International Narcotics Control Board Research Articles

Distributed Opioids in Morphine Equivalent: A Global Measure of Availability for Palliative Care

ContextEstimates of serious health-related suffering (SHS) demonstrate immense unmet need for palliative care, predominately in low- and middle-income countries (LMICs). Because opioids are essential medicines in palliative care (PC), measuring their availability can be used to evaluate the capacity of health systems to meet need. ObjectivesPresent the methodology for calculating Distributed Opioids in Morphine Equivalents (DOME)— introduced in the Lancet Commission on Global Access to Palliative Care and Pain Relief report - and how it can be used as a simple indicator to quantify unmet pain relief and PC need. MethodsUsing International Narcotics Control Board (INCB) data, DOME applies relative potency estimates to convert the annualized quantities of clinically appropriate opioids procured by a country to oral morphine equivalent milligrams. To quantify unmet need, an expert group proposed health condition-specific estimates for opioid need and used available data on the burden of SHS to posit the annual opioid quantity required by country for symptomatic treatment of pain or breathlessness. Comparing this to DOME generates DOME%SHSNEED, the proportion of opioids needed for palliative care that can be fulfilled by the opioid procured by a country during a year. ResultsDOME and DOME%SHSNEED can be used to measure, over time, the capacity of countries to meet PC need, as a key component of universal health coverage. Identifying access gaps disproportionately impacting LMICs can promote better health system performance and guide countries and institutions in policy making. ConclusionDOME and DOME%SHSNEED can be used to monitor health system progress to redress disparities and promote access to medically indicated opioid therapy in palliative care.

Analysis of opioid analgesics consumption in Africa: a longitudinal study from a 20-year continental perspective

Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in low-income regions including Africa. This study aimed to provide updated and comprehensive data on changes in opioid consumption, specifically in Africa. This longitudinal study has updated and expanded upon the International Narcotics Control Board data obtained from 1999 to 2021, assessing opioid consumption trends across all African countries. The defined daily doses for statistical purposes (SDDD) was used to determine the changes in opioid consumption in Africa. In addition, we used sub-analyses of the data to delve into individual substances, income levels, cancer incidence, cancer mortality, and sub-regional cluster analysis (based on the language spoken) to identify possible disparities and inform further research and tailored solutions. Our results indicate a persistently low and stagnant trend in opioid consumption between 2001-03 and 2019-21, from 73 SDDD (95% CI 69-77) to 55 SDDD (32-79). In-depth analysis revealed a morphine consumption increase from 735 SDDD in 1999 to 1115 SDDD in 2021. Moreover, opioid consumption was closely related to country-level income levels, with most of the low-income and lower-middle-income African countries reporting low opioid consumption. Notably, the escalating incidence and mortality rates associated with cancer in Africa indicated a misalignment with the trajectory of opioid use. Additionally, French-speaking African countries exhibited lower opioid usage than the rest of the continent, suggesting avenues for research into cultural, political, and social aspects. In the context of global doubling in opioid consumption, Africa has shown insufficient and stagnant opioid consumption during the last 20 years. These findings underscore the need for policy reform to facilitate safe and responsible opioid access in Africa, particularly for legitimate indications such as cancer pain and palliative care. None. For the French translation of the abstract see Supplementary Materials section.

Legislation alone is not enough to reduce prescriptions of benzodiazepines

Psychiatry and Clinical NeurosciencesVolume 77, Issue 5 p. 251-251 Editorial Legislation alone is not enough to reduce prescriptions of benzodiazepines Takashi Tsuboi MD, PhD, Corresponding Author Takashi Tsuboi MD, PhD [email protected] orcid.org/0000-0002-8253-8888 Department of Neuropsychiatry, Kyorin University School of Medicine, Mitaka, Japan Correspondence: Email: [email protected]Search for more papers by this author Takashi Tsuboi MD, PhD, Corresponding Author Takashi Tsuboi MD, PhD [email protected] orcid.org/0000-0002-8253-8888 Department of Neuropsychiatry, Kyorin University School of Medicine, Mitaka, Japan Correspondence: Email: [email protected]Search for more papers by this author First published: 02 May 2023 https://doi.org/10.1111/pcn.13536Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1Takeshima M, Yoshizawa K, Enomoto M et al. Effects of Japanese policies and novel hypnotics on long-term prescriptions of hypnotics. Psychiatry Clin. Neurosci. 2023; 77: 264– 272. 2Olfson M, King M, Schoenbaum M. Benzodiazepine use in the United States. JAMA Psychiat. 2015; 72: 136– 142. 3Panes A, Pariente A, Bénard-Laribière A et al. Use of benzodiazepines and z-drugs not compliant with guidelines and associated factors: A population-based study. Eur. Arch. Psychiatry Clin. Neurosci. 2020; 270: 3– 10. 4 The International Narcotics Control Board. Psychotropic Substances 2021. https://www.incb.org/incb/en/psychotropics/technical-report.html Volume77, Issue5May 2023Pages 251-251 ReferencesRelatedInformation

