cold,” are also a common risk factor in children (11,12). As noted, helminthic infections are relatively common in Africa and are associated with bronchial hyper-responsiveness and asthma (5,13); this is perhaps due to the presence of related raised immunoglobulin E (IgE) and a prominent Th2 immune response (5,14).Studies on asthma are few in Africa, with most publications mainly from South African and Nigerian populations (14). One main factor affecting research output is the diagnosis of asthma, which still remains a challenging issue (15,16). The WHO has emphasized that this has limited on-going research efforts globally (4,16). The International Union against Tuberculosis and Lung Diseases (IUATLD) published one of the first diagnostic and survey guidelines for asthma in 1984, but experts subsequently reported concerns about its precision and reliability (17). According to the Global Initiative for Asthma (GINA), detailed history, physical examination and spirometric lung function tests are vital to the diagnosis and management of asthma (10,18). Generally, a reduction in forced expiratory volume in one second (FEV₁) and peak expiratory flow (PEF) may be indicative of asthma, with the amount of reduction proportional to the severity of asthma (4). GINA proposed that an increase in FEV₁ of >12% and 200 mL in about 15-20 minutes following the inhalation of 200-400 μg of salbutamol or a 20% increase in PEF from baseline can be employed as standardized criteria in diagnosis of asthma (10). This, however, lacks sensitivity, as many asthmatics, especially those on treatment, may not exhibit an increase in FEV₁ and PEF when assessed (16,19). Thus, although asthma is characterized by significant reversibility of airway obstruction, an absence of reversibility may not always exclude the presence of asthma (20). The ISAAC established in 1991, remains the largest epidemiological study among children globally (1). ISAAC methodologies and scoring are currently the most widely employed by researchers in Africa (1,4). This involves both video and written questionnaires, as there were reports that video and pictorial representations of asthma symptoms may contribute to improved case recognition in younger children (1). However, this is still a subject of debate among experts (21). The European Community Respiratory Health Survey (ECRHS), which assessed the prevalence of atopy and symptoms of airway disease among older age groups in Western Europe, has been widely implemented and has reported significant geographic variations in the prevalence of asthma and atopy (9). Despite these revised guidelines, both ISAAC and ECRHS research groups have reported challenges in achieving high sensitivity and specificity in case ascertainment with the symptom “wheeze at rest in the last 12 months” (also regarded as current wheeze, or active wheeze), yielding the highest sensitivity and specificity (1).In Africa, problems including those arising from the over-utilization of health services, lack of trained staff and diagnostic apparatus, and non-availability and unaffordability of inhaled medications have hindered efforts to improve the management of asthma (22,23). The lack of organized health promotion programs, such as effective control strategies for environmental triggers, air pollutants, and occupational dusts have also contributed to the growing burden (24). The WHO has reported that the levels of asthma control and health responses in the continent have been below recommended standards, and that these have contributed to the size of the disease burden (3,4). In addition, although many African countries have national guidelines for the management of asthma and other CRDs, these guidelines have not been implemented in most rural areas (25,26). Economic analyses in many African settings have shown that direct costs from asthma are usually greater than the indirect costs. However, indirect costs represent a relatively higher proportion of total costs among pediatric than adult patients (8). Moreover, the wider economic burden on individuals, families, employers, and society, due to loss of future potential source of livelihood, has also been devastating in many resource-poor settings (22). It is believed that many children with asthma in Africa may fail to achieve their full potential if proper management and control measures are not put in place (1). It has been suggested that education of health care providers and the public is a vital element of the response to the challenge posed by asthma in Africa (4,27).By 2015, it is expected that world’s urban population will increase from 45% to 59%, with over half of this occurring in Africa (8). It is also expected that the prevalence of asthma and many chronic diseases in Africa will increase due to this growing population size and from effects of accompanying urbanization and adoption of western lifestyles (28). In light of this and of the low research output and poor availability of health services data on the burden of asthma in Africa, it is important to analyze the available data through a systematic review of the literature in order to attempt to quantify the burden, guide health priority settings, and inform the formulation of an appropriate health policy response.     

Pancreatic cancer mortality in Serbia from 1991-2010 – a joinpoint analysis

Aim

To analyze the trends of pancreatic cancer mortality in Serbia.

Methods

The study covered the population of Serbia in the period 1991 to 2010. Mortality trends were assessed by the joinpoint regression analysis by age and sex.

Results

Age-standardized mortality rates ranged from 5.93 to 8.57 per 100 000 in men and from 3.51 to 5.79 per 100 000 in women. Pancreatic cancer mortality in all age groups was higher among men than among women. It was continuously increasing since 1991 by 1.6% (95% confidence interval [CI] 1.1 to 2.0) yearly in men and by 2.2% (95% CI 1.7 to 2.7) yearly in women. Changes in mortality were not significant in younger age groups for both sexes. In older men (≥55 years), mortality was increasing, although in age groups 70-74 and 80-84 the increase was not significant. In 65-69 years old men, the increase in mortality was significant only in the period 2004 to 2010. In ≥50 years old women, mortality significantly increased from 1991 onward. In 75-79 years old women, a non-significant decrease in the period 1991 to 2000 was followed by a significant increase from 2000 to 2010.

Conclusion

Serbia is one of the countries with the highest pancreatic cancer mortality in the world, with increasing mortality trend in both sexes and in most age groups.According to the GLOBOCAN 2008 estimates, pancreatic cancer causes more than 270 000 deaths per year (accounts for 3.5% of all deaths), ranking ninth among the leading causes of cancer death in both sexes together (1-3). It is one of the most lethal malignant neoplasms, with the 5-year survival rate of less than 5% (4,5).The majority of pancreas cancer deaths (61%) occurs in developed countries, where pancreatic cancer is the fifth leading cause of death in men and the fourth in women (1,3,4). The highest mortality rates of pancreatic cancer are reported in North America (6.9 per 100 000) and Europe (from 6.6 per 100 000 in western Europe to 5.9 in southern Europe) and the lowest in less developed countries in South Asia and Central Africa (approximately 1.5 per 100 000) (3).Pancreatic cancer is more common in men than women – in 2008, age-adjusted worldwide mortality rates were 4.2 per 100 000 in men and 3.1 per 100 000 in women (3,4). It is predominantly a disease of the elderly, and almost 90% of all cases are diagnosed after the age of 55 years (3). In Serbia in 2008, pancreatic cancer was the fifth most common cause of cancer mortality in both sexes, with death rates similar to those in developed countries (8.3 per 100 000 in men and 5.5 in women) (3).In the recent decade, pancreatic cancer mortality in developed countries has been increasing (for example, in the USA by 0.5% per year for both sexes; in Japan by 0.6%, but only in women; in the European Union, also only in women) (6-8). Since there are no corresponding data for the Serbian population, the aim of the present study was to analyze time trends of pancreatic cancer mortality in Serbia for the period 1991-2010.     

