Towards leaving no one behind in North Macedonia: a mixed methods assessment of barriers to effective coverage with health services.

BACKGROUND: The Government of North Macedonia's Primary Health Care reform is committed to leaving no one behind on the path to Universal health Coverage (UHC). During mid-2022 to March 2023, the World Health Organization (WHO) collaborated with the Government and other national stakeholders for an assessment of barriers to effective coverage with health services experienced by adult citizens, with a specific focus on rural areas and subpopulations in situations of vulnerability. METHODS: This study constituted the piloting of a draft forthcoming WHO handbook on assessing barriers for health services, grounded in the Tanahashi framework for effective coverage with health services. In North Macedonia, the convergent parallel mixed methods study involved four sources. These were: a nationally representative Computer Assisted Telephone Interview Survey (1,139 respondents); 24 key informant interviews with representatives from government, professional associations, non-governmental and civil society organizations, and development partners; 12 focus groups in four regions with adults from vulnerable/high risk groups in rural areas and small urban settlements and an additional focus group with persons with disabilities; and a literature review. Instrument design was underpinned by the Tanahashi framework, which also orientated data triangulation and deductive analysis. The research team synergistically incorporated emerging themes in an inductive way. A key component of the assessment was participatory design of the study protocol with inputs from national stakeholders as well as participatory deliberation of the results and the ways forward. RESULTS: Despite considerable progress towards UHC in North Macedonia, the assessment elucidated remaining challenges. These included: insufficient numbers of health workers, in general and particularly in the more disadvantaged regions of the country; inadequate number of outpatient medicines covered by health insurance; distance and transportation obstacles, including indirect travel costs, particularly in rural areas; adverse gender norms and relations for both women and men inhibiting timely treatment seeking; perceived discrimination by providers on multiple grounds; bottlenecks including waiting times to get appointments for specialist referrals; and lack of patient adherence, due several factors including costs of medicines and health products. CONCLUSIONS: The outputs from this study of barriers to effective coverage with health services for adult citizens of North Macedonia are feeding into the ongoing Primary Health Care reform, and provide evidence for equity-related actions in the forthcoming National Development Strategy.

Normative Data of Handgrip Strength in Macedonian Children and Adolescents According to Chronological and Biological Age / Datos Normativos de la Fuerza de Prensión Manual en Niños y Adolescentes Macedonios Según la Edad Cronológica y Biológica

SUMMARY: The handgrip strength is used as a means of individual's health prediction during life. It is used as an indicator of the nutrition status, bone fragility, presence of sarcopenia and it correlates with certain diseases and clinical complications. The research goal was to analyze the results of the hand dynamometry test, based on the chronological and biological age, and to offer normative and referent standards about children and adolescents from the Republic of North Macedonia. The study was conducted on a sample of 4031 respondents of both sexes at the age 6-14 years. In order to achieve the research goals, the measured characteristics were of the weight, height, sitting height and handgrip strength. The body mass index and biological maturity values (APHV) were obtained by using formulas. On the basis of the obtained results, it can be concluded that statistically significant differences in handgrip strength are established between the boys and girls of all age categories. Also, statistically significant differences between boys and girls are established in the hand dynamometry test of all APHV levels. In general, the use of the APHV allows a better categorization of the performance of the studied children and adolescents. With boys, the correlation between the chronological age and test was 68 %, and with girls - 77 %. The normative referent standards of the hand dynamometry test are presented in percentiles for both sexes. Thye hand dynamometry test's results during childhood and adolescence should be analyzed and interpret on the basis of biological age, and not on the chronological age. These tools can help specialists who work with children and adolescents in ethnic and epidemiological context.