New Psychoactive Substances: A Potential Threat to Developing Countries.

New psychoactive substances (NPS) have become a global phenomenon, with over 134 countries and territories from all world regions reporting them. Since December 2021, governments, laboratories, and partner agencies have confirmed to the UNODC Early Warning Advisory (EWA) on NPS over 1124 substances. It is agreed that NPS control is one of the most challenging tasks for developing countries. Identifying the present and future threads of NPS is the most challenging task for law enforcement officials. The NPS research has a great impact on substance abuse policy-making and harm reduction strategies. The data in this study were collected from the official websites of online journals, Google Scholar, UNODC, International Narcotics Control Board (INCB), and the Department of Narcotics Control (DNC). Among the eleven groups of NPS, synthetic cannabinoids and cathinones are the most prevalent and alarming in developing countries. In Bangladesh, NPS abuse has been first identified in 2016. Almost 60 countries adopted legislative solutions to manage NPS by 2021, with many using or amending existing legislation and others employing novel legal mechanisms. It is widely agreed by researchers that reducing the menace of NPS requires increased awareness among all stakeholders. In the fight against the spread of NPS and its severe effects, law enforcement authorities and healthcare professional training must be seen as crucial aspects as well. Financing is also crucial for international organizations dealing with the NPS impact to continue fighting this war. The only way for policymakers to reduce NPS spread globally is through national and international cooperation.

Cross-Country Analysis of the Association of Cultural Dimensions with Prescription Opioid Consumption and Implications for Health Education

Background and Purpose: Over 247,000 people died in the U.S. from overdoses related to prescription opioids in 1999–2019, leading the WHO to deem the situation an epidemic. The purpose of this study is to examine whether culture is related to perceptions and behaviors around opioid consumption because culture has been shown, for example, to influence decision-making strategies, risk-taking, and responses to self-congruent communications. Methods: Scores for country-wide dimensions of culture from Hofstede and opioid consumption data from the International Narcotics Control Board were used to study a possible relationship. The relationship was tested by including a set of economic and socio-economic indicators from the World Bank, the United Nations, and PROSPERED. Results: The scores for the cultural dimension of individualism are correlated with opioid consumption on a country level, with higher levels of individualism connected to higher consumption. This correlation is robust to the inclusion of economic and socio-economic variables (GDP per capita, inflation, income inequality, unemployment, education, life expectancy, median age, and sick leave coverage). Conclusions and Importance: Because messages that reinforce a group’s cultural value are more meaningful and effective in motivating action, educational health messages about opioid consumption in the U.S. need to be designed with culture in mind to disrupt decisions to take opioid analgesics unless medically justified or to limit their use. More research is needed on how to design self-congruent individualistic versus collectivistic persuasive appeals.

Calculating worldwide needs for morphine for pain in advanced cancer and proportions feasibly met by country estimates of requirements and consumption. Retrospective, time-series analysis (1997-2017).

