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.     

Incidence and risk factors for venous and arterial thromboses in hospitalized patients with coronavirus disease 2019: data on 4014 patients from a tertiary center registry

AimTo evaluate the burden and predictors of thromboembolic complications in a large real-life cohort of hospitalized patients with established coronavirus disease 2019 (COVID-19).MethodsWe retrospectively reviewed the records of 4014 consecutive adult patients admitted to a tertiary-level institution because of COVID-19 from March 2020 to March 2021 for the presence of venous and arterial thrombotic events.ResultsVenous-thromboembolic (VTE) events were present in 5.3% and arterial thrombotic events in 5.8% patients. The majority of arterial thromboses occurred before or on the day of admission, while the majority of VTE events occurred during hospitalization. The majority of both types of events occurred before intensive care unit (ICU) admission, although both types of events were associated with a higher need for ICU use and prolonged immobilization. In multivariate logistic regression, VTE events were independently associated with metastatic malignancy, known thrombophilia, lower mean corpuscular hemoglobin concentration, higher D-dimer, lower lactate dehydrogenase, longer duration of disease on admission, bilateral pneumonia, longer duration of hospitalization, and immobilization for at least one day. Arterial thromboses were independently associated with less severe COVID-19, higher Charlson comorbidity index, coronary artery disease, peripheral artery disease, history of cerebrovascular insult, aspirin use, lower C reactive protein, better functional status on admission, ICU use, immobilization for at least one day, absence of hyperlipoproteinemia, and absence of metastatic malignancy.ConclusionAmong hospitalized COVID-19 patients, venous and arterial thromboses differ in timing of presentation, association with COVID-19 severity, and other clinical characteristics.

An increasing pool of evidence accumulating since the early days of the coronavirus disease 2019 (COVID-19) pandemic shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces pro-thrombotic state. Although the disease presents dominantly with respiratory symptoms, resulting in acute respiratory distress syndrome in a subset of patients (1-4), high frequencies of venous and arterial thromboses were observed (5). SARS-CoV-2 endothelial tropism and damage to the vasculature of the lungs, heart, extremities, and brain have been recognized as the key part of disease pathophysiology (6-9). In addition, coagulopathy due to upregulation of inflammatory prothrombotic proteins, platelet activation, and immobilization of patients due to functional deterioration or connection to the oxygen source further favor the development of thrombotic incidents. Vascular complications occur mostly in severe cases and are often associated with multiorgan failure and higher mortality. In some patients, they can also be the dominant clinical presentation. The most frequently noted thrombotic events are pulmonary embolism (PE) and deep vein thrombosis (DVT) (10), followed by stroke, acute limb ischemia, and acute coronary syndromes (11,12), developing despite the use of pharmacologic thromboprophylaxis in hospitalized COVID-19 patients.Vascular endothelial injury is not COVID-19 specific, as similar response was described in other acute infectious diseases (13,14). However, the large scale of the COVID-19 pandemic and associated strain on the health care system result in a substantial number of patients urgently presenting to the hospital or being under an increased risk of development of thromboembolic complications. Due to importance of this issue and scarcity of regional data that may help guide the medical care of COVID-19 patients, studies on this issue are highly needed. Thus, the aim of this study was to evaluate the burden of thromboembolic complications and their predictors in a large real-life cohort of hospitalized patients with established COVID-19.     

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.     

Posttraumatic stress disorder symptoms and coping with the lockdown among help-seeking veterans before and during the COVID-19 pandemic

AimsTo compare the severity of posttraumatic stress disorder (PTSD) symptoms and of particular PTSD clusters among help-seeking veterans before and during the COVID-19 lockdown. The second aim was to identify the main coping strategies used.MethodsMale war veterans (N = 176) receiving outpatient treatment at the Referral Center for PTSD were assessed at baseline (12-18 months before the pandemic declaration in March 2020) and during the COVID-19 pandemic lockdown (March-June 2020). The Life Events Checklist for DSM-5, PTSD Checklist for DSM-5, and The Brief COPE were used.ResultsDirect exposure to the virus in our sample was low, and the majority of participants followed the preventive measures. The severity of the overall PTSD symptoms and of clusters of symptoms significantly decreased compared with the first assessment. At the second assessment, all participants still fulfilled the PTSD diagnosis criteria. During the lockdown, the participants used emotion-focused and problem-focused coping rather than dysfunctional coping.ConclusionThe severity of PTSD symptoms decreased during the lockdown. Further research is needed to study the trajectories of long-term psychopathology.

