Parental involvement in the war in Croatia 1991-1995 and suicidality in Croatian male adolescents

Aim

To investigate the association between parental war involvement and different indicators of psychosocial distress in a community sample of early adolescents ten years after the war in Croatia 1991-1995.

Methods

A total of 695 adolescents were screened with a self-report questionnaire assessing parental war involvement, sociodemographic characteristics, and alcohol and drug consumption. Personality traits were assessed with the Junior Eysenck Personality Questionnaire; depressive symptoms with the Children’s Depression Inventory (CDI); and unintentional injuries, physical fighting, and bullying with the World Health Organization survey Health Behavior in School-aged Children. Suicidal ideation was assessed with three dichotomous items. Suicidal attempts were assessed with one dichotomous item.

Results

Out of 348 boys and 347 girls who were included in the analysis, 57.7% had at least one veteran parent. Male children of war veterans had higher rates of unintentional injuries (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.56 to 2.63) and more frequent affirmative responses across the full suicidal spectrum (thoughts about death – OR, 2.1; 95% CI, 1.02 to 4.3; thoughts about suicide – OR, 5; 95% CI, 1.72 to 14.66; suicide attempts – OR, 3.6; 95% CI, 1.03 to 12.67). In boys, thoughts about suicide and unintentional injuries were associated with parental war involvement even after logistic regression. However, girls were less likely to be affected by parental war involvement, and only exhibited signs of psychopathology on the CDI total score.

Conclusion

Parental war involvement was associated with negative psychosocial sequels for male children. This relationship is possibly mediated by some kind of identification or secondary traumatization. Suicidality and unintentional injuries are nonspecific markers for a broad range of psychosocial distresses, which is why the suggested target group for preventive interventions should be veteran parents as vectors of this distress.War represents a major stressor that can have long-lasting adverse influences on mental health (1). Milliken et al showed that upon the return from the Iraq war 42.7% of US combat veterans required mental health treatment (2). Most frequent psychopathological consequences of combat exposure are posttraumatic stress disorder (PTSD), anxiety, depression, and psychosomatic complaints (3,4). During the war in Croatia 1991-1995, more than 300,000 people were recruited to army service (5). Among Croatian war veterans, one of the most prevalent psychiatric diagnoses and the most common disorder comorbid with PTSD is depression (6-8). Veterans’ psychological distress inevitably impacts those with whom they interact (9). In fact, there is an association between psychopathological disturbances and a reduced effectiveness in parenting, perhaps because of veterans’ disrupted social functioning, emotional withdrawal, and decreased desire to interact with the children (9-11). Data on the influence of combat-related depression are scarce. Nonetheless, there is a significant body of evidence suggesting that “civilian” depression may negatively influence parenting behaviors (12,13) and that maternal mental health status following war affects children''s adjustment (14). Further, psychological disturbances in war veterans could have a negative horizontal impact on their wives (15,16), and even a long-lasting vertical influence on children and further generations (17,18). Since psychiatric disorders associated with war exposure are categorical and not dimensional (19), it is possible that even more veterans exhibit non-specific, sub-threshold psychological problems, which could negatively impact their social, familial, and parenting roles. In addition to the direct individual consequences, soldiers’ absence during deployment might exert negative influence on the structural stability of the community, which is critical for the welfare of youth because it produces consistency and continuity in social relationships. Thus, structural stability helps build trust, enhances social support, and facilitates social control through commitment to community values and norms (20). War also creates a situation of social-norm disintegration, leading to social anomie and an increase in suicidal phenomena (21), which was of particular interest for this investigation. The aim of this study was to explore the association between parental war involvement and mental health problems in children, including depression, risky behaviors, sleep related problems, and suicidal ideation and attempts.     

Association between total serum cholesterol and depression,aggression, and suicidal ideations in war veterans with posttraumatic stress disorder: a cross-sectional study

Aim

To investigate the relationship between total serum cholesterol and levels of depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder (PTSD) without psychiatric comorbidity.

Methods

A total of 203 male PTSD outpatients were assessed for the presence of depression, aggression, and suicidality using the 17-item Hamilton Depression Rating Scale (HAM-D₁₇), Corrigan Agitated Behavior Scale (CABS), and Scale for Suicide Ideation (SSI), respectively, followed by plasma lipid parameters determination (total cholesterol, high density lipoprotein [HDL]-cholesterol, low density lipoprotein [LDL]-cholesterol, and triglycerides). PTSD severity was assessed using the Clinician-Administered PTSD Scale for DSM-IV, Current and Lifetime Diagnostic Version (CAPS-DX) and the Clinical Global Impressions of Severity Scale (CGI-S), before which Mini-International Neuropsychiatric Interview (MINI) was administered to exclude psychiatric comorbidity and premorbidity.

Results

After adjustments for PTSD severity, age, body mass index, marital status, educational level, employment status, use of particular antidepressants, and other lipid parameters (LDL- and HDL- cholesterol and triglycerides), higher total cholesterol was significantly associated with lower odds for having higher suicidal ideation (SSI≥20) (odds ratio [OR] 0.09; 95% confidence interval [CI] 0.03-0.23], clinically significant aggression (CABS≥22) (OR 0.28; 95% CI 0.14-0.59), and at least moderate depressive symptoms (HAM-D₁₇≥17) (OR 0.20; 95% CI 0.08-0.48). Association of total cholesterol and HAM-D₁₇ scores was significantly moderated by the severity of PTSD symptoms (P < 0.001).

