Prevalence of somatic comorbidities among coronavirus disease 2019 patients in Croatia in the first pandemic wave: data from national public health databases.

AIM: To determine the prevalence of common somatic comorbidities among coronavirus disease 2019 (COVID-19) positive patients in Croatia in the first pandemic wave, and assess the differences in clinical outcomes depending on the presence of comorbidities. METHODS: We analyzed data from patients confirmed to be SARS-CoV-2-positive from February through May 2020. The data were obtained from clinical laboratories, primary health care providers, and hospitals. Previously recorded comorbidities, including diabetes, cancer, circulatory diseases, chronic pulmonary, and kidney disease, were analyzed. RESULTS: Among 2249 patients, 46.0% were men (median age 51 years; median disease duration 27 days). Hospitalization was required for 41.8% patients, mechanical ventilation for 2.5%, while 4.7% of all patients died. Patients who died were significantly older (median 82 vs 50 years, P<0.001) with a higher prevalence of all investigated comorbidities (all p's <0.001), more frequently required mechanical ventilation (34% vs 1%, P<0.001), and had shorter length of hospital stay (median 13 vs 27 days, P<0.001) with no sex preponderance. Patients requiring mechanical ventilation were significantly older (median age 70 vs 51 years, P<0.001), more frequently men (59.6% vs 45.7%, P=0.037), showed a higher prevalence of all comorbidities except ischemic heart and chronic kidney disease (all p's <0.001), and demonstrated a higher case-fatality rate (63.2% vs 3.2%, P<0.001). CONCLUSION: COVID-19 patients who died in the first pandemic wave in Croatia were more likely to suffer previous somatic comorbidities. This corroborates the findings of similar studies and calls for further research into the underlying disease mechanisms, hence providing ground for more efficient preventive measures.

Early Basal Cortisol Level as a Predictor of Hypothalamic-Pituitary-Adrenal (HPA) Axis Function After Pituitary Tumor Surgery.

PURPOSE: The purpose of this study was to evaluate the clinical relevance of the early postoperative basal cortisol level in assessing the postoperative hypothalamic-pituitary-adrenal (HPA) axis function after pituitary tumor surgery. METHODS: We performed a prospective observational study that enrolled 83 patients operated for pituitary adenoma or other sellar lesions at the University Hospital Center Zagreb between December 2013 and April 2017 (44 nonfunctioning pituitary adenomas, 28 somatotropinomas, 5 craniopharyngiomas, 2 prolactinomas resistant to medical therapy and 4 other lesions - Rathke's cleft cyst, arachnoid cyst, chondroma and gangliocytoma). Exclusion criteria were Cushing's disease, chronic therapy with glucocorticoids prior to surgery and preoperative adrenal insufficiency. Early postoperative basal cortisol levels (measured on the second postoperative day) and the Synacthen stimulation test (performed 3 months after the surgery with the peak cortisol level of>500 nmol/L considered as a normal response) were analyzed to assess HPA axis function during follow-up. RESULTS: ROC analysis showed a cut-off of the basal cortisol level of ≥300 nmol/L measured on the second postoperative day to predict normal postoperative HPA axis function with the sensitivity of 92.31%, specificity of 87.14% and positive predictive value of 57.14%. CONCLUSION: The basal cortisol level on the second postoperative day is a valuable tool to predict integrity of the HPA axis after pituitary tumor surgery. Our data suggest that the cortisol level of ≥300 nmol/L accurately predicts adrenal sufficiency and that in these patients glucocorticoid therapy can be withdrawn.

