Knowledge, motivation, and attitudes of Hungarian family physicians toward pandemic influenza vaccination in the 2009/10 influenza season: questionnaire study

Aim

To evaluate the knowledge, motivation, and attitudes of Hungarian family physicians toward pandemic influenza vaccination in the 2009/10 influenza season.

Method

A questionnaire with 20 questions was developed and sent to 232 family physicians in 3 largest Hungarian cities: Budapest, Debrecen, and Miskolc. The study was conducted in December 2009 and January 2010.

Results

A hundred and ninety eight (85%) physicians answered the questionnaire adequately. Respondents believed that the influenza outbreak represented less of a threat to their practices than to Hungary or the world as a whole. They mostly agreed that vaccination was important and were frequently dissatisfied with the support from health authorities. The proportion of vaccinated patients ranged between 2% and 53%, without differences according to geographical region, age, sex, and duration of physicians’ employment in family practice. Physicians who were satisfied with the payment for procedures and underwent vaccination themselves were more active in vaccination.

Conclusion

Health authorities should provide clear and evidence-based professional support to family physicians and should encourage them to get vaccinated against pandemic influenza, while insurance funds have to establish appropriate reimbursement system.In June 2009, the World Health Organization (WHO) announced the global pandemic of influenza A/California 07/09 (H1N1). In Hungary, the media and the leading Hungarian medical journal reported on the emergence of a novel strain of swine-origin virus (1). The symptoms were usually mild and prevention was important, with an emphasis on the adherence to hygiene and vaccination that was recommended for everyone at risk of becoming ill or of transmitting the virus. It was not recommended for pregnant women in the first trimester, due to a lack of experience with the vaccine in this population. The pandemic had been predicted by infectologists years before (2,3).The Hungarian government established the Committee for Pandemic, and family physicians were ordered to prepare weekly surveillance reports and lists of people who needed vaccinations. Posters on personal hygiene and behavior recommendations were displayed in public spaces (4) and at the end of the summer of 2009 thermo-gates were deployed at airports to detect incoming people with fever.Vaccination was provided free of charge for health care staff, inpatients in hospitals and nursing homes, people over 60 years of age, patients with chronic pulmonary or heart diseases, children and adults who were assumed to be in danger of infection, police officers, workers of the public transport and services, and patients on long-term aspirin treatment (2).Influenza AH1N1 variant arrived in Hungary in July 2009 (2,5). The Hungarian Fluval P (Omninvest, Pilisborosjenő, Hungary) vaccine was developed as a brand of the previously used Fluval H5N1 vaccine, containing thiomersal as preservative agent (6), which was added to other vaccines used in the USA as well (7). Clinical evaluation in Hungary started in August in line with the European Union regulations (8). After some modifications, the pharmaceutical authority allowed its use in adolescents and later in children.During the initial weeks, there were logistical problems with vaccine distribution. The vaccine was delivered by the local offices of the Chief Health Officer. For those who were vaccinated free of charge, the Hungarian Health Insurance Fund offered HUF 200 (cca € 0.75) extra payments to family physicians per injection. For those who were not vaccinated free of charge, the price was HUF 1000-1500 (€ 4-6) per injection.Through September and October 2009, lay press reported on a disagreement between experts on the safety and effectiveness of the vaccine. The most frequently discussed problem was the vaccination of pregnant women and children (1,3).Many family physicians lacked confidence in the vaccine and asked the patients to sign that they assume the responsibility for any side effects or complications. This practice was supported by the Medical Chamber and other professional organizations, but was prohibited by the Minister of Health. One of the patient organizations pressed charges against the government (9). There were family physicians who recommended the vaccination and others who dissuaded their patients from getting vaccinated. The issue whether to start an antiviral treatment with neuraminidase inhibitors was also widely discussed (10,11).For people who were vaccinated free of charge, a network of “vaccination-points” was organized by mid-November 2009 in the county offices of the health authority and in larger hospitals. At these points, the whole reimbursement was HUF 3000 ( ≈ € 11), covering the price of the vaccine and the procedure. However, some suspicions over the financial management of these points were raised (12).Different opinions on the effectiveness of the vaccine were published in daily newspapers and media broadcasts. Some opposition politicians suggested that key government officials were among the owners of the vaccine manufacturer (13). Many of the opposition politicians refused to be vaccinated, while prominent government members, including the Minister of Health, underwent vaccination in a highly publicized manner.In the mid-December, there were reports on deaths of mothers and their newborns attributable to H1N1. The position of the strongest opposition party toward vaccination then changed and the party opened its own “vaccination point” in the center of Budapest (14). One of the leading opposition politicians blamed the government for buying the cheaper vaccine (13). In October, 73% of the polled were against the vaccination and in November only 57% were against it, while 28% supported the vaccination and 15% hesitated. By mid-December, the ratio of vaccinated people was two times higher among the government supporters than among opposition supporters (13,15).The aim of this study was to evaluate the knowledge, motivation, and attitudes of family physicians regarding vaccination in the 2009/10 pandemic influenza season.     