Conclusion

Our results indicate that higher total serum cholesterol is associated with lower scores on HAM-D₁₇, CABS, and SSI in patients with chronic PTSD.Posttraumatic stress disorder (PTSD) is one of the few mental disorders with a clearly identifiable cause. It is an anxiety disorder caused by exposure to a traumatic event that presented a threat to the physical integrity of persons themselves or other people in their surroundings (1). Key neurochemical PTSD features include altered catecholamines regulation, alterations in serotonergic system, and alterations in systems of aminoacids, peptides, and opioid neurotransmitters (2).Associations between serum lipids and various psychiatric disorders and some behavioral aspects (like aggressive behavior) and/or suicidality have been widely explored. Lower total cholesterol levels were predominantly found in patients with major depressive disorder (MDD) (3-9). Significantly higher high-density lipoprotein cholesterol (HDL-cholesterol) levels were found in depressive patients than in controls (7). Some studies found significantly lower HDL-cholesterol levels (10) and a lower HDL-cholesterol/total cholesterol ratio (5) in patients with MDD than in controls.A negative correlation (11-13) between serum cholesterol level and aggressive behavior was also found, confirming the cholesterol-serotonergic hypothesis of aggression (14,15). Inadequate cholesterol intake could lead to decreased central serotonin activity, which is associated with an increased risk for impulsive-aggressive behavior (14-18). Depression (19-21) and aggression are well-known suicidality risk factors (15,22).The correlation between hypocholesterolemia, decreased central serotonin activity, increased depressive potential, and increased suicidality risk (23-27) was confirmed, implicating that hypocholesterolemia might be indirectly, ie, through decreased central serotonin activity and increased depression potential (20,25,28), associated with an increased suicidality risk (15,19-24,26,27). In patients with anxiety disorders other than PTSD, like panic disorder (PD), lower HDL-cholesterol and higher very low density lipoprotein cholesterol (VLDL-cholesterol) levels were found to be associated with higher suicide ideations/risk (29). Significantly lower serum total cholesterol and LDL cholesterol levels were found in suicidal patients with PD than in control subjects (30).Hypercholesterolemia was found to be associated with chronic, war-related PTSD (31-34). In a study from Bosnia and Herzegovina, not only hypercholesterolemia but also increased VLDL- and HDL-cholesterol levels were found in war veterans with PTSD in comparison with war veterans without psychiatric disorders (35). A Croatian study found no significant differences in the total serum cholesterol level, LDL-, and HDL-cholesterol between war veterans with PTSD, war veterans without PTSD, and healthy volunteers (36).The aim of this study was to investigate the relationship between serum cholesterol and levels of depression, aggression, and suicidal ideations in war veterans with PTSD free of other psychiatric premorbidity and comorbidity.     

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.     

The prevalence of domestic violence in primary care patients in Slovenia in a five-year period (2005-2009)

Aim

To estimate the prevalence of exposure to domestic violence in primary care patients in Slovenia and determine the associated factors.

Methods

In a systematic cross-sectional survey, 70 physicians from 70 family medicine practices from urban and rural settings conducted interviews with every fifth patient from January 15 to February 15, 2010.

Results

Of 2075 patients (98.8% response rate), 372 (17.9%) were exposed to psychological or physical violence in the family in the last five years. Factors that increased the chances of exposure to psychological and physical violence were female sex (odds ratio [OR], 3.27; 95% confidence interval [CI], 2.24-4.76; P < 0.001; OR, 4.52; 95% CI, 2.83-7.20; P < 0.001, respectively) and formal divorce (OR, 2.08; 95% CI, 1.35-3.21; P = 0.001; OR, 2.72; 95% CI, 1.73-4.29; P < 0.001, respectively). Factors that decreased the chances of exposure to psychological violence were age of 65 years or above (OR, 0.56; 95% CI, 0.33-0.96, P = 0.035) and single status (OR, 0.43; 95% CI 0.21-0.86, P = 0.016), while age of 65 years or above (OR, 0.43; 95% CI, 0.23-0.79, P = 0.007) and parenting of two children (OR, 0.51; 95% CI, 0.29-0.90, P = 0.020) decreased the chances of exposure to physical violence.

Conclusions

We found the rate of exposure to psychological and physical violence of 17.9%, which indicates that this problem is a serious public health issue that needs to be addressed by adequate measures. The identified risk and protective factors could serve as a valid guidance for family physicians dealing with physical violence.Domestic violence is a serious health issue, with consequences ranging from physical impairments to psychological symptoms, physical trauma, and death (1-3). Its prevalence is between 5% and 30% (4-6), and about 90% of the perpetrators are family members (1). The exposure to violence inevitably leads to more frequent use of health services, while unrecognized causes of health problems in victims of violence can lead to unnecessary consultations, unwarranted diagnostic procedures, and ineffective health care (5-10). Health services often miss the opportunity to prevent violence (11), probably because victims hesitate to disclose it and medical health providers hesitate to ask about it, even if a number of guidelines and recommendations has been published (12-17). A meta-analysis (18) has showed that 63% of female patients in primary health care would approve of screening on domestic violence, and the percentage is even higher among those who have experienced violence (18). However, despite the recommendations of professional organizations, only 10% of physicians actively ask their patients about violence (19). The aim of the study was to estimate the prevalence of domestic violence in family care settings in Slovenia and to identify the factors influencing it.     

Prevalence of erectile and ejaculatory difficulties among men in Croatia

Aim

To determine the prevalence and risk factors of erectile difficulties and rapid ejaculation in men in Croatia.

Method

We surveyed 615 of 888 contacted men aged 35-84 years. The mean age of participants was 54 ± 12 years. College-educated respondents and the respondents from large cities were slightly overrepresented in the sample. Structured face-to-face interviews were conducted in June and July 2004 by 63 trained interviewers. The questionnaire used in interviews was created for commercial purposes and had not been validated before.

Results

Out of 615 men who were sexually active in the preceding month and gave the valid answers to the questions on erectile difficulties and rapid ejaculation, 130 suffered from erectile or ejaculatory difficulties. Men who had been sexually active the month before the interview and gave the valid answers to the questions on sexual difficulties reported having erectile difficulties more often (77 out of 615) than rapid ejaculation (57 out of 601). Additional 26.8% (165 out of 615) and 26.3% (158 out of 601) men were classified as being at risk for erectile difficulties and rapid ejaculation, respectively. The prevalence of erectile difficulties varied from 5.8% in the 35-39 age group to 30% in the 70-79 age group. The association between age and rapid ejaculation was curvilinear, ie, U-shaped. Rates of rapid ejaculation were highest in the youngest (15.7%) and the oldest (12.5%) age groups. Older age (odds ratios [OR], 6.2-10.3), overweight (OR, 3.3-4.2), alcohol (OR, 0.3-0.4), intense physical activity (OR, 0.3), traditional attitudes about sexuality (OR, 2.8), and discussing sex with one’s partner (OR, 0.1-0.3) were associated with erectile difficulties. Education (OR, 0.1-0.3), being overweight (OR, 22.0) or obese (OR, 20.1), alcohol consumption (OR, 0.2-0.3), stress and anxiety (OR, 10.8-12.5), holding traditional attitudes (OR, 2.8) and moderate physical activity (OR, 0.1) were factors associated with rapid ejaculation.