Socioeconomic inequalities, health damaging behavior, and self-perceived health in Serbia: a cross-sectional study

Aim

To analyze the association of socioeconomic factors with self-perceived health in Serbia and examine whether this association can be partly explained by health behavior variables.

Methods

We used data from the 2007 Living Standards Measurement Study for Serbia. A representative sample of 13 831 persons aged ≥20 years was interviewed. The associations between demographic factors (age, sex, marital status, and type of settlement), socioeconomic factors (education, employment status, and household consumption tertiles), and health behavior variables (smoking, alcohol consumption) and self-perceived health were examined using logistic regression analyses.

Results

A stepwise gradient was found between education and self-perceived health for the total sample, men, and women. Compared to people with high education, people with low education had a 4.5 times higher chance of assessing their health as poor. Unemployed (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.29-2.10), inactive (OR, 2.82; 95% CI, 2.49-3.19), and the most deprived respondents (OR, 1.17; 95% CI, 1.02-1.34) were more likely to report poor self-perceived health than employed persons and the most affluent group. After adjustment for demographic and health behavior variables, the magnitudes of all associations decreased but remained clearly and significantly graded.

Conclusions

This study revealed inequalities in self-perceived health by socioeconomic position, in particular educational and employment status. The reduction of such inequalities through wisely tailored interventions that benefit people’s health should be a target of a national health policy in Serbia.Socioeconomic inequalities in health between and within countries have received considerable attention in health research. There are many measures that are of potential importance to the study of inequalities in health, but self-perceived health has been a very good source of information on subjective health status, incorporating aspects of both physical and mental health (1). This measure, based on a single-item, has been recommended as a population health measure by the World Health Organization and European Union Commission (2,3). The shape of health inequalities typically follows an inverse gradient, ie, the lower the socioeconomic status, the higher the probability of reporting a poor self-perceived health (4,5). Individuals with lower educational attainment or income, unemployed individuals, and individuals employed in manual occupations, are more likely to have poor self-perceived health (6-8). However, despite this typical pattern, the magnitude of socioeconomic inequalities in health varies widely in different populations (9).A consistent association between socioeconomic determinants and health related variables has been found in many European countries (10-12). Carlson demonstrated that the so-called European health divide, documented for mortality, was also noticeable in self-perceived health (13). Mackenbach et al compared the magnitude of inequalities in self-assessed health among 22 countries in Europe and found that in almost all countries the rates of poorer self-assessments of health were substantially higher in groups of lower socioeconomic status, while the magnitude of the inequalities between groups of higher and lower socioeconomic status was much larger in some countries than in others (14). On average, people from Eastern European countries rated their health worse than those from Western European countries (13,14). Poor health status in Eastern Europe may be influenced by unhealthy lifestyles associated with lack of information about health and behavior (15). East-west difference in health status may be partly explained by differences in health behaviors (such as smoking and alcohol consumption) and psychosocial factors (16).Despite the growing literature on this issue in central and west Europe, few studies have examined the impact of socioeconomic inequalities in self-rated health in southeastern Europe. In Serbia, a country still in the process of transition, little is known about health inequalities (17,18). Several recently published studies have brought to light the significance of socioeconomic inequalities in Serbia: in the prevalence of chronic diseases (19), morbidity status (20), and smoking habits of the population (21).The aim of this study was to analyze the association of socioeconomic factors with self-perceived health in Serbia using the 2007 Living Standards Measurement Study data (LSMS). Additionally, we examined whether this association can be partly explained by health behavior variables.     

Tuberculosis Incidence in Elderly in Serbia: Key Trends in Socioeconomic Transition

Aim

To examine tuberculosis incidence rates among the elderly in Central Serbia in 1992-2006 period, which was characterized by socioeconomic crisis and migration of population.

Methods

We analyzed all reported active tuberculosis cases in a 15-year period, especially among patients aged ≥65, according to the Annual Reports of the Institute of Lung Diseases and Tuberculosis in Belgrade and Central Tuberculosis Register. Population estimates with extrapolations were based on 1991 and 2002 census data.

Results

Total tuberculosis incidence rates showed a slight but non-significant decreasing trend (P = 0.535), and no significant increase was found in patients aged ≥65 years (P = 0.064), with an average age-specific incidence rate for the elderly of 64.0 (95% confidence interval, 60.7-67.4). The increase was significant in patients aged ≥70 years (y = 49.3549 + 2.1186x; P = 0.001), both in men (y = 62.8666 + 2.3977x; P = 0.005) and even more prominently in women (y = 39.8240 + 1.9150x; P < 0.001). The proportion of tuberculosis cases in the elderly peaked in 2005, with 35% of all tuberculosis cases.

Conclusion

High incidence rates and increasing time trend of tuberculosis in the elderly in Central Serbia is a serious problem, especially among those aged 70 years and over, who might present a target group for active case-finding of the disease.Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis complex. It can affect persons of any age and involve any site in the body. The risk of developing tuberculosis depends both on the risk of being infected and the risk of developing the active form of the disease. The former depends on the tuberculosis prevalence in the community, whereas the latter depends on many genetic and environmental factors (1-3). A total of 8-10 million people worldwide develop active tuberculosis per year, while at least 1.7 million people die from this disease (4,5). In 1993, the World Health Organization declared tuberculosis a global problem. The main reasons for this are the dramatically increasing number of immune-deficient people in the world and the problem of multi-drug resistant tuberculosis (5,6). In Europe, two tuberculosis trends can be observed, one being a declining epidemic in the west and the other an increasing one in the east (4).While human immunodeficiency virus (HIV) infection presents the greatest single risk factor for developing active tuberculosis, in countries with low HIV prevalence, other factors that decrease human immunity are of higher importance. All tuberculosis risk factors are more pronounced and even multiplied in patients belonging to tuberculosis risk groups, such as immigrants/refugees, prisoners, elderly in old-age homes, people with disabilities in asylums, and Roma populations in slums (3,7-9). Tuberculosis in the elderly is an increasing problem in many countries (4), because of age-related decline in immunity (1) and increasing longevity (10). While the latter happens predominantly in developed countries, the elderly in developing countries suffer from poverty, malnutrition and tobacco smoking, which are proven risk factors for tuberculosis (1,11,12). Thus, tuberculosis in the elderly is likely to be a lasting and even an increasing problem worldwide.Serbia is a country with intermediate tuberculosis incidence rate (4,13,14). A molecular epidemiologic analysis, performed in Belgrade, showed a recent frequent transmission of tuberculosis (15). The national tuberculosis mortality data show peak numbers in the elderly (16,17). In the 1990s, Serbia faced socio-economic crisis, civil war, and mass migration of population following disintegration of former Yugoslavia. We investigated whether tuberculosis in the elderly in Serbia increased in the 1992-2006 period.     

