Health policy developments in the Western Balkan Countries 2000-19: towards European Health and Health Care Policies.

BACKGROUND: Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia have committed to becoming European Union (EU) member states. This, among others, implies that candidate/potential candidate states adopt legally authorized EU policies, including health. The study aims to identify the main country-specific health policy areas critical to the EU accession health policy dimension and present the change in associated selected health indicators from 2000 to 2019. METHODS: The study draws on published reports and analyses of official statistics over time and cross-country. Health care policy adherence to the European Commission's recommended country-specific health actions was classified into five health policy areas: financing, payment, organization, regulation and persuasion. Key health policy areas for Western Balkan countries (WBCs) were identified. Health progress or lack thereof in catching up to the EU15 population health, health expenditure and the number of health professionals are measured. RESULTS: The European Commission prioritized financing and regulation for all WBCs in the five policy areas. Nine of the 18 analyzed selected health indicators showed divergence, and the other nine converged towards the EU15 averages. WBCs continue to face diverse public health challenges in improving life expectancy at birth, death rates caused by circulatory system diseases, malignant neoplasms, traffic accidents, psychoactive substance use, tuberculosis incidence, tobacco smoking prevalence and public-sector health expenditure. CONCLUSIONS: By 2019, there is limited evidence of WBCs catching up to the average EU15 health levels and health care policies. Closer attention towards EU health and health care policies would be favourable.

Unveiling The Neuropathology Tumour Landscape: 10-Year Statistical Analysis With Global Comparison - Single Centre Experience.

Introduction: Central nervous system (CNS) tumours represent a significant public health issue worldwide, and their incidence and distribution vary across different populations. Although studies on CNS tumours have been conducted in various countries, there is a lack of information regarding their patterns in Macedonia. Therefore, this study is aimed at investigating the distribution, histopathological types and subtypes and demographic features of CNS tumours in our country. Materials and Methods: A cross sectional study was conducted using the electronic database of the Institute of Pathology - Medical Faculty, University "Ss. Cyril and Methodius" in Skopje which contains data from 3286 received and analysed surgical specimens, mainly from the University Clinic of Neurosurgery in Skopje, and a smaller number of surgical specimens from the University Surgical Centre "St. Naum Ohridski" in Skopje between 2012 and 2022. The collected and analysed data includes patient age, sex and histopathological types and subtypes of the tumours. Results: The majority of CNS tumours were diagnosed in adults aged between 50-70, with a male to female ratio of 1.5:1. The most common location of the tumours was the cerebrum, followed by the pituitary gland and cerebellum. The most frequent histological groups were gliomas, with glioblastoma as the most common diagnosis, followed by meningiomas. Conclusion: Following a detailed and thorough review of the CNS tumours in our study, we can conclude that the R. of Macedonia follows global statistics and trends regarding brain tumours.

Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

Biologic Therapy in Inflammatory Bowel Disease - Results from a Single Tertiary Care Center in North Macedonia.

Medical therapies used for Inflammatory Bowel Disease (IBD) include conventional (e.g. 5-aminosalicylates, steroids, immunomodulators) and biologic (e.g. inhibitors of tumor necrosis factor - alpha, integrin inhibitors, interleukin inhibitors) medications. Biologics, due to their high cost, were unfortunately not covered by the public health insurance system in North Macedonia until 2019 and, therefore, not widely utilized for our IBD patients. In 2019, the University Clinic of Gastroenterology and Hepatology in Skopje developed a biologic therapy supply, provided by the National Health Insurance Fund, making this therapy available for a larger number of patients. This report presents the initial results of our prospective, single tertiary-care center study on the effects of biologic therapy in patients with IBD in North Macedonia. The study is focused on the evaluation of clinical outcomes after anti-tumor necrosis factor alpha (anti TNF-alpha) therapy in IBD patients with prior inadequate response to conventional medications.

Incidence and Prevalence of Vaginal Infections in Women of Reproductive Age in North Macedonia.