Conclusion

The prevalence of erectile difficulties was higher than the prevalence of rapid ejaculation in men in Croatia. The odds of having these sexual difficulties increased with older age, overweight, traditional attitudes toward sex, and higher level of stress and anxiety.A growing number of international studies on sexual health issues suggest that many women and men worldwide have sexual health problems (1-4). According to surveys based on community samples, the prevalence of male sex disturbances ranges between 10% and 50% (2,4). The most frequent male sexual disturbance seems to be premature or rapid ejaculation (5,6), reported to range from 4% to 29% (6). The Global Study of Sexual Attitudes and Behaviors estimated the prevalence of rapid ejaculation at approximately 30% across all age groups (7). Actually, it seems to be the most common of all male sexual disturbances (5-9). However, when objective definition of rapid ejaculation is attempted, problems arise (9,10). According to the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), rapid ejaculation is a persistent or recurrent onset of orgasm and ejaculation with minimal sexual stimulation before, upon, or shortly after penetration and before the person wishes it (11). It results in pronounced distress or interpersonal difficulties and is not exclusively due to the direct effects of a substance used (11). Although useful for clinical practice, this definition does not offer precise guidelines for epidemiological research. As indicated by large discrepancies in the prevalence rates (6), epidemiological analyses of rapid ejaculation are characterized by definition and measurement inconsistencies (1,10,12).In spite of the lack of agreement as to what constitutes rapid ejaculation (12) and the fact that it is not a well-understood problem (5,13), the consequences are well known. Chronic rapid ejaculation is accompanied by an array of psychological problems, including a psychogenic erectile dysfunction (14). Rapid ejaculation can seriously burden interpersonal dynamics and decrease sexual satisfaction (15) and sometimes the overall quality of intimate relationship (16,17). In addition to frustrations, withdrawal (including the lack of desire and cessation of sexual contacts), and strained relationship, rapid ejaculation causes changes in self-image and one’s sense of masculinity. It has been shown that rapid ejaculation has similar psychological impact as erectile problems, especially in terms of self-confidence and worries over the relationship, both the present and the future ones (14).Psychologically and culturally, erectile difficulties are the most dreaded male sexual problem (16,18,19), which not only result in deep frustration, but often lead to a crisis of masculine identity (19). Recent pharmacological breakthrough has initiated a rapid growth of interest in the epidemiology of erectile difficulties. Current studies suggest that a sizeable proportion of adult men suffer from erectile difficulties and that the likelihood of erectile difficulties increases with age (1-4). According to a recently published systematic review, the prevalence of erectile difficulties ranges from 2% in men younger than 40 years to over 80% in men aged 80 years or more (4). Due to the aging of population, the number of men with erectile difficulties is expected to be rising (20,21). The projection based on the results of the Massachusetts Male Aging Study (MMAS) from 1995 is that the number of men with the condition will more than double by 2025 (22).How do we explain considerable variations in reported prevalence rates of erectile difficulties? Methodological and conceptual differences between the studies (1,3,4,23) seem to be the main reason, although the effect of culture-specific perception of sexual problems should not be underestimated (24). In spite of a large number of population or community sample studies (18,20,25-38), inconsistent definitions and operationalization seriously hamper the analysis of the role of culture in perception and reporting of erectile difficulties in men.In transitional countries, sexual health is a rather neglected research area. The main reason for that is the lack of education and research training of possible investigators in the field of sexology. In Croatia, sexual health issues have only recently gained attention as a topic worthy of clinical (39) and non-clinical research (40,41). Our aim was to determine the prevalence of and risk factors for erectile difficulties and rapid ejaculation in a national sample of Croatian men.     

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.     

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.     

Body mass index and nutrition as determinants of health and disease in population of Croatian Adriatic islands

Aim

To investigate the relationships between body mass index (BMI), dietary habits, and cardiovascular risk factors in isolated Adriatic island populations of Croatia.

Methods

Random sample of subjects (n = 1001) was interviewed, using a validated questionnaire developed for this research program. Dietary habits were assessed on the basis of applied Food Frequency Questionnaire (FFQ). Biochemical analyses of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, and blood glucose were performed. Blood pressure (mm Hg), height (m), and weight (kg) were measured following standard procedures.

Results

Out of 1001 study participants, 507 (50.7%) were overweight (247 [48.7%] men and 260 [51.3%] women), whereas 268 (26.8%) were obese (122 [45.5%] men and 146 [54.5%] women). In both genders, there was a positive correlation between body mass index (BMI) and levels of triglycerides (P<0.001), glucose (P<0.001), diastolic blood pressure (P<0.001), and systolic blood pressure (male: P = 0.002, female: P<0.001). Logistic regression showed that female gender (OR, 2.31; 95% CI, 1.61-3.31), overweight (OR, 1.97; 95% CI, 1.34-2.88), obesity (OR, 1.90; 95% CI, 1.22-2.96), more frequent consumption of meat (OR 1.17; 95% CI, 1.06-1.30) and beer (OR 1.14; 95% CI, 1.03-1.27), and less frequent consumption of potatoes (OR 0.91; 95% CI, 0.83-0.99) were predictive for the presence of cardiovascular risk factors.