Improving breast cancer prediction using a pattern recognition network with optimal feature subsets

AimTo predict the presence of breast cancer by using a pattern recognition network with optimal features based on routine blood analysis parameters and anthropometric data.MethodsSensitivity, specificity, accuracy, Matthews correlation coefficient (MCC), and Fowlkes-Mallows (FM) index of each model were calculated. Glucose, insulin, age, homeostatic model assessment, leptin, body mass index (BMI), resistin, adiponectin, and monocyte chemoattractant protein-1 were used as predictors.ResultsPattern recognition network distinguished patients with breast cancer disease from healthy people. The best classification performance was obtained by using BMI, age, glucose, resistin, and adiponectin, and in a model with two hidden layers with 11 and 100 neurons in the neural network. The accuracy, sensitivity, specificity, FM index, and MCC values of the best model were 94.1%, 100%, 88.9%, 94.3%, and 88.9%, respectively.ConclusionBreast cancer diagnosis was successfully predicted using only five features. A model using a pattern recognition network with optimal feature subsets proposed in this study could be used to improve the early detection of breast cancer.

Cancer is the second leading cause of death globally, with 9.6 million deaths in 2018. The most common cancers in women are breast, lung, cervical, colorectal, and thyroid cancer, while men most frequently suffer from lung, liver, stomach, colorectal, and prostate cancer (1). Survival rates of breast cancer patients worldwide vary greatly. The low survival in underdeveloped countries can mainly be explained by a lack of early detection systems equipped with advanced technologies (2). A lower risk of dying from breast cancer is directly related to an earlier treatment (3). Therefore, an early diagnosis, necessary to increase the survival rate of breast cancer patients, continues to be the most significant component of breast cancer control (4).Several biomarker candidates for breast cancer have been reported in the literature (5), as well as different biomarker combinations (6-10). A combination of BMI, leptin levels, leptin/adiponectin ratio, and CA 15-3 levels as biomarkers for breast cancer has shown high reliability (9). Routine blood analyses, leptin, adiponectin, especially insulin, glucose, resistin, homeostatic model assessment (HOMA), monocyte chemoattractant protein-1 (MCP-1), age, and body mass index (BMI) data can also be used to diagnose breast cancer (10).Data-mining classification methods can aid in the diagnostic process due to their accuracy and rapidity (11). Hwa et al (6) have reported 85% predictive sensitivity for the classification of breast cancer using a software tool with a logistic regression model. In 2015, the relationship between serum irisin levels and breast cancer was analyzed using logistic regression analysis. Serum irisin levels were found to discriminate breast cancer patients with 91.1% specificity and 62.7% sensitivity (12). Patrício et al (10) used a support vector machine (SVM) for breast cancer prediction. The sensitivity and specificity values were in the range of 82%-88% and 85%-90%, respectively. Using K-nearest neighbor (KNN) and SVM algorithms, Gündoğdu (13) predicted breast cancer risk with 85.3% accuracy, 80.8% sensitivity, and 89.1% specificity.Pattern recognition networks (PRN) are artificial neural networks (ANNs) that are widely used to solve the classification problem (14), especially in the medical sciences. ANN models have been frequently used in cancer classification (15) and other areas of bioinformatics (16-19). Saritas and Yaşar (20) classified breast cancer with an accuracy of 86.95% when using ANN and with an accuracy of 83.54% when using Naïve Bayes algorithms (20).The aim of this study was to predict the risk for breast cancer by using a PRN with an optimal feature set, including the routinely collected blood analysis parameters and anthropometric data. A secondary aim was to improve the classification performances, including accuracy, sensitivity, specificity, Matthews correlation coefficient (MCC), and Fowlkes Mallows (FM) index, and to create a machine learning-based model that can help physicians in the early diagnosis of breast cancer.     

Venous thromboembolism in Croatia – Croatian Cooperative Group for Hematologic Diseases (CROHEM) study

Aim

To analyze the incidence and characteristics of venous thromboembolism (VTE) in Croatia.

Methods

The Croatian Cooperative Group for Hematologic Diseases conducted an observational non-interventional study in 2011. Medical records of patients with newly diagnosed VTE hospitalized in general hospitals in 4 Croatian counties (Šibenik-Knin, Koprivnica-Križevci, Brod-Posavina, and Varaždin County) were reviewed. According to 2011 Census, the population of these counties comprises 13.1% of the Croatian population.

Results

There were 663 patients with VTE; 408 (61.54%) had deep vein thrombosis, 219 (33.03%) had pulmonary embolism, and 36 (5.43%) had both conditions. Median age was 71 years, 290 (43.7%) were men and 373 (56.3%) women. Secondary VTE was found in 57.3% of participants, idiopathic VTE in 42.7%, and recurrent VTE in 11.9%. There were no differences between patients with secondary VTE and patients with idiopathic VTE in disease recurrence and sex. The most frequent causes of secondary VTE were cancer (40.8%), and trauma, surgery, and immobilization (38.2%), while 42.9% patients with secondary VTE had ≥2 causes. There were 8.9% patients ≤45 years; 3.3% with idiopathic or recurrent VTE. Seventy patients (10.6%) died, more of whom had secondary (81.4%) than idiopathic (18.6%) VTE (P < 0.001), and in 50.0% VTE was the main cause of death. Estimated incidence of VTE in Croatia was 1.185 per 1000 people.