Prevalence and incidence of attention-deficit/hyperactivity disorder in Slovenian children and adolescents: a database study from a national perspective

Aim

To estimate prevalence and incidence of attention deficit hyperactivity disorder (ADHD) in children and adolescents in Slovenia using different epidemiological models.

Methods

Data from the National Institute of Public Health of the Republic of Slovenia for the period 1997-2012 were analyzed. The database includes the annual number of newly diagnosed outpatients with ADHD in Slovenia. The evaluation for ADHD diagnoses was done in accordance with the Tenth Revision of the International Classification of Diseases (ICD-10) outpatient data codes. In model 1, a linear increase was proposed to fit the data in the period from 1997 to 2003 in order to extrapolate the data before 1997. In model 2 and 3, an exponential increase in the annual incidence rate was proposed.

Results

The incidence rate of ADHD diagnosis in 1997 was 0.032% and in 2012 it increased to 0.082%. Mean prevalence rate was 750 (95% confidence interval: 660-840) per 100 000 children and adolescents. It was estimated that the prevalence rate in 2020 would be 1% (95% confidence interval: 0.875-1.125), which is 6.3-fold higher than in 1997.

Conclusions

ADHD is a common mental health disorder among Slovenian children and adolescents, but it remained underdiagnosed compared with Western countries. Our results indicated a need for improved timely interventions in Slovenia, not only in child and adolescent psychiatry but also in primary settings and adult psychiatry, where ADHD should be more efficiently recognized.Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in childhood and adolescence, characterized by developmentally inappropriate inattention, hyperactivity, and/or impulsivity (1). It entails economic costs, causes family stress and academic and vocational adversity, and has a negative effect on the patient’s self-esteem (2). Although it is seen as a problem that takes place predominantly in childhood and adolescence, clinical and epidemiological research has shown that in 30–50% of patients ADHD persists into adulthood (3,4).Children exhibiting symptoms of inattention, hyperactivity, and impulsivity have been described previously (5). In 1980, the third edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-III) introduced the term “ADD (Attention-Deficit Disorder) with or without hyperactivity.” DSM-III-R (1987) replaced this term by the term ADHD and DSM-IV presented the subtypes of ADHD (6-9).ADHD affects 3% to 9% of children worldwide (10). In European countries, it is identified as a hyperkinetic disorder according to the 10th Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and in North America as ADHD (DSM-IV). DSM-IV criteria include a broader group of subjects than the ICD-10 criteria (11,12).While the popular press across Europe frequently comments on increased rates of ADHD diagnosis, questioning whether ADHD is overdiagnosed and overtreated, reviews of clinical practice suggest that in Europe ADHD is underdiagnosed and undertreated (13,14). ADHD is underdiagnosed especially in adults; which is why it is important to better understand the factors that contribute to accurate diagnosis (15). Diagnosis and management of ADHD include nonpharmacological treatment, including behavioral therapy, and pharmacological treatment with stimulants and nonstimulants (16). In many European countries including Slovenia, the incidence and prevalence of this disorder are not well researched. In Slovenia, there are also no national guidelines for ADHD treatment and diagnosis and no published data on the prevalence of ADHD (17,18). The primary aim of this study was to calculate the incidence and prevalence of ADHD diagnosis among children and adolescents in Slovenia in 2012, based on national data from 1997 to 2012. For this purpose, several different epidemiological models were developed. The secondary aim was to predict the number of Slovenian children and adolescents that will be diagnosed with ADHD in 2020.     

Patients with Combat-related and War-related Posttraumatic Stress Disorder 10 Years After Diagnosis

Aim

To establish how many patients diagnosed with posttraumatic stress disorder (PTSD) in 1996 used psychiatric facilities and had psychiatric symptoms 10 years later, and assess their sociodemographic characteristics, comorbid disorders, and type of treatment.

Methods

Medical records of patients diagnosed with PTSD in 1996 were reviewed in the period 2007-2009 and the patients who contacted a psychiatrist in that period (n = 85) and those who did not (n = 158) were compared.