Conclusion

Prevalence of obesity and related health outcomes was surprisingly high for the studied population. We found a correlation between BMI, dietary habits, and cardiovascular risk factors.The health of an individual and the population in general is the result of interactions between genetics and a number of environmental factors. An environmental factor of major importance is nutrition (1), which is also one of the key determinants of health care expenditures (2).Excessive body weight is a major problem in industrialized and developed countries where it has reached the proportions of an epidemic (3). Overweight and obesity have been related to increased morbidity and mortality rates due to diabetes mellitus, several forms of cancer, digestive disease, and coronary heart diseases (4,5).Furthermore, overweight and obesity are believed to represent an independent risk for cardiovascular diseases. A part of the increased risk of cardiovascular diseases conferred by increased body weight is explained by the effects on blood pressure, glucose tolerance, and plasma lipid metabolism (6,7). Because of the strong relationship between excessive body weight and these diseases, it is important to provide information on the determinants of overweight and obesity from population-based surveys (6,7).Body mass index (BMI) is an easily and reliably obtained measure of relative body size. It is often used as an indirect index of adiposity and has been strongly associated with cardiovascular disease risk (8).During the few last years, cardiovascular diseases have caused approximately 4.3 million deaths in Europe and 1.9 million deaths in the European Union (EU) per year, representing 49% of all deaths in Europe and 42% in the EU (9). In Croatia, these diseases also represent a leading cause of mortality and morbidity: the standardized death rate has been increasing for the last three decades, and reached 91.7 per 100 000 population in 2001 (10).At the same time, in Finland, Sweden, Norway, and Denmark, the mortality rates of standardized deaths rates from coronary heart disease have been declining at all ages over the past decades (11,12). The reasons for the decline are probably healthier lifestyle, reduction of risk factors, and better treatment of diseases. Populations in South European countries, such as France, Spain, and Portugal, have relatively low death rates due to the Mediterranean diet (13).Studies have suggested that health-conferring benefits of the Mediterranean diet are mainly due to high consumption of fish, fruit, and vegetables. More recent research has focused on other important factors, such as olives and olive oil. Fiber, especially from wholegrain-derived products, fruit, and vegetables, is an important source of dietary antioxidants (14). Furthermore, data suggest that the traditional Mediterranean dietary pattern is inversely associated with body mass index (BMI) and obesity (15).The aim of the study was to investigate the relationship between BMI and dietary habits and cardiovascular risk factors in isolated Adriatic island populations of Croatia.     

Glutathione S-transferase and microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease in Slovak population

Aim

To determine the risk of chronic obstructive pulmonary disease (COPD) associated with polymorphisms in the glutathione S-transferase (GST) M1, GST T1, and microsomal epoxide hydrolase (EPHX1) genes in a cohort of Slovak population.

Methods

Two hundred and seventeen patients with the diagnosis of COPD and 160 control subjects were enrolled in the study. Blood samples were collected from all subjects and the DNA from peripheral blood lymphocytes was used for subsequent genotyping assays, using polymerase chain reaction and restriction fragment-length polymorphism methods.

Results

In an unadjusted model, an increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.20-4.69; P = 0.008), compared with the carriers of the Tyr113 allele. However, after the adjustments for age, sex, and smoking status, the risk was not significant (adjusted OR, 1.79; 95% CI, 0.91-3.53; P = 0.093). In a combined analysis of gene polymorphisms, the genotype combination EPHX1 His113-His113/GSTM1 null significantly increased the risk of COPD in both, unadjusted (OR, 5.08; 95% CI, 1.70-20.43; P = 0.001) and adjusted model (OR, 4.87; 95% CI, 1.57-15.13; P = 0.006).

Conclusion

Although none of the tested gene polymorphisms was significantly related to an increased risk of COPD alone, our results suggest that the homozygous exon 3 mutant variant of EPHX1 gene in the combination with GSTM1 null genotype is a significant predictor of increased susceptibility to COPD in the Slovak population. The findings of the present study emphasize the importance of detoxifying and antioxidant pathways in the pathogenesis of COPD.Chronic obstructive pulmonary disease (COPD) represents a major public health care problem worldwide due to its increasing prevalence, morbidity, and mortality (1). Generally, COPD is characterized by progressive and only partially reversible airflow limitation (2). Although cigarette smoking is the most important risk factor for COPD, only 20%-30% of chronic smokers develop severe impairment of lung function associated with COPD (3). Besides smoking, other environmental and genetic factors and gene-environment interactions influence the development of COPD (4).Severe α-1-antitrypsin deficiency is a well established genetic risk factor for COPD that has provided a basis for the protease-antiprotease hypothesis in the pathogenesis of COPD (5,6). Other candidate genes that might play a role in the development of COPD are involved in endogenous protease/antiprotease imbalance, inflammatory processes, metabolism of mutagens and carcinogens in tobacco smoke, and in mucocilliary clearance (7). Interindividual differences in the polymorphisms of enzymes metabolizing the xenobiotic substances and free radicals contained in the cigarette smoke may play a role in the individual susceptibility to the decrease in lung functions in smokers (8).Microsomal epoxide hydrolase (EPHX1) is generally considered to be a protective enzyme involved in the defense from oxidative damage (9,10). Two common polymorphic sites in the EPHX1 gene that influence the enzyme activity can be detected (11). An exon 3 thymine-to-cytosine mutation changes Tyr residue 113 to His, thus reducing the enzyme activity by about 50%. The second mutation, an adenine-to-guanine transition in exon 4 of the gene, changes His residue 139 to Arg and results in the production of EPHX1 with the activity increased by about 25% (11). The combination of these polymorphisms leads to a formation of several functional phenotypes of EPHX1. The slow metabolizing type of EPHX1 was associated with emphysema and COPD (9). In another study, an association of slow metabolizing EPHX1 phenotype with an accelerated deterioration of lung function in smokers was observed (12). In addition, several studies conducted in different populations have suggested that the EPHX1 genotype may influence individual susceptibility to COPD (9,13-15). Nevertheless, other investigators failed to confirm an association between the EPHX1 gene polymorphisms and COPD (16-18).Glutathione S-transferases (GST) play a role in the detoxification of carcinogenic compounds contained in cigarette smoke and in the antioxidant protection (19,20). Recently, the GSTM1 and the GSTT1 gene polymorphisms have been excessively studied with respect to their potential contribution to the risk of COPD (8,17,21,22). The deficiency in the activity of GSTM1 and GSTT1 enzymes is caused by the inherited homozygous absence of the GSTM1 or GSTT1 gene, respectively (ie, GSTM1 null or GSTT1 null genotype). Previously, the homozygous GSTM1 null genotype has been associated with lung cancer (23), emphysema (21), and reductions in the lung function in Caucasian smokers with non-small-cell lung cancer (22). However, another study conducted in Koreans found no differences in the frequencies of polymorphic genotypes of GSTM1 and GSTT1 genes between patients with COPD and healthy smokers (17).Since current data on the potential associations between an increased COPD risk and genes encoding the enzymes metabolizing xenobiotic substances are inconsistent, the aim of our study was to analyze the relation between COPD and gene polymorphisms of EPHX1, GSTM1, and GSTT1 genes in a sample of Slovak population.     