Conclusion

Characteristics of VTE in Croatia are similar to those reported in large international studies. Improved thromboprophylaxis during the presence of risk factors for secondary VTE might substantially lower the VTE burden.Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major health problem in the world, associated with significant morbidity and mortality (1-9). Incidence rates for VTE mostly vary from 1 to 2 in 1000 individuals per year (1-5,7,9). PE, the most serious manifestation of VTE, has a mortality rate of more than 15% in the first 3 months after diagnosis, with short-term survival of less than 60% (10,11). Cohen et al estimated that the number of VTE-related deaths across the European Union (EU) was 543 454 per year, which was more than double the number of combined deaths in EU due to AIDS, breast and prostate cancer, and traffic accidents (8).VTE in survivors is associated with several chronic consequences of the disease that can severely impair the patients’ quality of life, including post-thrombotic syndrome (PTS) and pulmonary hypertension (PH), as well as recurrent VTE. PTS affects at least one-third of patients after DVT (8,12-15) and PH affects 4%-5% of patients after PE (8,16,17). VTE has significant incidence of recurrence: 10.1% at 6 months, 12.9% after 1 year, and 30.4% after 10 years (18).Total VTE-related costs to health care system are enormous. For example, the total cost of VTE to the UK National Health Service in 1993 was £235-£257 million (€349-€382 million), and the combined direct and indirect costs in 2004/2005 were approximately £640 million (€950 million), and are even higher when PTS is taken into account (8,19,20).VTE is a multifactorial disease, resulting from a complex interaction of genetic and acquired factors. Although some studies estimated that genetics was related to up to 60% of the risk of VTE (including FV Leiden and prothrombin G20210A mutations, deficiencies of protein C, S and antithrombin, and elevations of some procoagulant factors) (21), there is also a large number of acquired risk factors for VTE such as immobilization, surgery, trauma, cancer, pregnancy and puerperium, oral contraceptives, autoimmune diseases, and other disorders (1-8,21).In spite of the importance of VTE, there is not enough data on its incidence and characteristics in transitional countries. Also, although several studies analyzed the epidemiology of VTE in different study settings (1-9), there is still not much information on conditions present at the diagnosis of thrombosis, comparing idiopathic and secondary (provoked) VTE. Therefore, the Croatian Cooperative Group for Hematologic Diseases (CROHEM) analyzed the incidence and characteristics of idiopathic and secondary newly diagnosed VTE in Croatia in 2011, the year of the most recent national population census.     

Expression and possible prognostic role of MAGE-A4, NY-ESO-1, and HER-2 antigens in women with relapsing invasive ductal breast cancer: retrospective immunohistochemical study

Aim

To evaluate the possible prognostic role of the expression of MAGE-A4 and NY-ESO-1 cancer/testis antigens in women diagnosed with invasive ductal breast cancer and determine the expression of HER-2 antigen.

Methods

The expression of MAGE-A4, NY-ESO-1, and HER-2 antigens was evaluated immunohistochemically on archival paraffin-embedded samples of breast cancer tissue from 81 patients. All patients had T1 to T3, N0 to N1, M0 tumors and underwent postoperative radiotherapy and, if indicated, systemic therapy (chemotherapy and hormonal therapy). The antigen expression in women who were disease-free for 5 years of follow up (n = 23) was compared with that in women with either locoregional relapse (n = 30) or bone metastases (n = 28). Patient survival after 10 years of follow up was assessed.

Results

The three groups of women were comparable in terms of age, type of operation, tumor size, tumor grade, number of metastatically involved axillary lymph nodes, Nottingham prognostic index (NPI), progesterone receptor (PR) status, and adjuvant hormonal therapy. Estrogen receptors (ER) were positive in 13 women in the 5-year relapse-free group vs 8 in locoregional relapse and 7 in bone metastases group (P = 0.032). There were significantly fewer women who received adjuvant chemotherapy in the 5-year relapse-free group than in other two groups (7 vs 23 with locoregional relapse and 25 with bone metastases; P<0.001). This group also had a significantly better 10-year survival (14 women vs 1 with locoregional relapse and 1 with bone metastases; P<0.001). The three groups did not differ in the NY-ESO-1 or HER-2 expression, but the number of patients expressing MAGE-A4 antigen was significantly lower in the group with locoregional relapse (P = 0.014). In all groups, MAGE-A4 antigen expression was associated with the NY-ESO-1 antigen expression (P = 0.006), but not with tumor size and grade, number of metastatically involved axillary lymph nodes, or the ER and PR status. MAGE-A4-positive patients had a significantly longer survival than the MAGE-A4-negative patients (P = 0.046). This was not observed with NY-ESO-1 and HER-2 antigens.

Conclusion

Our results suggest that the MAGE-A4 antigen may be used as a tumor marker of potential prognostic relevance.Breast cancer is the most common malignancy in women (1). Its clinical course may vary from indolent and slowly progressive to rapidly metastatic disease. Identification of prognostic and predictive factors that reflect the biology of breast cancer is important for the assessment of prognosis and selection of patients who may benefit from adjuvant and/or systemic therapy. The important aspects of prognostic factors suitable for clinical use are their availability, reproducibility, and cost. In routine clinical practice, treatment decisions and selection of treatment modalities for each individual patient are based on the standard prognostic factors, such as age (1,2), menopausal status (3), tumor size (1-4), tumor grade (3-5), steroid-hormone receptor status (1-5), and nodal metastases (1-5).Variability in clinical course of breast cancer is partly related to tumor cell growth rate and other features, such as invasiveness or metastatic potential. Research in molecular biology has identified genes and their products involved in or associated with the malignant cell transformation and behavior. Moreover, expression of some of these molecules, such as p53 (1,6,7), Ki-67 (7,8), nm23 (1,7), catepsin D (1,7), Ep-CAM (9,10), HER-2 (1,2,6), and urokinase-type plasminogen activator and its inhibitor (1,11), is associated with the patient’s prognosis. As it seems that many genes and molecules might be involved in malignant transformation and cell behavior, other additional molecules may also be tested as potential prognostic factors.The cancer/testis (C/T) genes encode tumor-associated antigens (TAA) found in various tumors of different histological origin, but not in normal tissues other than testis (12,13). Their physiological function is unknown. Peptides derived from these antigens could be used as targets in active immunotherapy. Analysis of the expression of these genes or their products in malignancies could also be of potential diagnostic and/or prognostic relevance (14,15). Therefore, we performed a retrospective analysis of immunohistochemical expression of C/T antigens MAGE-A4 and NY-ESO 1 in women with invasive breast cancer. We also analyzed the expression of HER-2 antigen, because it has a prognostic and predictive role (1,16).     