Results

There were 36.7% of men and 20% of women diagnosed with PTSD in 1996 who contacted a psychiatrist in the period 2007-2009. Patients who contacted a psychiatrist and those who did not did not differ in sex, age, the number of visits and hospitalizations in 1996, and employment status. The majority of patients still had PTSD and/or were enduring personality change in the period 2007-2009, and 54.8% had some comorbidity (mostly depression, alcohol-related disorders, and personality disorders). Patients were most often treated with anxiolytics and antidepressants.

Conclusion

Ten years after the traumatic experience, one third of patients with PTSD received psychiatric help, regardless of their sex, age, and employment status. Half of them had comorbid disorders and the majority of them were treated with anxiolytics and antidepressants.Posttraumatic stress disorder (PTSD) is a mental disorder that develops in 9-25% of war veterans (1-4), mainly in the first two years after the traumatic experience (5,6), but sometimes can develop years later (7,8). A similar prevalence was also found among Croatian war veterans (5-9). In the majority of cases (80-98%), PTSD is comorbid with other mental disorders: alcohol abuse, depression, anxiety disorders, and somatization (5,9-11).PTSD can also develop after a war-related trauma that is not necessarily combat-related, and the lifetime prevalence of PTSD in this population is 15-38% (12) and the prevalence of anxiety and depressive disorders is even higher (13,14).Many patients in Croatia had symptoms of PTSD and used health facilities for treatment years after the war (5-9). In the former Yugoslavia, 84% of untreated war-related PTSD patients still had PTSD symptoms years after the war (15). Resolution of PTSD is observed in 50-60% of cases (4,16).Combat-related PTSD causes more functional impairment and is less responsive to treatment than PTSD related to other traumas (17-19). It is unclear whether this happens because there is indeed a difference between the two types of PTSD or some of the patients aggravate their symptoms in order to get compensation (17,18,20). Some studies show that the use of health facilities decreases after obtaining war veteran status and compensation, but others show that the patients who had obtained the status and compensation used medical facilities more often than those who had not (20-23).The aim of this study was to establish how many patients diagnosed with PTSD in 1996 used psychiatric facilities and had psychiatric symptoms 10 years later and assess their comorbidities, sociodemographic characteristics, and type of treatment.     

Ten-year follow-up of thyroid epidemiology in Slovenia after increase in salt iodization

Aim

To assess iodine supply and follow thyroid epidemiology for ten years after an iodine increase from 10 to 25 mg of potassium iodide per kilogram of salt in 1999.

Methods

In 2002 and 2003, we determined the thyroid size by palpation and ultrasound and measured urinary iodine concentration (UIC) in 676 schoolchildren from 34 schools throughout Slovenia. From 1999 to 2009, we followed the incidence of diffuse and nodular goiter, thyroid autonomy, Graves’ disease, and Hashimoto’s thyroiditis among adults in the stable catchment area of the University Medical Centre Ljubljana with 1 000 000 inhabitants.

Results

In children, only 1% had a goiter grade 2 (visible and palpable thyroid gland), median thyroid volume was 5.8 mL, and median UIC was 148 µg/L. In adults, the incidence of diffuse goiter and thyroid autonomy decreased significantly (2009 vs 1999, rate ratio [RR], 0.16; 95% confidence interval [CI], 0.12-0.21 and RR, 0.73; 95% CI, 0.62-0.86, respectively), with a lower incidence in younger participants in 2009 (P < 0.001). The incidence of multinodular goiter and solitary nodule increased (2009 vs 1999, RR, 1.55; 95% CI, 1.35-1.79 and RR, 1.72; 95% CI, 1.49-1.99, respectively). No long-term changes were observed for Graves’ disease (2009 vs 1999, RR, 0.95; 95% CI, 0.81-1.13), while the incidence of Hashimoto’s thyroiditis increased strongly (2009 vs 1999, RR, 1.86; 95% CI, 1.64-2.12).