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.     

Sick leave and its determinants in professional soldiers of the Slovenian Armed Forces

Aim

To assess whether demographic characteristics, self-rated health status, coping behaviors, satisfaction with important interpersonal relationships, financial situation, and current overall quality of life are determinants of sick leave duration in professional soldiers of the Slovenian Armed Forces.

Methods

In 2008, 448 military personnel on active duty in the Slovenian Armed Forces were invited to participate in the study and 390 returned the completed questionnaires (response rate 87%). The questionnaires used were the self-rated health scale, sick leave scale, life satisfaction scale, Folkman-Lazarus'' Ways of Coping Questionnaire, and a demographic data questionnaire. To partition the variance across a wide variety of indicators of participants’ experiences, ordinal modeling procedures were used.

Results

A multivariate ordinal regression model, explaining 24% of sick leave variance, showed that the following variables significantly predicted longer sick leave duration: female sex (estimate, 1.185; 95% confidence interval [CI], 0.579-1.791), poorer self-rated health (estimate, 3.243; 95% CI, 1.755-4.731), lower satisfaction with relationships with coworkers (estimate, 1.333; 95% CI, 0.399-2.267), and lower education (estimate, 1.577; 95% CI, 0.717-2.436). The impact of age and coping mechanisms was not significant.

Conclusion

Longer sick leave duration was found in women and respondents less satisfied with their relationships with coworkers, and these are the groups to which special attention should be awarded when planning supervision, work procedures, and gender equality policy of the Armed Forces. A good way of increasing the quality of interpersonal relationships at work would be to teach such skills in teaching programs for commanding officers.Self-rated health represents a person''s comprehensive and subjective assessment of his or her health, which incorporates the subjective feeling of health together with biological, psychological, and socio-economic dimensions (1,2), any present illness, symptoms, and the functional status (3). The term is frequently used in population research and social epidemiology as an indicator of a typical health behavior of the individual (4,5). Self-rated health is associated with physical fitness (3) and predicts morbidity and mortality (6-11).In middle-aged healthy individuals, self-rated health has several predictors: physical and psycho-social working conditions (12), economic situation, psychological status, and lifestyle (13). Among work-related factors the most important is stress, which has been shown to increase the likelihood of taking a sick leave (14-17). It has also been shown that the number of days of sick leave increased as self-reported health decreased (13,18). Sick leave duration has been found to have a negative correlation with self-rated health even over a period of 10 years (19).In Sweden, long-term sick leave (>90 days) was taken mostly by women in the public sector, and it was caused by depression-related illness and work-related stress (20). However, the impact of job-related stress as a reason for disability remains unexplained. It is unclear whether this impairment is a result of prolonged stress exposure or a pre-existing susceptibility factor. In a study of white-collar workers’ absenteeism, there was no association between employee’s psychological distress, type of employee, and productivity (21). However, in blue-collar workers high psychological distress resulted in an 18% increase in absenteeism rates (21). A study of 54 264 full-time employees from different levels of the corporate hierarchy showed that elevated psychological distress was associated with increasing absenteeism (22).Subjective health assessment is a valid health status indicator for middle-aged people (23) and can be used to study the relationship between stress, burnout, and organizational conditions at work. The validity of self-rated health can be confirmed by objective assessment methods, for example, by the number of visits to the physician, absenteeism from work, and mortality. In 2008, Erikksson analyzed the connection between sick leave and self-rated health in the Swedish population using the EQ-5D Questionnaire for Health Assessment (24).In Slovenia, only one epidemiological study on self-rated health was conducted, and it studied the factors leading to poor health ratings (25). Only a few studies have assessed the effects of threats, fears, or various other psychological difficulties on subjective health, and these have shown that subjective health was influenced by perceived threat and stress, a source of which can also be a chronic illness (26).In our previous study, we explored key psychological factors in the members of the Slovenian armed forces who reported poorer bio-psycho-social well-being and more burnout, and therefore had reduced working effectiveness and motivation (27). The present analysis specifically analyzed the predicting factors of absence from work due to illness in professional soldiers of the Slovenian Armed Forces.     

Chronic respiratory symptoms in Croatian Adriatic island metapopulations

Aim

To investigate the prevalence of chronic respiratory symptoms in 9 metapopulations on Adriatic islands in Croatia, and the relationship between respiratory symptoms and individual genetic background.

Methods

We obtained random sample of 1001 adult inhabitants of 9 Adriatic island villages in Croatia, that also included immigrants to these villages. European Union respiratory health questionnaire and World Health Organization non-communicable diseases questionnaire were used. Personal genetic histories were reconstructed, based on the two-generation ancestral pedigrees. Bivariate and multivariate methods were used in the analysis.

Results

Women reported the occurrence of acute dyspnea (P = 0.017), cough (P = 0.002), and asthma (P = 0.002) more often than men. Gender was the strongest predictor for acute and/or chronic cough (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.23-2.33) and asthma (OR, 2.00; 95% CI, 1.00-4.01), whereas smoking was the strongest risk factor for acute and chronic dyspnea (OR, 1.90; 95% CI, 1.21-2.99) and airway narrowing (OR, 1.84; 95% CI, 1.18-2.87). Residence on the northern islands increased the odds of allergy, whereas the highest odds ratio of 3.20 was associated with the interaction of northern residence and immigrant background. Genetic background was a significant predictor only for the occurrence of allergy symptoms.

