Diabetes mellitus (DM) as a chronic condition is a growing global problem. Its numerous complications, including ocular diseases, affect patients’ quality and length of life. Metformin is an effective, safe, and inexpensive first-line pharma-cotherapy for type 2 diabetes (T2D). The current evidence indicates metformin’s multiple sites of action and multiple molecular mechanisms leading to its beneficial impact on metabolism, inflammation, oxidative stress, aging, as well as to its cardiovascular, neurological, bone, and antiproliferative properties. These impacts are the result of its acting on adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Limited data suggest the protective role of metformin on microvascular ocular complications, including retinopathy, glaucoma, and age-related macular degeneration in patients with T2D. However, to confirm its mentioned protective and therapeutic effects, more large, randomized, double-blind, and placebo-controlled clinical studies are needed.

Objective: Inappropriate use of antibiotics is one of the major causes of resistance, and it is recognized as one of today’s most significant medical issue. Per standard of care antimicrobic treatment is not recommended for uncomplicated acute infections of the upper respiratory tract. However, despite this fact the most of antibiotics in ambulatory use are prescribed in these indications. The main objectives of this research was to evaluate the frequency of use of throat swabs in diagnostic purposes and subsequently prescribed antibiotic therapy in children with the diagnosis of bacterial tonsillitis or angina. Methods: An observational, retrospective study was conducted in the pediatric departments in of the Public Health Center of Canton Sarajevo. Data were collected from the available medical records sourced with relevant info on diagnostic swabs for upper respiratory infections and the applied treatment. Results: Data from 100 patients preschool and school age were collected. Results suggest that a significantly more frequent use of throat swabs is proven in preschool children compared to school age (p=0.008; χ²=7.100). In addition, results indicate that the prescription of beta-lactam antibiotics is preferred option of the treatment of tonsillitis and angina in whole sample. The preschoolers were more often prescribed cephalosporin antibiotics while school age children were the most frequently treated with the penicillin. Conclusion: Streptococcus is detected in 35–50% of cases of clinically diagnosed streptococcal pharyngitis, which makes the bacteriological confirmation of the agent necessary. Penicillin is recommended as the medication of the first choice for streptococcal tonsillopharyngitis. Also, the research reveals common appearance of mixed infections as a reason for preferred prescription of macrolides and cephalosporins. Keywords: tonsilopharyngitis, antibiotics, resistance

Aim To analyse frequency of chronic obstructive pulmonary disease (COPD) exacerbation in patients on therapy with inhaled corticosteroids (ICS) and relevant factors that influence the rate of COPD exacerbations in a subgroup of moderate illness, like FEV1, comorbidities and other concomitant therapy. Methods The study included patients with moderate COPD with at least 10 pack-years history of smoking and accompanying cardiovascular comorbidity. Demographic data, frequency of exacerbations and information about proscribed treatments - ICS alone or in combination with long acting beta agonist (LABA), were collected from medical records for the previous 12 months from the index date. Results Data were collected for 210 patients (170 males) with the mean age 65.63±8.66 years, 72 of which were treated with a fixed combination of long acting beta blocker (LABA) and ICS. Significantly more frequent exacerbations were detected in patients using ICS p<0.0001) and having higher Modified British Medical Research Council (mMRC) score p=0.004). No statistically significant difference was registered related to ratio of FEV1 /FVC (p=0.121) or a number of cardiovascular comorbidities per patient (p=0.969). CONCLUSIONS Our results present a small contribution to the current scientific discussion about the use of ICS in COPD treatment. Further prospective studies are needed to confirm the impact of ICS on the frequency of COPD exacerbations.

OBJECTIVE The aim was to study the association of the use of an oral antihyperglycemic agent metformin with the presence of ocular complications in patients with type 2 diabetes (T2D). METHODS Medical records were reviewed for 234 patients with diagnosed T2D. 81.2% (n=190) patients were using metformin and 18.8% (n=44) using other oral antihyperglycemic agents. Plasma glucose concentration, glycated haemoglobin, and the presence of ocular complications in patients treated with metformin were compared to those in patients treated with other oral antihyperglycemic agents. RESULTS Ocular complications occurred in 65 patients (27.8%). Patients treated with metformin had fewer ocular complications compared to patients treated with other oral antihyperglycemic agents (χ2=19.985; p<0.0001). After adjustment for gender, age, duration of T2D, serum concentration of cholesterol, smoking, body mass index and presence of other diseases, treatment with metformin decreased the odds of both glaucoma (OR=0.14, 95% CI: 0.03-0.57, p=0.006) and diabetic retinopathy (OR=0.33, 95% CI: 0.14-0.82, p=0.017) compared with other oral antihyperglycemic agents. CONCLUSION Our results suggest that metformin may have a protective effect on ocular complications, especially glaucoma, in patients with T2D. The effects of metformin either regarding prevention of ocular complications or ocular complications already developed in patients with T2D, should be further investigated.

