Longitudinal assessment of preoperative dexamethasone administration on cognitive function after cardiac surgery: a 4-year follow-up of a randomized controlled trial.

BACKGROUND: The pathogenesis of postoperative cognitive decline (POCD) is still poorly understood; however, the inflammatory response to surgical procedures seems likely to be involved. In addition, our recent randomized controlled trial showed that perioperative corticosteroid treatment may ameliorate early POCD after cardiac surgery. To assess the long-term effect of dexamethasone administration on cognitive function, we conducted a 4-year follow-up. METHODS: The patients were randomized to receive a single intravenous bolus of 0.1 mg kg- 1 dexamethasone or placebo 10 h before elective cardiac surgery. The endpoint in both groups was POCD incidence on the 6th day and four years postoperatively. RESULTS: Of the 161 patients analyzed previously, the current follow-up included 116 patients. Compared to the 62 patients in the placebo group, the 54 patients in the dexamethasone group showed a lower incidence of POCD on the 6th day (relative risk (RR), 0.510; 95 % confidence interval (CI), 0.241 to 1.079; p = 0.067, time interval also analyzed previously) and four years (RR, 0.459; 95 % CI, 0.192 to 1.100; p = 0.068) after cardiac surgery. The change in cognitive status between the two postoperative measurements was not significant (p = 0.010) among the patients in the dexamethasone group, in contrast to patients in the placebo group (p = 0.673). CONCLUSIONS: Although statistical significance was not reached in the current study, the prophylactic administration of dexamethasone seems to be useful to prevent POCD development following cardiac surgery. However, further large multicenter research is needed to confirm these directions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02767713 (10/05/2016).

Characteristics and clinical outcomes of patients with acute gastrointestinal bleeding related to anticoagulant or antiplatelet therapy: a retrospective study.

AIM: To investigate the demographic characteristics, endoscopic and laboratory findings, comorbidities and mortality rate of patients with gastrointestinal bleeding related to anticoagulant or antiplatelet therapy. METHODS: We reviewed the records of patients admitted for gastrointestinal bleeding to the Intensive Care Unit of the Department of Gastroenterology, University Hospital Split, between 2015 and 2019. The characteristics and clinical outcomes of patients taking anticoagulant/antiplatelet therapy were analyzed. RESULTS: The study enrolled 1367 patients, 434 (31.7%) of whom received anticoagulant/antiplatelet therapy (mean age 74.9±10.7 years; 64.3% men). The most frequently prescribed drug was acetylsalicylic acid (56.7%), the most common bleeding site was the stomach (41.3%), and the most prevalent cause of bleeding was ulcer (61.6%). Patients taking anticoagulant/antiplatelet therapy who died had significantly higher creatinine (P=0.011) and lower albumin (P=0.015). In the multivariate analysis, the factors that negatively affected survival were older age, higher creatinine, and lower albumin. Patients taking anticoagulant/antiplatelet therapy had slightly lower in-hospital mortality (8.3%) compared with other patients (10.3%). CONCLUSION: Although anticoagulant/antiplatelet therapy increases the risk of gastrointestinal bleeding, it does not directly affect the outcome, which is mainly determined by age and comorbidities.

IS IT TIME TO REDEFINE COGNITIVE DYSFUNCTION AFTER CARDIAC SURGERY? THE IMPORTANCE OF METHODOLOGICAL CONSISTENCY.

High incidence and significance of repercussions on patient health and healthcare system make postoperative cognitive dysfunction (POCD) a major problem following cardiac surgery. POCD frequency drops over time since surgery and its occurrence are related to different aspects of cognitive deterioration that markedly impair the patient quality of life. Therefore, a substantial number of papers have focused on this complex postoperative complication, however, with limited achievement in clarifying it. The underlying mechanisms of POCD development and contributing factors are still unclear. A significant issue in POCD research is the lack of uniformity in defining cognitive impairment among investigators, including unique terminology of cognitive changes, a battery of appropriate neuropsychological tests, timing of assessment, and statistical approach. Thus, the aim of this review is to address the difficulties in establishing POCD definition, with inclusion of specific recommendations based on recent publications.