Conclusion

Differences in respiratory findings among the island inhabitants were often associated with smoking prevalence. Interaction of residence on northern Adriatic islands and immigrant background proved to be the strongest predictor for the occurrence of allergy symptoms. This study indicated that environmental factors played a very important role in the occurrence of respiratory symptoms.Nonspecific respiratory symptoms in general population have recently received increased attention, as respiratory diseases are associated with a significant proportion of chronic morbidity (1,2). A complex interaction between genetic background and exposure to multiple environmental stimuli is widely recognized in the etiology of many lung diseases (3). The role of genetics is being intensively investigated, using predominately genome screens and association studies. These studies have identified regions of the genome which are linked with the phenotypes of asthma and atopy (4,5), or with the occurrence of chronic obstructive pulmonary disease (COPD) (6). The most important environmental risk factor for the development of respiratory diseases is tobacco smoke inhalation, either among smokers, or non-smokers through passive smoking (7,8). Air pollution, such as exposure to organic or inorganic dusts, fumes, or gasses, is another highly prevalent environmental risk factor.The most common chronic respiratory diseases are asthma and chronic obstructive pulmonary disease, two distinct inflammatory disorders, with different pathogenesis, clinical courses, and distinct treatment strategies (9,10). Asthma is a very common disorder, affecting people of all ages. Chronic obstructive pulmonary disease is a progressive, slow-onset debilitating disease of the airways, characterized by a gradual loss of lung function and reduction in life quality (11-13). The term COPD includes chronic bronchitis, emphysema, or a combination of these conditions. It is a highly prevalent smoking-related condition, thus representing a significant economic burden to the health care system (14).The aim of this study was to analyze the self-reported prevalence of asthma and other chronic respiratory symptoms in the population of 9 villages on Adriatic islands in Croatia, that also included immigrants to these villages. We also examined geographical variation among the studied villages in the prevalence of these symptoms and the possible relation of respiratory symptoms to the genetic background inferred on the basis of two-generation pedigrees.     

Pharmacotherapy of treatment-resistant combat-related posttraumatic stress disorder with psychotic features

Aim

To assess retrospectively the clinical effects of typical (fluphenazine) or atypical (olanzapine, risperidone, quetiapine) antipsychotics in three open clinical trials in male Croatian war veterans with chronic combat-related posttraumatic stress disorder (PTSD) with psychotic features, resistant to previous antidepressant treatment.

Methods

Inpatients with combat-related PTSD were treated for 6 weeks with fluphenazine (n = 27), olanzapine (n = 28) risperidone (n = 26), or quetiapine (n = 53), as a monotherapy. Treatment response was assessed by the reduction in total and subscales scores in the clinical scales measuring PTSD (PTSD interview and Clinician-administered PTSD Scale) and psychotic symptoms (Positive and Negative Syndrome Scale).

Results

After 6 weeks of treatment, monotherapy with fluphenazine, olanzapine, risperidone, or quetiapine in patients with PTSD significantly decreased the scores listed in trauma reexperiencing, avoidance, and hyperarousal subscales in the clinical scales measuring PTSD, and total and subscales scores listed in positive, negative, general psychopathology, and supplementary items of the Positive and negative syndrome scale subscales, respectively (P<0.001).

Conclusion

PTSD and psychotic symptoms were significantly reduced after monotherapy with typical or atypical antipsychotics. As psychotic symptoms commonly occur in combat-related PTSD, the use of antipsychotic medication seems to offer another approach to treat a psychotic subtype of combat-related PTSD resistant to previous antidepressant treatment.In a world in which terrorism and conflicts are constant threats, and these threats are becoming global, posttraumatic stress disorder (PTSD) is a serious and global illness. According to the criteria from the 4th edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1), exposure to a life-threatening or horrifying event, such as combat trauma, rape, sexual molestation, abuse, child maltreatment, natural disasters, motor vehicle accidents, violent crimes, hostage situations, or terrorism, can lead to the development of PTSD (1,2). The disorder may also be precipitated if a person experienced, saw, or learned of an event or events that involved actual or threatened death, serious injury, or violation of the body of self or others (3,4). In such an event, a person’s response can involve intense fear, helplessness, or horror (3,4). However, not all persons who are exposed to a traumatic event will develop PTSD. Although the stress reaction is a normal response to an abnormal situation, some extremely stressful situations will in some individuals overwhelm their ability to cope with stress (5).PTSD is a chronic psychiatric illness. The essential features of PTSD are the development of three characteristic symptom clusters in the aftermath of a traumatic event: re-experiencing the trauma, avoidance and numbing, and hyperarousal (1,6). The core PTSD symptoms in the re-experiencing cluster are intrusive memories, images, or perceptions; recurring nightmares; intrusive daydreams or flashbacks; exaggerated emotional and physical reactions; and dissociative experiences (1,6,7). These symptoms intensify or re-occur upon exposure to reminders of the trauma, and various visual, auditory, or olfactory cues might trigger traumatic memories (3,4). The avoidance and numbing cluster of symptoms includes efforts to avoid thoughts, feelings, activities, or situations associated with the trauma; feelings of detachment or alienation; inability to have loving feelings; restricted range of affect; loss of interest; and avoidance of activity. The hyperarousal cluster includes exaggerated startle response, hyper-vigilance, insomnia and other sleep disturbances, difficulties in concentrating, and irritability or outbursts of anger. PTSD criteria include functional impairment, which can be seen in occupational instability, marital problems, discord with family and friends, and difficulties in parenting (3,4,8). In addition to this social and occupational dysfunction, PTSD is often accompanied by substance abuse (9) and by various comorbid diagnoses, such as major depression (10), other anxiety disorders, somatization, personality disorders, dissociative disorders (7,11), and frequently with suicidal behavior (12). Combat exposure can precipitate a more severe clinical picture of PTSD, which may be complicated with psychotic features and resistance to treatment. War veterans with PTSD have a high risk of suicide, and military experience, guilt about combat actions, survivor guilt, depression, anxiety, and severe PTSD are significantly associated with suicide attempts (12).The pharmacotherapy treatment of PTSD includes the use of antidepressants, such as selective serotonin reuptake inhibitors (fluvoxamine, fluoxetine, sertraline, or paroxetine) as a first choice of treatment, tricyclic antidepressants (desipramine, amitriptyline, imipramine), monoamine oxidase inhibitors (phenelzine, brofaromine), buspirone, and other antianxiety agents, benzodiazepines (alprazolam), and mood stabilizers (lithium) (13-16). Although the pharmacotherapy of PTSD starts with antidepressants, in treatment-refractory patients a new pharmacological approach is required to obtain a response. In treatment-resistant patients, pharmacotherapy strategies reported to be effective include anticonvulsants, such as carbamazepine, gabapentine, topiramate, tiagabine, divalproex, lamotrigine (14,17); anti-adrenergic agents, such as clonidine (although presynaptic α2-adrenoceptor agonist, clonidine blocks central noradrenergic outflow from the locus ceruleus), propranolol, and prazosin (13,14), opiate antagonists (13), and neuroleptics and antipsychotics (14,17,18).Combat exposure frequently induces PTSD, and combat-related PTSD might progress to a severe form of PTSD, which is often refractory to treatment (19-21). Combat-related PTSD is frequently associated with comorbid psychotic features (11,14,17,19-21), while psychotic features add to the severity of symptoms in combat-related PTSD patients (19,22-24). These cases of a more severe subtype of PTSD, complicated with psychotic symptoms, require the use of neuroleptics or atypical antipsychotic drugs (14,17,25-27).After the war in Croatia (1991-1995), an estimated million people were exposed to war trauma and about 10 000 of the Homeland War veterans (15% prevalence) have developed PTSD, with an alarmingly high suicide rate (28). The war in Croatia brought tremendous suffering, not only to combat-exposed veterans and prisoners of war (29), but also to different groups of traumatized civilians in the combat zones, displaced persons and refugees, victims of terrorist attacks, civilian relatives of traumatized war veterans and terrorist attacks victims, and traumatized children and adolescents (30). Among Croatian war veterans with combat-related PTSD, 57-62% of combat soldiers with PTSD met criteria for comorbid diagnoses (8-11), such as alcohol abuse, major depressive disorder, anxiety disorders, panic disorder and phobia, psychosomatic disorder, psychotic disorders, drug abuse, and dementia. In addition to different comorbid psychiatric disorders, a great proportion of war veterans with combat-related PTSD developed psychotic features (8,11,25,26), which consisted of psychotic depressive and schizophrenia-like symptoms (suggesting prominent symptoms of thought disturbances and psychosis). Psychotic symptoms were accompanied by auditory or visual hallucinations and delusional thinking in over two-thirds of patients (25,26). Delusional paranoid symptoms occurred in 32% of patients (25,26). The hallucinations were not associated exclusively with the traumatic experience, while the delusions were generally paranoid or persecutory in nature (25,26). Although psychotic PTSD and schizophrenia share some similar symptoms, there are clear differences between these two entities, since PTSD patients still retain some insight into reality and usually do not have complete disturbances of affect (eg, constricted or inappropriate) or thought disorder (eg, loose associations or disorganized responses).This proportion of veterans with combat-related PTSD refractory to treatment (18-20) and with co-occurring psychotic symptoms requires additional pharmacological strategies, such as the use of neuroleptics (25) or atypical antipsychotics (14,17,26). Studies evaluating the use of antipsychotics in combat-related PTSD with psychotic features are scarce, and antipsychotics were frequently added to existing medication in the treatment of PTSD.In this study, we compared retrospectively the clinical effects of four antipsychotic drugs – a neuroleptic drug (fluphenazine) and three atypical antipsychotics (olanzapine, risperidone and quetiapine) – in treatment-resistant male war veterans with combat-related PTSD with psychotic features.     

