FEASIBILITY OF THE MULTIMODAL SMOKING CESSATION INTERVENTION DURING HOSPITALIZATION WITH SIX-MONTH FOLLOW-UP POST-DISCHARGE: A PILOT STUDY.

The main aim of this pilot project was to introduce multimodal smoking cessation intervention in the hospital setting and to analyze users' satisfaction and efficacy of the intervention within six months post-discharge. Multimodal intervention for smoking cessation was used and it consisted of the "5 A's" model (Ask, Advice, Assess, Assist, Arrange) for behavior change, printed self-help materials for smoking cessation, and telephone counseling (one, three and six months after discharge from the hospital). The main outcome of the study was smoking status at six months. A total of 103 participants were included in this pilot project. At six-month follow-up, 49% of participants self-reported continuous non-smoking. Among the remaining participants, 20 reported smoking reduction, 19 were still smoking, and 16 participants were unable to make contact with. In the logistic regression, among all analyzed variables, only two of them were positively associated with smoking cessation after six months: participants' response that they would like to quit smoking within the next six months (B=4.688; p=0.018) and answering that they did not smoke when they were ill and bed-ridden due to illness (B=3.253; p=0.020). Satisfaction with the intervention was very high; 70% of participants rated the intervention as 'excellent'. Therefore, multimodal smoking cessation intervention can be successfully introduced at hospital setting yielding high smoking abstinence rates at six months post-discharge and high level of user satisfaction. Healthcare workers who work in hospitals should be educated so they can provide such intervention on a regular basis.

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

PANDEMIC INFLUENZA A (H1N1) 2009 PRESENTING AS A MILD DISEASE IN CHILDREN IN A CROATIAN CLINICAL CENTRE.

Pandemic influenza A virus (H1N1) 2009 causes a disease that is epidemiologically and clinically not significantly different from seasonal influenza, but there are differences. The aim of the study was to display and compare epidemiological and clinical characteristics of pandemic influenza in children. At Dr. Fran Mihaljevic University Hospital for Infectious Diseases in Zagreb, in the first two seasons, the incidence of pandemic influenza virus A (H1N1) in particular was exhaustively analyzed only in patients with laboratory-confirmed pandemic influenza A virus (H1N1) 2009. In hospitalized children with documented influenza pandemic, moderate form of the disease predominated, which ultimately meant shorter hospital stay and fewer complications. Otitis media was the rarest complication in children in both seasons. In conclusion, children younger than 5 years, especially boys, were vulnerable groups for pandemic influenza, presenting as a mild disease with low mortality and few complications. Most of the affected children with influenza did not have important risk factors such as asthma and obesity, highlighted by other authors as significant risk factors.

Different features of influenza A H1N1pdm09 virus infection among adults in 2009/10 and 2010/11.

INTRODUCTION: Influenza A H1N1pdm09 virus infection causes an epidemiologically and clinically severe disease mostly characterized by pneumonia, resulting in a high mortality rate. The purpose of this study was to investigate and compare epidemiological and clinical characteristics of influenza A H1N1pdm09 virus infection in patients hospitalized during the pandemic (2009/10) and post-pandemic seasons (2010/11). METHODOLOGY: The data of patients with laboratory-confirmed influenza A H1N1pdm09 virus infection hospitalized and treated at the University Hospital for Infectious Diseases Dr. Fran Mihaljevic in Zagreb, Croatia in the first two seasons of appearance were analyzed. RESULTS: Compared to the pandemic season, in the post-pandemic season, patients were hospitalized longer, had higher values of inflammatory parameters, and were more often treated with antibiotics. The total number of risk factors in patients did not vary significantly between the two seasons. In the pandemic season, a significantly higher number of obese patients and patients with chronic lung disease was observed, whereas in the post-pandemic season, a statistically significant number of patients presented with symptoms of chronic cardiac and neuromuscular diseases. Primary viral pneumonia was frequently registered in younger adults during the pandemic season, whereas in the post-pandemic season, there were more cases of bacterial pneumonia. CONCLUSIONS: During the pandemic season, the influenza A H1N1pdm09 virus infection caused a severe disease with rare bacterial complications, especially in adult patients. The common characteristics of the influenza A H1N1pdm09 virus were lost in the post-pandemic season, assuming the shape and characteristics of the seasonal influenza A virus.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Relapsing Bacteraemia due to Corynebacterium striatum in a Patient with Peripheral Arterial Disease.