In the available literature on this subject there are many studies which describe the effects of sexually transmitted infections on pregnancy and fertility of women. Because of the frequency of the infections with the atypical bacteria of the Ureaplasma Spp., Mycoplasma Spp., Chlamydia Trachomatis, as well as HPV infections in women of reproductive age, it is easy to underestimate their importance when establishing the basis of the genital health of women of reproductive age. In this prospective analysis, conducted from 2014 to 2018 in the laboratory for HPV and Molecular diagnostics at the University Clinic of Gynaecology and Obstetrics in Skopje, North Macedonia, we analysed the results of 10,387 patients of all ages, of which 973 patients were of reproductive age. A Panel analysis was also conducted (including the above-mentioned pathogens). An HPV analysis was also conducted on 643 patients in this group. Within the group of 643 patients, there was a positive result for HPV in 26.7% of them, while in 40.9% there was a positive result for one or more pathogens on the Panel analysis of bacterial pathogens. The statistical analysis of the results showed that the most frequent of all bacterial pathogens within the Macedonian population of women of reproductive age is Ureaplasma Spp, with an incidence of 33%, followed by Mycoplasma Spp., with 7.8%, while Chlamydia Trachomatis was present in 6.4% of the cases. We should highlight that a co-infection with HPV was present in 18.5% of all the patients where there was analysis of both diagnostic procedures. The analysis of the results in the patients co-infected with HPV and at least one bacterial pathogen on the Panel Analysis, showed a very high statistical correlation (p<001).

Prevalence of keratoconus in refractive surgery practice population in North Macedonia.

PURPOSE: To determine the prevalence of keratoconus (KC) in relation to ethnicity in a group of people who consulted an ophthalmological care institution seeking for refractive surgery in N. Macedonia. METHODS: This was a cross-sectional, interventional retrospective study. Chart reviews were performed for all new patients attending between January 2016 and January 2020 at the Sistina Ophthalmology Hospital in Skopje. All patients were screened; KC diagnosis and classification were based on the corneal topography. Ethnicity and gender classifications were according to patients' self-opinions. RESULTS: A total of 2812 patients charts reviewed. The mean age was 31.71 years (SD ± 9.73), and 1209 (43%) were male. A total of 2050 (72.9%) declared themselves as Macedonians, 649 (23.1%) Albanians, 76 (2.7%) Turks and 37 (1.3%) in other ethnicities. Differences in age between the ethnic groups were statistically significant (x2 = 90.225, p < 0.001). KC was diagnosed in 343 patients (12.2%), while 9 (0.7%) were KC suspects and 6(0.21%) presented pellucid marginal degeneration. KC was more frequent in males (n = 246, 71.7% of total) and skewed toward younger patients. Increasing patients' age decreased the odds of KC diagnosis by 3.7% (95% CI 1.8%-4.4%) per annum. Males were four times more likely to be diagnosed with KC (AOR = 4.01; 95% CI 3.12-5.16). In comparison with Macedonian patients, Turks were more likely to be diagnosed with KC (AOR = 4.09; 95% CI 2.47-6.78). There was no difference between Macedonians and Albanians (p = 0.08). CONCLUSION: The prevalence of KC at a refractive surgery practice in N. Macedonia is much higher compared with general population (6.8/100,000) and similar to the prevalence in Middle East Asia. Nationwide screening programs are needed to diagnose the disease earlier.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia / Função tireoidiana de mulheres grávidas e resultados perinatais na Macedônia do Norte

Abstract Objective Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). Methods Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). Results Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypo thyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). Conclusion Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

Resumo Objetivo As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). Métodos Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). Resultados Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). Conclusão Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Epidemiology of Thyroid Carcinomas in North Macedonia (1999-2015).

OBJECTIVE: We have set as objective to analyze epidemiological data of diagnosed thyroid carcinoma (TC) cases, incidence and prevalence rate by gender, age, histopathological type, and statistical regions in R. of N. Macedonia during the period 1999 to 2015. MATERIAL AND METHODS: Retrospective analysis of medical data collected from the 2 state thyroid departments. Inclusion criteria included newly diagnosed cases of TC in appropriate years for the period 1999 to 2015. We have evaluated: yearly incidence rate, incidence and prevalence by gender, age, the distribution in 8 statistical state regions and histopathological types and subtypes representation. RESULTS: A total number of 422 TC patients were detected, average incidence rate of 1.22/105, with most prevalent papillary TCs79.5%, followed by follicular 10.9%, medullar 4.1%, anaplastic 3.1%, and other rare types with 2.3%. The highest incidence rate was detected in Skopje region, while the lowest in Southeast and the Polog region. The total prevalence rate for the female gender was 32.61/104 and for male 9.27/104 (f/m ratio = 3.52:1), with lowest female/male difference found in the elderly > 65 years (f/m = 2.21/1). CONCLUSION: Compared with regional epidemiological data we can conclude that Republic of N. Macedonia has very low incidence and prevalence rate, while female/male ratio was similar to that described in the literature. Our low incidence and prevalence rate may be due to 2 possible reasons, 1 would be insufficient diagnosis of only small portion of the real cases in the population, or the second reason may be a real low incidence resulting of specific etiopathogenetic circumstances.

