The effect of nasal douching by hypertonic 2.3 per cent sea water with algae extracts on the concentration of epidermal growth factor, transforming growth factor-α and interleukin-8 in nasal secretions of patients with nasal polyposis following endoscopic surgical treatment.

OBJECTIVE: To investigate epidermal growth factor, transforming growth factor-α and interleukin-8 production in nasal mucosa irrigated with hypertonic 2.3 per cent solution with algae extracts, in comparison to 0.9 per cent NaCl during the first two weeks after surgery for nasal polyposis, in relation to symptoms and local findings. METHODS: This prospective study included 20 nasal polyposis patients postoperatively irrigated with hypertonic solution and 20 nasal polyposis patients postoperatively irrigated with isotonic solution. We evaluated nasal symptom score, endoscopic score and mediator levels in nasal secretions before and after irrigation. RESULTS: Following treatment, nasal symptom score and endoscopic score were significantly lower in the hypertonic solution group (p = 0.023; p < 0.001, respectively). The increase in the epidermal growth factor and the decrease in the transforming growth factor-α and interleukin-8 concentration were higher in the hypertonic group (p < 0.001 for all mediators). CONCLUSION: Irrigation with a hypertonic solution was found to be more effective than an isotonic solution in nasal mucosa reparation.

Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase.

BACKGROUND: We aimed to characterize newer antiseizure medications (ASMs)-induced hepatotoxicity in children and identify signals of disproportionate reporting of hepatotoxicity-related adverse drug events (ADEs). RESEARCH DESIGN AND METHODS: Case reports reported to VigiBase were accessed using Empirica™ Signal software. To summarize characteristics of the retrieved cases, descriptive statistics were used. A disproportionality analysis was conducted using the Multi-item Gamma Poisson Shrinker algorithm, which calculates Empirical Bayesian Geometric Mean value and its lower and upper 95% confidence limits (EB05 and EB95, respectively). EB05 > 2, N > 0 was considered a signal. RESULTS: Based on 870 analyzed cases, a higher proportion of cases was reported in girls than in boys and in patients aged 2-11 years than in other age groups. Most cases were serious. In 25 cases, hepatotoxicity resulted in death. A high proportion of patients (n = 275, 31.61%) experienced hypersensitivity reactions, mostly due to lamotrigine. The disproportionality analysis yielded 17 signals concerning felbamate, lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and topiramate. Four signals were for severe liver injury and concerned felbamate, lamotrigine, levetiracetam, and topiramate. Gender-biased reporting frequency was detected for four ASM-ADE combinations. CONCLUSION: Our results should serve to raise clinicians' awareness about the potential association between several newer ASMs and drug-induced liver injury in children.

Drug-induced liver injury associated with the use of newer antiseizure medications in the elderly: an analysis of data from VigiBase.

BACKGROUND: Data on drug-induced liver injury (DILI) caused by newer antiseizure medications (ASMs) in the elderly are scarce and mainly come from literature case reports. We analyzed Individual Case Safety Reports (ICSRs) of DILI in elderly patients treated with newer ASMs reported to VigiBase. RESEARCH DESIGN AND METHODS: Empirica™ Signal software was used to retrieve ICSRs reported to VigiBase up to 31 December 2021 and to calculate Empirical Bayesian Geometric Mean and corresponding 90% confidence intervals (EB05, EB95) for each drug-event pair. EB05 > 2, N > 0 was considered a signal. Analysis by age subgroups and gender was performed to assess the influence of these factors on ICSR characteristics and identified signals. RESULTS: There were 1399 ICSRs reporting 1947 events of hepatotoxicity. 56.97% of the reports were reported in females, 67.05% were serious, and 3.36% resulted in death. For one or more events of hepatotoxicity, signals were detected for lamotrigine, levetiracetam, oxcarbazepine, topiramate, and zonisamide. Age- and gender-biased reporting frequency was identified for topiramate-induced hyperammonemia, with disproportionally higher reporting frequency in ≥75-year-old male patients. CONCLUSIONS: The results of our study indicate differences among newer ASMs in their potential to cause DILI in the elderly. Further studies are needed to confirm the associations identified in this study.

Lidocaine clearance as pharmacokinetic parameter of metabolic hepatic activity in patients with impaired liver.