La fuerza de prensión se utiliza como medio para predecir la salud del individuo durante la vida. Se utiliza como indicador del estado nutricional, fragilidad ósea, presencia de sarcopenia y se correlaciona con determinadas enfermedades y complicaciones clínicas. El objetivo de la investigación fue analizar los resultados de la prueba de dinamometría manual, con base en la edad cronológica y biológica, y ofrecer estándares normativos y referentes sobre niños y adolescentes de la República de Macedonia del Norte. El estudio se realizó en una muestra de 4031 encuestados de ambos sexos con edades comprendidas entre 6 y 14 años. Para lograr los objetivos de la investigación, las características medidas fueron el peso, la altura, la altura al sentarse y la fuerza de prensión. El índice de masa corporal y los valores de madurez biológica (APHV) se obtuvieron mediante fórmulas. Sobre la base de los resultados obtenidos, se puede concluir que se establecen diferencias estadísticamente significativas en la fuerza de prensión manual entre niños y niñas de todas las categorías de edad. Asimismo, se establecen diferencias estadísticamente significativas entre niños y niñas en la prueba de dinamometría manual de todos los niveles APHV. En general, el uso del APHV permite una mejor categorización del desempeño de los niños y adolescentes estudiados. En los niños, la correlación entre la edad cronológica y la prueba fue del 68 %, y en las niñas, del 77 %. Los estándares normativos referentes de la prueba de dinamometría manual se presentan en percentiles para ambos sexos. Los resultados de la prueba de dinamometría manual durante la infancia y la adolescencia deben analizarse e interpretarse en función de la edad biológica y no de la edad cronológica. Estas herramientas pueden ayudar a los especialistas que trabajan con niños y adolescentes en un contexto étnico y epidemiológico.

Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

UHPLC-Q-TOF analysis of pyrrolizidine alkaloids in North-Macedonian honey.

Honey contaminated with pyrrolizidine alkaloids (PAs) could pose a risk for human consumption, being a widely consumed food product. A fast and simple LC/MS method for the analysis of pyrrolizidine alkaloids in honey was optimised to collect occurrence data. The extraction efficiency was evaluated by a systematic study of multiple solvent mixtures and clean-up procedures. The best results for PA extraction were obtained using a formic acid/methanol mixture with subsequent clean-up by the QuEChERS method, resulting in a mean recovery range of 91.8-102%. The method validation showed satisfactory intra-day (RSD < 5.1%) and inter-day precision (RSD < 9.1%). The proposed method was applied to 14 samples. A total of six PAs and two N-oxides were detected, with levels between 89 and 8188 µg/kg. This assessment highlights the potential risk of intoxication and the need for further investigations regarding an effective quality system for manufacturers to control PAs in honey.

How to increase COVID-19 vaccination among a population with persistently suboptimal vaccine uptake? Evidence from the North Macedonia mobile vaccination and public health advice caravan.

Over three years since the first COVID-19 vaccine was approved, many countries still have suboptimal vaccination rates despite holding great amounts of vaccines. Overall, there is little evidence on which policies are more effective to encourage vaccination, particularly in countries where a large share of the population remains unvaccinated. In this study, we examine the effectiveness of a community-based intervention carried out in March 2022 in North Macedonia, a country with a large and persistent share of the population that remains unvaccinated. The intervention, spearheaded by the Ministry of Health and supported by the World Health Organization and UNICEF, consisted of a mobile caravan offering vaccination and public health advice to different locations across the country on different days. Results from our staggered difference-in-difference model show that the mobile vaccination caravan increased daily vaccination rates by 7.7 vaccines per 100,000 inhabitants during the three weeks after the day of the caravan visit. This corresponds to a 35 % increase with respect to pre-intervention vaccination rates. We estimate a cost-effectiveness of 25.4 US dollars (USD) per additional vaccination induced. These results point to mobile caravan vaccines as an effective and cost-effective strategy to increase COVID-19 vaccination rates, even in a context of persistently suboptimal uptake.

Family-focused intervention to promote adolescent mental health and well-being in Moldova and North Macedonia (FLOURISH): feasibility study protocol.