Attitudes toward Complementary and Alternative Medicine, Beliefs in Afterlife and Religiosity among Psychiatrists, Psychologists and Theologists.

BACKGROUND: The aim of our study was to investigate the differences in beliefs, attitudes toward CAM, beliefs in afterlife and religiosity among the sample of psychiatrists, psychologists, and theologists. Relationship among these constructs could have impact on the concept of mental health. SUBJECTS AND METHODS: Research was conducted in the Split urban area, Croatia, during 2017 on a sample of psychiatrists (n=51), psychologists (n=55), and theologists (n=25). Participants were presented a figure of the human body, which contained numbers identifying eight different regions of the body. Participants were asked to select which region best represents the location of the self, soul, and mind in the body. We used CAIMAQ (The Complementary, Alternative and Integrative Medicine Attitudes Questionnaire) which contains five subscales. The Afterdeath Beliefs Scale was used to measure the varieties of afterlife beliefs. Analyses showed that applied questionnaires have appropriate reliability and expected factor structure. RESULTS: The most frequent locations of the Soul were 9 (37%, Not located in any centralized region in the body) and 5 (31% chest), whereas Self and Mind were mostly located in the head (43% and 73%). Psychiatrists and psychologists have average scores on positive pole of CAIMAQ but did not differ significantly (p>0.05). There were statistical differences between theologists and psychologists/psychiatrists on two subscales: "nutritional counseling and dietary/food supplements can be effective in the treatment of pathology" and "attitudes toward a holistic understanding of the disease" (p<0.05). There were significant correlations between religion and three CAIMAQ subscales. Although they were mostly religious, psychiatrists and psychologists had a higher average score on Annihilation than theologists. They also did not believe in body resurrection and connection between behavior during life and after death. CONCLUSION: The results of our study could have impact on the concept of mental health and in the future must be deeper evaluated within qualitative research methodology.

Postoperative Cognitive Decline After Cardiac Surgery: A Narrative Review of Current Knowledge in 2019.

The growing number of publications concerning postoperative cognitive decline (POCD) after cardiac surgery is indicative of the health-related and economic-related importance of this intriguing issue. Significantly, the reported POCD incidence over the years has remained steady due to various unresolved challenges regarding the examination of this multidisciplinary topic. In particular, a universally accepted POCD definition has not been established, and the pathogenesis is still vaguely understood. However, numerous recent studies have focused on the role of the inflammatory response to a surgical procedure in POCD occurrence. Therefore, this traditional narrative review summarizes and evaluates the latest findings, with special attention paid to the difficulties of defining POCD as well as the involvement of inflammation in POCD development. We searched the MEDLINE, Scopus, PsycINFO and CENTRAL databases for the best evidence, which was classified according to the Oxford Centre for Evidence-based Medicine. To our knowledge, this is the first narrative review that identified class-1 evidence (systematic review of randomized trials), although most evidence is still at class-2 or below. Furthermore, we revealed that defining POCD is a very controversial matter and that the inflammatory response plays an important role in the mutually overlapping processes included in POCD development. Thus, developing the definition of POCD represents an absolute priority in POCD investigations, and the inflammatory response to cardiac surgery merits further research.

A Prospective Cohort Evaluation of the Cortisol Response to Cardiac Surgery with Occurrence of Early Postoperative Cognitive Decline.