Background: The study aimed to estimate lidocaine (LID) pharmacokinetic parameter values in patients with impaired liver function, level of correlation between the pharmacokinetic parameters and Child-Pugh class and change in pharmacokinetic parameters after liver tumor resection compared to the preoperative value. Methods: Patients with impaired liver function were subject to the LID test 1 day prior to, 3 and 7 days after the intervention. LID was administered in single i.v. dose of 1 mg/kg. Blood samples were collected at 15, 30 and 90 minutes after drug administration. Non-compartmental analysis was applied for calculating the pharmacokinetic parameters. Results: The study included 17 patients with the diagnosis of cirrhosis and 41 patients with liver tumor. In both groups of patients, the values of the coefficients of correlation show the best correlation between clearance (CL) and Child-Pugh score (-0.693, p<0.005) over other pharmacokinetic parameters. The results indicate worsening hepatic function on 3rd day after operation in comparison to the values of LID CL prior to operation (mean LID CL for patients with Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively; while for B class are 16.89 L/h, 22.65 L/h, respectively). On day 7th, the values of LID CL (mean value for patients with Child-Pugh class A and B are 40.98 L/h and 21.46 L/h, respectively) are increased in comparison to 3rd day after. Conclusions: LID pharmacokinetic parameters consequently changed according to the severity of liver impairment, assessed by Child-Pugh score. Values of LID CL and volume of distribution (Vd) coupled with standard biochemical parameters may be used for preoperative assessment of liver function and monitoring of its postoperative recovery.

Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria

Abstract The study aimed to estimate and compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) between the STOPP/START original (v1) and updated version (v2) among older patients in various settings, as well as associated factors. The study included 440 patients attending a community pharmacy, 200 outpatients and 140 nursing home users. An increase in the prevalence of STOPP v2 (57.9%) compared to v1 (56.2%) was not statistically significant in the total sample and within each setting (p>0.05). A decrease in the prevalence of START v1 (55.8%) to v2 (41.2%) was statistically significant (p<0.001) in the total sample and within each setting (p<0.05). Drug indication (32.9%) and fall-risk medications (32.2%) were most commonly identified for STOPP v2, while cardiovascular system criteria (30.5%) were the most frequently detected for START v2. The number of medications was the strongest predictor for both STOPP v1 and v2, with odds ratio values of 1.35 and 1.34, respectively. Patients' characteristics associated with the occurrence of STOPP and START criteria were identified. According to both STOPP/START versions, the results indicate a substantial rate of potentially inappropriate prescribing among elderly patients. The prevalence of PIMs was slightly higher with the updated version, while the prevalence of PPOs was significantly lower

The impact of treatment choices on potential drug-drug interactions in hypertensive patients.

AIMS: The aim of this study was to analyse potential drug-drug interactions (pDDIs) and their potential adverse drug reactions (ADRs) among hypertensive patients. Moreover, we investigated the possibility of reducing pDDIs with different treatment choices. METHODS: This was a cross-sectional study including all outpatients with hypertension and two or more medications, treated in a university hospital in Serbia. Lexicomp Interact (Lexi-Comp, Inc., Hudson, OH) was used for identification of pDDIs and potential ADRs. Treatment choices were explored according to patient characteristics, treatment guidelines and the interacting potential of drugs. Data were analysed using descriptive analysis and multiple logistic regression. RESULTS: A total of 350 patients were included in this study, with average age (77 [36-98] years and 6.1 [2.5]) medications. The majority of patients (86.0%) had at least one clinically significant pDDI, and the average was 3.78 (3.90) (range 1-25). Suggestions for treatment change aimed mainly at eliminating drug duplications, reducing the use of thiazide diuretics, sulfonylureas, alpha-lipoic acid and pentoxifylline and increasing the use of calcium-channel blockers, when appropriate. pDDIs would have decreased to 2.10 (2.52), P <.001, yet male gender, ≥6 medications, cardiovascular diseases, diabetes, benign prostatic hyperplasia, would be predictive of two or more pDDIs. The main potential adverse outcomes of pDDIs were hypotension, renal failure, hypoglycaemia, bradycardia and lactic acidosis. CONCLUSION: Careful choice of drugs can reduce but not eliminate pDDIs and their potential ADRs in hypertensive patients. Close monitoring for hypotension, renal failure, hypoglycaemia, bradycardia and lactic acidosis is necessary.

Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study.

BACKGROUND: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia. METHODS: A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup. RESULTS: During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002). CONCLUSIONS: Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality.

Telepharmacy service experience during the COVID-19 pandemic in the Republic of Srpska, Bosnia and Herzegovina.

The COVID-19 pandemic exerted a profound impact on health systems worldwide. Moreover, significant concerns were raised in terms of middle- and long-term consequences of postponing care in non-COVID patients. The primary aim of the study was to describe the remote pharmaceutical care service (telepharmacy) during the COVID-19 pandemic in the Republic of Srpska (RS), Bosnia and Herzegovina. The secondary aim was to identify service users' needs and concerns and to describe community pharmacists' interventions. Ten community pharmacists were appointed by the Pharmaceutical Society of the RS to deliver telepharmacy services. After obtaining users' verbal permission, pharmacists documented issues discussed with them. The prospective data collection included the period from April 13 to May 21, 2020. Descriptive and statistical analysis was performed using IBM SPSS Statistics software (ver. 22). A total of 71 service users' charts were analyzed. Telepharmacy users were on average 61.31 ± 13.27 years of age, with almost equal gender distribution. Patients with chronic or acute/subacute conditions were predominant with a share of 84.5%. Chronic diseases were the main reason for searching pharmacists' consultation (74.6%), 7% had a complaint about worsening of a chronic condition, 9.9% reported only acute/subacute conditions as ambulatory conditions, whereas 15.5% asked information about coronavirus or COVID-19. The vast majority of patients' and users' needs were addressed by a pharmacist during counseling and only 15.5% of the patients required immediate referral to a doctor for refill/prescribing purposes. Remote pharmaceutical care service (telepharmacy) is deemed a convenient model in the RS during the COVID-19 pandemic. Patients and users presented with explicit and specific needs and concerns, both COVID- and non-COVID-related, which should not be neglected. Community pharmacists showed a high level of resilience and ability in addressing patients' needs.

Effects of Pelargonium sidoides extract vs roxithromycin on chemokine levels in nasal secretions of patients with uncomplicated acute rhinosinusitis.

BACKGROUND: Previous investigations suggest the use of extract from the roots of Pelargonium sidoides (EPs 7630) for the therapy of uncomplicated rhinosinusitis. The aim of this prospective study was to compare the effects of herbal drug EPs 7630 and antibiotic roxithromycin on chemokine production in nasal mucosa and clinical parameters in patients with uncomplicated acute bacterial rhinosinusitis (ABRS). METHODS: Seventy-eight ABRS patients were divided into 26 patients receiving EPs 7630 tablets, 3 × 20 mg/day per os (group 1), 26 patients receiving roxithromycin tablets, 2 × 150 mg/day per os (group 2), both for 10 days, and 26 patients who received no therapy (Control group). We measured chemokine levels in nasal secretions by flow cytometry and assessed clinical parameters on day 0 and day 10 of investigation. RESULTS: EPs 7630 increased concentrations of MCP-1 (P = .001) and IP-10 (P = .049) and decreased levels of MIP-1α (P < .001), ENA-78 (P < .001), and IL-8 (P < .001). Roxithromycin increased levels of IP-10 (P = .049) and decreased levels of MCP-1 (P < .001), MIP-1α (P < .016), ENA-78 (P < .001), and IL-8 (P < .001). Comparison of the non-treated patients' group with groups 1 and 2 revealed significant improvement of all clinical parameters in treated patients (P < .001), but therapy with roxithromycin resulted in better improvement in nasal symptoms and endoscopic findings than therapy with EPs 7630. CONCLUSION: Our results suggest the presence of similar modulatory effects of both therapies on production of chemokines that regulate the function of neutrophils and monocytes in nasal mucosa. Roxithromycin shows better clinical efficacy than EPs 7630 in patients with uncomplicated ABRS. LEVEL OF EVIDENCE: 1b.

Impact of pharmacist's intervention on decreasing erlotinib interactions in the treatment of lung cancer patients in low resource settings.