Diabetic Macular Edema: Traditional and Novel Treatment

Diabetes is one of the leading public health problems worldwide. Diabetic macular edema (DME) is the main cause of vision loss in patients with diabetes. Ideal metabolic control of diabetes is the primary goal of treatment and the basic way of preventing and stopping the progression of DME. Although laser photocoagulation has been the standard treatment of DME for nearly three decades, superior outcomes can be achieved with novel, intravitreal anti-VEGF and steroid therapy. Novel treatment option for DME depends on visual acuity and location/extent of macular thickening based on optical coherence tomography scans. According to the International Clinical Classification Scale, DME is divided into no center-involving DME and center-involving DME (CI-DME). New guidelines recommend intravitreal treatment as the treatment of choice for patients with CI-DME and moderate visual impairment. Patients with no CI-DME and mild visual impairment should be treated with modified ETDRS laser photocoagulation and closely observed. Vitrectomy is the treatment of choice for patients with a tractional component of DME. Nowadays, traditional treatment goal of preventing blindness in patients with DME has been changed by the new goal aiming to restore impaired vision, prevent further vision loss and improve visual function. Therefore, many trials addressing this new concept have been underway worldwide.

SOME INDICATORS OF HEALTH CARE STATUS IN CROATIA.

The article presents the basic principles of health care, health care measures and strategic objectives of these measures in Croatia. The health of the population does not depend solely on the activities of the health care system but also on various demographic indicators. Our success in implementing health care depends largely on the structure of health facilities and health workers. The Croatian health system in late 2013 had permanently employed 74,489 workers. Out of these, 77% were health care workers. Most health care workers had only secondary school education (37.7%); physicians represented 17.4% of the workforce. On assessing the health of the population, certain health indicators are of utmost importance. The leading cause of deaths were circulatory diseases (in 2012, 24,988 persons died, 585.5/100,000). Neoplasms were the cause of death in 13,940 persons (326.6/100,000), then injuries and poisoning (69.1/100,000), diseases of the gastrointestinal system (53.1/100,000), and respiratory diseases (50.4/100,000). Data are presented on the basis of diseases reported from several national registries (cancer, psychoactive drug abuse, the disabled, diabetes, and suicides). The importance of vaccination for the control of infectious diseases in Croatia is especially emphasized, as well as the experience and excellent results achieved in this area. The epidemiological situation in Croatia in terms of infectious diseases can be assessed as favorable. This is due to the general living conditions, which contributed to the entire health system, making Croatia equal to other developed countries of Europe and throughout the world.

The clinical course of patients with adrenal incidentaloma: is it time to reconsider the current recommendations?

OBJECTIVE: The current guidelines for the management of adrenal incidentaloma advise hormonal and radiological follow-up of patients for 2-5 years after the initial diagnosis. However, the vast majority of adrenal incidentaloma are non-functional benign cortical adenomas that require no treatment, so the routine application of the current strategies often results in a number of unnecessary biochemical and radiological investigations. The aim of this study was to analyse the clinical course of patients with adrenal incidentaloma and to provide a critical review of the current management strategy of the disease. DESIGN AND METHODS: This was a retrospective study performed in the Croatian Referral Center for adrenal gland disorders. The study included 319 consecutive patients with adrenal incidentaloma, 174 of which were followed for at least 24 months. RESULTS: The vast majority of patients were diagnosed with benign adrenal masses, whereas in about 5% of them adrenal tumor corresponded to adrenal carcinoma or metastasis. Tumor density was found to be superior to tumor size in distinguishing benign adrenal masses from malignant tumors and pheochromocytomas. During the follow-up, no patient demonstrated a clinically significant increase in tumor size. In addition, no changes, either in metanephrines and normetanephrines or in the activity of renin-aldosterone axis, were observed during the follow-up. Six patients developed subclinical Cushing's syndrome (SCS) whereas eight patients with SCS showed biochemical remission during follow-up. CONCLUSION: The study suggests that the risk of an adrenal mass initially diagnosed as benign and non-functional becoming malignant or hormonally active is extremely low. Therefore, the clinical management of those patients should be tailored on an individual basis in order to avoid unnecessary procedures.

Chronic dietary exposure to aristolochic acid and kidney function in native farmers from a Croatian endemic area and Bosnian immigrants.

BACKGROUND AND OBJECTIVES: Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal. RESULTS: CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15-30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; P=0.02). CONCLUSIONS: Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time.

The changing pattern of cardiovascular risk factors: the CroHort study.

