Effectiveness of letters to patients with or without Cochrane blogshots on 10-year cardiovascular risk change among women in menopausal transition: 6-month three-arm randomized controlled trial.

BACKGROUND: Health information and patient education on lifestyle changes may have a positive effect on the prevention of many chronic conditions, especially cardiovascular diseases (CVDs). We performed a parallel, three-arm randomized controlled trial (RCT) of 6-month educational intervention in a form of letters containing a reminder of the participant's CVD risk with or without Cochrane blogshots to reduce CVD risk among women aged 45-65 with one or more known CVD risk factors. METHODS: The control group received a letter about their CVD risk at the beginning of the trial. The intervention groups received the initial letter about their CVD risk and remainder letters about their CVD risk every 2 months, with or without Cochrane blogshots: (1) effect of calcium in the prevention of high blood pressure, (2) effect of reducing saturated fat acids in eating habits, and (3) effects of green and black tea in CVD prevention. The primary outcome was CVD risk reduction calculated as the difference between the baseline and 6-month score for a 10-year risk of fatal CVD according to the ACC/AHA guidelines. RESULTS: After both interventions, CVD risk reduction was significantly higher compared to the control group (P < 0.001, Kruskal-Wallis H test). The number of participants who decreased their CV risk was 29% (20/70) in the control group, 69% (48/70) in the group receiving the reminder letters, and 70% (49/70) in the group receiving the reminder letters and blogshots. The number needed to treat to achieve risk reduction was 2.41 (95% CI = 1.77 to 3.78) for letters with a CVD risk reminder and 2.50 (1.81 to 4.03) for letters with a reminder and a blogshot. The group receiving reminder letters with Cochrane blogshots had a significant change in the category of CVD risk, mainly from high to moderate and from moderate to low CVD risk category. CONCLUSIONS: A simple and inexpensive intervention method in a form of letters reminding women about their CVD risk with or without providing additional health information in the form of Cochrane blogshots about interventions for important CVD risk factors may be effective in CVD management and could be considered by primary care providers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04601558. Retrospectively registered on October 19, 2020.

Serotonin 5-HT2A receptor polymorphisms are associated with irritability and aggression in conduct disorder.

In childhood and adolescence, overt antisocial and aggressive manifestations are typically diagnosed as conduct disorder (CD). Given that the emerging research has pointed to the influence of 5-HT2A receptors in the ontogeny of aggression, we aimed to analyze the association of its genetic polymorphisms with CD. The study included 228 male adolescent subjects (120 with and 108 without CD). CD was diagnosed according to Structured Clinical Interview for DSM-IV criteria, while evaluations of aggressive/dissociative behaviors were performed using psychometric questionnaires including the PCL-YV, OAS-M, KADS, and CBCL. Platelet 5-HT concentration was determined by spectrophotofluorometry. Genotyping of 5-HT2A receptor polymorphisms rs2070040, rs9534511, rs4142900, rs9534512 was performed using TaqMan SNP Genotyping Assays. Subjective irritability, physical aggression toward others, and antisocial behavior were strongly associated with the G allele of rs2070040 and rs4142900, and the C allele of rs9534511 and rs9534512. A significantly increased platelet 5-HT concentration in CD subjects, compared to controls, was lost after the correction according to the smoking status. Our results indicate an association of the studied HTR2A polymorphisms and their haplotypes with irritability and impulsivity traits, which may contribute to the aggressive and antisocial behavior in male adolescents with CD.

Differences in the Pattern of Non-Recreational Sharing of Prescription Analgesics among Patients in Rural and Urban Areas.