We describe the first reported case of Corynebacterium striatum (C. striatum) relapsing bacteraemia in a patient with peripheral arterial disease and proven Corynebacterium species colonization of a chronic foot ulcer, focusing on the difficulties in the management of the patient. We conclude that the optimal duration of the antibiotic treatment for relapsing C. striatum bacteraemia from a chronic ulcer should be 6 weeks together with surgical treatment.

Efficacy and safety of moxifloxacin in community acquired pneumonia: a prospective, multicenter, observational study (CAPRIVI).

BACKGROUND: Community acquired pneumonia (CAP) is a major cause of morbidity, hospitalization, and mortality worldwide. Management of CAP for many patients requires rapid initiation of empirical antibiotic treatment, based on the spectrum of activity of available antimicrobial agents and evidence on local antibiotic resistance. Few data exist on the severity profile and treatment of hospitalized CAP patients in Eastern and Central Europe and the Middle East, in particular on use of moxifloxacin (Avelox®), which is approved in these regions. METHODS: CAPRIVI (Community Acquired Pneumonia: tReatment wIth AVelox® in hospItalized patients) was a prospective observational study in 12 countries: Croatia, France, Hungary, Kazakhstan, Jordan, Kyrgyzstan, Lebanon, Republic of Moldova, Romania, Russia, Ukraine, and Macedonia. Patients aged >18 years were treated with moxifloxacin 400 mg daily following hospitalization with a CAP diagnosis. In addition to efficacy and safety outcomes, data were collected on patient history and disease severity measured by CRB-65 score. RESULTS: 2733 patients were enrolled. A low severity index (i.e., CRB-65 score <2) was reported in 87.5% of CAP patients assessed (n=1847), an unexpectedly high proportion for hospitalized patients. Moxifloxacin administered for a mean of 10.0 days (range: 2.0 to 39.0 days) was highly effective: 96.7% of patients in the efficacy population (n=2152) improved and 93.2% were cured of infection during the study. Severity of infection changed from "moderate" or "severe" in 91.8% of patients at baseline to "no infection" or "mild" in 95.5% at last visit. In the safety population (n=2595), 127 (4.9%) patients had treatment-emergent adverse events (TEAEs) and 40 (1.54%) patients had serious TEAEs; none of these 40 patients died. The safety results were consistent with the known profile of moxifloxacin. CONCLUSIONS: The efficacy and safety profiles of moxifloxacin at the recommended dose of 400 mg daily are characterized in this large observational study of hospitalized CAP patients from Eastern and Central Europe and the Middle East. The high response rate in this study, which included patients with a range of disease severities, suggests that treatment with broader-spectrum drugs such as moxifloxacin is appropriate for patients with CAP who are managed in hospital. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00987792.

First molecular analysis of West Nile virus during the 2013 outbreak in Croatia.

This is the second subsequent year of West Nile neuroinvasive disease (WNND) outbreak in Croatia. Between July and October 2013, 22 patients presented with symptoms of WNND: all with meningitis and 18 additionally with encephalitis. In contrast to 2012, where six autochthonous infections were confirmed in eastern Croatia, the majority of this year's cases occurred in and around the city of Zagreb, where no West Nile virus infections have been observed before. Viral RNA was recovered from two patients and phylogenetic analyses revealed West Nile virus lineage 2. This represents the first molecular characterization and phylogenetic analysis of the circulating West Nile virus strain in Croatia.

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche.

Influenza and hepatitis B vaccination coverage among healthcare workers in Croatian hospitals: a series of cross-sectional surveys, 2006-2011.

BACKGROUND: Healthcare workers (HCWs) are at an increased risk of exposure to and transmission of infectious diseases. Vaccination lowers morbidity and mortality of HCWs and their patients. To assess vaccination coverage for influenza and hepatitis B virus (HBV) among HCWs in Croatian hospitals, we conducted yearly nationwide surveys. METHODS: From 2006 to 2011, all 66 Croatian public hospitals, representing 43-60% of all the HCWs in Croatia, were included. Statistical analysis was performed using the Kruskal-Wallis analysis of variance, Dunn's multiple comparison analysis and the chi-square test, as appropriate. RESULTS: The median seasonal influenza vaccination coverage rates in pre-pandemic (2006-2008) seasons were 36%, 25% and 29%, respectively. By occupation, influenza vaccination rates among physicians were 33 ± 21%, 33 ± 22% among graduate nurses, 30 ± 34% among other HCWs, 26 ± 21% among housekeeping and the lowest, 23 ± 17%, among practical nurses (p < 0.01). In 2009-2010 season, seasonal influenza vaccination coverage was 30%, while overall vaccination coverage against pandemic influenza was fewer than 5%. Median vaccination coverage in the post-pandemic seasons of 2010-2011 and 2011-2012 decreased to 15% and 14%, respectively (reduction of 24% and 35%, respectively, p < 0.0001). Meanwhile, the median mandatory HBV vaccination coverage was 98%, albeit with considerable differences according to work setting (range 19-100%) and occupation (range 4-100%). CONCLUSIONS: We found substantial year-on-year variations in seasonal influenza vaccination rates, with reduction in post pandemic influenza seasons. HBV vaccination is satisfactory compared to seasonal influenza vaccination coverage, although substantial variations by occupation and work setting were observed. These findings highlight the need for national strategies that optimize vaccination coverage among HCWs in Croatian hospitals. Further studies are needed to establish the potential role of mandatory vaccination for seasonal influenza.