Croatia has a long tradition of non-communicable disease prevention, but also obstacles to the implementation of preventive programs related to the general attenuation of public health and primary health care sector. The aim of this study was to determine trends in behavioral and biomedical risk factors and evaluate primary non-communicable disease and cardiovascular prevention. Physical inactivity was a leading risk factor with increasing trend and prevalence of 33.9% and 38.9% in men and women in 2008. In 2008, obesity was present in 26.1% and 34.1%, and hypertension in 65.8% and 59.7% of men and women. During the follow-up only smoking and alcohol consumption in men decreased significantly, while alcohol consumption and obesity in women, and hypertension in both sexes significantly increased. In the present situation, with the existing trends and environment it will not be possible to stop negative trends. Revitalization of public health activities and primary health care is essential.

Lifestyle habits of people with self-reported diabetes: changes during a five-year period.

The aims of our study were to investigate the prevalence of risk factors in persons with previously known diabetes ("old DM"), persons with diabetes developed during the 2003-2008 period ("new DM") and diabetes-free individuals within the CroHort study. Risk factors were defined as physical inactivity, unhealthy nutritional regimen, smoking and excessive alcohol consumption, while diabetes status was self-reported. The most prevalent risk factor in both "old DM" and "new DM" group was physical inactivity (46.7% and 33.7% in 2003; 46.8% and 46.3% in 2008), then smoking (12.1% and 14.6%; 12.7% and 14.4%), unhealthy diet (8.8% and 13.8; 8.2% and 10.0%) and heavy alcohol consumption (11.1% and 6.0%; 7.8% and 13.8%). Diabetes-free individuals had higher rates of smoking and unhealthy diet, and lower rates of alcohol consumption and physical inactivity than both diabetes groups. These results indicate the need for comprehensive actions oriented towards persons with diabetes concerning physical activity.

The CroHort study: cardiovascular behavioral risk factors in adults, school children and adolescents, hospitalized coronary heart disease patients, and cardio rehabilitation groups in Croatia.

Based on repeated measurement of health behaviors the CroHort Study showed that health behavior explains a great deal more of class inequalities in mortality than observed in previous studies. These include decreasing prevalence of smoking and increase in obesity, hypertension and diabetes mellitus. The lowest prevalence of health risks was recorded among children and adolescents, followed by general adult population from the CroHort Study. Hospitalized coronary heart disease patients had higher risks prevalence than general population, while the highest prevalence of risks was recorded among patients in cardiac rehabilitation program. The higher levels of stress were associated to lower financial conditions, poorer social functioning and poorer mental health for both men and women. Higher levels of stress were also associated with heart problems, higher alcohol consumption in men while in women stress was associated to poorer general health, higher age and lower levels of education.

Health-related quality of life and fatigue in patients with adrenal incidentaloma.

The objective of the present study was to examine several dimensions of quality of life (QoL) and fatigue in patients with adrenal incidentaloma. This was a case-control study designed to analyze patient outcomes using three validated generic QoL questionnaires, EQ-5D, SF-36, and MFI-20, the results of which were compared to those obtained for age- and sex-matched controls. The study population comprised 139 consecutive patients with nonfunctioning adrenal masses (104 females, 35 males; age 59.1 ± 10.8) and 139 age- and sex-matched controls. Reduced QoL was found in patients with adrenal incidentaloma as compared to controls. Dimensions of QoL that were notably affected included mobility (P = 0.03), performance of usual activities (P = 0.002), and anxiety/depression (P = 0.04) as evaluated using the EQ-5D; physical functioning (P < 0.001), physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), social functioning (P = 0.001), and emotional role (P < 0.001) as evaluated using the SF-36; and physical fatigue (P = 0.04) as assessed using the MFI-20 questionnaire. In addition, perceived health on a visual analogue scale was also significantly lower in patients than in controls (64.8 ± 19.2 vs. 77.1 ± 15.1; P < 0.001). Patients with adrenal incidentaloma reported reduced QoL and a higher level of physical fatigue compared to age- and sex-matched controls. This subject will benefit from further studies comparing QoL outcomes of laparoscopic adrenalectomy versus no treatment in patients with adrenal incidentaloma.

Lifestyle habits of Croatian diabetic population: observations from the Croatian Adult Health Survey.