Aim In order to increase the database related to the antineoplastic potential of metformin, association between the use of metformin and risk of cancer occurence in patients with diabetes mellitus type 2 (DM2) was investigated. Methods In this cross-sectional study, medical records of patients with DM2 were reviewed for cancer occurence. Data on age, body mass index (BMI), alcohol and nicotine consumption, glucose and HbA1c levels, duration of DM2, medication used in the treatment of DM2 and cancer occurence were collected and analyzed. Unpaired Student's t-test or Mann-Whitney U test were used for comparisons between treatment groups, and logistic regression to asses how well our set of predictor variables predicts occurence of carcinoma. P-value less than 0.05 was considered statistically significant. Results The mean age of 234 included patients was 66.8±11.5 years, and DM2 duration was 7± 6.49 years. Mean glucose value was 8.51±4.17mmol/L, and HbA1c 7.74±1.53. Metformin therapy was prescribed in 190 (81%) patients. Cancer was diagnosed in 16 (6.8%) patients: prostate cancer in eight (3.4%), breast cancer in four (1.7%), rectal cancer in two (0.9%) and cancer of the uterus and cervix in one patient. Age, duration of DM2 and BMI did not contribute significantly to the model, while metformin use was shown to be a significant independent predictor (OR=0.049; 95% CI=0.013-0.181; p=0.001). Conclusion Our findings support the hypothesis that the use of metformin compared to the use of other oral antidiabetic drugs is associated with a lower risk of cancer in patients with DM2.

: Aim: Evaluation of the significance of micronuclei (MN) as biomarkers for evaluation the risk of malignant transformation in uterine cervix. MN are intracytoplasmic inclusion bodies from chromatin fragments or whole chromosomes. Their presence in cells is a reflection of chromosomal aberration during cellular mitosis. Patients and methods: MN screening was done in all selected cytopathological smears (conventional Papanicolaou test) by counting 1000 cervical squamous cells with a light microscope at a magnification of 1000x. Results: Comparisons between women with progressive increases in cervical intraepithelial neoplasia (CIN) and control group. The MN frequencies observed were significantly higher in the groups with cellular changes compared to the control group. Conclusion: The results described that the MN test in cervix smears could be incorporated into routine screening procedures as an additional criterion for early detection of cytopathologocal damage. However, additional detailed, systematic studies are needed to confirm this suggestion.

Racemic ketorolac clearance (CL) is significantly higher at delivery, but S-ketorolac disposition determines the analgesic effects. The aim of this study was to investigate the effect of pregnancy and postpartum period on enantiomer-specific (S and R) intravenous (IV) ketorolac pharmacokinetics (PKs). Data in women shortly following cesarean delivery (n=39) were pooled with data in a subgroup of these women that was reevaluated in the later postpartum period (postpartum group, n=8/39) and with eight healthy female volunteers. All women received single IV bolus of 30 mg ketorolac tromethamine. Five plasma samples were collected at 1, 2, 4, 6, and 8 hours and plasma concentrations were determined using high performance liquid chromatography. Enantiomer-specific PKs were calculated using PKSolver. Unpaired analysis showed that distribution volume at steady state (Vss, L/kg) for S- and R-ketorolac was significantly higher in women shortly following cesarean delivery (n=31) compared to postpartum group (n=8) or to healthy female volunteers (n=8). CL, CL to body weight, and CL to body surface area (CL/BSA) for S- and R-ketorolac were also significantly higher in women following delivery. In addition, S/R-ketorolac CL/BSA ratio was significantly higher at delivery. Paired PK analysis in eight women shortly following delivery and in postpartum group showed the same pattern. Finally, the simultaneous increase in CL and Vss resulted in similar estimates for elimination half-life in both unpaired and paired analysis. In conclusion, pregnancy affects S-, R-, and S/R-ketorolac disposition. This is of clinical relevance since S-ketorolac (analgesia) CL is even more increased compared to R-ketorolac CL, and S/R-ketorolac CL ratio is higher following delivery compared to postpartum period or to healthy female volunteers.

Aim: Evaluation of the significance of micronuclei (MN) as biomarkers for evaluation the risk of malignant transformation in uterine cervix. MN are intracytoplasmic inclusion bodies from chromatin fragments or whole chromosomes. Their presence in cells is a reflection of chromosomal aberration during cellular mitosis. Patients and methods: MN screening was done in all selected cytopathological smears (conventional Papanicolaou test) by counting 1000 cervical squamous cells with a light microscope at a magnification of 1000x. Results: Comparisons between women with progressive increases in cervical intraepithelial neoplasia (CIN) and control group. The MN frequencies observed were significantly higher in the groups with cellular changes compared to the control group. Conclusion: The results described that the MN test in cervix smears could be incorporated into routine screening procedures as an additional criterion for early detection of cytopathologocal damage. However, additional detailed, systematic studies are needed to confirm this suggestion.