BACKGROUND A recent study reported that patients with higher cortisol levels on the 1st postoperative morning after cardiac surgery exhibited an increased risk of early postoperative cognitive decline (POCD). Therefore, we conducted the current study to gain further insight into the stress response to a surgical procedure as a potential risk factor for early POCD after cardiac surgery. MATERIAL AND METHODS This prospective cohort study enrolled 125 patients undergoing elective cardiac surgery with or without cardiopulmonary bypass (CPB). Patient serum cortisol levels were determined 1 day before surgery (at 08: 00) and on the 1st (at 08: 00, 16: 00 and 24: 00), 3rd (at 08: 00), and 5th (at 08: 00) postoperative days. A battery of 9 neuropsychological tests were used to assess the participants 2 days before the surgical procedure and on the 6th postoperative day. POCD was defined as a decrease in performance of 1 SD or greater between the postoperative and preoperative z scores on at least 1 neuropsychological test. A mixed-design ANOVA was used to determine the correlations of the perioperative cortisol levels with the occurrence of POCD and with the surgical technique performed. RESULTS Mixed-design ANOVA showed no statistically significant differences in the cortisol levels between non-POCD and POCD patients (F=0.52, P=0.690) or between patients with and without CPB (F=2.02, P=0.103) at the 6 perioperative time points. CONCLUSIONS The occurrence of early POCD and the use of CPB were not associated with significantly higher cortisol levels in the repeated measurement design.

Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial.

BACKGROUND: Postoperative cognitive decline (POCD), a very common complication after cardiac surgery, is characterised by impairment of both memory function and intellectual ability as well as being associated with increased use of healthcare resources. The investigators focused on the role of the inflammatory response to a surgical procedure as a potential factor involved in the pathogenesis of POCD. OBJECTIVE: The use of prophylactic dexamethasone to attenuate the inflammatory response was hypothesised to reduce the risk of POCD. DESIGN: Randomised controlled study. SETTING: Single university teaching hospital, from March 2015 to January 2016. PATIENTS: A total of 169 patients scheduled for elective cardiac surgery were enrolled, and 161 patients were included in the analyses. INTERVENTION: Patients were randomised to receive a single intravenous bolus of 0.1 mg kg dexamethasone (n = 85) or placebo (n = 84) 10 h before the surgery. MAIN OUTCOME MEASURES: The primary outcome measure in both groups was the incidence of POCD on the 6th day after surgery. The investigators also evaluated the effect of dexamethasone on the incidence of systemic inflammatory response syndrome, postoperative C-reactive protein levels and postoperative serum S100ß protein levels. RESULTS: Compared to the placebo group, the dexamethasone group showed statistically significant reductions in the incidence of POCD (relative risk, 0.43; 95% confidence interval, 0.21 to 0.89; P = 0.02), the incidence of systemic inflammatory response syndrome (30.0 versus 58.0%, P < 0.001) and postoperative C-reactive protein levels (P < 0.001). Postoperative S100ß levels were insignificantly lower (P = 0.56) in the dexamethasone group. CONCLUSION: Preoperative administration of dexamethasone reduced the inflammatory response and thereby decreased the risk of early POCD after cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02767713.

Are postoperative behavioural changes after adenotonsillectomy in children influenced by the type of anaesthesia?: A randomised clinical study.