Conclusions

The change from mildly deficient to sufficient iodine supply was associated with a marked change in the incidence of thyroid epidemiology – a significant decline in the incidence of diffuse goiter and thyroid autonomy and a marked increase in the incidence of Hashimoto’s thyroiditis.Iodine is an essential element of thyroid hormones, crucial for the prevention of iodine deficiency disorders. Iodine supplementation is an important public health measure that influences the thyroid volume and determines the epidemiology of thyroid disorders. According to the World Health Organization (WHO) criteria, the main indicators of iodine supply are median urinary iodine concentration (UIC) and thyroid size in schoolchildren (1).There are limited and sometimes conflicting longitudinal studies on epidemiology of thyroid disorders after the increase in iodine intake in areas with previously mild iodine deficiency. A few studies reported an early increase in the incidence of hyperthyroidism due to Graves’ disease and thyroid autonomy (2-4), in some cases followed by a decrease (2,5). Some reported an increased incidence of hypothyroidism (5), probably due to a higher incidence of thyroid autoimmunity (6-8). All investigators observed a decrease in the incidence of diffuse goiter in young population (3,9-11), while the data in the elderly are controversial (3,12).The prevalence of goiter in Slovenia between the two world wars was up to 80% (13). In 1953, iodine prophylaxis was introduced with addition of 10 mg potassium iodide per kilogram of kitchen salt. In 1991 to 1994, an epidemiological study revealed a goiter grade 2 by WHO criteria in 11% of 1740 schoolchildren aged 13 years (14). The mean thyroid volume measured by ultrasonography was 7.2 mL and UIC was lower than 100 μg/g of creatinine in 73.7% of children, with a median of 82.9 μg/g of creatinine (14), which classified Slovenia a mildly iodine-deficient according to the WHO criteria. Therefore, in January 1999 the Ministry of Health issued a recommendation for mandatory salt iodization with 25 mg (within range of 20-30 mg) of potassium iodide.In this study, we investigated the iodine supply and incidence of different thyroid disorders in Slovenia after the increase in salt iodization in 1999. We assessed the iodine supply in a population of schoolchildren using UIC and measurement of thyroid volume. We also performed a ten-year follow-up on the incidence of different thyroid disorders, including goiter, thyroid autonomy, Graves’ disease, and Hashimoto’s thyroiditis in the adult population.     

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.     

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).     

Attitudes of Roma toward smoking: qualitative study in Slovenia

Aim

To understand the reasons for widespread smoking behavior among Roma in Slovenia for the purpose of developing successful smoking cessation interventions.

Method

A qualitative focus group approach using a combination of pre-structured and open-ended questions was applied to collect the data from the representative members of the Roma community in southern Slovenia. The discussions were audiotaped and transcribed, and the collected data analyzed according to qualitative content analysis theory.

Results

The content analysis revealed that smoking was a strong part of the cultural, ethnic, and individual identity of the Roma. Even children smoked. Doctor’s advice to quit smoking was usually not followed and the attempts to quit were usually unsuccessful. Difficult financial situation was never mentioned as a possible motive to quit. Roma held a tenacious belief that the harmful effects of smoking were in the hands of destiny and did not associate the smoking-related illness with the habit.

Conclusions

Traditional strategies for smoking cessation are largely ineffective among the Roma because of their different attitudes toward smoking. Therefore, innovative and culturally acceptable methods need to be developed.According to the 2002 Census, 0.2% of inhabitants in Slovenia are Roma. However, on the basis of reports of social centers and schools, their real number could be up to four times higher than this (1). The socio-economic status, education level, and employment rate among Roma are considerably worse than among other Slovenian population, which places many of them into the category of poor people and thereby, at increased health risk.From the cultural point of view, the Roma are a highly specific ethnic minority. These once nomadic people now mostly live in poor accommodation and have difficult housing situation. The health culture of the Roma and their use of health care are low despite the fact that most of them can obtain full state-provided medical insurance irrespective of their employment status (2). Due to low hygienic and microclimatic conditions, low health education, and excessive smoking, diseases of the respiratory system seem to be among their most important health problems (3-5). Although epidemiologic data hardly exist, the Roma are known to be heavy smokers. The Roma trust in traditional folk medicine and do not believe smoking is a health-threatening habit (2). The percentage of smokers among the Roma in Slovenia is unknown. Studies from other countries show that, similar to other cardiovascular risk factors, smoking is by far more frequent in Roma than in other populations (5,6).Countries with a Roma population, whose health status is usually poor and socioeconomic position the lowest in the country (7-10), realized that research into the health status of the Roma people is needed for the planning of health intervention strategies, such as antismoking campaign (11,12). From everyday practice we know that the Roma never stop smoking and that they smoke heavily. We performed a qualitative study to understand the reasons for widespread and heavy smoking among the Roma in Slovenia for the purpose of developing more successful public health actions against smoking in their community.     

Attitudes of Slovenian family practice patients toward changing unhealthy lifestyle and the role of family physicians: cross-sectional study

Aim

To assess patients’ attitudes toward changing unhealthy lifestyle, confidence in the success, and desired involvement of their family physicians in facilitating this change.

Methods

We conducted a cross-sectional study in 15 family physicians’ practices on a consecutive sample of 472 patients (44.9% men, mean age  [± standard deviation] 49.3 ± 10.9 years) from October 2007 to May 2008. Patients were given a self-administered questionnaire on attitudes toward changing unhealthy diet, increasing physical activity, and reducing body weight. It also included questions on confidence in the success, planning lifestyle changes, and advice from family physicians.