INTRODUCTION: Family-Focused Adolescent & Lifelong Health Promotion (FLOURISH) project will adapt, implement and evaluate a programme to support adolescent mental health and well-being through strategies, such as strengthening parenting practices, adolescent-caregiver relationships, adolescent and parent socioemotional skills, and social support. METHODS AND ANALYSIS: The project will focus on adolescents aged 10-14 years and their caregivers in North Macedonia and Moldova. The countries were selected based on implementation readiness of two organisations and a need for accessible evidence-informed services to help mitigate health risks due to economic, social and political challenges. Parenting for Lifelong Health (PLH) for Parents and Teens is a family-based programme developed for low-resource settings. PLH has been adapted with input from advisory groups. The programme includes additional components to strengthen impacts on adolescents: adolescent mental health tools, based on UNICEF's Helping Adolescents Thrive, adolescent peer support and participation booster. This pilot is first of three study phases. The pilot will be a feasibility testing of the adapted intervention and the assessment and implementation procedures to determine further refinements. The pilot will examine if the adapted programme is acceptable for adolescents, their families and providers, explore contextual factors relevant to embedding this programme into longer-term scale-up and investigate whether the programme can be delivered with fidelity and participation; whether the participants report changes in adolescent emotional and behavioural problems, well-being and other outcomes; and whether the study tools are feasible and appropriate. Pre-post adolescent and caregiver questionnaires will provide outcome data. Process evaluation will include attendance and fidelity data, and focus groups. We will examine delivery cost and resource requirements. ETHICS AND DISSEMINATION: The study was approved at the University of Klagenfurt (Austria), Medical Faculty at St. Cyril and Methodius University (North Macedonia) and National Committee of Ethical Expertise for Clinical Trials (Moldova). Through stakeholder engagement and dissemination, FLOURISH will advance scale-up of open-source family interventions. TRIAL REGISTRATION NUMBER: Trial registration: ID101095528; project page: https://www.flourish-study.org/about.html; https://www.linkedin.com/company/flourish-study/.

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.

Investigation of the Dynamics of Salmonellosis in the Republic of North Macedonia.

The main goals of this research are to determine the developmental tendency of salmonellosis in the Republic of North Macedonia and to determine the index of dynamics and the rate of decline/increase of salmonellosis in the Republic of North Macedonia. The research covers the period from 01.01.2012 until 31.12.2022. The data used to implement this study were obtained from the Institute of Public Health of the Republic of North Macedonia. The research included 2711 subjects who were sick with salmonellosis from 2012 to 2022. The following statistical methods of work are used: linear trend, dynamic index with a constant base, dynamic index with a variable base (chain index), rate of decline, and rate of increase. The results of the study suggest that in the period 2012-2022, the highest number of patients (n=373) and the highest incidence (18/100000) of salmonellosis were registered in 2018, and the lowest in 2020 (n=119, I=5.8/100000). From the linear trend values, it can be concluded that salmonellosis in the Republic of North Macedonia shows a decreasing tendency. The biggest increase in salmonellosis in the Republic of North Macedonia was in 2015 by 71% compared to 2014. The biggest decrease in salmonellosis in the Republic of North Macedonia was in 2020 by 48% compared to 2019. From the study, it can be concluded that food operators and manufacturers are observing the procedures of the HACCP control system for food safety, leading to a possible decrease in salmonellosis.

Cardio-Physiological and Anthropometric Profile of Elite International Handball Players from Top Ranking Macedonian Teams / Perfil Cardiofisiológico y Antropométrico de Jugadores Internacionales de Balonmano de Élite de Equipos Macedonios de Primer Nivel

SUMMARY: Monitoring of body composition and cardiophysiological parameters are main part of the general health status of handball players and significant indicators of their physical fitness. The assessment of body components, especially skeletal muscle mass and body fat mass are important because of their influence on sport performance. The aim of this study is to determine the body composition and cardiophysiological characteristics of elite handball players from Republic of North Macedonia. 27 male HB players from two top ranking teams from RNM were tested ergometrically with Bruce protocol for determination of maximal oxygen consumption; body analysis was made with bioelectrical impedance analyzer, InBody 720. Anthropometric parameters were as follows: mean height was 190.4±7.8 cm and weight 96.3±15.5 kg, skeletal muscle mass (SMM)=47.11±6.69 kg; BMI=26.38±3.1; BF%=15.04±6.01 and WHR=0.9±1.8. The result of ergometrical test produce mean VO2 max=43.92 ml/kg/min which is 100.46 % of reference value. The body composition of elite international handball players from the top handball teams in Republic of North Macedonia showed similar body components as other European handball players. The obesity diagnose parameters were negatively associated with exercise time and maximal oxygen consumption.