The aim of this study was to assess the behavioural risk factors in Croatian diabetic population and to compare them with the lifestyle habits of individuals with no known history of diabetes. The study was a part of the Croatian Adult Health Survey (CAHS), a cross-sectional survey that provided comprehensive health assessment of the Croatian adult population. Risk factors were defined as an unhealthy nutritional regimen, excessive alcohol consumption, smoking and lack of physical activity. Physical inactivity was the most prevalent risk factor observed in a significant number of both diabetic and non-diabetic subjects (44.8% and 29.1%). It was also the only behavioural risk factor that was more prevalent in the diabetic individuals as compared to those without diabetes. Alcohol consumption did not vary significantly between the two groups (5.8% vs. 6.3%), while unhealthy dietary pattern and smoking were less frequent in respondents with diabetes (10.0% vs. 16.5% and 14.3% vs. 23.2%, respectively). Among diabetic patients, a significantly larger proportion of men than women reported smoking (19.2% vs. 10.0%), whereas no such sex-related differences were observed in other behavioural risk factors. Although the most prominent risk factor in diabetic patients was physical inactivity, a significant proportion of respondents with diabetes also reported the presence of other risk factors investigated in this survey. Since the majority of diabetic patients do not reach their treatment goals, there is a substantial need for curative and preventive interventions. Given the importance of physical activity in the treatment and prevention of diabetes and the high proportion of inactive diabetic patients, any future preventive programme in Croatia should address that risk as well.

Clinical study on the effect of simvastatin on paraoxonase activity.

Human paraoxonase (PON1) is a serum high-density lipoprotein-associated phosphotriesterase. High-density lipoprotein (HDL) plays the role of a carrier and the site of action of this enzyme. According to a majority of authors, PON1 acts as an antioxidant, preventing low-density lipoprotein (LDL) peroxidation. However, due to the fact that in vivo serum PON1 is predominantly associated with HDL, its major physiological role might be to protect HDL, rather than LDL, from oxidation. Nevertheless, the physiological substrate of PON1 still remains to be discovered. The objective of this study was to determine changes in PON1 activity during treatment with simvastatin (CAS 79902-63-9, Lipex) in patients with type IIa and/or IIb hyperlipoproteinemia. PON1 activity was assessed in 32 patients with hyperlipoproteinemia type IIa or IIb with an LDL cholesterol concentration higher than 4.2 mmol/l. Patients received simvastatin in a daily dose of 20 mg. The lipid status and PON1 activity were assessed at baseline, as well as 3 and 6 months after the beginning of treatment. The study demonstrated a statistically significant lipid lowering effect of simvastatin on total and LDL cholesterol, and an increase in PON1 activity in patients with both types of hyperlipoproteinemia. No statistically significant correlation was observed either between changes in PON1 activity and HDL, HDL2, HDL3 and LDL cholesterol and triglyceride levels, or between their first differences in patients with both type IIa and IIb hyperlipoproteinemia. The obtained results suggest that the antioxidant properties of simvastatin might be caused by a mechanism independent of apoAI-containing lipoprotein concentration. The antioxidant properties of simvastatin, which play an important role in HDL protection from oxidation, could be the mechanism inducing the increase in PON1 activity.

Clinical study on the effect of simvastatin on butyrylcholinesterase activity.

Although the physiological function of serum butyrylcholinesterase (BuChE) has not yet been clarified, there is evidence that this enzyme is involved in serum lipoprotein metabolism. It has been suggested that serum BuChE is positively correlated with LDL (low-density lipoprotein) and negatively with HDL (high-density lipoprotein) levels. The objective of this study was to determine whether the activity of BuChE changes during treatment with simvastatin (CAS 79902-63-9). The effects of simvastatin therapy on serum lipoproteins and plasma BuChE activity were studied in 15 patients with type IIa and 17 patients with type IIb hyperlipoproteinemia. Beside the expected influence on serum lipid concentration, a statistically significant decrease in BuChE activity in patients with hyperlipoproteinemia type IIa and IIb during treatment with simvastatin was not observed.