Results

Nearly 20% of patients planned to change their eating habits, increase physical activity, and reach normal body weight. Approximately 30% of patients (more men than women) said that they wanted to receive advice on this issue from their family physicians. Younger patients and patients with higher education were more confident that they could improve their lifestyle. Patients who planned to change their lifestyle and were more confident in the success wanted to receive advice from their family physicians.

Conclusion

Family physicians should regularly ask the patients about the intention of changing their lifestyle and offer them help in carrying out this intention.Unhealthy lifestyle, including unhealthy diet and physical inactivity, is still a considerable health problem all over the world. Despite publicly available evidence about the health risks of unhealthy lifestyle, people still find it hard to improve their unhealthy diet and increase physical activity. Previous studies have shown that attitudes toward lifestyle change depended on previous health behavior, awareness of unhealthy lifestyle, demographic characteristics, personality traits, social support, family functioning, ongoing contact with health care providers, and an individual’s social ecology or network (1-4).As community-based health education approaches have had a limited effect on health risk factors reduction (3,5), the readiness-to-change approach, based on two-way communication, has become increasingly used with patients who lead an unhealthy lifestyle (3,6,7). Family physicians are in a unique position to adopt this approach, since almost every patient visits his/hers family physician at least once in five years (8). Previous studies showed that patients highly appreciated their family physicians’ advice on lifestyle changes (9,10). Moreover, patients who received such advice were also more willing to change their unhealthy habits (3,7,11). The reason for this is probably that behavioral changes are made according to the patient’s stage of the motivational circle at the moment of consultation (12), which can be determined only by individual approach.Although family physicians are convinced that it is their task to give advice on health promotion and disease prevention, in practice they are less likely to do so (13). The factors that prevent them from giving advice are time (14,15), cost, availability, practice capacity (14), lack of knowledge and guidelines, poor counseling skills (16), and personal attitudes (17). It also seems that physicians’ assessment varies considerably according to the risk factor in question. For example, information on diet and physical activity are often inferred from patients’ appearance rather than from clinical measurements (14). Also, health care professionals seldom give advice on recommended aspects of intervention that could facilitate behavioral change (18). As a large proportion of primary care patients are ready to lose weight, improve diet, and increase exercise (19), it is even more important that their family physicians provide timely advice.So far, several studies have addressed patients’ willingness to make lifestyle change (2-5,20) and the provision of professional advice (3,5,7,10,11). However, none of these studies have investigated the relation between these factors. So, the aim of our study was to assess the relation between patients’ attitudes toward changing unhealthy lifestyle, confidence in success, and the desired involvement of their family physicians in facilitating the change.     

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.     

Highly efficient nuclear DNA typing of the World War II skeletal remains using three new autosomal short tandem repeat amplification kits with the extended European Standard Set of loci

Aim

To perform an efficiency study of three new amplification kits with the extended European Standard Set (ESS) of loci for autosomal short tandem repeat (STR) typing of skeletal remains excavated from the World War II mass graves in Slovenia.

Methods

In the beginning of the 2011, we analyzed 102 bones and teeth using the PowerPlex ESX 17 System (Promega), AmpFiSTR NGM PCR Amplification Kit (Applied Biosystems), and Investigator ESSplex Kit (Qiagen). We cleaned the bones and teeth, removed surface contamination, and ground them into a powder using liquid nitrogen. Prior to DNA isolation with Biorobot EZ1 (Qiagen), 0.5 g bone or tooth powder was decalcified. Nuclear DNA of the samples was quantified using real-time polymerase chain reaction. All three kits used the same extract with the amplification conditions recommended by the manufacturers.

Results

We extracted up to 131 ng DNA/g of powder from the bones and teeth. All three amplification kits showed very similar efficiency, since DNA typing was successful with all amplification kits in 101 out of 102 bones and teeth, which represents a 99% success rate.