INTRODUCTION: This study aimed to analyze differences in sharing of prescription analgesics between rural and urban populations. METHODS: We surveyed 1000 participants in outpatient family medicine settings in Croatia. We used a 35-item questionnaire to analyze patients' characteristics, pain intensity, prescription analgesic sharing behavior, and perception of risks regarding sharing prescription medications. RESULTS: Prescription analgesic sharing was significantly more frequent in the rural (64%) than in the urban population 55% (p = 0.01). Participants from rural areas more commonly asked for verbal or written information than those from urban areas when taking others' prescription analgesics (p < 0.001) or giving such analgesics (p < 0.001). Participants from rural areas more commonly informed their physician about such behavior compared to those from urban areas (p < 0.01), and they were significantly more often asked about such behavior by their physician (p < 0.01). Perceptions about risks associated with sharing prescription medication were similar between rural and urban populations. CONCLUSIONS: There are systematic differences in the frequency of prescription analgesics and associated behaviors between patients in family medicine who live in rural and urban areas. Patients from rural areas were more prone to share prescription analgesics. Future studies should examine reasons for differences in sharing prescription analgesics between rural and urban areas.

Detention in Juvenile Correctional Facilities Is Associated with Higher Platelet Monoamine Oxidase B Activity in Males.

Juvenile delinquency is related to several biological factors, yet very few vulnerability biomarkers have been identified. Previous data suggest that the enzyme monoamine oxidase B (MAO-B) influences several personality traits linked to the propensity to engage in delinquent behavior. Building on this evidence, we assessed whether conduct disorder (CD), juvenile delinquency adjudications, or detention in a correctional facility were associated with either platelet MAO-B activity or the MAOB rs1799836 polymorphism. The study enrolled 289 medication-free male youths, including 182 individuals detained in a correctional facility (with or without a diagnosis of CD). Of the remaining 107 participants, 26 subjects had a diagnosis of CD, and 81 were mentally healthy controls. Platelet MAO-B activity was determined by spectrophotofluorometry, while MAOB rs1799836 was genotyped using qPCR. Platelet MAO-B activity, corrected for age and smoking, was significantly higher in juvenile detainees (p < 0.001), irrespective of CD diagnosis. MAOB rs1799836 was not associated with platelet MAO-B activity or with detention in a correctional facility, CD diagnosis, or delinquent behavior. These data suggest that detention in a juvenile correctional facility increases platelet MAO-B activity in male adolescents. Future studies are needed to determine the mechanisms and functional significance of MAO-B peripheral elevation in juvenile male detainees.

Knowledge and attitudes of patients in primary care on off-label treatment.

OBJECTIVE: To examine primary care patients' knowledge and attitudes on off-label treatment. METHODS: In 47 primary care offices in Osijek-Baranja County, 1300 patients were given questionnaires about their knowledge and attitudes on off-label treatment. Questionnaires were completed voluntarily and anonymously. RESULTS: Majority of patients (96.3%) had no knowledge about off-label treatment, and upon having it explained, 42.3% would not accept such treatment under any circumstances, while 54.5% would never accept such treatment for their children. Patients place more trust in primary care doctors than in hospital doctors; 69.6% of patients strongly believe that primary care doctors would not expose them to off-label treatment while only 41.2% of them think the same in relation to hospital doctors. In case of serious consequences following off-label therapy 49.9% of patients would sue doctors who prescribed it. CONCLUSION: Patients in primary care possess limited knowledge about off-label treatment. Most patients do not wish to be exposed to such treatment, and are particularly reluctant to have their children exposed to it. In case of serious side effects, half of the patients would sue doctors who had prescribed the off-label therapy.

The temperament and character traits in patients with major depressive disorder and bipolar affective disorder with and without suicide attempt.

