Epidemiological and clinical features of leptospirosis in a highly endemic area over three time periods.

OBJECTIVES: To present the features of human leptospirosis over three time periods (1970-1975; 2000-2005; 2010-2015), to compare the collected data and to determine whether the incidence, seasonal and spatial distribution, prevalence of presumptive infective serogroups and clinical features have changed over the last 50 years. METHODS: Epidemiological and clinical data obtained from patients hospitalised and treated in a well-known endemic focus of leptospirosis, Koprivnica-Krizevci County in Croatia, were analysed. RESULTS: We observed a steady decline in the overall incidence of leptospirosis and a change in the patient age distribution, with the age ratio changing in favour of middle-aged and older patients. Although leptospirosis was most frequently diagnosed in August in all time periods, the number of cases increased in autumn. The most prevalent serogroup during the first and the second time period was Icterohaemorrhagiae, while in the third time period, the serogroup Australis prevailed. We also noted an increase in the number of severe clinical manifestations. CONCLUSIONS: This retrospective research demonstrates a continuous decline in the incidence of human leptospirosis in Croatia. The pattern of disease has changed from predominantly mild clinical forms observed in children to more severe clinical forms observed in middle-aged to older patients, especially those working in agriculture. Additional epidemiological changes included an increase in the number of cases during the autumn months and changes in prevailing serogroups. Statistical analysis revealed a significant relationship between the severity of the clinical picture, patient age and presumed sources of infection.

Evaluation of brainstem involvement in multiple sclerosis.

BACKGROUND/AIMS: the aim of the present study was to determine the optimum method to detect brainstem lesions in patients with Multiple Sclerosis (MS). METHODS: 72 patients with the diagnosis of relapsing-remitting MS were prospectively included. brainstem functional system score (bSfS) (part of the expanded disability status scale (edSS) evaluating brainstem symptomatology) was calculated. Magnetic resonance imaging (Mri) was performed on 1.5t and t1, t2, pd and fluid-attenuated inversion recovery (flair) sequences were analyzed for presence of brainstem lesions. auditory evoked potentials (aep) and ocular and cervical vestibular evoked myogenic potentials (oVeMp and cVeMp) were performed according to the standardized protocol. RESULTS: from 72 patients, 18 (25%) had clinical involvement of the brainstem. Mri showed brainstem involvement in 29 (40%) patients. of the neurophysiological tests, aep showed pathological result in 16 (22%) patients, oVeMp in 36 (50%) patients, cVeMp in 18 (25%) patients, and VeMp (combination of oVeMp and cVeMp) in 45 (63%) patients. VeMp detected brainstem lesions in higher percentage than clinical examination, Mri and aep, which was statistically significant (< 0.0001, 0.012 and < 0.0001, respectively). CONCLUSIONS: results of the present study have shown that VeMps are the optimal method to detect brainstem lesions in multiple sclerosis and that they detect them significantly better than clinical examination, aep or Mri.

Perspectives of primary care physicians on academic detailing for antimicrobial stewardship: feasibility and impact assessment.

OBJECTIVE: To understand primary care physicians' perspectives on academic detailing from an antimicrobial stewardship team to combat antibiotic overuse for upper respiratory infections and bronchitis in the COVID-19 era, which will help prevent avoidable outpatient visits. METHODS: In this prospective study, 14 female Croatian physicians completed standardized qualitative interviews using a semi-structured guide. The data were analyzed using inductive methodology based on reflexive thematic analysis. We used a theoretically informed approach based on a conceptual framework of healthcare intervention implementability focused on three domains: acceptability, fidelity, and feasibility. RESULTS: We identified six key themes highlighting barriers to changing prescribing practices, with patient pressure and specialist recommendations having an impact on the effectiveness of academic detailing. Despite challenges, primary care physicians described appreciation of direct interaction with evidence-based practices and reported usefulness, effectiveness, and further need for academic detailing. CONCLUSION: This study highlights the complex dynamics involved in implementing healthcare interventions and provides valuable insights for enhancing strategies directed at improving antibiotic prescribing practices. Specifically, our findings emphasize factors influencing behavior changes in physicians' antibiotic prescribing. The authors advocate for a collaborative approach involving community and hospital-based professionals to provide tailored guidance and address questions, ultimately improving prescribing practices.