The COVID-19 pandemic has severely threatened the physical and mental health of individuals around the world. Stressors have included isolation, self-isolation or quarantine, restricted movement and physical contact, infection fears, loss of loved ones, lack of supplies, inadequate information (“infodemic”), financial loss, and social stigma (1-3). During emergencies, mental health requires special consideration due to increased rates of stress-related mental health problems and limited availability of mental health services (2-5).Depending on the emergency context, particular groups of people are at an increased risk of experiencing social and psychological problems (6), and ex-combatants have been repeatedly shown to be one of them (7).Exposure to a new traumatic or stressful life event might affect posttraumatic stress disorder (PTSD) symptoms. A growing body of research shows that such exposure is a risk factor for worsening of the condition in various groups of PTSD patients (8,9). This mainly happens if the subsequent event is of the same type as the initial stressors, serving as a reminder and as an additional traumatic factor with a “wear and tear” effect on the exposed person (10-13).Regarding the coping strategies used among PTSD patients, combat veterans with PTSD report a more ineffective and dysfunctional coping style, with the avoidance coping style as a predictive factor of the overall PTSD symptom severity (14-16). PTSD patients try to avoid confrontation with trauma-reminders, intrusive memories, and trauma-related thoughts and emotions (17,18). Some authors emphasize the importance of differentiating between coping strategies with PTSD symptoms and coping strategies with actual traumatic or stressful events as they depend on various factors related to the specific traumatic exposure (19).Twenty-five years after the Homeland War in Croatia (1991–1995), veterans still suffer from numerous health problems and have been highly prevalent among the users of the health facilities for PTSD treatment (20-22). The same is true for PTSD patients treated in the Referral Center of the Ministry of Health of the Republic of Croatia (RCPTSD) at the Clinical Hospital Center (CHC) Rijeka. A recent study revealed high rates of overall symptoms and severe posttraumatic symptoms (ie, complex PTSD) in this population years after the war ended (23).The COVID-19 pandemic lockdown in Croatia started on March 19, 2020. According to Oxford University, Croatia introduced the world''s strictest restrictions in relation to the number of the infected (24,25). On March 21, 2020, mental health experts from RCPTSD recommended self-help strategies for staying in good mental health and advice for front-liners on how to deliver psychological first aid (26,27). On the same day, the Croatian Psychiatric Association Expert Group released recommendations for the organization of psychiatric care, psychiatric interventions, and psychopharmacological treatment of mental conditions during the COVID-19 pandemic, and for de-escalation and appropriate communication techniques with aggressive patients (28-30). In RCPTSD, mental health service was restructured to be delivered via the internet or hotlines during the pandemic, with a possibility for urgent outpatient and inpatient treatment. On April 27, 2020, the lifting of restrictions began.To our knowledge, no study worldwide has examined the psycho-social correlates of the COVID-19 pandemic lockdown in veterans with PTSD. Therefore, we aimed to compare the severity of PTSD symptoms and of particular PTSD symptom clusters before and during the COVID-19 pandemic lockdown. Second, we identified the main coping strategies that veterans used during the lockdown.     

Red cell distribution width is a potent prognostic parameter for in-hospital and post-discharge mortality in hospitalized coronavirus disease 2019 patients: a registry-based cohort study on 3941 patients

AimTo investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients.MethodsWe retrospectively analyzed the records of 3941 consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission.ResultsThe median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI; and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index).ConclusionRDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a systemic infectious disease usually presenting with fever and respiratory symptoms (1). Although the most frequent serious manifestation of COVID-19 is pneumonia, the disease has been associated with cardiovascular, neurological, and gastrointestinal symptoms (2). Systemic inflammatory response mediated by high interleukin-6 concentrations induced by SARS-CoV-2 infection is associated with more severe clinical presentation, respiratory deterioration, and death (3,4). The presence of prior chronic comorbidities substantially affects the survival of COVID-19 patients (1).Anisocytosis, ie, unequal red blood cells (RBC) size, is a sensitive marker of distress in erythropoiesis or RBC destruction. It can be induced by various metabolic and inflammatory stimuli, nutrient deficiencies, infections, spleen disorders, and specific drugs interfering with RBC production (5). Anisocytosis can be quantified as a coefficient of variation of mean cell volume termed red blood cell distribution width (RDW), which is obtained by automatic cell counters. Higher RDW levels have recently gained attention as they are uniformly associated with unfavorable presentation and inferior outcomes in many chronic metabolic and malignant diseases (6-12). More severe clinical presentation and higher mortality rates were also found in COVID-19 patients with higher RDW levels (13-16). However, an association of RDW with other clinical outcomes in hospitalized COVID-19 patients, as well as the relationship with increased mortality in the context of other established prognostic scores, are not well defined. Thus, we aimed to investigate clinical and prognostic significance of RDW in a large cohort of hospitalized COVID-19 patients from our institution. We hypothesized that RDW was associated with more severe COVID-19 on admission and higher death rate.     

Effect of the coronavirus disease 2019 pandemic on people with Parkinson's disease: experience from a Croatian regional center

AimTo assess the effect of social isolation due to the coronavirus disease 2019 (COVID-19) pandemic on physical and mental health of Parkinson’s disease patients treated at the University Hospital Center Rijeka.MethodsThis cross-sectional telephone study involved Parkinson’s disease patients who had at least one control examination at University Hospital Center Rijeka in 2020 and were Croatian citizens. A questionnaire was used to obtain data on the socio-demographic characteristics and the severity of motor, anxiety, depression, and non-motor symptoms.ResultsThe final sample included 87 patients. Most patients reported subjective worsening of motor symptoms. Patients who lived alone had worse motor scores than those not living alone. The majority of patients reported worsening of anxiety symptoms. Significant worsening of anxiety symptoms was found in patients who lived alone, had a longer disease duration, and had avoided check-ups. Fewer patients had depression symptoms than motor and anxiety symptoms. Significantly higher Hamilton Depression Rating Scale scores were observed in patients with a longer disease duration. Significant worsening of non-motor symptoms was identified in patients who lived alone, were less educated, had a longer disease duration, and had a higher Charlson comorbidity index.ConclusionPatients who live alone, have longer disease duration, are less educated, avoid check-ups, and have more comorbidities are more vulnerable to the negative effects of social isolation.