Lack of access to therapeutic opioids continuing causes global health inequalities. Access to morphine for symptom control is regulated under the terms of the Single Convention on Narcotics, countries must submit annual morphine requirement estimates and report consumption to the International Narcotics Control Board (INCB). INCB indicates access to morphine is increasing, however, estimated needs are unreported so changing proportions of needs feasibly met by requirements and consumption are unknown. Retrospective time series-analysis taking cross-sections every five years of gaps between calculated needs for morphine for people who die from cancer and total treatable using estimates of requirements and consumption (1997, 2002, 2007, 2012, 2017). We calculated need using INCB-recommended methods (80% of people who die from cancer require 67.5mg of morphine daily for 90 days (6.075g)) for countries reporting estimates and consumption using Global Burden of Disease cancer deaths by country. Gaps between calculated need and total treatable population using estimates and consumption were calculated. We report proportions of need feasibly met by estimates and consumption for included countries, by World Bank Income group. Global availability of morphine increased, from estimates sufficient to treat 86% of calculated needs in 1997, to 701% in 2017. However, proportion of countries estimating requirements feasibly meeting >100% of calculated needs rose only from 16% to 30%. Almost all Low-and-Middle-Income Countries submitted inadequate estimates with little change in 20 years. Consumption was lower than calculated needs at all time-points. Very few countries reported consumption greater than their estimate of requirement. Most countries submitted morphine estimates insufficient to meet analgesic needs of people who died from cancer. Estimates of requirements contextualise future Consumption, and increases in adequacy of estimates and consumption were minimal over 20 years. Annual publication of calculated morphine needs alongside estimates and consumption may be a key step to drive countries' accountabilities.

Switzerland's Dependence on a Diamorphine Monopoly.

In 2021, the manufacturer of diamorphine reported a possible impending shortage for Switzerland and Germany. This led us to investigate this controlled medicine’s manufacture, market, and regulatory constraints. Based on our analysis of legal texts and gray literature in the form of reports and documents, we propose recommendations to prevent and address diamorphine shortages in Switzerland. Diamorphine, also known as pharmaceutical “heroin,” is used medically to treat persons with severe opioid use disorder in a handful of countries. The controlled medicine is manufactured from morphine, which, in turn, is extracted from opium poppies. Studying data from the International Narcotics Control Board for 2019, we find that Switzerland accounts for almost half of the worldwide medical consumption of diamorphine. It manufactures more than half of the worldwide total and keeps the largest stocks. Moreover, Switzerland is dependent on a sole supplier of diamorphine (monopoly). As a niche product, diamorphine has an increased risk of shortage. Such a shortage would immediately threaten a valuable public health program for around 1,660 Swiss patients. We believe it is urgent to curtail the monopoly and ensure a stable supply for the future.

DRUG BUSINESS AS A THREAT TO SECURITY IN CENTRAL ASIA

Based on the latest data from the UN Office on Drugs and Crime, the International Narcotics Control Board, as well as researches of the experts on illicit drug trafficking this article reveals the causes and factors that contribute to the growth of cultivation and production of drugs in Afghanistan. Particular attention is paid to the peculiarities and new trends in illicit drug trafficking from Afghanistan, the negative consequences of the business of drugs and its impact on security in Central Asia.

Transportation of therapeutic and controlled drugs across international borders: a descriptive analysis of information available to travellers.

Transportation of medications across borders can present challenges for international travellers. We investigated the provision of official country-specific information available to individuals travelling with medications. Data from official government sources relating to restrictions on the transportation of medications for personal use were analysed to determine compliance with international recommendations and identify variation in practice between countries. Schedule 1 drug classifications and import restrictions for narcotic and psychotropic drugs varied widely between countries. Some countries do not conform to recommendations from the International Narcotics Control Board. Healthcare professionals should be broadly aware of country-specific restrictions on therapeutic drug transportation and be able to direct travellers to definitive sources of information.

Comment on Häuser et al.: Medical use of opioids in Europe—Methodological concerns about data from the International Narcotics Control Board

-

Should INCB Consumption Data Be Utilized to Guide Opioids Policy?