[ISKRA guidelines on antimicrobial treatment and prophylaxis of urinary tract infections--Croatian national guidelines]. / ISKRA smjernice antimikrobnog lijecenja i profilakse infekcija mokracnog sustava--hrvatske nacionalne smjernice.

These guidelines refer to diagnosis, antimicrobial treatment and prophylaxis of urinary tract infections in adults and children older than 12 years of age and cover lower urinary tract in females, uncomplicated pyelonephritis, complicated UTI with or without pyelonephritis, asymptomatic bacteriuria and recurrent UTI. These guidelines do not cover sexually transmitted diseases. The guidelines are primarily intended for use by general practitioners and specialists working in primary health care and hospitals. The members of the Working Group for the development of guidelines on antimicrobial treatment and prophylaxis of urinary tract infections were appointed by the Croatian Ministry of Health and Social Welfare. The project was financially supported by the Dutch government and professional assistance was provided by international consultants. The evidence for this guidelines is based on a systematic review of the literature, local antibiotic resistance data, the existing clinical protocols on the treatment and prophylaxis of UTIs, as well as suggestions and comments made by colleagues physicians during more than 50 continuous medical education courses held in the last three years on antimicrobial treatment and prophylaxis of UTIs. Draft version of the guidelines was available for comments on the web site http://iskra.bfm.hr and during the two-month piloting period the guidelines were widely presented to general practitioners, specialists working in primary care and hospitals--urologists, gynecologists, infectious disease specialists, nephrologists. The final version of the guidelines was approved by the Intersectoral Coordination Mechanism for the Control of Antimicrobial Resistance (ISKRA) Board.

Antimicrobial stewardship effectiveness on rationalizing the use of last line of antibiotics in a short period with limited human resources: a single centre cohort study.

OBJECTIVE: Antibiotics reserve (ARs) are given as a last line of treatment when other antibiotics are no longer effective. Rising threat of antimicrobial resistance makes growing use of ARs a real problem to patient safety. A single centre interventional cohort study was conducted in order to measure impact on clinical outcomes of A-team programme with limited human resources in a short period. A-team programme started on 01. September 2017. RESULTS: In 3 months preintervention and 3 months intervention period, from 3038 and 3156 hospitalized adult patients, 249 (59% of them were male, median age = 69 years) and 96 (51% of them were male, median age = 70 years) received parenteral ARs. Total duration of hospitalization of patients on AR was reduced from 28 to 17 days of hospitalization on 100 patient-days (OR = 1.92; 95% CI 1.83-2.01; p < 0.001) with no statistical significant difference in rehospitalisation due to infection of patients that were treated with ARs within 2 months after discharge. Despite short period of time and limited human resources, A-team restrictive interventions rationalised parenteral AR use and led to positive impact on clinical outcomes. These results could help our and other A-teams in similar situation in continuing with the programme to bring more evidence.

[Human anaplasmosis (ehrlichiosis)]. / Humana anaplazmoza (erlihioza)--prikaz bolesnika.