⁴Department of Neurology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia

The coronavirus disease 2019 (COVID-19) pandemic has thoroughly changed many aspects of human daily life (1). From December 31, 2019 to February 21, 2021, there were 112 348 223 COVID-19 cases worldwide and 36 607 500 in Europe. In Croatia, 240 017 people were infected and 5449 died (1). Poorer outcomes and higher mortality rates have been reported in older adults and people with comorbidities such as cardiovascular disease, diabetes, hypertension, chronic obstructive pulmonary disorder, and chronic kidney disease (2). Recent studies suggest that people with Parkinson''s disease have an increased death rate (3,4).During the pandemic, people belonging to risk groups were forced to limit their social life and reduce the number of contacts. Any change in behavior that greatly alters a person''s life requires the flexibility to adapt to new circumstances. This cognitive process depends on dopaminergic function (5). A deficient dopamine-dependent adaptation can lead to feelings of helplessness and increased psychological stress (5). Higher levels of psychological stress can worsen motor and non-motor symptoms of Parkinson''s disease, but also trigger psychiatric comorbidities such as depression and anxiety (6). Physical activity can alleviate the progression of Parkinson''s disease symptoms, so a lack of activity often worsens motor symptoms (5,7). A further significant problem during the COVID-19 pandemic is avoidance of follow-up examinations (4,5,8,9). Delaying or avoiding medical care may increase the risk of morbidity and mortality associated with otherwise treatable or preventable diseases (9).The main aim of this study was to assess the effect of social isolation due to the COVID-19 pandemic on physical and mental health in Parkinson’s disease patients treated at the Clinic of Neurology of University Hospital Center Rijeka. The specific aims were to assess the effect of social isolation on 1) non-motor symptoms, 2) the occurrence of depression, 3) the occurrence of anxiety, and 4) avoiding check-ups, in people with Parkinson''s disease.     

The associations of age,sex, and comorbidities with survival of hospitalized patients with coronavirus disease 2019: data from 4014 patients from a tertiary-center registry

AimTo investigate how age, sex, and comorbidities affect the survival of hospitalized coronavirus disease 2019 (COVID-19) patients.MethodsWe retrospectively analyzed the records of 4014 consecutive adults hospitalized for COVID-19 in a tertiary-level institution from March 2020 to March 2021.ResultsThe median age was 74 years. A total of 2256 (56.2%) patients were men. The median Charlson-comorbidity-index (CCI) was 4 points; 3359 (82.7%) patients had severe or critical COVID-19. A significant interaction between age, sex, and survival (P < 0.05) persisted after adjustment for CCI. In patients <57 years, male sex was related to a favorable (odds ration [OR] 0.50, 95% confidence interval [CI] 0.29-0.86), whereas in patients ≥57 years it was related to an unfavorable prognosis (OR 1.19, 95% CI 1.04-1.37). Comorbidities associated with inferior survival independently of age, sex, and severe/critical COVID-19 on admission were chronic heart failure, atrial fibrillation, acute myocardial infarction, acute cerebrovascular insult, history of venous thromboembolism, chronic kidney disease, major bleeding, liver cirrhosis, mental retardation, dementia, active malignant disease, metastatic malignant disease, autoimmune/rheumatic disease, bilateral pneumonia, and other infections on admission.ConclusionAmong younger patients, female sex might lead to an adverse prognosis due to undisclosed reasons (differences in fat tissue distribution, hormonal status, and other mechanisms). Patient subgroups with specific comorbidities require additional considerations during hospital stay for COVID-19. Future studies focusing on sex differences and potential interactions are warranted.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a systemic disease presenting with predominantly respiratory symptoms. Up to 15%-20% of affected individuals develop high inflammatory state and severe intensity of symptoms requiring hospital admission in (1). Age and comorbidities were among the earliest recognized clinical risk factors for adverse disease course, and have consistently been shown to affect the severity of presentation and survival of COVID-19 patients. Unfavorable disease course has been especially associated with chronic metabolic comorbidities, such as arterial hypertension, diabetes mellitus, hyperlipoproteinemia, and obesity (2-7). Charlson comorbidity index (CCI), a summary measure of comorbidities validated as a prognostic tool in a number of chronic and malignant diseases (8,9), has also been associated with an adverse COVID-19 clinical course (10-15).Since elderly patients who are more frail and more prone to more severe COVID-19 are also more burdened with comorbidities, in some patients it is almost impossible to distinguish whether clinical deterioration and adverse clinical outcomes are attributable to COVID-19 or to prior comorbidities. Higher inflammatory state associated with COVID-19 might lead to clinical decompensation of chronic comorbidities, and vice versa, prior comorbidities and elevated baseline inflammatory state might predispose to more severe COVID-19. Due to this complex relationship and the need for better understanding how and to what extent particular comorbidities affect the survival of COVID-19 patients, we aimed to investigate the associations of age, sex, and comorbidities with survival in a large cohort of hospitalized COVID-19 patients treated in our institution. We hypothesized that older age, male sex, and higher comorbidity burden were associated with higher death rates.     