Vaccination intention among healthcare workers during the first wave of the coronavirus disease 2019 pandemic in relation to knowledge: a cross-sectional study in Croatia,Slovenia, Serbia,and Poland

AimTo analyze SARS-CoV-2 vaccination intention and acceptance in relation to the knowledge about coronavirus disease 2019 (COVID-19) among healthcare workers (HCWs) in Croatia, Slovenia, Serbia, and Poland.MethodsIn spring 2020, an online survey was distributed among HCWs by using snowball sampling. The questionnaire was fully completed by 623 respondents: 304 from Croatia, 86 from Slovenia, 90 from Serbia, and 143 from Poland. The survey collected data on demographic characteristics (age, gender, education), vaccination acceptance, and knowledge about COVID-19.ResultsA total of 31% of respondents declared their intention to be vaccinated when a vaccine against COVID-19 is available, and 45% were undecided. Vaccination intention was associated with age, educational level, and knowledge about the pandemic, and differed significantly among the countries. Younger HCWs (18-25 years) and those with higher education more frequently expressed vaccination acceptance. Vaccination acceptance score was not associated with gender.ConclusionsHCWs with higher knowledge were more likely to express vaccination intention. Improving the knowledge about COVID-19 and increasing HCWs'' education might also increase vaccination acceptance among HCWs, and consequently in the general population.

When in early March 2020, the SARS-CoV-2 virus began to spread in Europe, the governments of Croatia, Slovenia, Serbia, and Poland relatively quickly imposed containment measures, including a closure of kindergartens and schools, and a ban on public life. The measures seemed to be successful, as in the first wave of the pandemic these countries had lower COVID-19 infection and death rates than some Western European countries such as Italy, France, Spain, and the United Kingdom (1). It soon became clear that, in addition to prevention, diagnosis, and treatment, the pandemic can be limited globally only by the introduction of vaccines against COVID-19 (2). The success of a vaccination program depends on the uptake rates in the population, especially among health care workers (HCWs) (3). Better knowledge about the disease and higher perceived severity of COVID-19 have been shown to increase vaccine acceptance (4).HCWs play an important role as health educators and can help in disease control by disseminating accurate information in communities. According to the theory of knowledge, attitude, and practice, successful disease control requires good knowledge of the disease (5). HCWs'' lack of such knowledge can delay treatment and lead to rapid spread of infection (6,7). Indeed, HCWs were shown to have inadequate knowledge about COVID-19 (8).HCWs have a higher risk of becoming infected with COVID-19 than the general population (3,9,10) and are potential transmitters of the virus in the clinical setting. However, they can also help the lay population understand and accept vaccination. In Southeast Asia, HCWs had higher acceptance of COVID-19 vaccination than the general population, due to a higher perceived risk of COVID-19 infection (11). Chinese HCWs had higher willingness to receive future vaccination compared with lay population (12). Because HCWs are the most important sources of information and the strongest authority when it comes to vaccination decisions (13-15), their opinions and vaccination intentions should be assessed, and the relation between key sociodemographic factors and vaccination intentions should be investigated.Due to the importance of HCWs'' vaccination uptake during the COVID-19 pandemic in Central and Eastern Europe, this study analyzed HCWs'' vaccination acceptance in Croatia, Slovenia, Serbia, and Poland in relation to their knowledge about COVID-19. Based on the findings of previous research on influenza vaccination uptake (17), we hypothesized that the countries would significantly differ in COVID-19 vaccination intention and acceptance among HCWs and that vaccination acceptance would be influenced by gender, education, knowledge, and attitudes.     

Increasing prevalence of breast cancer among Saudi patients attending a tertiary referral hospital: a retrospective epidemiologic study

Aim

To determine the pattern of breast diseases among Saudi patients who underwent breast biopsy, with special emphasis on breast carcinoma.

Methods

A retrospective review was made of all breast biopsy reports of a mass or lump from male and female patients seen between January 2001 and December 2010 at the King Khalid University Hospital, Riyadh, Saudi Arabia.

Results

Of 1035 breast tissues reviewed, 939 specimens (90.7%) were from female patients. There were 690 benign (65.8%) and 345 (34.2%) malignant cases. In women, 603 (64.2%) specimens were benign and 336 (35.8%) were malignant. In men, 87 specimens (90.6%) were benign and 9 (9.4%) were malignant. All malignant cases from male patients belonged to invasive ductal carcinoma and the majority of malignant cases from female patients belonged to invasive/infiltrating ductal carcinoma. The proportion of malignancy was 18% in patients younger than 40 years and 63.2% in patients older than 60 years. The mean age of onset for malignancy was 48.6 years. The annual percentage incidence of malignant breast cancer steadily increased by 4.8%, from an annual rate of 23.5% in 2000 to 47.2% in 2007.

Conclusion

Among Saudi patients, there is a significant increase in the incidence of breast cancer, which occurs at an earlier age than in western countries. Continued vigilance, mammographic screening, and patient education are needed to establish early diagnosis and perform optimal treatment.Increased awareness and efficient breast cancer information-dissemination campaign led to an increased number of diagnosed cases of breast cancer. According to the American Cancer Society, about 1.3 million American women annually are diagnosed with breast cancer and about 465 000 die from the disease (1). The number of deaths has decreased since 1990, probably due to an earlier detection and advances in treatment. According to 2000-2004 Saudi National Cancer Registry data, there were 127.8 per 100 000 women with breast cancer and mortality rate was 25.5 per 100 000 (2).Most palpable breast masses are benign; less than 30% of women with palpable masses have a diagnosis of cancer (3-5). Approximately 4% of breast cancers present with a palpable mass without mammographic or ultrasonographic evidence of the disease (6). Therefore, evaluation of a breast mass should be done by taking into consideration patient’s history, physical examination, imaging, and biopsy. Definitive diagnosis in nearly all cases is established by needle biopsy. Because of the low specificity of mammography, many women undergo unnecessary breast biopsy. As many as 65%-85% of breast biopsies are performed on benign lesions (7), which subjects the patients to avoidable emotional and physical burden.Similarly to other countries, breast cancer in Saudi Arabia is the most common cancer in women (7). The Saudi National Cancer Registry reported a rising proportion of breast cancer among women of all ages, from 10.2% in 2000 to 24.3% in 2005 (8). A significant majority of these breast cancers (almost 80%) were of the infiltrating ductal type. The average age at presentation of breast cancer in Arab countries is 48 years, which is a decade earlier than in western countries (9). The median age of onset of breast cancer among Saudi women is 46 years (8). Due to the increasing incidence, several articles have been published on screening for breast cancer and on public awareness programs initiated by the Saudi Arabian government and non-governmental sectors (10-13). This study aims to describe the epidemiological characteristics of breast mass lesions of patients examined at the King Khalid University Hospital, Riyadh, Saudi Arabia from 2001 to 2010.     