BACKGROUND: Negative postoperative behavioural changes (NPOBCs) are very frequent in children after surgery and general anaesthesia. If they persist, emotional and cognitive development may be affected significantly. OBJECTIVE: To assess whether the choice of different anaesthetic techniques for adenotonsillectomy may impact upon the incidence of NPOBC in repeated measurements. DESIGN: A randomised, controlled, parallel-group trial. SETTING: University Hospital Split, Croatia. PATIENTS: Sixty-four children (aged 6 to 12 years, ASA 1 to 2) undergoing adenotonsillectomy assigned into one of two groups: sevoflurane (S) (n = 32) or total intravenous anaesthesia (TIVA) (n = 32). INTERVENTIONS: Permuted-block randomisation with random block sizes of 4, 6 and 8, administering anaesthesia, and evaluation of NPOBC with the Post Hospitalization Behavior Questionnaire (PHBQ: 27 items describing six subscales). The PHBQ was filled out by parents at postoperative days (POD) 1, 3, 7 and 14, and 6 months after surgery. MAIN OUTCOME MEASURES: Differences in numbers of NPOBCs between two anaesthesia techniques, and NPOBC analysis by subscales. RESULTS: The prevalence of at least one NPOBC after surgery ranged from a maximum of 80% [95% confidence interval (CI) 71 to 90%] on POD 1 to a minimum of 43% (95% CI 31 to 56%) 6 months after surgery. Absolute risk reduction for at least one NPOBC in the TIVA group compared with the S group increased from 0.24 on POD 1 to 0.55 6 months after surgery. The number of NPOBCs was also lower in the TIVA group [median 5, interquartile range (IQR) 2 to 10] than in the S group (median 22, IQR 10 to 32) (P < 0.001). The overall number of NPOBCs within PHBQ subscales was significantly lower in the TIVA group than in the S group. The largest difference in the number of NPOBCs between groups was observed for the separation anxiety subscale (mean 5, 95% CI 1 to 9; P < 0.001) followed by the general anxiety subscale (mean 4, 95% CI 3 to 5; P < 0.001) and apathy/withdrawal subscale (mean 3, 95% CI 1 to 5; P < 0.001). CONCLUSION: The prevalence of NPOBC after elective adenotonsillectomy in 6 to 12-year-old children was very high (80%). The choice of anaesthetic technique for adenotonsillectomy in children influenced the incidence and type of NPOBC. Sevoflurane/nitrous oxide anaesthesia was associated with more frequent and prolonged NPOBCs than TIVA, especially in the separation anxiety, general anxiety and withdrawal/apathy subscales.

Clinical scoring systems in predicting health-related quality of life of children with injuries.

The aim of the study was to explore the association between Glasgow Coma Scale (GCS), Paediatric Index of Mortality (PIM2) and Injury Severity Score (ISS), and the long-term outcome of children with injuries. The health related quality of life (HRQL) was assessed by using the Royal Alexandra Hospital for children Measure of Function (RAHC MOF), 12 months post discharge. Out of 118 children with injuries (9% of all patients), 75 had injury of the head as the leading injury. There were no significant differences at admission in the severity of clinical condition, as expressed by PIM2 and ISS, between patients with head injuries and patients with other injured leading body regions. Children with head injuries had significantly worse HRQOL than children with other leading injured body region (p < 0.045), and children from road traffic accidents had significantly worse HRQL (p = 0.004), compared to other mechanisms of injury. HRQL correlated significantly with GCS (p = 0.027), but not with ISS and PIM2. As the conclusion, among all scoring systems applied, only GCS, which demonstrates severity of head injury, showed significant impact on long-term outcome of injured children.

Health-care seeking behaviour for tuberculosis symptoms in Croatia.

BACKGROUND: Early detection and treatment of tuberculosis (TB) patients have been key principles of TB control. Therefore, it is important to understand the causes of delay and to estimate their magnitude in order to plan interventions that yield the maximum benefit. METHODS: A total of 240 subjects aged ≥ 15 year with pulmonary TB were interviewed. Patient delay was defined as the period (in days) from the appearance of any symptoms to the first visit to a medical provider. RESULTS: The median patient delay was 38 days. When using the median as a cut-off to define long patient delay, being an ex-smoker (P = 0.036), current smoker (P = 0.030), coughing (P = 0.021) and losing weight (P = 0.050) were found to be significant. Having high level of education (P = 0.014) was associated with short delay. Being an ex-smoker (P = 0.050, adjusted odds ratio (aOR) = 1.940, 95% CI 1.001-3.759), current smoker (P = 0.029, aOR = 2.077, 95% CI 1.076-4.012) and having a cough (P = 0.022, aOR = 2.032, 95% CI 1.108-3.727), were significant in multivariate logistic regression, while having high level of education remained associated with short delay (P = 0.016, aOR = 0.286, 95% CI 0.103-0.791). The most common reasons for delay were supposed influenza or symptoms improving over time (34.5%) and underestimated symptoms (32.9%). CONCLUSION: People with smoking habits and health-seeking behaviour that may favour advanced disease and prolonged infectiousness as well as people with the lowest level of education contributed to TB delay. To reduced patient delay, efforts should be made to increase TB knowledge, which has to be adjusted to the less-educated segments of the population.