Psychiatric heredity and posttraumatic stress disorder: survey study of war veterans

Aim

To explore the prevalence of psychiatric heredity (family history of psychiatric illness, alcohol dependence disorder, and suicidality) and its association with the diagnosis of stress-related disorders in Croatian war veterans established during psychiatric examination.

Methods

The study included 415 war veterans who were psychiatrically assessed and diagnosed by the same psychiatrist during an expert examination conducted for the purposes of compensation seeking. Data were collected by a structured diagnostic procedure.

Results

There was no significant correlation between psychiatric heredity of psychiatric illness, alcohol dependence, or suicidality and diagnosis of posttraumatic stress disorder (PTSD) or PTSD with psychiatric comorbidity. Diagnoses of psychosis or psychosis with comorbidity significantly correlated with psychiatric heredity (φ = 0.111; P = 0.023). There was a statistically significant correlation between maternal psychiatric illness and the patients’ diagnoses of partial PTSD or partial PTSD with comorbidity (φ = 0.104; P = 0.035) and psychosis or psychosis with comorbidity (φ = 0.113; P = 0.022); paternal psychiatric illness and the patients’ diagnoses of psychosis or psychosis with comorbidity (φ = 0.130; P = 0.008), alcohol dependence or alcohol dependence with comorbidity (φ = 0.166; P = 0.001); psychiatric illness in the primary family with the patients’ psychosis or psychosis with comorbidity (φ = 0.115; P = 0.019); alcohol dependence in the primary family with the patients’ personality disorder or personality disorder with comorbidity (φ = 0.099; P = 0.044); and suicidality in the primary family and a diagnosis of personality disorder or personality disorder with comorbidity (φ = 0.128; P = 0.009).