Conclusion

The commercially available ESX 17, ESSplex, and NGM kits are highly reliable for STR typing of World War II skeletal remains with the DNA extraction method optimized in our laboratory.DNA typing of bone and tooth samples has been successfully used in anthropological studies and forensic identification analysis (1,2). Nuclear DNA is the preferred genome of amplification for forensic purposes as it is individually specific and provides bi-parental kinship information (3). The success of DNA typing in old bones and teeth is often limited by small amounts of endogenous DNA, presence of polymerase chain reaction (PCR) inhibitors, DNA degradation, and an exceptional risk of contamination (4-6). Mitochondrial DNA testing has been regularly employed in the forensic identification of aged skeletal remains (7-10). Recently, some articles have reported a successful typing of nuclear short tandem repeats (STR) from ancient material using an increased number of cycles (11-18). In 2009 and 2010, new amplification kits were developed to meet the European Network of Forensic Institutes and the European DNA Profiling group recommendations for increasing the European Standard Set (ESS) of loci to improve its discrimination power and to fulfill the increasing requirements regarding sensitivity and reproducibility for the analysis of minute amounts of DNA by adopting five additional mini-STRs: D2S441, D10S1248, D22S1045, D1S1656, and D12S391 (19,20). Some validation, concordance, and population studies (21-28) have been published for new amplification kits with the extended ESS of loci. It was shown that the new kits are robust enough to genotype degraded DNA samples through the use of mini STR loci and have increased tolerance to common inhibitors and increased sensitivity to obtain full profiles from low-level DNA samples from casework (27,29,30). However, no study has been performed using new amplification kits on old skeletal remains. We attempted to obtain autosomal STR profiles from the World War II bones and teeth with three new commercially available amplification kits with the extended ESS of loci using the PCR protocols recommended by the manufacturers without increasing the number of cycles or any other modification of protocols.     

Incidence and mortality trends of leukemia and lymphoma in Croatia, 1988-2009

Aim

To investigate the time trends of leukemia and lymphoma in Croatia from 1988-2009, compare them with trends in other populations, and identify possible changes.

Methods

The data sources were the Croatian National Cancer Registry for incidence data, Croatian Bureau of Statistics for the numbers of deaths, and United Nations population estimates. Joinpoint regression analysis using the age-standardized rates was used to analyze incidence and mortality trends.

Results

Acute lymphoblastic leukemia and chronic lymphocytic leukemia incidence did not significantly change. Acute myeloid leukemia incidence significantly increased in women, with estimated annual percentage change (EAPC) of 2.6% during the whole period, and in men since 1998, with EAPC of 3.2%. Chronic myeloid leukemia incidence significantly decreased in women (EAPC -3.7%) and remained stable in men. Mortality rates were stable for both lymphoid and myeloid leukemia in both sexes. Hodgkin lymphoma non-significantly increased in incidence and significantly decreased in mortality (EAPCs of -5.6% in men and -3.7% in women). Non-Hodgkin lymphoma significantly increased in incidence in women (EAPC 3.2%) and non-significantly in men and in mortality in both men (EAPC 1.6%) and women (EAPC 1.8%).

Conclusion

While Croatia had similar leukemia and lymphoma incidence trends as the other countries, the mortality trends were less favorable than in Western Europe. The lack of declines of leukemia incidence and non-Hodgkin lymphoma mortality could be attributed to late introduction of optimal therapies. As currently the most up-to-date diagnostics and treatments are available and covered by health insurance, we expect more favorable trends in the future.Leukemias and lymphomas contribute 5% to the overall cancer incidence in Croatia (1). They comprise disease entities diverse in etiology, incidence, prognosis, and treatment. The four major leukemia subtypes include acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML), while lymphomas include Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).Estimated 5-year relative survival for patients diagnosed between 2000 and 2002 in Europe, according to EUROCARE-4 results, is 43.4% for the overall group of leukemias. CLL has the highest 5-year survival rate (70.2%), followed by CML (37.2%), ALL (28.8%), and AML (15.8%). Five-year survival rates for lymphomas were 81.9% for HL and 53.6% for NHL (2).Recognized environmental risk factors for leukemia are exposure to ionising radiation (3-5), chemicals such as benzene (6), pesticides (7), chemotherapy (8), cigarette smoking (9), genetic disorders (10,11), family history in case of CLL (12), infection with HTLV-I (13), socio-economic status (14), and obesity (15). However, those risk factors could explain only a minority of cases, and leukemia etiology remains largely unknown. Environmental risk factors for NHL are exposure to pesticides, solvents (16,17) and HIV infection (18), while those for HL include HIV (19) and Epstein-Barr virus infection (20).The last decades brought significant improvements in diagnosis and treatment of leukemias and lymphomas. The aim of our study was to investigate the time trends of leukemia and lymphoma in Croatia from 1988-2009, compare them with trends in other populations, and identify possible changes.     

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.     

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.     

Blood lactate levels in patients receiving first- or second- generation antipsychotics

Aim

To compare the blood lactate levels between patients with psychotic disorder receiving first- and those receiving second-generation antipsychotics.

Methods

The study was conducted at the psychiatric inpatient and outpatient clinics of the Split Clinical Hospital from June 6, 2008 to October 10, 2009. Sixty patients with psychotic disorder who were assigned to 6-month treatment were divided in two groups: 30 received haloperidol (first generation antipsychotic) and 30 received olanzapine (second generation antipsychotic). Blood lactate levels, other metabolic parameters, and scores on the extrapyramidal symptom rating scale were assessed.