Outcomes with Ventricular Assist Device Therapy for Advanced Heart Failure in North Macedonia: First Annual Report

INTRODUCTION: Mechanical circulatory support by a continuous-flow ventricular assist device (VAD) improves survival and quality of life in selected patients with advanced heart failure. Developing countries have been struggling to construct a contemporary and effective health care system to manage advanced heart failure. This observation represents the first annual report on clinical outcomes with VAD for patients with advanced heart failure in the Republic of North Macedonia. METHODS: Data from all patients with VAD implantations between November 2018 and December 2019 were collected. The etiology of the heart failure was dilated cardiomyopathy in 4 patients (57%), ischemic cardiomyopathy in 2 (28%), and hypertrophic cardiomyopathy in 1 (14%). The primary outcome was survival; secondary outcomes included adverse events defined according to the Interagency Registry for Mechanically Assisted Circulatory Support. RESULTS: A total of 7 patients (85% males, median age 56 years) received a VAD; 5 of them received left VAD, and the remaining 2 received biventricular VAD. There were no deaths. Observed morbidity during a mean follow-up of 216 days included 3 bleeding events in 1 patient, 2 patients with superficial driveline infection, and 1 minor stroke and a pump thrombosis, which were treated with VAD exchange. Significant improvement in quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire and the Functional Independence Measure™ instrument, was seen with all patients. CONCLUSIONS: Our results demonstrate a successful initiation of the VAD program in the Republic of North Macedonia. Proper training of a dedicated HF team supports the reproducibility of this treatment in developing countries.

Non-Opioid Substances Acute Poisonings with Suicidal Intent in Patients with Opioid Use Disorder.

INTRODUCTION: Several epidemiological studies have evaluated the role of illicit drug use in suicide behaviour. AIM: To assess patients with opioid use disorder and suicidal intent related to behavior, severity of acute poisoning and the most commonly used non-opioid substances. MATERIALS AND METHODS: This cross sectional study included 67 patients diagnosed with opioid use disorder. The study was conducted at the University Clinic of Toxicology in Skopje over a 5-year period (2013-2017). The following variables were examined: gender, age, duration and route of opioid administration, duration of hospitalization, and types of substances used in acute poisoning. Assessment of patients' behavior and severity of poisoning was made by using the Suicide Behaviours Questionnaire-Revised and the Poison severity score. RESULTS: The majority of patients were male (88.1%). The mean age of patients was 30±6.1 years. The average duration of opioid use disorder was 8.5±3.9. A single poisoning was found in 62.7%, double poisoning in 25.4%, and triple poisoning in 11.9% of participants. Benzodiazepines were most commonly used by the patients (55.2%). The largest number of patients (32.8%) had minor Poison severity score (PSS), and only 17.9% had severe PSS. None of the patients had a fatal suicide attempt. 86.6% of patients had a score of ≥7 indicating a high risk of repeat suicide attempts. CONCLUSION: Benzodiazepines were most commonly used as a single or combined substance in patients with opioid use disorder. PSS indicated that most of the participants were with minor PSS and with high risk of a repeat suicide attempt.

Coping with Cystic Fibrosis in the Republic of Macedonia-Parent Perspective.

INTRODUCTION: Cystic fibrosis (CF) is a progressive, life-threatening, genetic disease which mainly damages the lungs and the digestive system. It's a complex medical condition, with several individual forms and variation in the symptoms severity. Few factors such as age of establishing the diagnosis, the number and the type of infections and their management, best treatment options, comorbid conditions etc. can influence the patient's overall health, disease progression and quality of life. Many CF patients will reach adulthood, so coping with the chronic disease is very important for the overall health and everyday living. AIM OF THE STUDY: To screen the quality of life in CF patients in the Republic of Macedonia, from the parent perspective. SUBJECTS AND METHODS: In the study we have included 55 parents of CF patients. We have created a questionnaire, specially designed for this survey, with questions related to their everyday coping with CF and quality of life. RESULTS: The majority of the parents refer to the overall typical social and emotional life of their children, addressing some difficulties concerning the financial aspect of the disease and still significantly having fear from the stigma in the society. CONCLUSION: CF patients and their families in the Republic of Macedonia must overcome many obstacles on daily basis. Despite that, they can still have full and meaningful lives.