El seguimiento de la composición corporal y los parámetros cardiofisiológicos son una parte principal del estado de salud general de los jugadores de balonmano y son indicadores importantes de su condición física. La evaluación de los componentes corporales, especialmente la masa muscular esquelética y la masa grasa corporal, son importantes debido a su influencia en el rendimiento deportivo. El objetivo de este estudio fue determinar la composición corporal y las características cardiofisiológicas de jugadores de balonmano de élite de la República de Macedonia del Norte. Se evaluaron 27 jugadores masculinos de HB de dos equipos de primer nivel de RNM ergométricamente con el protocolo de Bruce para determinar el consumo máximo de oxígeno; el análisis corporal se realizó con el analizador de impedancia bioeléctrica InBody 720. Los parámetros antropométricos fueron los siguientes: talla media 190,4±7,8 cm y peso 96,3±15,5 kg, masa músculo esquelética (SMM)=47,11±6,69 kg; IMC=26,38±3,1; %GC=15,04±6,01 y RCC=0,9±1,8. El resultado de la prueba ergométrica produce un VO2 máximo medio = 43,92 ml/kg/ min, que es el 100,46 % del valor de referencia. La composición corporal de los jugadores de balonmano internacionales de élite de los mejores equipos de balonmano de la República de Macedonia del Norte mostró componentes corporales similares a los de otros jugadores de balonmano europeos. Los parámetros diagnósticos de obesidad se asociaron negativamente con el tiempo de ejercicio y el consumo máximo de oxígeno.

Once-weekly semaglutide use in glucagon-like peptide-1 receptor agonist naïve patients with type 2 diabetes in North Macedonia: Real-world data from the MIRAGE study.

AIMS: The MIRAGE study aimed to evaluate the real-world use of once weekly (OW) subcutaneous semaglutide in glucagon-like peptide-1 receptor agonist naïve type 2 diabetes patients in routine clinical practice in North Macedonia. METHODS: MIRAGE was a multicentre, single-arm, retrospective and 30-weeks study, conducted in North Macedonia. Primary [change in glycated haemoglobin (HbA1c)] and secondary endpoints [change in body weight, fasting plasma glucose (FPG), lipid parameters, blood pressure, waist circumference, glycaemic and weight-loss target achievement] were evaluated between baseline and end of study (EOS). RESULTS: Baseline characteristics of 314 patients enrolled in the study were, mean age: 55.5 years, HbA1c: 9.0 %, diabetes duration: 7.8 years, body weight: 105.2 kg and waist circumference: 114 cm. Patients at EOS experienced statistically significant estimated mean change in HbA1c: -2.2 % points, body weight: -9.0 kg, and FPG: -4.1 mmol/L (all p < 0.0001). At EOS, 62.1 % patients achieved HbA1c < 7 %, and 79.3 % had ≥ 1 % HbA1c reduction. A weight reduction of ≥ 3 % and ≥ 5 % was noted in 88.3 % and 73.3 % patients, respectively. No new safety concern has emerged. CONCLUSIONS: Findings from MIRAGE study demonstrated glycaemic and weight-loss benefits of semaglutide, with improvements in other cardiometabolic parameters. The study supports real-world OW subcutaneous semaglutide use in North Macedonia.

Thallium hyperaccumulation status of the violets of the Allchar arsenic-thallium deposit (North Macedonia) confirmed through synchrotron µXRF imaging.

The abandoned Allchar Mine in the Republic of North Macedonia is a globally unique deposit with the highest known grades of thallium (Tl) and arsenic (As) mineralization. We aimed to determine the distribution of As and Tl in whole dehydrated shoots of the three Viola taxa using synchrotron micro-X-ray fluorescence analysis. Additionally, soil and plant organ samples were collected from all three Viola taxa at the Allchar site and analysed using inductively coupled plasma-atomic emission spectrometry. Concentrations of Tl were extremely high in all three Viola taxa (up to 58 900 mg kg-1), but concentrations of As were highly variable with V. tricolor subsp. macedonica and V. allchariensis having low As (up to 20.2 and 26.3 mg kg-1, respectively) and V. arsenica having the highest concentrations (up to 381 mg kg-1). The extremely high Tl in all three species is endogenous and not a result of contamination. Arsenic in V. tricolor subsp. macedonica and V. allcharensis is strongly affected by contamination, but not in V. arsenica where it appears to be endogenous. The pattern of As enrichment in V. arsenica is very unusual and coincides with Ca-oxalate deposits and Br hotspots. The results of this study could form the basis for more detailed investigations under controlled conditions, including plant dosing experiments.