Conclusion

The study confirmed that parental and familial positive history of psychiatric disorders puts the individual at higher risk for developing psychiatric illness or alcohol or drug dependence disorder. Psychiatric heredity might not be necessary for the individual who was exposed to severe combat-related events to develop symptoms of PTSD.There are several risk factors associated with the development of posttraumatic stress disorder (PTSD), such as factors related to cognitive and biological systems and genetic and familial risk (1), environmental and demographic factors (2), and personality and psychiatric anamnesis (3).They are usually grouped into three categories: factors that preceded the exposure to trauma or pre-trauma factors; factors associated with trauma exposure itself; and post-trauma factors that are associated with the recovery environment (2,4).There are many studies which support the hypothesis that pre-trauma factors, such as ongoing life stress, psychiatric history, female sex (3), childhood abuse, low economic status, lack of education, low intelligence, lack of social support (5), belonging to racial and ethnic minority, previous traumatic events, psychiatric heredity, and a history of perceived life threat, influence the development of stress related disorders (6). Many findings suggest that ongoing life stress or prior trauma history sensitizes a person to a new stressor (2,7-9). The same is true for the lack of social support, particularly the loss of support from significant others (2,9-11), as well as from friends and community (12-14). If the community does not have an elaborated plan for providing socioeconomic support to the victims, then the low socioeconomic status can also be an important predictor of a psychological outcome such as PTSD (2,10,15). Unemployment was recognized as a risk factor for developing PTSD in a survey of 374 trauma survivors (16). It is known that PTSD commonly occurs in patients with a previous psychiatric history of mental disorders, such as affective disorders, other anxiety disorders, somatization, substance abuse, or dissociative disorders (17-21). Epidemiological studies showed that pre-existing psychiatric problems are one of the three factors that can predict the development of PTSD (2,22). Pre-existing anxiety disorders, somatoform disorders, and depressive disorders can significantly increase the risk of PTSD (23). Women have a higher vulnerability for PTSD than men if they experienced sexually motivated violence or had pre-existing anxiety disorders (23,24). A number of studies have examined the effects of gender differences on the predisposition for developing PTSD, with the explanation that women generally have higher rates of depression and anxiety disorders (3,25,26). War-zone stressors were described as more important for PTSD in men, whereas post-trauma resilience-recovery factors as more important for women (27).Lower levels of education and poorer cognitive abilities also appear to be risk factors (25). Golier et al (25) reported that low levels of education and low IQ were associated with poorer recall on words memorization tasks. In addition, this study found that the PTSD group with lower Wechsler Adult Intelligence Scale-Revised (WAIS-R) scores had fewer years of education (25). Nevertheless, some experts provided evidence for poorer cognitive ability in PTSD patients as a result or consequence rather than the cause of stress-related symptoms (28-31). Studies of war veterans showed that belonging to racial and ethnic minority could influence higher rates of developing PTSD even after the adjustment for combat exposure (32,33). Many findings suggest that early trauma in childhood, such as physical or sexual abuse or even neglect, can be associated with adult psychopathology and lead to the development of PTSD (2,5,26,34,35). Surveys on animal models confirm the findings of lifelong influences of early experience on stress hormone reactivity (36).Along with the reports on the effects of childhood adversity as a risk factor for the later development of PTSD, there is also evidence for the influence of previous exposure to trauma related events on PTSD (9,26,28). Breslau et al (36) reported that previous trauma experience substantially increased the risk for chronic PTSD.Perceived life threats and coping strategies carry a high risk for developing PTSD (9,26). For instance, Ozer et al (9) reported that dissociation during trauma exposure has high predictive value for later development of PTSD. Along with that, the way in which people process and interpret perceived threats has a great impact on the development or maintenance of PTSD (37,38).Brewin et al (2) reported that individual and family psychiatric history had more uniform predictive effects than other risk factors. Still, this kind of influence has not been examined yet.Keeping in mind the lack of investigation of parental psychiatric heredity on the development of stress-related disorders, the aim of our study was to explore the prevalence and correlation between the heredity of psychiatric illness, alcohol dependence, suicidality, and the established diagnosis of stress-related disorders in Croatian 1991-1995 war veterans.     

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.     

Scientific production of research fellows at the Zagreb University School of Medicine, Croatia

Aim

To evaluate scientific production among research fellows employed at the Zagreb University School of Medicine and identify factors associated with their scientific output.

Method

We conducted a survey among research fellows and their mentors during June 2005. The main outcome measure was publication success, defined for each fellow as publishing at least 0.5 articles per employment year in journals indexed in the Current Contents bibliographic database. Bivariate methods and binary logistic regression were used in data analysis.

Results

A total of 117 fellows (response rate 95%) and 83 mentors (100%) were surveyed. The highest scientific production was recorded among research fellows employed in public health departments (median 3.0 articles, interquartile range 4.0), compared with those from pre-clinical (median 0.0, interquartile range 2.0) and clinical departments (median 1.0, interquartile range 2.0) (Kruskal-Wallis, P = 0.003). A total of 36 (29%) research fellows published at least 0.5 articles per employment year and were considered successful. Three variables were associated with fellows’ publication success: mentor’s scientific production (odds ratio [OR], 3.14; 95% confidence interval [CI], 1.31-7.53), positive mentor’s assessment (OR, 3.15; 95% CI, 1.10-9.05), and fellows’ undergraduate publication in journals indexed in the Current Contents bibliographic database (OR, 4.05; 95% CI, 1.07-15.34).

Conclusion

Undergraduate publication could be used as one of the main criteria in selecting research fellows. One of the crucial factors in a fellow’s scientific production and career advancement is mentor’s input, which is why research fellows would benefit most from working with scientifically productive mentors.Decreasing interest in scientific involvement among young graduate physicians has been identified in a number of studies (1-6). Various solutions for reversing this trend have been proposed in an attempt to increase the interest in scientific research among physicians. What was most commonly reported as having a positive effect on physicians’ research interest was undergraduate involvement in scientific work and subsequent publication of a research article (7-9). Other studies demonstrated that program characteristics and faculty size had an effect on publication output (10,11). The role of a supportive mentor (10,12), or a Resident Research Director (13) were also positively associated with scientific production. An additional year devoted to clinical research among surgical residents increased their scientific output (14). However, a recent study failed to confirm undergraduate scientific involvement as the predictor of productive scientific career in radiology (15). Only critical attitude, independence, inventiveness, and curiosity were correlated with research activity (16). Other undergraduate indicators, including grade point average, did not contribute to increased scientific production later in career (16). The situation is becoming even more worrying knowing that high initial interest in scientific research among recently graduated physicians decreased as their residency progressed (17). The reasons for a decreased publication output might include a lack of time, low interest in research, and insufficient mentor support (18). Inadequate senior staff and statistical or secretarial support were identified as major barriers to research activity (19). The same study identified high demand for clinical productivity, lack of protected research time, and a lack of research funding as additional obstacles (19).In 1991, Ministry of Science, Education, and Sports of the Republic of Croatia established a program for research fellows, with an aim to attract the best graduate students to the positions at academic and research institutions. The number of research fellows gradually increased from 995 in 1991 to 2510 at the end of 2005 (20). Career advancement criteria for research fellows are strict, and defined by the Law on Scientific Work and Higher Education (21). Research fellows employed by the Zagreb University School of Medicine represented a total of 5% of all research fellows in Croatia in 2004 and 26% of all fellows employed in the biomedical field (20). The aim of this study was to evaluate the scientific production among research fellows from Zagreb University School of Medicine. We also aimed to identify the factors associated with a successful scientific output, which is the main career advancement requirement for research fellows.