BACKGROUND: This study aimed to demonstrate that having clinical pharmacist as a member of oncology team in low and middle income countries might lead to significant reduction in the number of erlotinib interactions in the treatment of non-small cell lung cancer patients. METHODS: A group of 44 patients was labeled as intervention group and they were analyzed prospectively in the period from 1 January 2017 to 1 May 2018 during clinical pharmacist's participation in regular weekly multidisciplinary oncology team meetings. The control group consisted of 44 out of 110 patients treated with erlotinib before the involvement of a clinical pharmacist in oncology team, match paired with 44 patients in intervention group. RESULTS: Clinically significant interactions were identified in two-thirds of studied patients (57 out of 88). Most drug interactions, 38%, potentially result in decrease of serum concentration of erlotinib. Clinical pharmacist provided therapy modification suggestions for 32 out of 44 (72.72%) patients in the intervention group, most of which were accepted by doctors. In the intervention group, there were significantly less clinically significant interactions compared to the control group (10 versus 24, p = 0.002). Progression-free survival was significantly longer in the pharmacist's intervention group (p = 0.001). CONCLUSIONS: Clinical pharmacist's intervention led to significant decrease in erlotinib interactions which may result in treatment optimization of lung cancer patients.

Pentoxifylline with metformin treatment improves biochemical parameters in patients with nonalcoholic steatohepatitis.

BACKGROUND: The progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with Nash. Setting: Outpatient hepatology clinic. METHODS: A prospective trial was conducted. The first cohort included patients with biopsy-proven Nash, while the second cohort consisted of patients with biopsy-confirmed NAFLD. Blood tests were checked at baseline and every three months. Pentoxifylline at a dosage of 400 mg t.i.d. and Metformin at the dosage of 500 mg t.i.d. were introduced for six months in Nash group. The impact of the treatment was assessed based on biochemical results after combined treatment with low-cost medications. RESULTS: All 33 Nash patients completed 24 weeks of treatment. We observed significant improvement (p<0.05) of median values after treatment for the following parameters: serum uric acid levels decreased by 51.0 mmol/L, calcium decreased for 0.27 mmoL/L, magnesium showed an increase of 0.11 mmoL/L. Insulin resistance improved as a reduction of HOMA - IR by 1.3 was detected. A significant decrease of median in liver enzymes, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase by 24.0 U/L, 9.1 U/L, 10.8 U/L respectively, was noted. CONCLUSIONS: Pentoxifylline and Metformin may provide possible treatment option in Nash. Some new potential benefit of the therapy in improving liver function whilst decreasing cardiovascular risk was perceived.

Effects of Pelargonium sidoides extract on chemokine levels in nasal secretions of patients with non-purulent acute rhinosinusitis.

OBJECTIVE: Previous investigations suggest the use of extract from the roots of Pelargonium sidoides (EPs 7630) for improvement of the symptoms of uncomplicated upper airway inflammations, due to its antimicrobial and immunomodulatory actions. The aim of this investigation was to evaluate the effects of EPs 7630 on chemokine production in nasal mucosa and clinical parameters of patients with acute postviral rhinosinusitis (APRS). METHODS: Twenty-six (n = 26) APRS patients and 25 (n = 25) control subjects were included in this prospective study. We measured the concentrations of thirteen chemokines in nasal secretions of APRS patients and controls by flow cytometry. The patients with APRS were treated by EPs 7630 20 mg oral tablets, three times daily for 10 days. We compared the chemokine levels in nasal secretions, nasal symptoms and endoscopic findings in patients, before and after therapy. RESULTS: We found higher Total Symptom Score (TSS) and higher concentrations of MCP-1, MIP-1α, MIP-1ß, MIP-3α, ENA-78 and IL-8 in nasal secretions of APRS patients than in controls. After therapy by EPs 7630, we found significant improvement in all symptoms and endoscopic findings of APRS. The concentrations of MCP-1, IP-10 and MIP-1ß were significantly increased and levels of MIP-1α, ENA-78, GROα and IL-8 significantly decreased in nasal fluid samples after therapy. No adverse effects were reported during the treatment. CONCLUSION: Our results suggest the presence of modulatory effects of EPs 7630 on production of chemokines regulating the function of neutrophils and monocytes in the site of inflammation of the nasal mucosa in patients with APRS.