Prevalence of Specific Types of Human Papiloma Virus in Cervical Intraepithelial Lesions and Cervical Cancer in Macedonian Women.

INTRODUCTION: Cervical cancer is a malignancy originating in the transformation zone of the cervix, most commonly in the squamous cells. It is the fourth most common cancer in women worldwide, and the third most common cause of female cancer death. Genital human papilloma viruses (HPV) are sexually transmitted and approximately 630 milion people worldwide are infected. More than 200 genotypes, subtypes and variants have been reported, 13-15 being oncogenic type, which could be responsible for cervical intraepithelial lesions (CIN) or cancer. AIM: Aim of this study was to evaluate the prevalence of this infection and to identify specific types of human papiloma virus in cervical intraepithelial lesions and cervical cancer in Macedonian women. MATERIAL AND METHODS: The study was conducted at the University Clinic for Obstetrics and Gynecology, Skopje, Macedonia, in a period of four years. The study was performed on a cohort of 1895, 18 - 73 year old patients who during primary examination had already abnormal PAP smear test. Cervical cells were collected in the lithotomy gynecological position of the patient, using endocervical cytobrush and cotton-tipped swab, and both were placed in sterile test tube with phosphate buffered saline. Samples were stored at temperature of 2 - 8 °C and Human Pappiloma Virus (HPV) genotyping was analyzed within 7 days by multiple Polymerase Chain Reaction (PCR) methods. RESULTS: The mean age of enrolled women was 40,8 years±10.36 SD(minimum of 18 and maximum 73 years. Among the patients, the presence of HPV by using PCR was detected in 40,68 % (769 patients) and was highly associated with cervical abnormalities. The prevalence of HPV was highest (82,1%) in women aged 20-years or less and it decreased with age and was lowest (19,9%) among patients older than 50 years. The prevalence of oncogenic types of the virus was higher if the cytologic diagnosis is CIN 3/Carcinoma in situ (CIS). In these patients detection of high risk HPV was in 79,1% females with CIN 3 and 97,5 % in females with CIS. The lowest prevalence was detected in patients with atypical squamous cells of undetermined significance (ASCUS) (23,9%) and CIN 1-25 (6%). Results of HPV typing show that genotypes were found either single or multiple in both single and multiple infections. We have seen that HPV 16, 18 and 31 were the most common types detected among the patients from Macedonia. HPV 16 was present even in 52,1 % of women with CIS and in 41,2% in women with CIN 3. HPV type 31 ranked second in patients wit CIN1, CIN2, CIN3 but HPV 18 ranked second in patients with CIS with (12,8%). Surprisingly, patients with mixed infection had more low grade intraepithelial squamous lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL) then CIS. CONCLUSION: Among Macedonian women, HPV 16, 31 and 18 were HPV types strongly associated with intraepithelial cervical lesions and cervical cancers. The prevalence of high risk HPV was highest in youngest women, but the risk was highest among patients with invasive cervical cancer (ICC). Surprisingly, patients with mixed infection had more LSIL and HSIL then CIS.

BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of Macedonia.

PURPOSE: We aimed to establish the spectrum of BRCA1/2 mutations among the breast cancer (BC) patients from the Republic of Macedonia. METHODS: We used targeted next-generation sequencing (NGS), Sanger DNA sequencing, and multiplex ligation probe amplification analysis (MLPA) to search for point mutations and deletions/duplications involving BRCA1 and BRCA2-coding regions. RESULTS: We have analyzed a total of 313 BC patients, enriched for family history of cancer, early age of onset and bilateral and/or triple negative (TN) BC. A total of 26 pathogenic mutations were observed in 49 unrelated BC patients (49/313, 15.7%). BRCA2 mutations (27/49, 55.1%) were more common than BRCA1 mutations (22/49, 44.9%). We identified five novel point mutations, one in BRCA1 (c.4352_4356delA) and four in BRCA2 (c.151G>T, c.4707_4708delCA, c.7811_7814delTGTG, and c.9304_9305delG), as well as two novel deletions involving parts of the BRCA1 gene (c.81-?_593+?del and c.5470-?_5530+?del). The most common mutations were c.181T>G, c.5266dupC, and c.3700_3704del5 in BRCA1 and c.7879A>T, c.8317_8330del14 and c.5722_5723delCT in BRCA2 gene. Thus far, BRCA2 c.7879A>T and c.8317_8330del14 mutations have been described in several isolated cases; however, our study is the first one showing that they have a founder effect among Macedonian population. Nine recurrent mutations account for 65.3% of all of the detected mutations allowing for implementation of a fast first-step BRCA1/2 mutational screening strategy in our country. CONCLUSION: This study provides a comprehensive view of known and novel BRCA1/2 mutations in BC patients from the Republic of Macedonia and contributes to the global spectrum of BRCA1/2 mutations in breast cancer.