BACKGROUND: Suicide and mood disorders (especially major depressive disorder (MDD) and bipolar affective disorder (BD)) represent a significant global health burden. Major depressive disorder and bipolar affective disorder have been associated with increased risk for suicide. Some specific suicide risk factors might be found in underlying individual personality traits. Specific personality features may predispose an individual to mood disorders (MDD or BD) hence increased suicide risk. The specificity of this research is in the assessment of personality features during the acute phase of illness immediately after suicide attempt which resulted in psychiatric inpatient treatment. SUBJECTS AND METHODS: The study included 119 unrelated Caucasian participants with MDD-severe depressive episode without psychotic symptoms (MDD) and BD-severe depressive episode without psychotic symptoms (BD-sDE). Both groups of patients with MDD and BD-sDE were divided into the suicide attempters and non-suicidal group. The diagnoses of the severe depressive episode without psychotic symptoms in major depressive disorder (MDD; F32.2) and bipolar disorder (BD-sDE; F31.4) were made according to ICD-10 (WHO 1992) diagnostic criteria. Methods of suicide attempts were also assessed according to ICD-10 and a self-report questionnaire, the Temperament and Character Inventory (TCI) was applied. RESULTS: The participants who exhibited suicide attempt had significantly higher scores on harm-avoidance (HA) (p<0.001), significantly lower score on persistence (PS) (p=0.037) and lower score, however not statistically significant, on novelty-seeking (NS) (p=0.319) regarding temperament dimensions. In character dimensions, the patients with suicidal attempt had significantly lower scores on self-directedness (SD) (p<0.001) and significantly lower scores on cooperativeness (CO) (p=0.001). CONCLUSION: Patients who had suicide attempt may have some significantly different personality traits than non-suicidal patients with mood disorders. The combination of high harm-avoidance (HA) and low self-directedness (SD) may be specific for depressive episode while the combination of high HA, novelty-seeking (NS), and self-transcendence (ST) with low SD may be related to suicide attempts during the depressive episode in bipolar disorder. The novelty-seeking (NS), self-transcendence (ST) and self-directedness (SD) may be specific for suicidal group of bipolar patients.

Psychotropic medications in older adults: a review.

BACKGROUND: Prevalence of prescribing psychotropic medications, particularly inappropriate prescription, is widespread in older adults, both in nursing home residents as well as community-dwelling older adults. This review describes prevalence and prevention of inappropriate prescribing and risk factors associated with psychotropic medications. METHODS: MEDLINE and GOOGLE SCHOLAR data base were searched for the key words "older adults", "psychotropic drugs", "inappropriate prescribing", "nursing home residents", "community-dwelling older adults". The study was limited to the articles published in English in the period from 2007 to 2014. The list of references includes additional articles that were searched manually. RESULTS: The utilization of different psychotropic medications is prevalent among older adults worldwide, regardless of whether they live in nursing homes or in the community. Among older adults, nursing home residents are the most vulnerable individuals for potentially inappropriate drug prescription. The most common potentially inappropriate prescribed medications in the elderly are benzodiazepines, particularly long-acting, antipsychotics and antidepressants, particularly SSRIs. All classes of listed medications have been associated with different adverse events, particularly falls and falls-related fractures and increased risk for mortality. Many different pharmacological and non-pharmacological interventions, such as monitoring polypharmacy, reviewing medications, spending more time in the institution by a physician, reducing the number of prescribers in the institution as well as greater involvement of geriatricians, general practitioners and pharmacists should be implemented to reduce this health issue. CONCLUSION: The prevalence of prescribing psychotropic medications to older adults is high. Inappropriate prescribing of psychotropic drugs and polypharmacy are present in institutionalized and non-institutionalized older adults and can cause adverse health events, and can significantly reduce the quality of life of these vulnerable groups. Multidisciplinary approach is needed in addressing widespread problem of prevalence of psychotropic medications in older adults.

Detection of thallium and uranium in well water and biological specimens of an eastern Croatian population.

Abstract Using inductively-coupled plasma mass spectrometry (ICP-MS), we measured the concentrations of thallium and uranium in local water resources from three villages (Celije, Draz, and Potnjani) in eastern Croatia, with the aim to determine if they were associated with the levels of these same elements in the serum, urine, and hair collected from the residents of this area. The exposure of the local population to thallium and uranium through drinking water was generally low. ICP-MS was capable of measuring the levels of both of the elements in almost all of the analysed samples. Although there were differences in the concentrations of both elements in water samples and biological specimens taken from the residents, they did not reach the maximum contaminant level in any of the four sample types studied. Although hair was previously reported as an excellent indicator of occupational and environmental exposure to various elements, our study did not confirm it as a reliable biological material for tracing thallium and uranium levels, mainly due to the very low concentrations of these elements, often well below the detection limit. However, our results have shown that the concentration of thallium and uranium in drinking water can be effectively traced in urine samples.