Results

Patients receiving haloperidol had significantly higher blood lactate levels than patients receiving olanzapine (P < 0.001). They also more frequently had parkinsonism, which was significantly correlated with both haloperidol treatment at 1 month (P < 0.001) and 6 months (P = 0.016) and olanzapine treatment at baseline (P = 0.016), 3 months (P = 0.019), and 6 months (P = 0.021). Also, patients receiving haloperidol had significant correlation between blood lactate and dystonia at 1 month (P < 0.001) and 6 months (P = 0.012) and tardive dyskinesia at 1 month (P = 0.032). There was a significant difference between the treatment groups in lactate levels at all points from baseline to month 6 (P < 0.001).

Conclusion

It is important to be aware of the potential effect of haloperidol treatment on increase in blood lactate levels and occurrence of extrapyramidal side effects. Therefore, alternative antipsychotics should be prescribed with lower risk of adverse side effects.

Trial identification number

NCT01139463Due to their heterogeneity, antipsychotics are difficult to classify, but they are frequently categorized as the first- and second-generation based on the incidence of extrapyramidal side effects, ie, antidopaminergic activity (1,2). First-generation antipsychotics have dominant antidopaminergic activity and pronounced extrapyramidal side effects (1), while second-generation antipsychotics have a pronounced effect on other neurotransmitter systems, as well as sporadic extrapyramidal side effects.Antipsychotics block numerous neurotransmitter receptors in a manner that induces therapeutic effects and side effects, which may vary in intensity and produce serious consequences (3-7). Extrapyramidal side effects (adverse cardiovascular, hematological, gastrointestinal, sexual, and urologic effects) are most frequently manifested in first-generation antipsychotics due to their non-selective dopaminergic block (1,8-10). The consequence of a dopaminergic effect on the tuberoinfundibular system causing dopamine to inhibit prolactin secretion is hyperprolactinemia (11,12), with possible consequences such as tissue hypoxia and mortality (13-15).Particular attention today is paid to the effects of first-generation antipsychotics on metabolic disorders. Numerous studies have shown that first-generation antipsychotic therapy may lead to metabolic changes, particularly changes in the regulation of glucose, lipid levels, and body weight (3-5,13-21). These side effects are associated with increased mortality and substantial morbidity including diabetes, hypertension, and cardiovascular disease (22,23). In many years of clinical practice, we have empirically observed that treatment with certain antipsychotics causes, along with recognized and described metabolic disorders, an increase in the blood lactate levels. Increased lactate levels are generally associated with increased morbidity and mortality in patients with chronic illnesses or critically ill patients (13,14,24-26). A review of the literature did not find any studies on the effect of antipsychotic therapy on lactate levels or such changes as a part of other antipsychotic side effects. Therefore, it is important to investigate this phenomenon in patients taking first- or second-generation antipsychotic medication.We hypothesized that a 6-month treatment with haloperidol or olanzapine would change blood lactate levels and cause extrapyramidal side effects in patients without prior antipsychotic treatment.     

Alcohol abuse as the strongest risk factor for violent offending in patients with paranoid schizophrenia

Aim

To determine predictive risk factors for violent offending in patients with paranoid schizophrenia in Croatia.

Method

The cross-sectional study including male in-patients with paranoid schizophrenia with (N = 104) and without (N = 102) history of physical violence and violent offending was conducted simultaneously in several hospitals in Croatia during one-year period (2010-2011). Data on their sociodemographic characteristics, duration of untreated illness phase (DUP), alcohol abuse, suicidal behavior, personality features, and insight into illness were collected and compared between the groups. Binary logistic regression model was used to determine the predictors of violent offending.

Results

Predictors of violent offending were older age, DUP before first contact with psychiatric services, and alcohol abuse. Regression model showed that the strongest positive predictive factor was harmful alcohol use, as determined by AUDIT test (odds ratio 37.01; 95% confidence interval 5.20-263.24). Psychopathy, emotional stability, and conscientiousness were significant positive predictive factors, while extroversion, pleasantness, and intellect were significant negative predictive factors for violent offending.