Parental involvement in the war in Croatia 1991-1995 and suicidality in Croatian male adolescents.

AIM: To investigate the association between parental war involvement and different indicators of psychosocial distress in a community sample of early adolescents ten years after the war in Croatia 1991-1995. METHODS: A total of 695 adolescents were screened with a self-report questionnaire assessing parental war involvement, sociodemographic characteristics, and alcohol and drug consumption. Personality traits were assessed with the Junior Eysenck Personality Questionnaire; depressive symptoms with the Children's Depression Inventory (CDI); and unintentional injuries, physical fighting, and bullying with the World Health Organization survey Health Behavior in School-aged Children. Suicidal ideation was assessed with three dichotomous items. Suicidal attempts were assessed with one dichotomous item. RESULTS: Out of 348 boys and 347 girls who were included in the analysis, 57.7% had at least one veteran parent. Male children of war veterans had higher rates of unintentional injuries (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.56 to 2.63) and more frequent affirmative responses across the full suicidal spectrum (thoughts about death - OR, 2.1; 95% CI, 1.02 to 4.3; thoughts about suicide - OR, 5; 95% CI, 1.72 to 14.66; suicide attempts - OR, 3.6; 95% CI, 1.03 to 12.67). In boys, thoughts about suicide and unintentional injuries were associated with parental war involvement even after logistic regression. However, girls were less likely to be affected by parental war involvement, and only exhibited signs of psychopathology on the CDI total score. CONCLUSION: Parental war involvement was associated with negative psychosocial sequels for male children. This relationship is possibly mediated by some kind of identification or secondary traumatization. Suicidality and unintentional injuries are nonspecific markers for a broad range of psychosocial distresses, which is why the suggested target group for preventive interventions should be veteran parents as vectors of this distress.

Comparison of the Impact of Insulin Degludec U100 and Insulin Glargine U300 on Glycemic Variability and Oxidative Stress in Insulin-Naive Patients With Type 2 Diabetes Mellitus: Pilot Study for a Randomized Trial.

BACKGROUND: There is an ongoing discussion about possible differences between insulin degludec (IDeg-100) and glargine U300 (IGlar-300). There is little data and head-to-head comparison of IDeg-100 and IGlar-300 regarding their simultaneous impact on glycemic variability and oxidative stress in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: In our randomized, open-label, crossover study, we compared the impact of IDeg-100 and IGlar-300 on glycemic variability and oxidative stress in insulin-naive patients with T2DM. METHODS: We recruited a total of 25 adult patients with T2DM (7 females) whose diabetes was uncontrolled (HbA1c ≥7.5%) on two or more oral glucose-lowering drugs; a total of 22 completed the study. Mean age was 57.3 (SD 6.99) years and duration of diabetes was 9.94 (SD 5.01) years. After the washout period, they were randomized alternately to first receive either IDeg-100 or IGlar-300 along with metformin. Each insulin was administered for 12 weeks and then switched. At the beginning and end of each phase, biochemical and oxidative stress parameters were analyzed. On 3 consecutive days prior to each control point, patients performed a 7-point self-monitoring of blood glucose profile. Oxidative stress was assessed by measuring thiol groups and hydroperoxides (determination of reactive oxygen metabolites test) in serum. RESULTS: IGlar-300 reduced mean glucose by 0.02-0.13 mmol/L, and IDeg-100 reduced glucose by 0.10-0.16 mmol/L, with no significant difference. The reduction of the coefficient of glucose variation also did not show a statistically significant difference. IGlar-300 increased thiols by 0.08 µmol/L and IDeg-100 increased thiols by 0.15 µmol/L, with no significant difference (P=.07) between them. IGlar-300 reduced hydroperoxides by 0.040 CARR U and IDeg-100 increased hydroperoxides by 0.034 CARR U, but the difference was not significant (P=.12). CONCLUSIONS: The results of our study do not show a significant difference regarding glycemic variability between patients receiving either insulin IDeg-100 or IGlar-300, although IGlar-300 showed greater dispersion of data. No significant difference in oxidative stress was observed. In a larger study, doses of insulins should be higher to achieve significant impact on glycemic parameters and consequently on glycemic variability and oxidative stress. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04692415; https://clinicaltrials.gov/ct2/show/NCT04692415.