SIRT1 and Klotho expression in the heart and kidneys of rats with acute and chronic renovascular hypertension

AimTo evaluate Klotho and SIRT1 expression in the heart and kidneys of rats with acute and chronic renovascular hypertension.MethodsFour and sixteen weeks after the induction of renovascular hypertension by clipping the left renal artery, systemic blood pressure, serum angiotensin II level, and the expression of Klotho and SIRT1 proteins and oxidative stress indices in the heart and kidneys were assessed.ResultsSIRT1 level was significantly reduced in the ischemic (left) kidney in acute and chronic phases of hypertension. In the heart, it decreased in the acute phase, but increased in the chronic phase. Klotho levels in the heart and kidneys did not change significantly in either hypertension phase. Superoxide dismutase (SOD) activity in the heart significantly decreased, and SOD, total antioxidant capacity, and malondialdehyde in the ischemic kidney significantly increased during the development of hypertension. Serum angiotensin II level significantly increased in the acute phase of hypertension.ConclusionDevelopment of renovascular hypertension was associated with a reduction of SIRT1 expression in the heart and ischemic kidney. As angiotensin II and SIRT1 counteract each other''s expression, a SIRT1 reduction in the heart and kidney, along with the influence of systemic/local angiotensin II, seems to be partly responsible for hypertension development. A combination of SIRT1 agonists and angiotensin II antagonists may be considered for use in the treatment of renovascular hypertension.

Hypertension is one of the leading causes of disease burden worldwide, doubling the risk of coronary artery diseases (1). The prevalence of hypertension in US adults in the 2013-2016 period ranged from 26.1% in the age group 20-44 to 78.2% among people older than 65 years (2). Despite antihypertensive treatment, blood pressure of more than half of American adults is not controlled (3). Thus, to be able to produce more effective drugs, the underlying mechanisms of hypertension should be investigated.The most common cause of death in hypertensive patients is hypertensive heart disease, which results from functional and structural adaptation of the heart to high blood pressure (1). Secondary hypertension is most frequently a result of primary kidney disease. On the other hand, hypertension is a risk factor for kidney damage and end-stage renal disease (1).Hypertension and related cardiovascular diseases are age-dependent (4,5). The aging of the cardiovascular system is an important process determining longevity (6).Sirtuins are a family of enzymes encoded by SIRT1 to SIRT7 in mammals that play important roles in longevity (7). These enzymes are abundantly expressed in the nucleus and cytoplasm of several tissues, including the heart and vascular endothelium (8). The most well-known member of the sirtuin family is SIRT1, which plays beneficial roles in age-associated metabolic, inflammatory, and cardiovascular diseases (9). SIRT1 has anti-oxidant, anti-inflammatory, and anti-apoptotic effects in the endothelium and prevents endothelial senescence and dysfunction (10,11). Several studies showed that SIRT1 protected against atherosclerosis (10-13). Increasing SIRT1 expression in mice improved vascular remodeling and hypertension caused by angiotensin II (14). In addition, through reducing SIRT1 expression, hyperglycemia causes vascular damage (15).Klotho is a membrane-bound protein that exerts anti-aging function (16). Klotho deficiency leads to premature aging phenotype and shortens the lifespan (17), while its increased gene expression increases life expectancy (18). Klotho is involved in the prevention of arteriosclerosis, inducing its effects even in tissues that do not express it, which indicates its endocrine role (16). A recent study on Klotho haplodeficient mice showed that Klotho deficiency led to arteriosclerosis and hypertension, but these effects were diminished by increasing SIRT1 activity (19).One of the experimental models to evaluate secondary hypertension is 2-kidney-1-clip (2K1C) hypertension (20). In this model, a clamp is placed on one of the renal arteries to induce ischemia, while the other renal artery remains intact. This procedure steadily increases blood pressure due to an increased activity of the renin-angiotensin system in the acute phase, and sodium and water retention in the chronic phase (20,21). As SIRT1 and Klotho play a role in blood pressure regulation, and the kidneys play a role in secondary hypertension, we hypothesized that these two proteins may partake in the development of acute and chronic renovascular hypertension. Therefore, the aim of this study was to assess the expression of these two proteins in the heart and in the ischemic and non-ischemic kidneys of 2K1C rats. On the other hand, it has been shown that angiotensin II infusion increases oxidative stress and blood pressure, and that the deleterious effects of angiotensin II on blood pressure and the kidneys can be prevented by an inhibition of reactive oxygen species after angiotensin II infusion (22) and in 2K1C rats (23). Furthermore, it has been shown that SIRT1 exerts its beneficial effects by reducing oxidative stress (11,24). Therefore, the amount of oxidative stress in the heart and kidneys of the experimental animals was also assessed.     