Healthcare associated Clostridioides difficile infection in adult surgical and medical patients hospitalized in tertiary hospital in Belgrade, Serbia: a seven years prospective cohort study.

Introduction: Clostridioides difficile (C. difficile) infection (CDI) is one of the most common healthcare-associated (HA) infections in contemporary medicine. The risk factors (RFs) for HA CDI in medical and surgical patients are poorly investigated in countries with a limited resource healthcare system. Therefore, the aim of the study was to investigate differences in patients' characteristics, factors related to healthcare and outcomes associated with HA CDI in surgical and medical patients in tertiary healthcare centre in Serbia.Materials and Methods: A prospective cohort study was conducted including adult patients diagnosed with initial episode of HA CDI, first recurrence of disease, readmission to hospital, while deaths within 30 days of CDI diagnosis and in-hospital mortality were also recorded. Patients hospitalized for any non-surgical illness, who developed initial HA CDI were assigned to medical group, whereas those who developed initial HA CDI after surgical procedures were in surgical group. The data on patients' characteristics and factors related to healthcare were collected, too.Results: During 7-year period, from 553 patients undergoing in-hospital treatment and diagnosed with CDI, 268 (48.5%) and 285 (51.5%) were surgical and medical patients, respectively. Age ≥ 65 years, use of proton pump inhibitors, chemotherapy and fluoroquinolones were positively associated with being in medical group, whereas admission to intensive care unit and use of second- and third-generation cephalosporins were positively associated with being in surgical group.Conclusions: Based on obtained results, including significant differences in 30-day mortality and in-hospital mortality, it can be concluded that medical patient were more endangered with HA CDI than surgical ones.

Potential drug-drug interactions associated with clinical and laboratory findings at hospital admission.

Background Drug-drug interactions represent one of the causes of adverse therapy outcomes through deteriorated efficacy or safety. However, the true extent of harm related to drug-drug interactions is not well established due to a lack of recognition and understanding. Objective The aim of this study was to investigate the association of potential drug-drug interactions with patients variables recorded at admission. Setting A cross-sectional correlation study was performed on the Cardiology ward of the University Clinical Hospital Center in Belgrade, Serbia. Method Data were retrospectively obtained from medical records and LexiInteract was used as the screening tool for potential drug-drug interactions. Main outcome measure Clinical and laboratory parameters recorded at the patients admission. Results A total of 351 patient records entered the analysis, with the mean age of 70 ± 10 years. The prevalence of potentially relevant drug-drug interactions was 61% (N = 213). After controlling for patient characteristics, nine potential drug-drug interactions were significantly associated with laboratory values outside the range and five potential drug-drug interactions with inadequate clinical parameter values. Potential drug-drug interactions were associated with abnormalities in blood count, metabolic parameters, electrolyte imbalance and renal function parameters. Association with inadequate control of systolic, diastolic blood pressure, as well as heart rhythm was also shown. Conclusion Drug-drug interactions were associated with patients clinical and laboratory findings. Our findings may assist in the identification of patients with increased likelihood of suboptimal therapy outcomes. Generating evidence through post-marketing drug-drug interactions research would lead to improvement in clinical decision-support systems, increased effectiveness and utilization in everyday clinical practice.

Adverse drug reactions caused by drug-drug interactions in cardiovascular disease patients: introduction of a simple prediction tool using electronic screening database items.

Objective: Cardiovascular disease (CVD) drugs have been frequently implicated in adverse drug reaction (ADR)-related hospitalizations. Drug-drug interactions (DDIs) are common preventable cause of ADRs, but the impact of DDIs in the CVD population has not been investigated. Hence, the primary aim of the study was to identify DDIs associated with ADRs in CVD patients at hospital admission. The second aim was to develop a simple tool to identify high-risk patients for DDI-related adverse events. Methods: An observational study was conducted on the Cardiology Ward of University Clinical Hospital Center. Data were obtained from medical charts. A clinical panel identified DDIs implicated in ADRs, using LexiInteract database and Drug Interaction Probability Scale. Statistics were performed using PASW 22 (SPSS Inc.). Results: DDIs contributed to hospital admission with a total prevalence of 9.69%. DDI-related ADRs affected mainly cardiac function (heart rate or rhythm, 41.07%); bleeding and effect on blood pressure were equally distributed (17.86%). Non-cardiovascular ADRs were found in 23.21% of DDIs. After admission, 73% of the identified DDIs led to changes in prescription. Prediction ability of calculated DDI adverse event probability scores was rated as good (AUC = 0.80, p < .001). Conclusions: CVD patients are highly exposed to adverse DDIs; about one in ten patients hospitalized with CVD might have a DDI contributing to the hospitalization. Given the high prevalence of CVD, DDI-related harm might be a significant burden worldwide. Identification of patients with high DDI adverse event risk might ease the recognition of DDI-related harm and improve the use of electronic databases in clinical practice.