Conclusion

This study found an association between alcohol abuse and the risk for violent offending in paranoid schizophrenia. We hope that this finding will help improve public and mental health prevention strategies in this vulnerable patient group.Individuals with schizophrenia have an increased risk of violence (1), but different studies report different risks (1,2). Anglo-American studies commonly report higher prevalence rates than European studies (3,4). These patients have also been reported to have up to 4-6 times higher violent behavior rate than the general population (3-5). Nonetheless, less than 0.2% patients suffering from schizophrenia commit homicide (in 20-year period) and less than 10% of commit a violent act (3). Also, patients with schizophrenia contribute to 6%-11% of all homicides and homicide attempts (3-5).In general, aggressiveness is usually associated with anti-social personality features, juvenile delinquency, and psychoactive substance abuse (6). In patients with schizophrenia violence and violent offending is associated with a great number of risk factors, such as premorbid affinity to violent behavior, alcohol abuse, younger age, lower socioeconomic status (6,7), deinstitutionalization, longer duration of untreated psychosis, later onset of first episode of psychosis (1,4,8), lower social status, broken families, asocial behavior of parents, loss of father at an early age, a new marriage partner in the family, and growing up in an orphanage (9).Several studies (10-12) looked at four basic personality dimensions and their role in violence in patients with schizophrenic illness spectrum: impulse control, affect regulation, narcissism, and paranoid cognition. Impulsivity and immature affect regulation were associated with most neuropsychiatric disorders, and were particularly predictive of affinity for addictive disorders, while paranoid cognition and narcissism were predictive of violence acts (10-12).The causes of schizophrenia may be genetic, early environmental, and epigenetic risk factors (13,14), which may further modulate the risk of violent offending among individuals with this disease (1,15). Until recently, very little has been reported about the predictive factors of violence and violent offending in the patient population in Croatia. The Croatian population has during the last two decades been exposed to environmental and socio-demographic changes (eg, Croatian War 1991-1995 and post-war period), which might have had an impact on predictive risk factors. Therefore, we conducted a cross-sectional study of in-patients with paranoid schizophrenia with or without history of physical violence and violent offending (inclusive of homicide) in several hospitals in Croatia during one-year period.     

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.     

Prevalence of 845G>A HFE mutation in Slavic populations: an east-west linear gradient in South Slavs

Aim

To compare A allele frequencies of the 845G>A mutation of 10 Slavic populations in central, eastern, and southern Europe between each other and with other European populations.

Methods

The 845G>A mutation from the DNA of 400 Polish neonates collected in 2005-2006 was analyzed by polymerase chain reaction-restriction fragment length polymorphism. The data were compared with reports from other countries.

Results

We identified 381 GG homozygotes, 18 GA heterozygotes, and 1 AA homozygote. The 845A allele frequency was 2.5%, which makes the summary figure for Poland from this and previous studies 3.5%. The average prevalence for Poland and other West Slavic countries was 3.6%, similar to Russia (inhabited by the East Slavs, 3.5%). The average prevalence in South Slavic countries was 2.2%, gradually decreasing from 3.6% in Slovenia to 0% in Bulgaria, with a longitudinal linear gradient (adjusted R² = 0.976, P < 0.001).

Conclusions

The West and East Slavs, together with Finland, Estonia, Germany, Austria, Hungary, Slovenia, and Croatia, form a group with 845A allele frequencies between 3% and 4%. In the South Slavs, there is a gradual decline in the prevalence of 845A allele from northwest to southeast, with a surprisingly exact east-west linear gradient.In 1996, two major HFE gene mutations (845G>A and 187C>G) responsible for an inherited form of hemochromatosis were identified (1). Hereditary hemochromatosis is a common autosomal recessive disorder characterized by increased iron absorption. It has significant clinical consequences such as liver cirrhosis, diabetes mellitus, arthropathy, cardiomyopathy, and endocrine dysfunction (2). A total of 60% to 96% of patients with hemochromatosis in Europe have the mutation 845G>A in exon 4. This causes cysteine to tyrosine substitution at position 282 (C282Y) of the polypeptide chain, resulting in destabilization of one of the bridging sulfide molecules disrupting HFE binding to β2-macroglobulin (1,3). The HFE polypeptide chain loses its ability to bind to transferrin receptor, and this results in a 200-300% increase in iron absorption from food. The severity of symptoms in homozygotes is variable and depends on the race, age, sex, and diet (2,4,5). Merryweather-Clarke et al (6) reported the highest prevalence of 845A HFE in northwestern Europe (5.2 to 10.1%), ie, Sweden, Norway, UK, and Ireland. In Finland, Hungary, Poland, Russia, Austria, Germany, Czech Republic, and Slovakia the prevalence was between 3.2 and 4%. In southern Europe (Greece, Romania, Italy, and Spain), the prevalence is very low (6-18) and in Turkey it is almost non-existent (7). According to more recent data, France (6.1%) can now be added to the northwestern group (19,20). As the major comparison of the prevalence between European countries by Merryweather-Clarke et al (6) included few data on Slavic populations, we further assessed the 845A HFE frequency in the Polish population and compared it with other Slavic populations and previously published results, as well as determined its distribution across the entire Europe.