OBJECTIVE: The north part of Croatia, especially the Koprivnica-Krizevci County is a well known endemic area of several tick-transmitted diseases including tick-borne encephalitis, Lyme borreliosis and tularemia. Each summer numerous patients develop a nonspecific febrile illness after tick bite, etiology of which is sometimes never established. PURPOSE OF WORK: The aim of this prospective study was to determine whether the infection with Anaplasma phagocytophilum was associated with febrile illnesses occurring after tick bite. The epidemiological, clinical and laboratory characteristics, and diagnostic procedures in patients suffering from confirmed and probable anaplasmosis are presented. PATIENTS AND METHODS: A prospective study to assess the potential ehrlichial etiology of febrile illnesses after tick bite was conducted at the Department of Infectious Disease, General Hospital, Koprivnica, Croatia, during the period from January 1998 to August 2004. The study included patients of all age groups with acute febrile illness (temperature higher than 38 degrees C) manifesting within 30 days of a tick bite, in whom a recent infection with Anaplasma phagocytophilum was established serologically by seroconversion or at least 4-fold increase in antibody titer to anaplasma antigen (defined as confirmed cases of anaplasmosis), or by the presence of positive IFA titer > or = 1: 256 in acute and convalescent phase serum samples without demonstrating a 4-fold titer change (defined as probable cases of anaplasmosis), and with no alternative explanation for the acute febrile illness. Thorough medical histories were collected, physical examinations performed, and several laboratory tests carried out. Giemsa-stained peripheral blood smears were examined by high microscopy for the presence of ehrlichial morulae within leukocytes. Acute and convalescent phase serum samples were tested by use of an indirect immunofluorescence assay (IFA) for the presence of specific IgG antibodies to Anaplasma phagocytophilum antigen. At the same time all serum samples were tested for other tick borne agents including tick-borne encephalitis virus, Borrelia burgdorferi sensu lato and Ehrlichia chaffeensis. Serological tests were performed at the Institute of Microbiology and Immunology, School of Medicine, University of Ljubljana, Ljubljana, Slovenia. Oral consent was obtained from all patients enrolled in the study. RESULTS: Of 132 patients included in the study during the 7-year period, eight (6%) patients were diagnosed with anaplasmosis, without any additional diagnosis, and were included in the analysis. Three patients fulfilled the case definition criteria for confirmed anaplasmosis, while five had probable anaplasmosis (three men and five women aged 17-43). Clinically, the disease presented as a nonspecific, flu-like febrile illness with leukopenia, thrombocytopenia and moderately elevated aminotransferases. Intracytoplasmic morulae were not seen in leukocytes in blood smears. Specific antimicrobial therapy was administered in four patients. All patients recovered rapidly and no long-term consequences were found during the one-year follow-up. CONCLUSION: We report on the first patients meeting the case definition criteria for confirmed and probable anaplasmosis. The frequency and new concepts in the disease were analyzed.

[Hepatitis caused by tick-borne meningoencephalitis virus (TBEV)--a rare clinical manifestation outside the central nervous system involvement]. / Hepatitis uzrokovan virusom krpeljnog meningoencefalitisa--rijetka klinicka manifestacija izvan sredisnjeg zivcanog sustava.