ContextThe International Narcotics Control Board's (INCB) opioids consumption data are often cited in the literature and by policy makers to benchmark the adequacy of pain management among different countries. This practice may be inaccurate as INCB data does not account for variations in disease burden and use of other pain medications and only controls for population sizes differences among countries. ObjectiveTo demonstrate that INCB consumption data may not be an accurate/sensitive indicator for pain management adequacy due to significant inter-country variations in disease burden and in the use of pain medications that are not reported by INCB. MethodsWe compared opioid consumption data between 2012 and 2016 for Jordan and King Hussein Cancer Center vs five high-income countries (United States of America, United Kingdom, France, Sweden, and Japan) taking into consideration the cancer burden in those countries. In addition, we examined the significance of tramadol utilization in the setting of cancer pain management. ResultsJordan's INCB-reported opioid consumption is ostensibly low at a median of 291 sDDD/million inhabitants/day. Compared to Jordan, the median consumption in the five HICs is 34 (range 4–172) times that of Jordan. However, when consumption is adjusted to cancer burden data, the gap is significantly reduced to a median of 2 (range 0.2–24) times that of Jordan and in the case of one institution's experience, the gap is eliminated. Furthermore, Jordan's tramadol's median consumption between 2012–2016 of 176 kg is equivalent to 127% of morphine consumption on an equianalgesic basis. ConclusionINCB data should not be utilized to benchmark the adequacy of pain management among different countries without taking into consideration variations in disease burden and the use of tramadol and other pain drugs.

Cuidados paliativos: percurso na atenção básica no Brasil

In 2022, an important international report was published on the “value of death” not only in the field of health, but in relation to human societies in general. This report proposed to reimagine systems related to end of life in which death is understood not only as a physiological event but also as a relational and spiritual phenomenon with a value of its own and inseparable from life. It identifies the low priority given by most governments worldwide to the issue of alleviating suffering and supporting bereavement, evidenced by the low investment in palliative care. At the same time, we are witnessing in Brazil changes that threaten the feasibility of palliative care policies in primary health care. The denial of finitude within health systems is reflected in global indicators such as the quality of death index of The Economist magazine, in which Brazil ranks 42nd, the global atlas of palliative care of the World Hospice and Palliative Care Alliance, where Brazil is in level 3b, and the global trends in opioid consumption of International Narcotics Control Board of the World Health Organization, in which opioid consumption in Brazil is in the hundreds of doses per million inhabitants per day. Despite notable advances in the legislative and executive fields with regard to palliative care, the Brazilian Unified National Health System (SUS) and primary health care have suffered important structural setbacks that will impact the design of public policy for palliative care. The goal of this article is to undertake an initial analysis of the impacts of current policies within this context and their repercussions in the construction of a solid policy for palliative care.

Palliative care: pathway in primary health care in Brazil.

In 2022, an important international report was published on the "value of death" not only in the field of health, but in relation to human societies in general. This report proposed to reimagine systems related to end of life in which death is understood not only as a physiological event but also as a relational and spiritual phenomenon with a value of its own and inseparable from life. It identifies the low priority given by most governments worldwide to the issue of alleviating suffering and supporting bereavement, evidenced by the low investment in palliative care. At the same time, we are witnessing in Brazil changes that threaten the feasibility of palliative care policies in primary health care. The denial of finitude within health systems is reflected in global indicators such as the quality of death index of The Economist magazine, in which Brazil ranks 42nd, the global atlas of palliative care of the World Hospice and Palliative Care Alliance, where Brazil is in level 3b, and the global trends in opioid consumption of International Narcotics Control Board of the World Health Organization, in which opioid consumption in Brazil is in the hundreds of doses per million inhabitants per day. Despite notable advances in the legislative and executive fields with regard to palliative care, the Brazilian Unified National Health System (SUS) and primary health care have suffered important structural setbacks that will impact the design of public policy for palliative care. The goal of this article is to undertake an initial analysis of the impacts of current policies within this context and their repercussions in the construction of a solid policy for palliative care.

Opioid availability statistics from the International Narcotics Control Board do not reflect the medical use of opioids: comparison with sales data from Scandinavia.