Exploring Sirolimus Pharmacokinetic Variability Using Data Available from the Routine Clinical Care of Renal Transplant Patients - Population Pharmacokinetic Approach.

BACKGROUND: Due to wide intra- and inter-individual pharmacokinetic variability and narrow therapeutic index of sirolimus, the therapeutic drug monitoring (TDM) of sirolimus with detailed biochemical and clinical monitoring is necessary for dose individualization in kidney transplant patients. The purpose of the study was to explore and identify factors that contribute to pharmacokinetic variability by developing and validating a population model using routine TDM data and routinely monitored biochemical and clinical parameters. METHODS: The data obtained by routine monitoring of 38 patients over a period of one year from the sirolimus treatment initiation, were collected from patients' records. Population analysis was performed using the software NONMEM®. The validity of the model was tested by the internal and external validation techniques. RESULTS: The pharmacokinetic variability was partially explained with patient's age and liver function. CL/F was found to decrease with age. According to the developed model, sirolimus CL/F decreases by, in average, 37% in patients with aspartate aminotransferase (AST) greater than 37 IU/L. The internal and external validation confirmed the satisfactory prediction of the developed model. CONCLUSIONS: The population modeling of routinely monitored data allowed quantification of the age and liver function influence on sirolimus CL/F. According to the final model, patients with compromised liver function expressed via AST values require careful monitoring and dosing adjustments. Proven good predictive performance makes this model a useful tool in everyday clinical practice.

A Simple Index for Nonalcoholic Steatohepatitis-HUFA-Based on Routinely Performed Blood Tests.

Background and objectives: Data suggests that nearly 30% of the general population have steatosis and up to 5% of this population develops nonalcoholic steatohepatitis (NASH). Liver biopsy is still considered to be the gold standard for the diagnosis of NASH. Great effort is being made toward the identification of sensitive diagnostic tests that do not involve invasive procedures to address a common concern in patients with the nonalcoholic fatty liver disease-whether they have NASH or simple steatosis. We aimed to investigate the independent predictors and develop a non-invasive, easy-to-perform, low-cost set of parameters that may be used in clinical practice to differentiate simple steatosis from NASH. Methods: А cross-sectional study of nonalcoholic fatty liver disease (NAFLD) patients divided into two groups: group I-simple steatosis (SS) and group II-biopsy-proven NASH. Strict inclusion criteria and stepwise analysis allowed the evaluation of a vast number of measured/estimated parameters. Results: One hundred and eleven patients were included-82 with simple steatosis and 29 with biopsy-proven NASH. The probability of NASH was the highest when homeostatic model assessment of insulin resistance (HOMA-IR) was above 2.5, uric acid above 380 µmol/L, ferritin above 100 µg/L and ALT above 45 U/L. An acronym of using first letters was created and named the HUFA index. This combined model resulted in an area under the receiver operator characteristic curve (AUROC) of 0.94, provided sensitivity, specificity, positive predictive value and a negative predictive value for NASH of 70.3%, 95.1%, 83.1% and 90.0%, respectively. Conclusion: We suggest a simple non-invasive predictive index HUFA that encompasses four easily available parameters (HOMA-IR, uric acid, ferritin and ALT) to identify patients with NASH, which may reduce the need for a liver biopsy on a routine basis in patients with NAFLD.

Efficacy of hypertonic (2.3%) sea water in patients with aspirin-induced chronic rhinosinusitis following endoscopic sinus surgery.