Efficacy and safety of inferior turbinate coblation-channeling in the treatment of nasal obstructions.

The aim of this study was to evaluate the safety and effectiveness of coblation-channeling in the treatment of inferior turbinate hypertrophy. The study was conducted in the Department of ENT Head and Neck Surgery, Split University Hospital Center, Split, Croatia. Fifty-two patients with inferior turbinate hypertrophy who were refractory to medical therapy were evaluated for coblation. The procedures were performed under local anesthesia using an ArthroCare ReFlexUltra 45 wand; three submucosal channels were made per turbinate. Clinical examinations, a questionnaire on individual nasal symptoms (hyposmia, nasal drainage and post-nasal drip), a 10-cm visual analog scale (VAS) grading general nasal obstructions, and rhinomanometry before and 8 weeks after the treatment were administered to assess treatment outcomes. No adverse effects were encountered. Nasal breathing was significantly improved in all patients, decreasing the VAS from a median of 7 (range 2-9) to 1 (range 0-3) (p < 0.001). Total nasal resistance decreased from 0.44 Pa +/- 0.50 to 0.24 Pa +/- 0.11 (p = 0.005). Improvement was statistically significant for all three symptoms (hyposmia [p = 0.005], nasal drainage [p = 0.003] and post-nasal drip [p < 0.001]). In this paper, we demonstrate that coblation-channeling of the hypertrophic inferior turbinate is an effective and safe way to reduce nasal obstruction symptoms.

Succinylcholine use in adult anesthesia - A multinational questionnaire survey.

There are no definitive evidence based standards regarding use of succinylcholine (SCh) for anesthesia induction. However, there is a global trend toward eliminating SCh not only in elective, but also in emergency surgery in adults. The aim of the study was to survey the use of SCh in adult elective and emergency anesthesia practice in several European countries and the United States by questionnaire. One hundred and seventy anesthesiologists out of 201 possible, from six institutions in five countries (Croatia, Bosnia and Herzegovina, Hungary, United Kingdom, and the United States) anonymously completed the questionnaire about their use of SCh. The questionnaire was structured to assess the respondents': frequency of use of SCh in adult surgery (elective and emergency), reasons for use or rejection of SCh, positive and negative attributes of SCh, and observed side effects in their practice. Differences in use were tested using X2-test when appropriate. There was a significant difference in the use of SCh between countries for elective surgery with the lower use in UK and Hungary (chi2=45.8, p <0.001). One hundred and seventeen (69%) use it regularly. In emergency surgery 165 (97%) anesthesiologists use it without any significant difference among countries (chi2=2.13, p<0.711). The top indications for SCh use were anticipated difficult intubation/ventilation (74%), caesarean section (54%), and obesity and/or hiatus hernia (49%). The top reasons against SCh use were adequate substitutes (87%), fear of arrhythmias (45%), and anaphylaxis (19%). The most desirable reported drug features were: rapid onset (88%), short duration (64%), and effective relaxation (61%). Forty-six per cent of the surveyed anesthesiologists stated they had never experienced a complication with its use. The most frequently reported side effects were myalgias (47%), bradycardias (42%), and prolonged blockade (39%). Allergic reactions were reported by 13%, and asystole by 12% of physicians. From our survey it is possible to conclude that succinylcholine is still regularly used, at least by surveyed anesthesiologists in Europe and USA, in adult anesthesia practice, especially in elective surgery for which it may be least suited. This reflects the discrepancies between the international guidelines for the use of SCh and the clinical practice of many anesthesiologists in different countries. The regional differences in SCh usage may be considered through anesthesia cultures and practice variations depending on country.