Plasma levels of soluble TGF β receptor type III: no apparent promise as a marker in acute pancreatitis

AimTo assess the potential of the soluble transforming growth factor β receptor type III (sTGFβrIII), a key regulator in TGFβ signaling, as a biomarker for diagnosis and stratification of patients with acute pancreatitis (AP).MethodsIn this small prospective pilot study, patients’ (N = 22) plasma samples were obtained at three time points: the first and fourth day of hospitalization and the day of hospital discharge. Healthy controls’ plasma (N = 25) was obtained at a single time point. Concentration of sTGFβrIII in plasma was determined by ELISA. Data were analyzed by fitting linear or linear mixed models.ResultsPlasma sTGFβrIII levels at presentation (day 1) were similar in AP patients and healthy participants, irrespectively of the disease severity. sTGFβrIII levels in patients were constant during hospital stay.ConclusionThese observations do not support further evaluation of plasma sTGFβrIII levels in this setting, but do not exclude a potential biological role of TGFβ and membrane-bound TGFβrIII in AP pathophysiology.

Acute pancreatitis (AP) is an inflammatory condition of the pancreas most commonly caused by bile stones or excessive alcohol use (1). It has a wide spectrum of presentations – from mild (most commonly) to life threatening – and may trigger a systemic inflammatory response that could lead to organ dysfunction. An accurate and timely diagnosis and risk stratification are critical for treatment and the optimization of follow-up. This might be of a particular interest in initially milder-to-moderate forms of the disease that could deteriorate over subsequent days (2). Risk stratification in AP is an ongoing challenge considering the limitations of current prognostic scores, which are predominantly based on clinical and radiological findings. Although certain biochemical indicators are essential for diagnosis (serum amylase and lipase), they are without or of limited predictive value (C-reactive protein [CRP], procalcitonin) (2,3). Some cytokines found in plasma, such as interleukin 6 or 8, show promise in severity discrimination, however, they are not routinely used in clinical practice for this indication (4,5).Transforming growth factor β (TGF β) is a pleiotropic cytokine involved in the regulation of vital cellular processes (eg, maturation and differentiation; cell homeostasis and/or death) (6) as well as in the pathophysiology of malignant diseases, inflammation, and autoimmunity (7-9). TGFβ mediates its signaling mainly through TGFβ receptor type III (TGFβrIII), a homodimeric co-receptor that facilitates signal transduction by promoting ligands to the type II TGFβ receptor without intrinsic kinase activity (6,8). Unlike other TGFβ receptors, it is abundantly expressed on almost every human cell type (8,10). TGFβrIII generates, possibly via ectodomain shedding, a soluble form of the receptor (sTGFβrIII) (11-13), a potent TGFβ neutralizing agent with a confirmed presence in plasma (14-17). The connection between TGF-β and inflammation is a complex one (6,18). It seemingly involves TGFβrIII, and might be context-dependent, similarly to the role of TGF-β in cancer formation and progression (16,19-22). Generally, TGFβ is a strong anti-inflammatory cytokine. Disruption of its signaling results in an increased T-cell response (23), and TGFβrIII has been implicated in Th 17 lymphocyte (CD4+ and CD8+) activation (20,24). In relation to AP specifically, TGFβrIII mRNA was found to be moderately increased in AP tissue samples (25). Taken together, it appears plausible to assume that the plasma levels of the soluble form – sTGFβrIII – might be a biochemical marker in AP. To investigate the feasibility of this hypothesis, we conducted a pilot study in patients with mild-to-moderate AP.     

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.     

Waning immunity six months after BioNTech/Pfizer COVID-19 vaccination among nursing home residents in Zagreb,Croatia

AimTo assess the humoral immunity to COVID-19 in nursing home residents six months after vaccination.MethodsThis seroepidemiological research enrolled 118 residents of one nursing home in Zagreb. All participants received two doses of BioNTech/Pfizer COVID-19 and had no previously detected SARS-CoV-2 infection. The samples were tested for the presence of neutralizing antibodies using a virus neutralization test. A SARS-CoV-2 strain isolated in Vero E6 cells from a Croatian COVID-19 patient was used as a stock virus. Neutralizing antibody titer was defined as the reciprocal of the highest serum dilution that showed at least 50% neutralization. Neutralizing antibody titer ≥8 was considered positive.ResultsSixty-four (54%) participants had a positive neutralizing antibody titer, 27 (23%) had a low positive titer (titer 8), and 27 (23%) had a negative titer. Women had a significantly higher median titer than men (16 [interquartile range, IQR 24] vs 8 [IQR 12], Mann-Whitney U = 1033, P = 0.003). Age was negatively but not significantly correlated with neutralizing antibody titer (Spearman’s rho -0.132, P = 0.155).ConclusionAlmost half of the participants (46%) had a negative or low positive titer six months after having been fully vaccinated. This study suggests that humoral immunity among nursing home residents considerably wanes six months after BioNTech/Pfizer COVID-19 vaccination. Our results could contribute to the discussion about the need for a booster dose.