BACKGROUND: Aspirin-induced chronic rhinosinusitis (CRS) is a severe progressive persistent disease, usually associated with nasal polyps (NPs). AIM/OBJECTIVE: To compare effect of hypertonic (2.3% NaCl) sea water and isotonic 0.9% NaCl on symptoms and endoscopic findings in those patients in the period of 1 month after endoscopic sinus surgery (ESS). MATERIAL AND METHODS: This prospective, randomized study included 30 patients with aspirin-induced CRS undergoing ESS. Patients were divided into two groups of 15 subjects and one of the two nasal irrigation solutions was administered in each group. Intensity of 5 symptoms (nasal obstruction, nasal discharge/postnasal drip, facial pain/pressure, headache and trouble sleeping) and endoscopic findings were assessed during the 1st, 7th, 14th, 21st and 28th days after the nasal packs removal. RESULTS: We found significantly lower total symptom score (TSS) during the 7th (p = .009), 14th (p = .003), 21st (p < .001) and the 28th day (p = .001), lower total endoscopic score (TES) on the 21st (p = .002) and 28th day (p = .001), lower nasal obstruction, facial pain/pressure, headache and trouble sleeping, and lower nasal mucosal edema, nasal secretion and nasal crusting in patients treated by hypertonic sea water. CONCLUSION AND SIGNIFICANCE: Hypertonic sea water should be recommended douching solution in the early postoperative care of patients with aspirin-induced CRS.

The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis.

BACKGROUND: Data suggest cystatin C (CysC) levels and hepatic artery resistive index (HARI) correspond to the progression of chronic liver disease. We aimed to evaluate the clinical significance of these parameters in assessment of fibrosis in patients with liver cirrhosis. METHODS: The cross-sectional study included 63 patients with liver cirrhosis. A control group consisted of 30 age- and gender-matched healthy persons. RESULTS: We confirmed significantly higher values of CysC in patients with cirrhosis compared to control group (p = 0.036). Average value of HARI in the examined group was increased (0.72 ± 0.06) and there was the statistically significant difference compared to controls (0.66 ± 0.03) (p < 0.001). We found statistically significant correlation between HARI and CysC in the study group. Analyzing the possibility of distinguishing healthy subjects from patients with fibrosis, we have found that the area under the curve is far greater in the HARI index than CysC. Comparison of CysC among Child⁻Pugh stages and correlation with a model for end-stage liver disease (MELD) score showed statistically significant results. CONCLUSION: We confirmed HARI is a more accurate parameter than CysC in discriminating healthy subjects from patients with fibrosis, while CysC could be a better indicator of the stage of liver cirrhosis.

Association between Adverse Effects and Parental Beliefs about Antiepileptic Medicines.

Background and Aim: Adverse effects are common in children treated with antiepileptic medications and may affect parental beliefs about treatment. The aim of the study was to investigate the relationship between adverse effects and parental beliefs about antiepileptic drugs used for the treatment of their children. Methods: The study was performed at the University Children's Hospital, Belgrade, Serbia from 2013⁻2015. Parents of children treated with valproic acid, carbamazepine or lamotrigine, were eligible. They were asked to fill in the Beliefs about Medications Questionnaire (BMQ) and The Liverpool Adverse Events Profile (LAEP). Results: Parents of 127 children (average age 9.88 ± 4.16 years) of whom 111 had epilepsy (67 generalized, 44 focal) and 16 with febrile seizures participated in the study. Nervousness and/or agitation, weight gain, restlessness, headache, difficulty in concentrating, feeling of aggression and upset stomach were most frequent adverse effects, reported in 37% of the population. BMQ-specific necessity scores significantly correlated with parental education; parents with elementary school showed lower scores than those with higher education. The presence of difficulty in concentrating of their child was associated with higher BMQ concern scores (20.73 ± 4.25 vs. 18.99 ± 3.60, p = 0.043) as well as necessity scores (18.42 ± 3.31 vs. 16.40 ± 2.73, p = 0.017). Higher scores of BMQ-general overuse were reported in the presence of a headache (8.79 ± 2.81 vs. 7.64 ± 2.72, p = 0.027). Conclusions: The main finding of our study is that parental beliefs about antiepileptic drugs were associated with the presence of adverse effects. Understanding this relationship could allow physicians and pharmacists to structure better educational programs for parents of children treated with antiepileptic drugs. Education should be more focused towards understanding the adverse effects of antiepileptics which could alleviate parental concerns and strengthen their beliefs about the necessity of medication use in their children.