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.

Cases of Crimean-Congo haemorrhagic fever in North Macedonia, July to August 2023.

The last report of Crimean-Congo haemorrhagic fever (CCHF) in North Macedonia was more than 50 years ago in the northwest. We report on a fatal CCHF case following a Hyalomma tick bite in the east of the country in July 2023. Tracing of 67 contacts identified CCHF in one healthcare worker (HCW) providing care for the patient. Monitoring of contacts is concluded (including further 11 HCW contacts), thus far 28 days after the death of the case no additional cases were identified.

Developing modern primary care nursing in North Macedonia.

BACKGROUND: Nurses have the potential to make a real impact on the health and well-being of people and populations and contribute to the realisation of delivery of Universal Health Coverage. However, in many parts of the world, the education and practice of nursing and nurses' position in health care and society are restricted by a range of social, cultural, economic and political factors. In North Macedonia, the Ministry of Health in partnership with the WHO Country Office launched a primary healthcare strategy supporting the development of nurses in primary care to fulfil their full scope of service. AIMS: To present information on the education, practice and position of nursing, in particular primary care nursing, in North Macedonia and to describe the ongoing initiatives to support the further development of nursing. APPROACH: Background documents reviewed, and visits to healthcare settings, organisations, interviews with individuals and groups and workshops undertaken in 2019-2020. FINDINGS: Three key areas of development were identified: education of nurses, their service delivery and practice in primary care, and their position in health care and society, all underpinned by the need for workforce planning. The findings formed the basis of a 10-year plan: Making Change Happen: The Nursing and Midwifery Development Roadmap. DEVELOPMENTS: To support the proposed primary care pilots, during the 2020/2021 COVID-19 pandemic, an on-line modular programme for primary care nurses was developed and delivered with the support of members drawn from The National Working Group for Moving Primary Care Nursing Forward in North Macedonia. Further work is planned to develop initial nurse education and to pilot changes in primary care. CONCLUSIONS: The launch of the primary healthcare strategy stimulated initiatives to improve the education, position and practice of primary care nursing. The COVID-19 pandemic required flexibility and changes to the original plans.

Laparoscopic Donor Nephrectomy in the Republic of North Macedonia.

Introduction: Hand-assisted laparoscopic living donor nephrectomy has become the technique of choice for living donor kidney donations. Since 2018, 30 procedures have been performed at our clinic using this technique. The goal of this comparative analysis was to determine how surgical technique, specifically, hand-assisted laparoscopic living donor nephrectomy with hand assistance may affect early graft function when compared to open classical nephrectomy. Material and methods: Retrospective analyses were performed, comparing the two techniques of kidney donation. Kidney transplantation was performed with the open standard technique in both groups. The primary outcome was early graft function, and levels of urine output, and plasma creatinine were analyzed at three time points. A secondary outcome was the quality of the operative technique, which was determined by the time of warm ischemia, blood loss, and duration of surgery. Additionally, we noted all complications, length of hospital stay, and patient satisfaction. Results: In terms of warm ischemia time, there was no statistically significant difference between donors in both groups. It is important to note that in 2 recipients from Group II we did not observe diuresis at the conclusion of the operation. The recipients' diuresis was 515 ml ± 321SD in group I and 444 ml ± 271SD in group II. At 3, 12, and 36 hours postoperatively, there were statistically significant differences in the average serum creatinine values (p 0.05) in favor of group I. Similar results were observed in the second time measurement at 12 h and the third time measurement at 36 h for serum urea levels in recipients. The difference in serum urea values between the recipients in the groups at the first measurement (3h) following surgery was not statistically significant. Conclusion: Hand-assisted laparoscopic donor nephrectomy is recognized as a safe and effective treatment. Donors in this situation have a different profile from other surgical patients; hence, they do not undergo surgery due to their own medical condition but for an altruistic reason, and with hand-assisted living donor nephrectomy. Such patients receive all the advantages of minimally invasive surgery. The two main objectives of a donor nephrectomy are to give the recipient the best possible kidney and to ensure the donor's complete safety.

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).

Increased risk of brucellosis misdiagnosis in regions that lose their endemicity.