Prognostic value of serum nicotinamide phosphoribosyltransferase in patients with bladder cancer

Aim

To analyze the serum nicotinamide phosphoribosyltransferase (Nampt) level and its prognostic value in bladder cancer (BC).

Methods

The study included 131 patients with transitional cell BC and 109 healthy controls from the West China Hospital of Sichuan University in the period between 2007 and 2013. Nampt concentration in serum was measured by commercial ELISA kits for human Nampt.

Results

The serum Nampt protein level in patients with BC (mean ± standard deviation, 16.02 ± 7.95 ng/mL) was significantly higher than in the control group (6.46 ± 2.08 ng/mL) (P < 0.001). Serum Nampt level was an independent prognostic marker of non-muscle-invasive BC, with a higher serum Nampt level (>14.74 ng/mL) indicating shorter recurrence-free survival rate (hazard ratio = 2.85, 95% confidence interval, 1.01-8.06; P = 0.048).

Conclusion

Our results suggest that serum Nampt level may serve as a biomarker of BC and an independent prognostic marker of non-muscle-invasive BC.Bladder cancer (BC) is the ninth most common cancer diagnosis worldwide (1) and the most expensive cancer to treat (2). Among men it is the fourth most common cancer, with incidence four times higher than in women (3). In China, BC caused 17 365 deaths in 2005, with a steady increase in mortality between 1991 and 2005 (4). Of newly diagnosed BC cases, 70%-80% will present with non-muscle-invasive disease, 50%-70% will recur despite endoscopic and intravesical treatments, and 10%-30% will progress to muscle-invasive disease (5,6). Most recurrences occur within 5 years (7). Therefore, to develop improved, more effective prevention and treatments there is a need to find new biomarkers of tumorigenesis and prognosis of BC.Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the mammalian NAD⁺ biosynthesis of a salvage pathway (8). Previous studies have shown that it is significantly increased in primary colorectal cancer (9-11), lung cancer (12), breast cancer (13), prostate cancer (14) and gastric cancer (15). Thus, Nampt may be a good biomarker of malignant potential and stage progression (12,16). Our previous study revealed that genetic variants in NAMPT may predict BC risk and prognosis (17). In the present study, we analyzed the serum Nampt level and its prognostic value in BC.     

Levels of self-reported depression and anxiety among HIV-positive patients in Albania: a cross-sectional study

Aim

To gain an initial perspective of mental health issues facing the Human Immunodeficiency Virus (HIV)-positive population at the University Hospital Center of Tirana (UHCT) HIV/AIDS Ambulatory Clinic.

Methods

From June-August 2009, we conducted semi-structured interviews with 79 patients (93% response rate) at the UHCT HIV/AIDS Ambulatory Clinic. The interviews assessed patient-reported histories of mental health diagnoses, patients’ demographics, and current emotional health status.

Results

The percentage of patients who reported a history of diagnosis of depression or anxiety was high – 62.3% and 82.3%, respectively. Factors associated with a history of depression included having been diagnosed with anxiety (P < 0.001), having a higher number of barriers to care (P < 0.001), having a higher number of current medical and social needs (P < 0.001), or having not obtained antiretroviral therapy (ART) abroad (P = 0.004). Factors associated with a history of anxiety included having been on first-line ART (P = 0.008), having been diagnosed with HIV for shorter periods of time (P = 0.043), having been diagnosed with depression (P < 0.001), having a higher number of current medical and social needs (P = 0.035), or having not obtained ART abroad (P = 0.003).

Conclusions

Mental health problems are widespread among the known HIV-positive patient population in Albania. The high prevalences of anxiety and depression and of dual diagnoses of these conditions suggest the need for more mental health care for HIV-positive patients in Albania.Mental health is one of the co-morbidities that is often overlooked in treating patients for Acquired Immune Deficiency Syndrome from Human Immunodeficiency Virus (HIV/AIDS) (1-3). In particular, the rates of depression and anxiety are higher than those in the general population (1-6). Depression is second only to substance abuse as the most prevalent psychiatric disorder among HIV-positive patients (5). In the context of HIV/AIDS, depression has also been shown to lead to more social isolation, lower antiretroviral medication adherence, and faster progression to AIDS (7-14). Anxiety, especially among those that have recently been diagnosed with HIV, has been shown to be more prevalent among patients with stress or excess social stigma related to their diagnosis (15-17). Anxiety can also correlate with lower adherence to antiretroviral therapy (ART) and medical recommendations (18,19).With mental health issues affecting medical treatment of HIV, mechanisms to reduce their burden among HIV-positive patients have been explored. Treatment of depression has been shown to improve adherence to ART along with the quality of life for HIV-positive patients (5,20,21). Community-based group therapy has also been shown to decrease psychiatric symptoms in HIV-positive patients or in regions with high prevalence of HIV, while treatment with ART may reduce both anxiety and depression (22,23). However, with all the advances in the field of mental health, there is still a paucity of data from developing countries (especially Eastern and Central Europe) on the relationship between HIV/AIDS and mental health (18).With the growing epidemic of HIV in Eastern Europe and possible spread to South Eastern Europe, an understanding of the mental health issues facing HIV-positive patients will be vital for the improvement of medical services and treatment for HIV (18,24-29). This is especially true in countries that have only recently initiated psychological services for HIV positive patients. Albania, which boasts a low prevalence of HIV, is one such country that initiated psychological services soon after the introduction of ART in 2004 (30,31). High levels of risky behavioral patterns (including low condom usage and high rates of needle sharing among injection drug users), the recent sociopolitical changes, and the under-resourced prevention and surveillance capabilities, have placed the Albanian population at risk for a rising local HIV epidemic (30-34). In fact, previous studies have suggested that the prevalence of HIV in Albania may be 150-fold the current Ministry of Health estimate (35,36). Thus, an initial patient-driven assessment of the mental health issues of patients under HIV/AIDS medical care in Albania is warranted. In this study, we examined the prevalence of HIV-positive patients’ self-reported histories of mental health diagnoses in Albania. This study also examined effects of ART on mental health and associations with depression and anxiety.     