By October 2021, more than 238 million coronavirus disease (COVID-19) cases were confirmed and around 4.9 million deaths recorded across more than 200 countries (1). COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a serious threat to public health systems. In many European countries, COVID-19-related deaths of nursing home residents contribute to more than one third of all COVID-19-related deaths (2). The high morbidity and mortality observed among residents in long-term care facilities are a major challenge for disease prevention and control in such settings (3).The most effective intervention for preventing the spread of infectious diseases is vaccination. Various SARS-CoV-2 vaccine types have been developed, including mRNA vaccines, adenovirus-based vector vaccines, DNA vaccines, inactivated vaccines, and recombinant subunits vaccines. All vaccines so far approved in the European Union are either mRNA vaccines using lipid nanoparticles as vectors for mRNA delivery or adenovirus-based vector vaccines. All these vaccines target the spike protein, which is the main antigen component of SARS-CoV-2 structural proteins (4,5).Humoral immunity acts as an important part of immunity against viral infection, mainly through the production of neutralizing antibodies against viruses. Neutralizing antibodies play a critical role in controlling SARS-CoV-2 infection (6). In addition, the presence of each SARS-CoV-2-specific CD4+ and CD8+ T cells was associated with a milder disease (7). However, there has been much controversy over the role of humoral immune response in COVID-19, including the dynamics of antibody response, correlation with disease severity, and duration of neutralizing antibodies and memory B-cell response (8).Recent studies have shown that the neutralizing antibody level highly predicts immune protection. Croatia started mass vaccination against SARS-CoV-2 on December 27, 2020. Nursing home residents have been prioritized due to a high case fatality. After vaccination, restrictive counter-epidemic measures introduced in nursing homes were eased. However, the number of infected nursing homes residents has recently increased, prompting a discussion about the need for a booster dose. This study aimed to assess the extent of waning immunity in this population by measuring neutralizing antibody titers in one nursing home to assess the need for a third vaccine dose.     

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).     

Association between social capital,health-related quality of life,and mental health: a structural-equation modeling approach

AimTo explore the association(s) between demographic factors, socioeconomic status (SES), social capital, health-related quality of life (HRQoL), and mental health among residents of Tehran, Iran.MethodsThe pooled data (n = 31 519) were extracted from a population-based survey Urban Health Equity Assessment and Response Tool-2 (Urban HEART-2) conducted in Tehran in 2011. Mental health, social capital, and HRQoL were assessed using the 28-item General Health Questionnaire (GHQ-28), social capital questionnaire, and Short-Form Health Survey (SF-12), respectively. The study used a multistage sampling method. Social capital, HRQoL, and SES were considered as latent variables. The association between these latent variables, demographic factors, and mental health was determined by structural-equation modeling (SEM).ResultsThe mean age and mental health score were 44.48 ± 15.87 years and 23.33 ± 11.10 (range, 0-84), respectively. The prevalence of mental disorders was 41.76% (95% confidence interval 41.21-42.30). The SEM model showed that age was directly associated with social capital (P = 0.016) and mental health (P = 0.001). Sex was indirectly related to mental health through social capital (P = 0.018). SES, HRQoL, and social capital were associated both directly and indirectly with mental health status.ConclusionThis study suggests that changes in social capital and SES can lead to positive changes in mental health status and that individual and contextual determinants influence HRQoL and mental health.Mental health is defined by World Health Organization (WHO) as “a state of well-being in which every individual realizes his/her own potential, can cope with the normal pressures of life, can work productively, and is able to make a contribution to his/her community” (1,2). Mental health and associated disorders have received increasing attention worldwide, largely due to their impact on socio-economic and overall health status of patients (3). Mental health problems remain a global concern, and account for a large fraction of diseases (4,5).The overall prevalence of mental disorders in Iran between 2000 and 2008 ranged from 12.5% to 38.9% and was similar in urban (20.9%) and rural areas (21.3%) (6). Anxiety and depression were more prevalent than somatization and social dysfunction (7). The provinces with the highest prevalence of mental problems were Chaharmahal with 38.3% and Golestan with 37.3% (8).Mental health is usually determined by a complex interaction of sociocultural, psychological, environmental, and demographic factors (9). The prevalence of mental health disorders is significantly associated with age, marital status, educational level, employment, and health-related to quality of life (HRQoL) (10). HRQoL incorporates physical and socio-emotional functioning and is used to measure individual''s perception of health status, welfare, and well-being in a society (11). A frequently used psychometrical tool for the assessment of HRQoL is Short-Form Health Survey (SF-12). Its two main components are physical component summary (PCS) and mental component summary (MCS), both of which are associated with mental health (12). Previous studies have confirmed a bidirectional association between physical health and depression (as one of the main dimensions of mental health) (13). However, it is not clear whether there is a causal relationship between them (13,14).The suggested mechanisms by which depression could lead to physical disability and decreased HRQoL are poor health behaviors, increased risk of physical disease, and characteristics of depression (eg, decreased pain threshold) (15). On the other hand, physical disability can lead to depression and deterioration of mental health due to restriction of social activities and loss of social capital (15). Ultimately, this bilateral association between depression and poor physical health can lead to increasing health risks (14).Mental disorders such as depression and anxiety are also influenced by socioeconomic status (SES) (16). SES is commonly conceptualized as an individual or group’s relative social standing or class (16,17). The main predictors of SES are education level, income, and occupation (15,17,18). The correlations between SES and mental health have been explained by various mechanisms. It has been found that negative impact of low SES on mental health (19) can be reduced by the mediating effect of social capital and physical health (4,18).Social capital has been defined as individual’s social networks and social interactions, shared norms, values, and understandings that facilitate collective action within or among groups. It can act as a protective factor, promoting mental health status by reducing socioeconomic inequalities (4,20) and play an important role in reducing the prevalence of mental disorders (4). Previous studies have found that social ties and support significantly improve mental health (9). Nonetheless, the association between social capital, mental health, quality of life, and SES is not consistently reported (21,22). This population-based study aims to explore the association between demographic factors, SES, social capital, HRQoL, and mental health among Tehran residents using structural-equation modeling (SEM).     