The association between the catechol-O-methyltransferase Val108/158Met polymorphism and hyperactive-impulsive and inattentive symptoms in youth.

RATIONALE: Hyperactivity, impulsivity, and inattention are major symptoms occurring in attention-deficit/hyperactivity disorder. This disorder is highly heritable, multifactorial, polygenic, and associated primarily with dysfunctions of dopaminergic, noradrenergic, and serotonergic systems. OBJECTIVES: The present study tested the possible association of the catechol-O-methyltransferase (COMT) Val108/158Met (rs4680) polymorphism with hyperactive-impulsive and inattentive symptoms in male youth. METHOD: Polymorphism COMT Val108/158Met was analyzed in 807 male unrelated Caucasian young subjects: 231 healthy controls, 195 subjects with moderate hyperactive symptoms and 254 subjects with moderate inattentive symptoms, 111 subjects with severe hyperactive symptoms and 90 subjects with severe inattentive symptoms, all evaluated using Swanson, Nolan, and Pelham Questionnaire IV criteria. RESULTS: The frequency of the COMT genotypes, alleles, and the homozygous Met/Met genotype versus Val carriers (χ²) test with standardized residuals) differed significantly between subjects without and subjects with hyperactive-impulsive and inattentive symptoms. In addition, significantly higher hyperactive-impulsive and inattentive scores were found in subjects with the Met/Met genotype compared to carriers of other COMT genotypes. These significant results were due to the more frequent occurrence of Met/Met genotype or the Met allele in subjects with moderate and severe hyperactive-impulsive and inattentive symptoms compared to matched controls. CONCLUSION: These results suggest that the Met/Met genotype or the Met allele of the COMT Val108/158Met, contributing to higher dopaminergic activity, are significantly overrepresented in subjects with moderate or severe hyperactive-impulsive and inattentive symptoms, and that this polymorphism is significantly associated with hyperactive-impulsive and inattentive symptoms in young boys and adolescents.

Association between brain-derived neurotrophic factor Val66Met and obesity in children and adolescents.

Obesity in children and adolescents is a worldwide health problem, characterized by various somatic, psychosocial and psychiatric complications, and is often associated with adult obesity and related complications. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with important roles in feeding behavior, food intake regulation, energy metabolism and weight control. A common polymorphism of the BDNF genotype (Val66Met) has been associated with various forms of eating disorders, alterations in body mass index (BMI) values and obesity in adult populations. The aim of this study was to determine the association between the gene variants of the BDNF Val66Met polymorphism and obesity in 300 healthy Caucasian children and adolescents of the same ethnic background of Croatian origin, subdivided according to the BMI percentile, but without any form of eating disorders. The frequency of the Met/Met, Met/Val and Val/Val genotypes, Met and Val alleles, and Met carriers (the combined Met/Met and Met/Val genotypes versus the homozygous Val/Val genotype) differed significantly between underweight, normal weight, overweight and obese children, and the presence of one or two Met alleles contributed to this significant effect. These results showed for the first time the significant association between the presence of one or two Met alleles and obesity in ethnically homogenous groups of healthy Caucasian children and adolescents. These data confirmed the major role of BDNF in energy metabolism, food regulation and BMI.

The treatment of autistic children with risperidone.

Autism is a pervasive developmental disorder characterised by impairment in social interaction and communication, with unusual behavior. In some cases the pharmacotherapy is prescribed and the most studied antipshychotic drugs include haloperidol and risperidone. In this paper we displayed the treatment of two cases of autism in boy and girl with risperidone. With the use of risperidone in girl, we have achieved reduction of psychomotor symptoms and reduction of hetero-aggressive and self-destructive behavior, and in boy we have also achieved reduction of psychomotoric symptoms, with improvement in contact with his surrounding, he had less learning problems and he has felt familiar not only with his mother, but with other persons. Research on the use of risperidone in the treatment of autistic disorders among children in Croatia are rare, given the limited use of risperidone in children younger than 15years, the question arises about the need to expand the scope of application of risperidone in younger age groups.