Mycoplasma pneumoniae in adult community-acquired pneumonia increases matrix metalloproteinase-9 serum level and induces its gene expression in peripheral blood mononuclear cells.

BACKGROUND: The objective of this study was to assess the concentration of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) in peripheral circulation and their mRNA expression in peripheral blood mononuclear cells (PBMCs) in patients with CAP caused by M. pneumoniae. MATERIAL/METHODS: We prospectively analyzed MMPs in 40 hospitalized patients with M. pneumoniae CAP on admission, and in the convalescent phase. Twenty healthy men were used as controls. Quantitative real-time PCR and ELISA tests were used. RESULTS: MMP-9 mRNA expression in PBMCs was increased in the acute phase of illness compared to the control group as well as in convalescent phase in which case it was statistically significant (Mann-Whitney; p=0.028). The same was found for MMP-9 plasma levels (Mann-Whitney test; p<0.001; p=0.001). Circulating MMP-2 concentration in acute patients was significantly lower than in the control group and convalescent phase (Mann-Whitney test; p=0.012; p=0.001), while no MMP-2 mRNA expression was found in PBMCs. The plasma level of MMP-9 correlated with leukocyte count in peripheral circulation (r=0.67, p<0.001). CONCLUSIONS: We conclude that M. pneumoniae in adult CAP induces activity of MMP-9 in peripheral blood circulation.

Liver involvement during influenza infection: perspective on the 2009 influenza pandemic.

Elevation of liver transaminase levels is a frequent observation during systemic infections. The aim of our study was to investigate liver damage during pandemic 2009 influenza A/H1N1 infection in comparison with seasonal influenza. Serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase (GGT) were significantly higher in patients with pandemic influenza compared to seasonal influenza, which was strongly correlated with hypoxia. Moreover, a positive correlation between C-reactive protein and serum GGT, alkaline phosphatase, and lactate dehydrogenase was noticed. Our findings support the hypothesis that the pandemic 2009 influenza A/H1N1 is an illness with a significant immune response to infection leading to hepatocellular injury.

[Guidelines on hand hygiene in health care institutions]. / Smjernice za higijenu ruku u zdravstvenim ustanovama.

Healthcare associated infections (HCAI) are huge problem all over the world, and 5-10% of all hospitalized patients will develop infection during hospitalization. From the times of I. P. Semelweiss we know that clean hands are the most important single factor that can decrease the number of HCAI. World Health Organization (WHO) has recognised this problem and developed Guidelines for hand hygiene in healthcare institutions. This also was the reason of developing Croatian national Guidelines. The main goal of the Guidelines was to decrease number of HCAI associated with the hands of healthcare workers. These Guidelines are meant for all healthcare workers and other hospital staff who come to the direct contact with patients. An interdisciplinary team of experts developed these Guidelines using WHO Guidelines, other existing guidelines and literature reviews for hand hygiene. Grades of evidence for specific recommendations were determined using CDC/HICPAC grading system. Categorization is based on existing data, theoretical basis, applicability and economic impact. After a broad discussion in different professional societies, Guidelines were accepted. Guidelines include recommendations for hand hygiene indications, hand hygiene technique, surgical hand preparation, choosing hand hygiene preparations, skin care, nails, glove use, patients and visitors hand hygiene, role of education, as well as role of healthcare institution and role of government. Furthermore, in the Guidelines the concept of "Five moments for hand hygiene" is explained in detail, and main literature data are presented.

Electrocardiographic changes in hospitalized patients with leptospirosis over a 10-year period.