The vicious interplay between disrupted sleep and malignant brain tumors: a narrative review

Malignant brain tumors are among the most aggressive human neoplasms. One of the most common and severe symptoms that patients with these malignancies experience is sleep disruption. Disrupted sleep is known to have significant systemic pro-tumor effects, both in patients with other types of cancer and those with malignant brain lesions. We therefore provide a review of the current knowledge on disrupted sleep in malignant diseases, with an emphasis on malignant brain tumors. More specifically, we review the known ways in which disrupted sleep enables further malignant progression. In the second part of the article, we also provide a theoretical framework of the reverse process. Namely, we argue that due to the several possible pathophysiological mechanisms, patients with malignant brain tumors are especially susceptible to their sleep being disrupted and compromised. Thus, we further argue that addressing the issue of disrupted sleep in patients with malignant brain tumors can, not just improve their quality of life, but also have at least some potential of actively suppressing the devastating disease, especially when other treatment modalities have been exhausted. Future research is therefore desperately needed.

The annual incidence of tumors of the central nervous system (CNS) is little over 22 per 100 000 in the general population (1). Around a third of these lesions are malignant. Among the malignant tumors, gliomas are by far the most common type, constituting over 80% of the number. Among gliomas, the most aggressive type (glioblastoma) is the most common one, making up over a half of all newly diagnosed gliomas (2,3). The five-year survival of patients with malignant CNS tumors is around 30%, with patients being diagnosed a glioblastoma having a five-year survival rate of less than 5%. All this goes to show how malignant CNS tumors are some of the most aggressive human malignancies today. It also shows how the vast accumulated knowledge on the disease origin and progression still has not translated into significant improvement of the overall survival of these patients. New treatment modalities are therefore desperately needed.Besides the devastating diagnosis of a malignant brain tumor, these patients often experience a wide variety of severe symptoms, which significantly diminish their quality of life (4). There has been an increasing awareness of the importance of supportive and palliative care in patients suffering from malignant brain tumors, especially those in whom other treatment modalities have been exhausted (5-7). One of the most commonly reported symptoms is sleep disturbance (4,8-12).Sleep is a recurrent, physiological phenomenon, which consists of many measurable factors (12) and is ubiquitous throughout the natural world (13-16). It is a highly active, easily reversible process, which is crucial not only for the physical and mental well-being of all living organisms, but also for the very concepts we as humans have of ourselves and the world around us (17). There are many theories regarding the possible function of sleep, ranging from the physiological explanations such as rest of individual cells (18) to behavioral explanations of why a biological system needs periodic inactivity (19). There is a growing understanding of how the modern lifestyle disrupts the natural circadian rhythm in humans, consequences of which are still not sufficiently explored (20).Sleep disruption has a well known detrimental role for an organism. Indeed, patients with disrupted sleep have been found to have a higher prevalence of several diseases, such as cardiovascular disorders (21), cognitive impairment (22), various metabolic disorders and obesity (23,24), and systemic and local inflammation (25,26). Furthermore, sleep can be impaired in many ways. The current classification of sleep disorders consists of several clinical entities such as insomnia, parasomnia, hyper-somnolence, sleep-related movement disorders, etc (27). However, this article refers to all of this broad pathology as “sleep disturbance,” primarily for clarity and simplicity sake. In addition, research on disrupted sleeping patterns in patients with malignant lesions usually also encompasses all of these entities into this broader term (28,29).     

Urine fibroblast growth factor 23 levels in hypertensive children and adolescents