OBJECTIVE: North part of Croatia, especially the Koprivnica-Krizevci County has been a well-known endemic area of tick-borne encephalitis (TBE) for more than 50 years. To date, this disease caused by tick-borne encephalitis virus (TBEV) has retained the leading position among inflammatory diseases of the central nervous system (CNS), with an average morbidity of 19 patients per year. In 88% of patients the infection manifested with signs of meningitis or meningoencephalitis with a biphasic course. TBE may take a more severe course with different neurologic dysfunction or even lethal outcome. There have been isolated reports on some rare clinical manifestations outside CNS involvement caused by TBEV, including transient hepatitis, pancreatitis, and myocarditis. These manifestations have been most frequently detected during the initial stage of disease but also as a complication, or as an individually separate clinical entity. The incidence rate of these manifestations is not known. Until now, such clinical manifestations outside CNS have not been reported in the county. It was the reason to present the characteristics of liver failure in our patients suffering from TBE. Purpose of Work: To determine the frequency of elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with TBEV infection, to note the time from the detection to disappearance of elevated AST and to investigate and establish whether the degree of liver failure influences the course and outcome of TBE. PATIENTS AND METHODS: The study was conducted from January 1991 until September 2004, and included patients with TBEV infection and elevated AST and ALT, examined at the Department of Infectious Diseases, Koprivnica General Hospital. Study patients were of all age groups and occupation. On their first examination detailed epidemiologic and patient history data were collected, with special reference to the history of alcohol abuse, disease of the liver or biliary tract, or any other apparent cause of liver failure. Clinical examination and laboratory tests were performed. Patients were classified into four groups as suffering from meningitis, meningoencephalitis, meningoencephalomyelitis, or abortive form of disease. The acute stage of meningoencephalitis was classified as mild, moderate or severe, depending on meningeal symptoms and severity of clinical signs of encephalitis, and presence of focal CNS signs. ELISA test was used to detect specific IgM and IgG antibodies. Serum samples were tested for other tick-borne diseases, including human monocyte and granulocyte ehrlichiosis. Oral consent was obtained from all patients enrolled in the study. RESULTS AND DISCUSSION: During the study, recent infection with TBEV was proven in 261 patients. Liver function tests were done in 115 (44%) patients. Elevated AST and ALT activity was found in 25 (22%) patients, without bilirubin and alkaline phosphatase increase. All these were County residents, with a male sex predominance, aged 28-70 (median 41) years, and none had received TBE vaccination. Elevated AST and ALT activities were detected during the first stage of TBE in 16 (64%) and during the second stage of meningoencephalitis in 9 (36%) patients suffering from TBE. Elevated activity of AST was observed in 76% and of ALT in 96% of study patients. The most frequently observed elevated AST and ALT activity was two- or threefold the usual normal values. The time of the first detection of elevated AST and ALT activity could not be precisely determined, since all laboratory findings were performed during the first examination of patients. In the initial stage of disease, patients were mostly tested between 2-5 days from the onset of disease, and during the first week in the second stage of meningoencephalitis. Elevated AST and ALT activities were transient and normalized in 3-4 weeks. The importance of elevated AST and ALT activity for the course and prognosis of TBE was not verified in this study. CONCLUSION: The first patients with hepatitis as one of the possible manifestation outside CNS involvement caused by TBEV are described. The prevalence and new concepts on this type of the disease were investigated in the study.

[The effect of antiepileptic drug therapy on cognitive evoked potentials and reaction time]. / Utjecaj terapije antiepilepticima na kognitivne evocirane potencijale i brzinu motoricke reakcije.

UNLABELLED: It is well known that antiepileptic drugs have side effects on cognitive and behavioral functioning of the treated patients. AIM: Our goal was to investigate their effect on cognitive evoked potential peak latencies and patient reaction times to target stimuli for two different, acoustic and visual stimulating paradigms. Therefore, a control group of healthy subjects and three groups of patients treated with antiepileptic drugs (carbamazepine, phenobarbital) were compared. PATIENTS AND METHODS: Group 1 of 19 epileptic patients had undertherapeutic and group 2 of 16 patients had a therapeutic concentration of these drugs. Group 3 of 18 patients were treated with carbamazepine in therapeutic dose for nonepileptic reasons. The N1, P2, N2, P3a and P3b peak latencies as well as reaction time to the same target stimuli were analyzed. RESULTS AND DISCUSSION: Obtained for acoustic and visual stimulating paradigm in the control group showed no significant differences results suggesting it to be sufficient to use simple acoustic paradigm for screening. The hypothesis that antiepileptic drugs influence the parameters of cognitive evoked potentials when used as polytherapy was confirmed. The reaction time measured in the same groups showed statistically significant differences between healthy subjects and drug treated patients. The effect of antiepileptic drugs on peak latencies of cognitive evoked potentials was statistically significant, and an even greater effect was recorded on the reaction time of treated patients. CONCLUSION: The results obtained in the study were in accordance with our hypothesis that this neurophysiological method could be successfully used as a screening method to check the cognitive and motor state of antiepileptic medication.