The Importance of Perioperative Prophylaxis with Cefuroxime or Ceftriaxone in the Surgical Site Infections Prevention after Cranial and Spinal Neurosurgical Procedures.

Introduction Surgical site infections pose a significant problem in the treatment of neurosurgical procedures, regardless of the application of perioperative prophylaxis with systemic antibiotics. The infection rate in these procedures ranges from less than 1% to above 15%. Different antibiotics and administration regimes have been used in the perioperative prophylaxis so far, and there are numerous comparative studies regarding their efficiency, however, it is generally indicated that the choice thereof should be based on information and local specifics connected to the most probable bacterial causers, which would possibly contaminate the surgical site and cause infection, and moreover, the mandatory compliance with the principles of providing adequate concentration of the drug at the time of the anticipated contamination. Objective Comparing the protective effect of two perioperative prophylactic antibiotic regimes using cefuroxime (second generation cephalosporin) and ceftriaxone (third generation cephalosporin) in the prevention of postoperative surgical site infections after elective and urgent cranial and spinal neurosurgical procedures at the University Clinic for Neurosurgery in Skopje in the period of the first three months of 2016. Design of the study Prospective randomized comparative study. Outcome measures Establishing the clinical outcome represented as prevalence of superficial and deep incision and organ/space postoperative surgical site infections. Material and method We analyzed prospectively 40 patients who received parenteral antibiotic prophylaxis with two antibiotic regimes one hour before the routine neurosurgical cranial and spinal surgical procedures; the patients were randomized in two groups, according to the order of admission and participation in the study, alternately, non-selectively, those persons who fulfilled inclusion criteria were placed in one of the two programmed regimes with cefuroxime in the first, and cefotaxime in the second compared group. All relevant demographic and perioperative patient data were analyzed for both comparative groups, especially the factors known to cause disposition (predisposition) to infections. The prevalence of postoperative infections was evaluated as the primary outcome in both comparative groups, while the secondary outcome was the postoperative infection rate after cranial and spinal neurosurgical procedures at the Neurosurgical clinic in Skopje (having in consideration that so far no data have been published in this context), as well as the prevalence of the risk factors for occurrence of postoperative infections, pre-surgically in patients undergoing neurosurgical interventions locally in the Republic of Macedonia. Results A total of three cases of postoperative infections were registered, two of which classified as superficial incisional, while one case organ/space infection - meningitis (elective intervention) without etiological confirmation. Both comparative groups were statistically similar, without any statistically significant differences in the basic demographic and perioperative characteristics, especially in relation to the incidence of the factors, which, regardless of the antibiotic prophylaxis, show predisposition to postoperative infections. All three cases with infections were registered in the group of persons who received prophylaxis with ceftriaxone preoperatively, with isolated etiological S. aureus agent (elective intervention) in one of them, and methicillin resistant staphylococcus aureus (MRSA) in another (urgent intervention) with superficial incisional SSI. There was no case of SSI in the group of patients who received cefuroxime before surgery. Conclusion Administration of parenteral antibiotics before surgery reduces the incidence of postoperative infections after neurosurgical procedures, especially in cases with increased risk factors for SSI, such as ACA score of ≥ 2/3, the duration of the surgical intervention ≥ 4 hours, contaminated wound and comorbidities. Perioperative antibiotic prophylaxis should be directed to better coverage of the S.aureus arrays.

Trigonocephaly - Our Experience and Treatment in the Republic of Macedonia.