Human plasma glycome in attention-deficit hyperactivity disorder and autism spectrum disorders.

Over a half of all proteins are glycosylated, and their proper glycosylation is essential for normal function. Unfortunately, because of structural complexity of nonlinear branched glycans and the absence of genetic template for their synthesis, the knowledge about glycans is lagging significantly behind the knowledge about proteins or DNA. Using a recently developed quantitative high throughput glycan analysis method we quantified components of the plasma N-glycome in 99 children with attention-deficit hyperactivity disorder (ADHD), 81 child and 5 adults with autism spectrum disorder, and a total of 340 matching healthy controls. No changes in plasma glycome were found to associate with autism spectrum disorder, but several highly significant associations were observed with ADHD. Further structural analysis of plasma glycans revealed that ADHD is associated with increased antennary fucosylation of biantennary glycans and decreased levels of some complex glycans with three or four antennas. The design of this study prevented any functional conclusions about the observed associations, but specific differences in glycosylation appears to be strongly associated with ADHD and warrants further studies in this direction.

The case report of treatment strategy for Anorexia nervosa with psychotic elements in adolescent.

Eating disorders in early childhood are the same frequency in boys and girls. During adolescence eating disorders are ten (10) times more frequent in girls than in boys. Worrying is the fact that eating disorders are the third chronic illness among adolescents after obesity and asthma. Depicting this adolescent we tried to show difficulty of treatment of this disorder, where in the beginning is important to stabilize body weight and prevent somatic damages such as: heart damage, amenorrhoea, changes in EKG (electrocardiogram) and electrolyte dysbalance that could endanger the life of patient. Simultaneously it is important to recognize and treat comorbid psychological disturbances such as in this case: depression, delusions with occasional psychotic reactions combined with unrealistic thinking about the layout of her own body. There is still no cure for the treatment of eating disorders which are in growing number of reports among male adolescents.

Suicidal behavior and suicide among children and adolescents-risk factors and epidemiological characteristics.

In last decade suicide attempts and suicides among youngsters are increasing greatly and are one of the leading causes of mortality in this age group. Epidemiological data are pointing on more frequent trend of self-destructive behavior among youngsters in the world as well as in our country. Risk factors which influence on increasing number of suicide attempts and suicides in this age are different in etiology: interference of genetic influences, family dynamics and external environment (school, friends, social environment, peers, television, video, and internet). Croatia as a country in transition is also following trends in the world according to epidemiological data, what is for sure great challenge for all who participate in dealing with youngsters, especially psychiatric services. In the planning of treatment is very important to include family with intention to accomplish optimal therapeutic effect. Also, it is very important to warn parents on their part of responsibility in upbringing and developing of their adolescent.

[The role of zinc in the treatment of hyperactivity disorder in children]. / Uloga cinka u lijecenju hiperaktivnog poremecaja u djece.