Emotion work and burnout: cross-sectional study of nurses and physicians in Hungary

Aim

To investigate predictors of occupational burnout, such as emotion work, among health care workers and compare the frequencies of burnout and emotion work in nurses and physicians.

Method

A cross-sectional survey was conducted in 2007 and 2008 among 80 physicians and 76 nurses working in a variety of health care settings in Hungary. The survey contained sociodemographic questions and work- and health-related questions from, respectively, the Maslach Burnout Inventory-Human Services Survey and the Hungarian version of the Frankfurt Emotion Work Scale. To identify the dimensions of emotion work associated with burnout, linear regression analyses were carried out. To analyze differences in burnout and emotion work between nurses and physicians, independent t tests were used.

Results

Nurses reported significantly higher emotional dissonance and fewer regulation possibilities, such as interaction and emotion control, than physicians. However, no differences were found in the level or frequency of burnout. Nurses had fewer regulation requirements regarding sensitivity and sympathy. Linear regression analyses showed that emotional dissonance for emotional exhaustion (β = 0.401) and display of negative emotions for depersonalization (β = 0.332) were the strongest predictors of burnout.

Conclusion

The factors that should be taken into account when developing prevention and intervention programs differ for nurses and physicians. In nurses, the focus should be on stressors and emotional dissonance, while in physicians it should be on work requirements and display and regulation of negative emotions.During the last decade, the topic of emotion work has gained a much greater significance in organizational and health psychology. As defined by Zapf et al, emotion work occurs when employees are required by the employer to regulate their emotions in order to display appropriate emotions to the client (1). Emotion work determines the quality of social interaction between the caregiver and client. Action theory distinguishes 3 aspects of emotion work requirements: regulation requirements, regulation possibilities, and regulation problems. Regulation requirements (display of emotions) are related to properties of the hierarchical-sequential organization of action and constitute the complexity of decision. Regulation possibilities refer to the concept of control. Regulation problems, also known as emotional dissonance, are the discord between felt and expressed emotions and occur when stressors disturb the regulation of action (1,2). Current burnout research is greatly facilitated by theories explaining work stress (3-6). Using Karasek’s job demands control model, the research group of LeBlanc and DeJonge investigated emotional job demands (3-5). It was also found that health care workers are at high risk for emotional exhaustion resulting from interaction with clients (6,7).Burnout is a syndrome of emotional exhaustion, depersonalization, and reduced personal accomplishment occurring in people-oriented and service work (8). Emotional exhaustion refers to feelings of being depleted of one’s emotional resources. Depersonalization is a negative and cynical attitude and behavior toward clients. Reduced personal accomplishment is the self-perception of a decline in one’s own competence and self-efficacy. Burnout has most often been studied in caregiving professionals, such as clinicians, psychologists, social workers, and nurses (9-17). Indeed, several studies have directly measured the emotional aspects of job demands dealing either with emotion work (18-20) or burnout (21-24). However, few studies investigating the relationship between burnout and emotion work have been conducted in the nursing and health care profession, particularly in Hungary and Eastern Europe (25). The differences in burnout and emotion work between nurses and physicians have been studied in the Netherlands, Germany, and Spain (3-5,14,26). Some studies have suggested that physicians experience more burnout than nurses (14,16), while others have suggested the opposite (17).Recently, burnout has been conceptualized as a psychological syndrome that takes place in response to chronic interpersonal stressors on the job (6). According to Zapf, burnout makes individuals no longer able to adequately manage their emotions while interacting with clients (27). According to the model of emotion work by Grandey (28), antecedents of emotion regulation are the situational variables, eg, interaction between the caregiver and client.A relationship between burnout and emotion work has recently been found in the health care setting in Western European countries (3,4,29-31). Health care professionals, especially nurses, are at high risk of burnout because their job requires a high level of emotion work (18-20,32,33). Most studies have found a positive relationship between emotion work and burnout, suggesting that emotional dissonance may predict emotional exhaustion and depersonalization (25,34). Demerouti (35) argues that contribution of job demands and resources to explaining burnout may vary across occupations because these features differ across occupations. Burnout literature usually focuses on general variables that predict burnout and does not distinguish between predictors across health professions (6,8). Thus, we hypothesized that differences in emotion work can be detected between nurses and physicians, although the predictors of the syndrome do not vary.This study assesses the relationships between burnout and emotion work in a sample of Hungarian health care professionals and investigates how emotional job demands relate to the frequency of burnout.     

The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats

Aim

To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity.

Methods

Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α₂-adrenoreceptor agonist), yohimbine (α₂-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine.

Results

Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepam-induced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity.

Conclusion

The results suggest that α₂-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity.Benzodiazepines are used for their anxiolytic, sedative-hypnotic, muscle relaxant, and anticonvulsant properties in the treatment of a variety of neuropsychiatric disorders (1,2), including anxiety and depression, which are often related to disturbances in the activity of hypothalamic-pituitary-adrenal (HPA) axis (3,4). Although these drugs exert most of their pharmacological effects via γ-aminobutyric acid_A (GABA_A) receptors (5,6), benzodiazepine administration has been associated with alterations in neuroendocrine function both in experimental animals and humans (7-9). However, even after years of extensive studies, the complex mechanisms by which these widely used drugs produce their effects on the HPA axis are still not known.Although most of the previous studies have demonstrated that classical benzodiazepines such as diazepam decrease the HPA axis activity in stressful contexts (10-14), under basal conditions they have been shown to stimulate (9,11,15-18), inhibit (15,19-22), and not affect (17,23-25) the HPA axis activity. Such diverse results might be related to several factors such as the dose and gender (15,16,20,21,26-28), or may also be a consequence of the net effect of non-selective benzodiazepines on the various GABA_A receptor isoforms (9).Our previous studies demonstrated that while diazepam (1 mg/kg) produced no change in plasma corticosterone levels in male rats (15,20), it decreased basal levels of corticosterone in female rats (15,26). However, although diazepam inhibited the HPA axis activity of female rats following administration of lower doses (1 or 2 mg/kg) (15,20,21,26), it stimulated the HPA axis activity following administration of high doses (10 mg/kg) (15,16,26). Moreover, whereas the suppressive effect of the lower doses of diazepam (2.0 mg/kg) on the HPA axis activity in female rats involves the GABA_A receptor complex (21), increases in corticosterone levels by a higher dose of diazepam (10 mg/kg) do not involve the stimulation of GABA_A receptors (16). In addition, stimulatory effect of 10 mg/kg diazepam on the HPA axis activity in rats seems not to be mediated by the benzodiazepine/GABA/channel chloride complex or by peripheral benzodiazepine receptors, but rather by a cyclic adenosine monophosphate (AMP)-dependent mechanism (18).Since our previous results suggested that the effect of a high dose of diazepam on the activity of the HPA axis in female rats might be due to a blockade of α₂-adrenergic receptors (16), the aim of this study was to elucidate whether noradrenergic system also has a modulatory role in the inhibitory effect of 2.0 mg/kg diazepam on basal plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in female rats.     