INTRODUCTION: Prematurely fused metopic suture results in developmental anomaly named trigonocephaly. The treatment of trigonocephaly is a surgical reconstruction, starting from the simple suturectomy toward the complicated cranial vault reconstructions with aim to obtain enough endocranial space for normal development of the brain and aesthetic correction as well. THE AIM: The aim of our paper is to present our experience on this pathology in the Republic of Macedonia, stressing the trigonocephaly as one of the rare forms of craniosynostosis. Our material: During a period of 20 years (from 1996 to 2015) at the Pediatric department of the Clinic for Neurosurgery in Skopje, we observed 18 babies with trigonocephaly, including one with Carpenter syndrome and trigonocephaly, 14 males and 4 females. All children had simple trigonocephaly, one had syndromic trigonocephaly (Carpenter's syndrome). According to Oi and Matsumoto classification done in 19865 severe trigonocephaly is observed in 11 cases and, moderate trigonocephaly in 7 cases. Our method: Our treatment consisted of slightly modified Di Rocco's3 surgical procedure named "shell" operation, adding transposition of the "bone flap". RESULTS: The postoperative period was uneventful except for the expected forehead swelling. The babies were discharged from the hospital on average at the 8th postoperative day. At the three months control after the surgery, the head had excellent aesthetic appearance, with regular psychomotor development according to the age of the patient (Fig 3а and 3b). We had no serious complications except the expected postoperative swelling of the forehead. All operated children had excellent "long term" aesthetic effect and normal psychomotor development. CONCLUSION: The early recognition of these anomalies including all craniosynostoses, the deformities of the newborn and infant's head and the preventive operative reconstruction would prevent abnormal disturbance of the psychomotor development during the child's growth. The multidisciplinary approach can prevent new disabled individuals in the society. Our technique allows shortening the entire surgical procedure, especially in the departments where blood saving devices are not available.

Congenital Anomalies of the Kidney and Urinary Tract in Children Born Small for Gestational Age.

INTRODUCTION: Congenital anomalies of the kidney and urinary tract (CAKUT) represent several types of malformations with occurrence of 1 in about 500 live births. OBJECTIVE: Small for gestation age (SGA) may influence in prevalence of CAKUT and progression of chronic kidney disease (CKD) in children. The aim of this study was to elaborate our experiences with detected CAKUT in a cohort of SGA born children in Macedonia. METHODS: Our cohort consisted of 100 SGA born children investigated for associated congenital anomalies of urinary tract. We analyzed anthropometric and clinical birth data in children with diagnosed CAKUT and estimated the stage and time of onset of CKD by biochemical and imaging technics. RESULTS: We revealed 7 (7.0%) SGA born children with congenital anomalies of the urinary tract. Their mean birth weight was very low 1855 gr (-3.93 SDS) and the birth length 45.57cm (-2.17 SDS), as well. A significant growth failure with reduced weight and BMI were noticed at the time of diagnosis. A diagnosis of CAKUT in 4/7 was established in the first few months of life, but in others 3 later in early childhood. Three children revealed with unilateral kidney agenesis, 2 had hypo-dysplastic kidneys and in 2 children was found vesicoureteral reflux. Normal glomerular filtration rate was estimated in 2 children with CAKUT. Stage 2 CKD with GFR 60-90 ml/minx1.73m2 had 3 children, 1 patient was graded in stage 3 and one child needed kidney transplantation, stage 5 CKD. CONCLUSIONS: We presented 7 SGA born children with CAKUT. An early recognition, assessment and treatment of these anomalies might improve their quality of life.

Associations between racial discrimination, smoking during pregnancy and low birthweight among Roma.

Background: Racial discrimination may increase the risk of low birthweight (LBW), but has not been studied among Roma, the largest minority population in Europe. Moreover, few studies test both institutional and interpersonal forms of racial discrimination on health. Our objective was to examine associations between institutional and interpersonal racial discrimination with LBW, and to test potential mediation by smoking during pregnancy. In 2012-2013, Romani women interviewers surveyed 410 Romani women in Serbia and Macedonia. We measured institutional discrimination (neighborhood segregation, legal status of housing and neighborhood socioeconomic status), interpersonal discrimination [Everyday Discrimination Scale (EDS)], birthweight and smoking by self-report or interviewer report. We estimated relative risks for discrimination on LBW and separately on smoking during pregnancy using log-binomial regression, adjusting for age, parity, years at residence and wealth. The indirect effect of high EDS via smoking on LBW was estimated using inverse odds weighting mediation. Living in a low SES neighborhood showed a 2-fold risk of LBW [adjusted risk ratio (aRR) = 2.4, 95% CI = 1.2, 5.0]; aRRs for segregation and illegal housing were weaker (aRR = 1.8, 95% CI = 0.7, 4.3; aRR = 1.3, 95% CI = 0.6, 2.6, respectively). Institutional measures were not associated with smoking. High EDS was associated with LBW (aRR = 2.4, 95% CI = 1.1, 5.2) and smoking during pregnancy (aRR = 1.4, 95% CI = 1.1, 1.8); the indirect effect of EDS on LBW via smoking was not significant. Interpersonal discrimination and living in a low SES neighborhood were associated with LBW among Roma. Interventions to improve Romani health may benefit from a human rights approach.