Randomized Clinical Trial Comparing Concomitant and Tailored Therapy for Eradication of Helicobacter pylori Infection.

As high clarithromycin resistance (>20%) in the Split-Dalmatia region of Croatia hinders the treatment of H. pylori infection, the primary objective of this study was to compare concomitant quadruple with the tailored, personalized therapy as first-line eradication treatment of H. pylori. In an open-label, randomized clinical trial, 80 patients with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 gr, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or tailored therapy in accordance with the results of the antimicrobial susceptibility testing. Eradication status was assessed 4 weeks after treatment. Eradication rates were significantly higher in tailored group than in concomitant group both in intention-to-treat (70 vs. 92.5%, p = 0.010) and per-protocol (87.5 vs. 100%, p = 0.030) analysis in the setting of increasing antibiotic resistance (clarithromycin 37.5%, metronidazole 17.5%, dual resistance 10%). Adverse effects were more frequent in the concomitant group (32.5 vs. 7.5%, p = 0.006). Tailored therapy achieves higher eradication with a lower adverse events rate. With the increasing resistance of H. pylori strains to antibiotic treatment, eradication regimes with such characteristics should be strongly considered as a reasonable choice for first-line treatment.

Ki-67 quantitative evaluation as a marker of cervical intraepithelial neoplasia and human papillomavirus infection.

OBJECTIVE: To assess the value of Ki-67 quantitative analysis in cervical intraepithelial neoplasia (CIN) in relation to CIN grading and human papillomavirus (HPV) group typing. METHODS: Cervical samples selected retrospectively from 106 cases were analyzed immunohistochemically for Ki-67-positive nuclei in 3 epithelial layers and by polymerase chain reaction for HPV typing. RESULTS: The proportion of high-risk HPV positivity was 0% in normal controls and 30% in CIN 1, 57% in CIN 2, and 90% in CIN 3 groups, and there was no low-risk HPV finding in CIN 2 and CIN 3 cases (P < 0.001). High-risk HPV-positive cases exhibited significantly more Ki-67-positive nuclei per 100-mum basal membrane, which were more frequent in the middle and upper third layers of the epithelium compared with low-risk HPV and HPV-negative cases (P < 0.001). The differences among the CIN groups in the total number and in the percentages of Ki-67-positive nuclei in the lower, middle, and upper third layers of the epithelium were significant (P < 0.001). With the cutoff value of more than 33% Ki-67-positive nuclei in the middle and the upper third layers of the epithelium, Ki-67 staining demonstrated 98.4% sensitivity (60/61 cases) and 97.8% specificity (44/45 cases) for the detection of CIN 2/CIN 3 in our study group. CONCLUSIONS: The Ki-67 immunostaining proved to be predictive for high-risk HPV infection, and it can differentiate reactive lesions from cervical dysplasias. Ki-67 quantitative analysis in 3 epithelial layers is a sensitive and specific method of differentiation between CIN 1 and CIN 2/CIN 3 grades and can be a valuable adjunctive method for more accurate CIN grading.

Job satisfaction among medical doctors in one of the countries in transition: experience from Croatia.

Our aim was to explore and compare the job satisfaction between family physicians and hospital specialists in Split, Croatia. The survey was carried out in 2005 and 2006. A validated questionnaire was composed of two parts: 92 statements and questions about job satisfaction in the form of a Lickert scale (range 1-5) and eight questions concerning demographic issues. The questionnaire was completed and returned by 165 hospital specialists from the University Hospital and by 131 family physicians from the Split County. Response rate for family physicians was 39.81% and 41.46% for hospital specialists. Hospital doctors were divided in two groups: internal and surgical. There were no significant differences between family physicians and hospital specialists in total job satisfaction (F = 1.02; p = 0.41). Family physicians were more satisfied with their workplace conditions than internal medicine specialists (19.37 +/- 4.23 vs. 17.37 +/- 4.59; F = 5.93; p = 0.003), and less satisfied with the possibilities for postgraduate training than surgeons (5.27 +/- 1.90 vs. 6.59 +/- 2.07; F = 9.26; p < 0.001). Global job satisfaction was rather low but does not differ between the three medical groups. Disparities were observed in some segments (opportunity for further training and academic advancement, vacation, and salary). The reason for the family physician's relative satisfaction may be due to stable working conditions, independence in organizing work schedules and personal responsibility.