Over the last decades, the epidemiology of human brucellosis globally has been subjected to significant changes, with the eradication of many existing endemic hot spots. This paper describes three cases with initial misdiagnosis of brucellosis that were managed during 2011-2017 in Republic of North Macedonia, country that until recently has been declared as endemic region. In spite of the fever, constitutional symptoms, focal disease (spondylitis, pneumonia and orchitis) and previous contact with domestic animals, brucellosis was not initially recognized, and patients were inadequately managed. Brucellosis should be part of differential diagnostic considerations in patients exposed to contacts with animals, with osteoarticular symptoms and signs, constitutional manifestations and different organ involvements in endemic regions where its incidence is diminishing.

Prevalence of congenital hypothyroidism in North Macedonia: data from a newborn screening program conducted for twenty years.

BACKGROUND: Congenital hypothyroidism (CH) is a common endocrine disorder that can be treated if timely detected by newborn screening, optimizing the developmental outcome in affected children. In the present study, we analyze the data of the national newborn thyroid screening program in North Macedonia collected over twenty years, including the CH prevalence as well as its geographical and ethnic variations. METHODS: The thyroid-stimulating hormone (TSH) was measured on a filter paper blood spot sample using the DELFIA fluoroimmunometric assay. A TSH value of 15 mIU/L whole blood was used as the cutoff point until 2010 and 10 mIU/L thereafter. RESULTS: Out of 377,508 screened live births, a total of 226 newborns with primary CH were detected, providing an overall prevalence of 6.0 per 10,000. Lowering the TSH cutoff led to an apparently increased prevalence of the transient CH, from 0.2 to 2.4 per 10,000 live births (p < 0.0001) with an impact on the overall prevalence of primary CH (from 4.0 to 7.1 per 10,000, p=0.0001). Taking ethnicity into account, the significantly highest primary CH prevalence of 11.3 per 10,000 live births was observed among the Roma neonates, with a predominance of permanent CH (75.5%). There were also regional differences in the prevalence of primary CH. The highest primary CH prevalence of 11.7 per 10,000 live births was observed in the Vardar region, together with the highest regional prevalence of the transient CH (3.2 per 10,000). The highest prevalence of permanent CH was observed in the Pelagonia region (6.6 per 10,000) where the largest percentage of the Roma population lives. CONCLUSIONS: The overall CH prevalence is high in North Macedonia, with substantial ethnic and geographical variations. Further analysis to elucidate the causes for the significant variations in the CH prevalence including environmental factors is warranted.

Mutational Spectrum and Genotype-phenotype Correlations in Neurofibromatosis Type 1 Patients from North Macedonia: Identification of Ten Novel NF1 Pathogenic Variants

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, characterized by multiple café-au-lait macules, axillary and inguinal freckling, tumors of the nervous system, and iris hamartomas. More than 3,100 different pathogenic variants have been reported in the NF1 gene, including missense, nonsense, frameshift, in-frame, splicing, and large deletions. Aims: To determine the NF1 mutational spectrum in patients with NF1 from the Republic of North Macedonia. Study Design: A cohort study. Methods: Molecular analyses included reverse transcription and cDNA sequencing of the NF1 gene and next-generation sequencing using the TruSight Cancer panel, along with the multiple ligation probe amplification method to detect single nucleotide variants and copy number variations. Direct DNA sequencing was also used for the family member analysis. Results: Our 9-year study of patients suspected of having NF1 in the Republic of North Macedonia encompassed molecular characterization of 30 cases of the disease. We identified 28 unique pathogenic NF1 variants (NM_001042492.3), of which ten were novel: c.208delA; c.341_364del; c.1480_1481delTT; c.2325+1G>C; c.2495_2496dupAC; c.2533_2541del; c.4517delC; c.5844C>G; c.6971delA; c.7605_7606delGAinsAT. In addition to the variant spectrum analysis, our research revealed two positive genotype-phenotype correlations. One between the clinical manifestation of cognitive impairment and gross deletions in the NF1 gene, and the other between cognitive impairment and truncating variants located in the RAS-GAP functional domain. Conclusion: This is the first study of NF1 patients in the Republic of North Macedonia, and it contributes ten novel variants to the global spectrum of pathogenic NF1 variants. It also corroborates the crucial importance of NF1 genetic testing for a prompt and precise diagnosis, particularly in younger patients.