Opioid analgesics are essential in clinical practice, but their excessive use is associated with addiction risk. Increases in opioid prescription rates have fuelled an epidemic of opioid addiction in the USA, making statistics on medical opioid use a critical warning signal. A dramatic 150% increase in Swedish opioid access 2001-2013 was recently reported based on data from the International Narcotics Control Board (INCB; Berterame et al. 2016) in conflict with other studies of opioid use in the Nordic countries. This article aims to analyse to what degree published INCB statistics on opioids in Scandinavia (Denmark, Norway and Sweden) reflect actual medical use and study the methodological reasons for putative discrepancies. Data on aggregated total national sales of opioids for the whole population, including hospitals, were collected from the Swedish e-Health Authority. Total sales data for Denmark and drugs dispensed at pharmacies in Norway are publicly available through the relevant authorities' websites. INCB opioid statistics during the period 2001-2013 were markedly inconsistent with sales data from Scandinavia, calling the reliability of INCB data into question. INCB-data were flawed by (a) over-representing the volume of fentanyl, (b) under-reporting of codeine, and (c) by not including tramadol. Opioid availability, as expressed by INCB statistics, does not reflect medical opioid use. It is crucial to underline that INCB statistics are based on the manual compilation of national production, import and export data from manufacturers and drug companies. This is not the same amount that is prescribed and consumed within the health care system. Moreover, there are methodological problems in the INCB reports, in particular concerning fentanyl, codeine and tramadol. We suggest that INCB should carefully review the quality of their data on medical opioids.

Serious health-related suffering and palliative care in South Asian countries.

South Asia, with a population of 1.79 billion, has close to 9.9 million individuals experiencing serious health-related suffering (SHS). South Asia accounts for 10.23% of the world's cancer incidence. The prevalence of cancer mortality in the region is 68.44%, significantly higher than the world average of 59.74%. This poor outcome highlights the need to focus on SHS in the region. This review was undertaken to assess the current status of palliative care inequities in the region and to guide future action. Using morphine-equivalent doses of opioid analgesics (excluding methadone) per cancer death as a proxy measure for access to palliative care, the International Narcotics Control Board data in 2020 show poor access to palliative care. Less than 4% of those in need are able to access palliative care in India, whereas in Afghanistan only 0.2% have access. Inappropriate end-of-life care (EOLC) and catastrophic out-of-pocket health expenditure compound the problem. The solutions involve the introduction of national programs for palliative care, demonstration of culturally appropriate best practices as proof of concept, favourable legislation for medical opioid access, community participation, engagement of civil society to improve awareness, inclusion of palliative and adding EOLC to medical education and need-based research. http://links.lww.com/COSPC/A30.

Early Detection of Prescription Drug Abuse Using Doctor Shopping Monitoring From Claims Databases: Illustration From the Experience of the French Addictovigilance Network.

Opioid analgesics and maintenance treatments, benzodiazepines and z-drugs, and other sedatives and stimulants are increasingly being abused to induce psychoactive effects or alter the effects of other drugs, eventually leading to dependence. Awareness of prescription drug abuse has been increasing in the last two decades, and organizations such as the International Narcotics Control Board has predicted that, worldwide, prescription drug abuse may exceed the use of illicit drugs. Assessment of prescription drug abuse tackles an issue that is hidden by nature, which therefore requires a specific monitoring. The current best practice is to use multiple detection systems to assess prescription drug abuse by various populations in a timely, sensitive, and specific manner. In the early 2000's, we designed a method to detect and quantify doctor shopping for prescription drugs from the French National Health Data System, which is one of the world's largest claims database, and a first-class data source for pharmacoepidemiological studies. Doctor shopping is a well-known behavior that involves overlapping prescriptions from multiple prescribers for the same drug, to obtain higher doses than those prescribed by each prescriber on an individual basis. In addition, doctor shopping may play an important role in supplying the black market. The paper aims to review how doctor shopping monitoring can improve the early detection of prescription drug abuse within a multidimensional monitoring. The paper provides an in-depth overview of two decades of development and validation of the method as a complementary component of the multidimensional monitoring conducted by the French Addictovigilance Network. The process accounted for the relevant determinants of prescription drug abuse, such as pharmacological data (e.g., formulations and doses), chronological and geographical data (e.g., impact of measures and comparison between regions), and epidemiological and outcome data (e.g., profiles of patients and trajectories of care) for several pharmacological classes (e.g., opioids, benzodiazepines, antidepressants, and methylphenidate).

Global, regional, and national consumption of controlled opioids: a cross-sectional study of 214 countries and non-metropolitan territories.