[Succinylcholine use by anesthesiologists in Croatia--is it really abandoned?]. / Uporaba sukcinil-kolina medu hrvatskim anesteziolozima--je li taj lijek zaista odbacen?

The aim was to establish the prevalence of succinylcholine use among Croatian anesthesiologists in adult elective and emergency surgery, as well as in pediatric surgery, regarding gender, position, working place, and working experience of physicians. The anesthesiologists were expected to express their personal opinions regarding the drug, as well as experienced side effects in their own clinical practice. A total of 125 anesthesiologists (out of 590 in Croatia) from both university and county hospitals in Croatia anonymously filled out the questionnaire regarding the use of succinylcholine (Appendix 1). The questionnaire was structured to assess the use of succinylcholine in adult elective and emergency surgery, and in pediatric anesthesia, to obtain the reasons for the preference or rejection of succinylcholine, and information about observed side effects. The differences in use regarding gender, position, working place, and working experience were tested using chi-squared test and Fisher's exact test. p < 0.05 was considered significant. Vast majority (approximately 70%) of anesthesiologists in Croatia still use succinylcholine. The percentages of anesthesiologists that never use succinylcholine in adult elective, adult emergency and pediatric surgery were 20%, 6%, and 31%, respectively. There were no significant differences in the use of succinylcholine regarding position, working place, and working experience, but male anesthesiologists used it less frequently in pediatric anesthesia compared with their female colleagues (chi2 = 5.08; p = 0.02). Forty-two per cent never experienced a complication from the drug use. The most frequently reported side effects were bradycardias (67%) and myalgias (54%), followed by prolonged blockade (33%), and allergy (33%). Asystole was reported by 10% of the respondents. In conclusion, succinylcholine is still widely used by anesthesiologists in Croatia. The majority of surveyed physicians were aware of its possible dangerous adverse effects, but still use it in certain situations. Therefore, indications and contraindications for its use deserve expert consensus guidelines based on the available scientific evidence.

Randomised clinical trial comparing concomitant and hybrid therapy for eradication of Helicobacter pylori infection.

BACKGROUND: The primary objective of this study was to compare concomitant and hybrid therapy in the first line eradication treatment of Helicobacter pylori infection in Split-Dalmatia County, Croatia, in which clarithromycin resistance is above 20%. The secondary objective of the study was to determine and compare compliance and adverse events rate between these therapeutic protocols. MATERIALS AND METHODS: In an open-label, randomised clinical trial 140 patients total with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 g, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or hybrid (esomeprazole 40 mg and amoxicillin 1 g twice daily during 14 days with adding metronidazole 500 mg and clarithromycin 500 mg twice daily, in the last 7 days,) treatment group. RESULTS: Eradication rates for concomitant group and hybrid therapy group were 84.1% (58/69) and 83.1% (59/71) respectively in the intention-to-treat analysis and 96.7% (58/60) and 95.2% (59/62) in per-protocol analysis. There was no significant difference between the groups (ITT analysis: P = 0.878; PP analysis: P = 0.675). Adverse events were more frequent in the concomitant group (33.3% vs 18.3%, P = 0.043). There was no difference among groups regarding compliance rate. CONCLUSION: Hybrid therapy has similar eradication rate as concomitant therapy, with lower adverse events rate. In the era of increasing antibiotic resistance, eradication regime with less antibiotic's usage, as hybrid therapy, should be reasonable first line treatment choice for H. pylori infection. Clinical Trials, gov: NCT03572777.