Zinc is an essential cofactor of more than 100 enzymes, including metalloenzymes and metalloenzyme complexes, which are necessary in the metabolism of carbohydrates, fatty acids, proteins and nucleic acids. It is an important factor in the metabolism of neurotransmitters, prostaglandins, and for maintaining brain structure and function. Dopamine is one of the most important factors in the pathophysiology of hyperactivity disorder, and the hormone melatonin has an important role in the regulation of dopamine. Because zinc is necessary in the metabolism of melatonin, it can be assumed that zinc is a very important factor in the treatment of attention deficit and hyperactivity disorder (ADHD). It is known that deficit of some minerals and vitamins is connected with hyperkinetic disorder. Preliminary investigations in humans show that many children with ADHD have lower zinc concentration in relation to healthy children. Zinc sulfate as an adjunct to methylphenidate has favorable effects in the treatment of ADHD children, pointing to the possible association of zinc deficit and ADHD pathophysiology. Zinc concentration can only point to some other factors (malnutrition) that can lead to ADHD, but is not a factor that has a causative role in ADHD. Therefore, zinc supplementation to nutrition or to ADHD therapy may be of great benefit in ADHD children with zinc deficit or low plasma zinc concentration. ADHD occurs in different cultures, mostly before seven years of age. In children younger than five years it is difficult to make an accurate diagnosis because their behavior is more variable than in older children. Hyperactive disorder is mostly observed in younger age, i.e. in childhood and adolescence. The majority of the main characteristics are less pronounced or completely lost in adult age. In the 1960s, the disorder was named "minimal cerebral dysfunction" and was most often the consequence of head trauma or low birth weight. Later, the term was changed as hyperactive reaction in childhood. Recent studies estimate its prevalence to three of ten hyperactive children, and there are data that about 4% of children have the complete frame of the disorder. The condition is more common in boys than in girls. The reason probably lies in the fact that girls primarily develop attention disorder and cognitive problems (concentration, memory, thinking), and less often have symptoms of aggressive and impulsive behavior, thus boys being earlier referred for examination. There are many theories about the possible origin of hyperactive disorder, and one of the most widely studied is the theory of the role of dopamine, which is supported by the results of treatment in these children with dopamine agonists like methylphenidate and amphetamines. Recent studies do not neglect the influence of maternal intake of food and drink additives, alcohol consumption and smoking during pregnancy, soil contamination, and low birth weight. Zinc is a coenzyme of the enzyme delta-6 desaturase, which is important in the anabolism of polyunsaturated long chain fatty acids, linolic and linolenic acids that constitute neuronal membrane. Studies point to the possible association of zinc deficiency and ADHD pathophysiology. In ADHD children with zinc deficiency or low plasma zinc concentration, zinc dietary supplementation or during therapy for ADHD may be of great benefit. A study of ADHD treatment with zinc sulfate as a supplement to methylphenidate showed beneficial effects of zinc supplementation in the treatment of children with ADHD. The dose of zinc sulfate used was 55 mg/day, which is equivalent to 15 mg zinc. The improvement achieved in ADHD children with the use of zinc sulfate appears to confirm the role of zinc deficiency in the etiopathogenesis of ADHD. Additional studies are needed to identify the real and efficient dose of zinc.

Shared psychotic disorder ("folie a deux") between mother and 15 years old son.

We presented a rare case in clinical practice: fifteen (15) years old male adolescent with shared psychotic disorder with his thirty seven (37) years old mother. In this case of "folie d deux" child was the passive psychotic partner and his mother who was the dominant psychotic partner. Both patients shared the same paranoid and imperative delusions. With complete psychiatric anamnesis, clinical interview, psychological testing, EEG (examination-electroencephalography) examination and control examinations we came to the diagnosis and efficacious pharmacological intervention for son.

Circadian rhythm of blood leptin level in obese and non-obese people.

Leptin, an adipose tissue hormone, has circadian variations in its secretion. Aims of this study were to show how circadian rhythm depends on fat tissue distribution in obese and non-obese subjects. The research was carried out on 70 subjects (37 men and 33 women) with an average body mass index (BMI) of 25.22 kg/m2. Concentration of leptin in blood was measured at 8.30 a.m., 12.30 p.m. and 6.30 p.m. Basal leptin level correlated strongly with all isolated regions of subcutaneous fat tissue in women and obese subjects. Circadian changes of blood leptin level in non-obese people are more significant than these changes in obese people. Differences in circadian pattern of leptin secretion between obese and non-obese subjects were probably caused by enlarged volume of subcutaneous fat tissue in obese people. Lean subjects have subcutaneous fat in physiological range which allows influence of some hormones (insulin or cortizol) or food intake on leptin secretion.