Obesity in Childhood and Adolescence, Genetic Factors.

Obesity and excess weight are a pandemic phenomenon in the modern world. Childhood and adolescent obesity often ends up in obesity in adults. The costs of obesity and its consequences are staggering for any society, crippling for countries in development. Childhood obesity is also widespread in Macedonia. Metabolic syndrome, dyslipidemia and carbohydrate intolerance are found in significant numbers. Parents and grandparents are often obese. Some of the children are either dysmorphic, or slightly retarded. We have already described patients with Prader-Willi syndrome, Bardet-Biedl syndrome or WAGR syndrome. A genetic screening for mutations in monogenic obesity in children with early, rapid-onset or severe obesity, severe hyperphagia, hypogonadism, intestinal dysfunction, hypopigmentation of hair and skin, postprandial hypoglycaemia, diabetes insipidus, abnormal leptin level and coexistence of lean and obese siblings in the family discovers many genetic forms of obesity. There are about 30 monogenic forms of obesity. In addition, obesity is different in ethnic groups, and the types of monogenic obesity differ. In brief, an increasing number of genes and genetic mechanisms in children continue to be discovered. This sheds new light on the molecular mechanisms of obesity and potentially gives a target for new forms of treatment.

Rare Renal Disease in Macedonia - An Update.

Rare renal diseases (RRD) are an important category of rare disease (RD) as they can do great damage to the patients, families and society. The patient may undergo years even decades of numerous investigations including invasive procedures and yet not have definitive and precise diagnose and therefore, no opportunity for appropriate treatment. The great progress in molecular genetic techniques characterized many Mendelian diseases on molecular level. This gave the possibility for appropriate prevention and treatment interventions, genetic counseling and prenatal diagnosis. Herein, we summarize the current status of RRD in Macedonia. The research interest of Macedonian clinicians and scientists is focused on the genetics of congenital anomalies of the kidney and urinary tract (CAKUT), steroid resistant nephrotic syndrome, nephrolithiasis and nephrocalcinosis, cystic diseases and cilliopathies with collaborations with eminent laboratories in Unites States and Europe. This collaboration resulted in detection of new genes and pathophysiological pathways published in The New England Journal of Medicine and in other high impact journals. Macedonian health professionals have knowledge and equipment for diagnosis of RRD. Unfortunately the lack of finances is great obstacle for early and appropriate diagnosis. Participation in the international registries, studies and trials should be encouraged. This would result in significant benefit for the patients, health professionals and science.

Human Papillomavirus as a Potential Risk Factor for Oral Premalignant Lesions.

Oral premalignant lesions (OPLs) and numerous alterations of oral mucosa remain unsolved due to their complex etiopathogenesis. Human papillomaviruses (HPVs), in particular, have been reported as the possible risk factors or cofactors. The aim of the study was to determine the association of different HPV types with oral premalignant lesions, and the potential role of smoking and alcohol use. Eighty patients (mean age ± SD, 52.45±5.56) of both genders, 19 (23.75%) male and 61 (76.25%) female, were enrolled in the study. Study group included 40 patients diagnosed with OPLs (leukoplakia, erythroplakia, actinic keratosis and lichen planus), while control group included another 40 patients with healthy oral mucosa. Genotyping of the HPV types was performed by qualitative real-time HPV typing polymerase chain reaction test. HPV DNA was detected in 30% (12/40) of study group patients and 2.5% (1/40) of control group patients. The results revealed the presence of HPV16 in 15% (6/40), HPV56 in 10% (4/40), and HPV18 in 5% (2/40) of study group cases, and HPV31 in 1 (2.5%) control group patient. Th e association of oral HPV positivity and smoking/alcohol use in the study group was not statistically significant (p<0.05). In conclusion, high-risk HPV types are associated with oral premalignant disorders. However, it remains unknown whether HPV acts as an innocent bystander or it has a role in initiating development of premalignant lesions. Smoking and alcohol use were not associated with the existing oral HPV infection.