BACKGROUND: The aim of this study was to investigate the incidence and type of ECG changes in patients with leptospirosis regardless of clinical evidence of cardiac involvement. MATERIAL/METHODS: A total of 97 patients with serologically confirmed leptospirosis treated at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic" in Zagreb, Croatia, were included in this retrospective study. A 12-lead resting ECG was routinely performed in the first 2 days after hospital admission. Thorough past and current medical history was obtained, and careful physical examination and laboratory tests were performed. RESULTS: Abnormal ECG findings were found in 56 of 97 (58%) patients. Patients with abnormal ECG had significantly elevated values of bilirubin and alanine aminotransferase, lower values of potassium and lower number of platelets, as well as more frequently recorded abnormal chest x-ray. Non-specific ventricular repolarization disturbances were the most common abnormal ECG finding. Other recorded ECG abnormalities were sinus tachycardia, right branch conduction disturbances, low voltage of the QRS complex in standard limb leads, supraventricular and ventricular extrasystoles, intraventricular conduction disturbances, atrioventricular block first-degree and atrial fibrillation. Myopericarditis was identified in 4 patients. Regardless of ECG changes, the most commonly detected infection was with Leptospira interrogans serovar Australis, Leptospira interrogans serovar Saxkoebing and Leptospira kirschneri serovar Grippotyphosa. CONCLUSIONS: The ECG abnormalities are common at the beginning of disease and are possibly caused by the direct effect of leptospires or are the non-specific result of a febrile infection and metabolic and electrolyte abnormalities. New studies are required for better understanding of the mechanism of ECG alterations in leptospirosis.

The occurrence of hemorrhagic fever with renal syndrome in southern parts of Bosnia and Herzegovina.

Bosnia and Herzegovina (B&H) has been known as an endemic region for hemorrhagic fever with renal syndrome (HFRS) for over 50 years. Multiple epidemics of this disease have been registered so far, especially in endemic parts of Central and Northeastern Bosnia, as well as the Sarajevo region. Seroepidemiological investigations demonstrate naturalization of Hantaviruses and their wide spread in B&H. However, there are no studies from the southern areas of B&H, and endemic foci of this disease are unknown. The aim of this study was to determine the distribution and serologic prevalence of Hantavirus infections by testing for specific IgG antibodies against hantaviruses in the population of Herzegovina. This study included two groups of participants. The target group consisted of 300 participants from exposed professional and population groups, and control group included 100 educators with lower exposure to HFRS. Identification of specific IgG antibodies against hantaviruses in 16 participants confirmed an initial assumption about the presence of Hantavirus infections in the region of interest. Seroprevalence of 5% was registered in the "exposed" and 1% in the "unexposed" group. Simultaneous circulation of Puumala (PUU) and Dobrava (DOB) viruses was discovered. The frequency of positive antibody results was higher in the population above 50 years of age, and three times more prevalent in men then at women. The highest proportion of exposed participants (80%) was registered in the municipalities which geographically belong to high or mountainous Herzegovina.

Zoonoses and vector-borne diseases in Croatia - a multidisciplinary approach.

Emerging and re-emerging infectious diseases create constant and serious concerns for public health. The majority of emerging infectious diseases (EID) are wildlife zoonotic diseases and vector-borne diseases. Croatia has a long tradition in the control, management and research of EID zoonotic diseases and vector-borne diseases. There has also been a long and advantageous tradition in the collaboration of different experts and professionals in EID research in Croatia involving physician clinicians in infectious diseases, microbiologists, pathologists, veterinarians and animal scientists, ecologists, forestry experts, wildlife scientists, public health specialists and epidemiologists and laboratory scientists. The University Hospital for Infectious Diseases in Zagreb established the Centre for Emerging and Re-emerging Infectious Diseases in liaison with national and international partners from Europe and the United States. This Centre is working in line with the 'One Health initiative' which recognises the inter-relationships between human, animal and environmental health.

Imported case of nephropathia epidemica--a case report.

A 41-year-oldpatient was hospitalized in hypotensive phase of nephropathia epidemica. The diagnosis was confirmed by serology. It is highly likely that the patient was exposed to infected aerosol of bank voles in endemic area of Sweden. The disease clinically manifested with fever, headache, abdominal and back pain, vision disturbances. Pathologic laboratory findings included thrombocytopenia, leukocytosis, increased values of C-reactive protein, blood urea and creatinine, abnormal chest X-ray and transient electrocardiogram abnormalities.