[An abortive type of tick-borne meningoencephalitis]. / Abortivni oblik krpeljnog meningoencefalitisa.

OBJECTIVE: Tick-borne encephalitis (TBE) was detected in the Koprivnica-Krizevci County 50 years ago. To date, it has retained the leading position among inflammatory diseases of the central nervous system (CNS), with an average morbidity of 20 patients per year. In 88% of patients, the infection manifested with signs of meningitis or biphasic meningoencephalitis (ME). Monophasic course was recorded in only 12% of patients of older age, during which the first initial stage remained inapparent, and the disease manifested only with ME stage. An abortive type of TBE virus infection with fever, headache and other general symptoms of infection is presented. The initial stage of the disease, without subsequent CNS involvement, is rarely described. PURPOSE OF WORK: To determine the frequency and present epidemiological, clinical and laboratory characteristics as well as diagnostic procedures in patients suffering from abortive type of TBE. PATIENTS AND METHODS: A prospective study was conducted in the period from 1997-2002, and included patients with possible tick-borne disease, examined at the Infectious Disease Department of the Koprivnica General Hospital. According to the set criteria, the study included patients of all age groups, sex and occupation, patients with febrile disease (T 38 degrees C) that developed within 6 weeks from the tick bite, patients who showed no signs of ME on their first examination, and patients in whom serologic analysis revealed recent infection with TBE virus. On admission to the hospital, detailed epidemiological and history data were collected, and clinical examination and laboratory testing were performed. ELISA test was used to detect specific IgM and IgG antibodies. At the same time all serum samples were tested for other tick-borne diseases, including Lyme disease and human monocyte and granulocyte ehrlichiosis. Oral consent was obtained from all patients enrolled in the study. RESULTS: A total of 127 patients met the study criteria. Specific antibodies to TBE virus were detected in 49 (38.5%) patients. After the latency period, 43 (87.7%) patients developed the second stage of ME disease. An abortive type of infection with TBE virus, without subsequent CNS involvement, was recorded in 6 (12.2%) patients. The diagnosis was confirmed in the first initial stage in 12% of patients and during the second ME stage in the remaining 37 (75.5%) patients. Active immunization against TBE was not conducted in any patient. CONCLUSION: We report on the first patients diagnosed with an abortive type of TBE virus infection in the Koprivnica-Krizevci County. The frequency of and new knowledge about this type of disease were assessed in the study.

Auditory evoked potentials and vestibular evoked myogenic potentials in evaluation of brainstem lesions in multiple sclerosis.

OBJECTIVE: The aim of this study was to determine the roles of magnetic resonance imaging (MRI), auditory evoked potentials (AEP) and vestibular evoked myogenic potentials (VEMP) in the evaluation of brainstem involvement in multiple sclerosis (MS). PATIENTS AND METHODS: Altogether 32 patients with the diagnosis of MS participated in the study. The following data was collected from all patients: age, gender, Expanded Disability Status Scale (EDSS) score, brainstem functional system score (BSFS) (part of the EDSS evaluating brainstem symptomatology), and involvement of the brainstem on the brain MRI. AEP and ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were studied in all patients. RESULTS: BSFS, MRI, AEP, oVEMP and cVEMP involvement of the brainstem was evident in 9 (28.1%), 14 (43.8%), 7 (21.9%), 12 (37.5%) and 10 (31.0%) patients, respectively. None of the tests used showed statistically significant advantage in the detection of brainstem lesions. When combining oVEMP and cVEMP 18 (56.3%) patients showed brainstem involvement. This combination showed brainstem involvement in greater percentage than BSFS or AEP, with statistical significance (p=0.035 and p=0.007, respectively). CONCLUSION: VEMP is a reliable method in detection of brainstem involvement in MS. It is comparable with MRI, but superior to clinical examination or AEP.