Introduction:The consumption of opioids has increased globally since the 1990s. Previous studies of global opioid consumption have concentrated on morphine alone or a subset of opioids, with a focus on cancer pain and palliative care. In this study, we have determined the global, regional, and national consumption of all controlled opioids, including anaesthetics, analgesics, antidiarrheals, opioid substitution therapies, and cough suppressants.Methods:We conducted a cross-sectional study using data from the International Narcotics Control Board (INCB). We calculated mean opioid consumption (mg/person) globally, regionally, and nationally for 2015–2017, where consumption refers to the total amount of controlled opioids distributed for medical purposes and excludes recreational use. We ranked countries by total consumption and quantified the types of opioids consumed globally.Results:Between 2015 and 2017, 90% of the world’s population consumed only 11% of controlled opioids. An average of 32 mg/person was consumed annually, but this was not equally distributed across the world. Consumption was the highest in Germany (480 mg/person), followed by Iceland (428 mg/person), the United States (398 mg/person) and Canada (333 mg/person). Oxycodone (35%) was the most heavily consumed controlled opioid globally, followed by morphine (15.9%), methadone (15.8%) and tilidine (14%).Conclusion:Large disparities persist in most of the world in accessing essential opioid medicines. Consumption patterns should continue to be monitored, and collaborative strategies should be developed to promote access and the appropriate prescribing of opioids in all countries and non-metropolitan territories.

The Oxford Catalogue of Opioids: A systematic synthesis of opioid drug names and their pharmacology.

AimThe growing demand for analgesia, coupled with an increasing need to treat opioid dependence and overdose, has escalated the development of novel opioids. We aimed to quantify the number of opioid drugs developed and to catalogue them based on their pharmacology.MethodsWe conducted a systematic search of seven sources in November 2020, including the WHO's Anatomical Therapeutic Classification index, the British National Formulary, the IUPHAR/BPS Guide to Pharmacology, the International Narcotics Control Board Index of Names of Narcotic Drugs, the WHO's International Nonproprietary Names MedNet service, Martindale's Extra Pharmacopoeia and the Merck Index, to include opioid drugs that targeted or had an effect or coeffect at one or more opioid receptors. We extracted chemical and nonproprietary names, drug stems, molecular formulas, molecular weights, receptor targets, actions at opioid receptors and classes based on their origins. We used descriptive statistics and calculated medians and interquartile ranges where appropriate.ResultsWe identified 233 opioid drugs and created an online resource (https://www.catalogueofopioids.net/). There were 10 unique drug stems, and “‐fentanil” accounted for one‐fifth (20%) of all opioids. Most of the drugs (n = 133) targeted mu‐opioid receptors and the majority (n = 191) were agonists at one or more receptors. Most (82%) were synthetic opioids, followed by semisynthetic opioids (16%) and alkaloids (3%).ConclusionThis catalogue centralizes and disseminates information that could assist researchers, prescribers and the public to improve the safe use of opioids.

Relation between opioid consumption and inclusion of opioids in 137 national essential medicines lists

IntroductionOpioids are deemed essential medicines by the World Health Organization (WHO). However, many countries have inadequate access to them. Whether including opioids in national essential medicines lists (EMLs) influences national...

TRAFFICKING OF SYNTHETIC OPIOIDS AND NEW PSYCHOACTIVE SUBSTANCES AS A GENERAL SECURITY RISK AND THE INTERNATIONAL DRUG CONTROL SYSTEM

The global drug control system, enshrined by the Single Convention on Narcotic Drugs of 1961, the Convention on Psychotropic Substances of. 1971, and the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances of 1988. The UN body mandated to monitor the implementation of the Conventions, the International Narcotics Control Board, and the various control mechanisms prescribed by the Conventions provide a robust control system for the licit trade, production and manufacture of drugs. With the development of new psychoactive substances (NPS), in particular non-scheduled synthetic opioids such as fentanyl and its analogues, create new risks and dangers to the general public, as well as to the front-line officers most directly exposed to them in the drug supply chain. Author's of this paper wishes is to present to the general public the organization and operation of the International Narcotics Control Board and the various control mechanisms prescribed by the said conventions.Also, as mass drug use and drug offenses impair the security of each country, this problem is of global importance. Therefore, the aim of this paper is to present this problem in the right way, but also to show the unity of humanity in the fight against this problem. At the same time, this paper contains several recommendations that are current for every country in the world and for the Republic of Serbia.