AimTo determine the correlation of urinary fibroblast growth factor 23 (FGF23) excretion with blood pressure and calcium-phosphorus metabolism.MethodsThe study included 42 hypertensive (17 girls) and 46 healthy children and adolescents (17 girls) aged 6-18 years admitted to the Department of Pediatrics and Nephrology, Medical University of Białystok between January 2013 and December 2013. FGF23 in urine was measured using Human Intact FGF-23 ELISA Kit.ResultsHypertensive participants had significantly higher urine FGF23/creatinine values than the reference group (8.65 vs 5.59 RU/mg creatinine, P = 0.007). Urine FGF23/creatinine positively correlated with systolic blood pressure in all participants. In hypertensive patients, urine FGF23/creatinine positively correlated with serum calcium and negatively with serum 25(OH)D, urinary calcium, phosphorus, and magnesium.ConclusionThis study found that FGF23 may play an important role in the pathogenesis of hypertension in children and adolescents, but our results should be confirmed by further studies.Hypertension is a chronic medical condition and a major risk factor for cardiovascular disease, heart failure, and chronic kidney disease (CKD). Hypertension was found to be associated with several factors, among them calcium-phosphorus imbalance, lack of vitamin D, and serum parathyroid hormone (PTH) (1-5). However, far too little attention has been paid to phosphates and hormonal mechanisms responsible for their regulation, especially since the consumption of phosphorus has considerably increased in recent years. Some studies have shown that serum phosphorus increases BP (11,12). However, recent studies have found that high phosphorus intake reduces BP, when the diet is rich in calcium (6-8), while other have shown that BP was reduced by low phosphorus and high calcium diet (9,10).Phosphate concentration is primarily regulated by PTH and fibroblast growth factor 23 (FGF 23) – phosphatonin, produced by osteoblasts/osteocytes in the bone, which, similarly to PTH, stimulates phosphaturia. FGF23 decreases renal calcitriol production and inhibits PTH secretion. Its main function is to maintain phosphate homeostasis by increasing urinary phosphate excretion and decreasing serum 1,25(OH)₂D (13,14) In patients with CKD, it positively correlated with PTH secretion (15,16). The increase in FGF23 in those patients led to an early development of secondary hypertension by suppression of 1,25(OH)₂D production (17), and low phosphate intake of phosphorus binders caused 35% decrease in plasma FGF23 level (18). However in healthy individuals no changes in FGF23 levels were observed after both phosphate deprivation and loading (19,20).FGF 23 is also involved in renal sodium handling (21) and, what is even more interesting, it suppresses the expression of angiotensin-converting enzyme-2 (ACE2) in CKD-mice and thereby activates renin-angiotensin-aldosterone system (RAAS) (22). FGF23 can also influence the RAAS indirectly through vitamin D (23), which probably reduces renin gene expression and secretory activity of the juxtaglomerular apparatus, the main place of production of renin (24).The investigation of the effect of FGF23 on hypertension is not confined to in vitro models. Hypertensive people were found to have significantly higher plasma FGF23 level than normotensive people (25). FGF23 was shown to have an association with markers of inflammation in individuals with CKD stages 2-4 (26), and with impaired endothelium-dependent vasodilatation in healthy individuals and early CKD patients (27). This effect of FGF23 might also result indirectly from a decrease in 1,25 (OH)₂D (28). FGF23 also correlated with asymmetrical dimethylarginin (ADMA), which is an endogenous inhibitor of NO synthase and a biomarker of endothelial dysfunction (29).So far, however, the relevance of FGF23 in primary arterial hypertension has been under-investigated. What is more, available data focus on adult hypertensive patients and possible relation of phosphorus intake and increased FGF23 concentration to elevated BP (25). There is a paucity of similar data in children and adolescents. The aims of this research were to determine whether urinary excretion of FGF23 in hypertensive children and adolescents was higher than in healthy controls and whether its urinary level correlated with serum calcium, phosphorus, vitamin D, and PTH concentrations. Reference group data were obtained from the OLAF study, which established the reference blood pressure range for Polish children and adolescents. A strong correlation between serum and urine FGF23 was previously confirmed (r = 0.92, P < 0.001) (30).     

Awareness,knowledge, use,and attitudes toward evidence based medicine in a developing country: survey of physicians in a canton in Bosnia and Herzegovina

Aim

To assess awareness, knowledge, use, and attitudes toward evidence-based medicine (EBM) and The Cochrane Library (CL) among physicians from Zenica-Doboj Canton (ZDC), Bosnia and Herzegovina.

Methods

In this cross-sectional study, a self-administered anonymous questionnaire was sent by post to all state owned health institutions (2 hospitals and 11 Primary Health Care Institutions) in ZDC. The main outcome measures were physicians’ awareness of the Cochrane, awareness and use of CL, access to EBM databases, and access to internet at work. 358 of 559 physicians responded (63.69%).

Results

23.18% of respondents stated they had access to EBM databases, but only 3.91% named the actual EBM databases they used. The question on the highest level of evidence in EBM was correctly answered by 35.7% respondents, 34.64% heard about Cochrane and 32.68% heard about CL. They obtained information about CL mostly on the internet and from colleagues, whereas the information about EBM was obtained mainly during continuous medical education.

Conclusion

Although the attitudes toward EBM are positive, there is a low awareness of EBM among physicians in ZDC. Open access to the CL should be used more. Educational interventions in popularizing EBM and Cochrane are needed to raise awareness both among students and practicing physicians, and finally among lay audience.Evidence based medicine (EBM) is described as an integration of individual clinical expertise, the best available external clinical evidence from systematic research, and individual patients’ predicaments, rights, and preferences, in making clinical decisions about their care (1,2). However in many settings there are still barriers to its implementation (3-6).Awareness, knowledge, use, and attitudes toward EBM have been assessed worldwide (6,7). Attitudes toward EBM were mostly positive and participants welcomed the promotion of EBM (6-11). Barriers to practicing EBM differed between developing and developed countries. For example, respondents from Iran (8) reported that a major barrier was the lack of EBM training courses, while those from the Netherlands and Belgium reported limited time, attitudes, knowledge, and skills (5,12-14).Systematic reviews with or without meta-analysis produced by The Cochrane Library (CL) are considered as the “gold standard” in EBM (15-18). Cochrane systematic reviews (CSRs) can raise the quality of health care, especially in developing countries with scarce resources. For example, CSRs have been shown to provide invaluable evidence in creating national reimbursement lists (19).A nation-wide study among physicians in Croatia concluded that there was low awareness about EBM and the CL (30%), and additional educational interventions were required (6). Unlike Croatia, Bosnia and Herzegovina (BH) has no organized Cochrane activity (20). Our study aimed to assess the awareness, knowledge, use, and attitudes toward EBM and the CL (as the only available EBM database in BH with unrestricted access) among physicians in Zenica-Doboj Canton (ZDC), to help in the implementation of educational activities that would improve the use of EBM and the CL.