Can laboratory evaluation differentiate between coronavirus disease-2019, influenza,and respiratory syncytial virus infections? A retrospective cohort study

AimTo identify clinical and laboratory parameters that can assist in the differential diagnosis of coronavirus disease 2019 (COVID-19), influenza, and respiratory syncytial virus (RSV) infections.MethodsIn this retrospective cohort study, we obtained basic demographics and laboratory data from all 685 hospitalized patients confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus, or RSV from 2018 to 2020. A multiple logistic regression was employed to investigate the relationship between COVID-19 and laboratory parameters.ResultsSARS-CoV-2 patients were significantly younger than RSV (P = 0.001) and influenza virus (P = 0.022) patients. SARS-CoV-2 patients also displayed a significant male predominance over influenza virus patients (P = 0.047). They also had significantly lower white blood cell count (median 6.3 × 10⁶ cells/μ) compared with influenza virus (P < 0.001) and RSV (P = 0.001) patients. Differences were also observed in other laboratory values but were insignificant in a multivariate analysis.ConclusionsMale sex, younger age, and low white blood cell count can assist in the diagnosis of COVID-19 over other viral infections. However, the differences between the groups were not substantial enough and would probably not suffice to distinguish between the viral illnesses in the emergency department.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus causing coronavirus disease 2019 (COVID-19). First identified in the Chinese province of Hubei in late 2019, COVID-19 was declared a global pandemic by the World Health Organization in March 2020 (1).As of July 2021, there were more than 180 million confirmed COVID-19 cases and more than four million patients who died due to the disease complications (2). Moreover, the disease caused a substantial economic and social burden (3), and affected health care quality (4-7).The diagnosis of COVID-19 is currently determined primarily by molecular methods and antigen tests (8,9). Radiographic diagnosis is possible as well (10,11). This practice often consumes valuable time and expensive equipment (12). There is a growing need to accelerate the diagnostic process by enabling point-of care diagnosis in various ambulatory settings, while keeping it accurate to ensure the necessary precautionary measures (13).The clinical presentation of SARS-CoV-2 infection resembles that of other respiratory viruses, with predominant symptoms of fever, cough, fatigue, and dyspnea (14-17). Hematological abnormalities, including leukopenia, lymphopenia, and thrombocytopenia, are common among COVID-19 patients, as well as elevated levels of C-reactive protein (CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and ferritin (14,15,18-21). Some of these inflammatory markers correlated with disease severity and mortality (22,23).The influenza season of 2021 in the Northern hemisphere was relatively weak in contrast with predictions. Low to zero rates of influenza were detected in several countries. This was attributed to social distancing, masks wearing, and a reduced number of air travelers (24). Despite a growing number of vaccinated individuals (25), the emergence of new SARS-CoV-2 variants suggest that COVID-19 is here to stay. Seasonal viruses such as influenza virus and respiratory syncytial virus (RSV) could rebound in the following winter, with the loosening of restrictions.Differentiating between COVID-19 and other respiratory viral illnesses on clinical grounds alone can be very challenging. These viral infections share similarities in the transmission route and symptoms (26-28). Several small studies attempted to delineate the differences in the clinical presentation of SARS-CoV-2 and influenza infections (29-31). In this study, we aimed to identify demographic and laboratory parameters that can assist in the early differentiation between SARS-CoV-2, influenza, and RSV infections in the emergency department.     

Adverse drug reactions caused by drug-drug interactions reported to Croatian Agency for Medicinal Products and Medical Devices: a retrospective observational study

Aim

To analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence.

Methods

In this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them.

Results

HALMED received 1209 reports involving at least two drugs. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n = 4) was significantly higher (P < 0.001) than among the remaining reports (580 out of 1982; n = 2, respectively). Actual drug-drug interactions most frequently involved nervous system agents (34.0%), and interactions caused by antiplatelet, anticoagulant, and non-steroidal anti-inflammatory drugs were in most cases serious. In only 12 out of 94 reports, actual drug-drug interactions were recognized by the reporter.

Conclusion

The study confirmed that the Spontaneous Reporting Database was a valuable resource for detecting actual drug-drug interactions. Also, it identified drugs leading to serious adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education.Adverse drug reactions (ADR) are among the leading causes of mortality and morbidity responsible for causing additional complications (1,2) and longer hospital stays. Magnitude of ADRs and the burden they place on health care system are considerable (3-6) yet preventable public health problems (7) if we take into consideration that an important cause of ADRs are drug-drug interactions (8,9). Although there is a substantial body of literature on ADRs caused by drug-drug interactions, it is difficult to accurately estimate their incidence, mainly because of different study designs, populations, frequency measures, and classification systems (10-15).Many studies including different groups of patients found the percentage of potential drug-drug interactions resulting in ADRs to be from 0%-60% (10,11,16-25). System analysis of ADRs showed that drug-drug interactions represented 3%-5% of all in-hospital medication errors (3). The most endangered groups were elderly and polimedicated patients (22,26-28), and emergency department visits were a frequent result (29). Although the overall incidence of ADRs caused by drug-drug interactions is modest (11-13,15,29,30), they are severe and in most cases lead to hospitalization (31,32).Potential drug-drug interactions are defined on the basis of on retrospective chart reviews and actual drug-drug interactions are defined on the basis of clinical evidence, ie, they are confirmed by laboratory tests or symptoms (33). The frequency of potential interactions is higher than that of actual interactions, resulting in large discrepancies among study findings (24).A valuable resource for detecting drug-drug interactions is a spontaneous reporting database (15,34). It currently uses several methods to detect possible drug-drug interactions (15,29,35,36). However, drug-drug interactions in general are rarely reported and information about the ADRs due to drug-drug interactions is usually lacking.The aim of this study was to estimate the incidence of actual and potential drug-drug interactions in the national Spontaneous Reporting Database of ADRs in Croatia. Additionally, we assessed the clinical significance and seriousness of drug-drug interactions and their probable mechanism of action.