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Official websites use. Share sensitive information only on official, secure websites. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Introduction: The use of opioids has increased markedly in the past decades in European countries, especially for treatment of non-cancer pain including painful chronic musculoskeletal conditions. However, there are some notable differences in the relative levels of use between geographical areas and some distinct, context-specific patterns of weak and strong opioid use. The aim of this work is to describe real world trends in dosage forms and population exposure in the prescription opioid use on isolated geographically area: The Canary Islands of Gran Canaria, Lanzarote and Fuerteventura, Spain. For this, several factors such as living in a rural or urban area, population over 65 years of age, population density or socioeconomic status were analyzed. Methods: Data were extracted from the wholesalers who supply the community pharmacies at the population level. Prescription opioid use was measured as defined daily doses DDD per 1, inhabitants per day. A model based on covariance analysis with two nested fixed factors and one co-variable was used for contrast analysis at different level. Results: The overall DDD per inhabitants per day and year variation rate in Spain was very similar to that obtained for Gran Canaria and Fuerteventura 0. Lanzarote is completely different in all issues, where the opioid consumption rate remained stable during the study period, but with a decreasing tendency. The dispensation level of strong opioids varied between islands, from Tramadol with acetaminophen and Tramadol in monotherapy were the most consumed forms of the weak opioids, whereas Buprenorphine was the most used strong opioid followed by Fentanyl, although demand for it varied between islands, the transdermal formulations were the most frequent pharmaceutical preparation. Conclusion: The differences in prescription opioid use are most likely explained by the opioid prescribing practices in each island, whereas factors such urbanicity level, population age, population density and status socioeconomic does not help to explain the differences in prescription opioid use across rural and urban areas. Keywords: opioid prescription, wholesaler, defined daily dose, socio-economic status, strong opioids, rural, Canary islands, Spain. Chronic pain including the musculoskeletal pain are an important public health problem, responsible for disabilities, distress, and quality of life impairment de Sola et al. Among the musculoskeletal MSK conditions that cause the most disability in terms of years lived with disability are low back pain, neck pain, osteoarthritis and rheumatoid arthritis. Furthermore, according to the Global Burden of Disease GBD study, low back pain and osteoarthritis are the largest contributors to years of productive life lost in the workforce compared to other noncommunicable diseases GBD, The physiopathology of chronic pain has been recognized to involve complex interactions between physical, psychological and social factors, and that its appropriate management requires both pharmacological and non-pharmacological treatment Broekmans et al. Although opioids were originally formulated for acute and cancer pain, their use has expanded to the treatment of severe acute pain and moderate to severe chronic pain that does not respond to other medications British Pain Society, The prevalence and factors associated with the use of opioids among patients with chronic non-cancer pain CNCP was analyzed by De Sola et al. In this study, factors such as being male, young age, polymedicated patients, smokers and payment type, were associated with higher prevalence rates. However, non-white and Asian patients, and those treated by a physician trained in complementary medicine were less likely to use opioids. However, other studies suggest that women are more likely to be prescribed opioids in CNCP. This study showed that there was a sustained increase in the prescription of strong opioids at high doses, and in mainly elderly patients, predominantly low-income women. Birke et al. Serdarevic et al. Other studies have reported that factors such as urbanicity level living in a rural or urban area demographic variables sex and gender , population over 65 years of age, employment rate, socio-economic status, etc. For example, Davies et al. This study showed the associations between higher rates of opioid prescribing and lower socio-economic conditions. Areas of greatest deprivation had more than twice the rate of opioid prescription than the least deprived areas. Similar results were reported in another countries Davies et al. Serra-Pujadas et al. The results show that socio-economic status has a major impact on the use of opioids, with the most deprived areas having the highest levels of opioid use. In addition, and particularly in these areas, women have much higher rates of use of weak opioids than men. Bedene et al. In this study, female sex, older age, lower socioeconomic status, smoking, and obesity were associated with an increased risk of opioid prescription. Additionally, they observed that poor self-perceived health, depressive symptoms and loneliness, lower household income, and being divorced or widowed were associated with opioid prescription. Keyes et al. According to these authors, social norms, cultural traditions, attitudes, availability and policies might explain the broad differences in the prevalence of opioid use across rural and urban areas. The rural areas were found to have higher rates of opioid prescription, higher-rates of high-dose opioid prescription or fewer resources for inpatient and outpatient opioid treatment, etc. They found that increased opioid use led to worse labor market outcomes in the long run. For example, Mordecai et al. Ashaye et al. However, the differences between areas were not significant. Curtis et al. Higher rates of high-dose prescribing were associated with practice list size, rural location and deprivation. However, there was wide geographical variation across England. The most deprived areas had the highest levels of opioid use. Oliva et al. The aim of this work is to analyze the use of prescription opioids in the three islands that make up the province of Las Palmas, Canary Islands, Spain Gran Canaria, Lanzarote and Fuerteventura as an example of an isolated geographical area with an urban and rural population. In this context, a model, based on covariance analysis ANCOVA with two nested fixed factors and one co-variable, was used for the contrast analysis. For this purpose, the raw data obtained from the wholesalers that supply the community pharmacies at the population level were used as a database, which is a novel approach. The different opioid types were identified in the database by their ATC-code. Opioids indicated for analgesia all start with N02A. A few other opioids are also relevant as analgesics, such as methadone and codeine. These drugs are not routinely included in the usual opioid use statistics, because they are not only indicted for analgesia Jarlbaek, In this case, codeine combined with other analgesics was also excluded as these drugs may be used in other pathologies. This type of classification was used by Svendsen et al. This study used raw data from wholesalers supplying community pharmacies at the population level in the province of Las Palmas for the period — The data collected cover the entire distribution of the drug in the evaluated area, since there are no other supply channels that could disturb the results obtained. The data provided were the number of packages sold of the different pharmaceutical preparations according to the ATC classification, the date of sale, the national code and the name of the pharmaceutical preparation active pharmaceutical ingredient API , dose, strength and units. The postcode ZIP , which provides information on the municipality where the community pharmacy is located, but not its identity, was also included, thus maintaining its anonymity in accordance with current Spanish data protection legislation Data Protection Law in Spain, The dataset contained the prescriptions corresponding to all residents of the province of Las Palmas who are registered in the municipal population register and have access to the Spanish national health service. The Spanish national healthcare system guarantees a universal healthcare system to all residents of Spain. For this reason, the data correspond to the medicines that are dispensed in pharmacies by the public health system, but we do not have data on hospitals. The use of prescription opioids for each API was expressed in population doses per day, equivalent to the defined daily dose DDD per 1, inhabitants per day, where the number of DDDs was the total amount of the API consumed in a certain time period in this case, day divided by the DDD. Population data were downloaded from a publically accessible demographic database and are shown in Table 1 National Statistics Institute, Demographic data and administrative distribution of the province of Las Palmas. The following model based on covariance analysis ANCOVA with two nested fixed factors and one co-variable was used to analyze variation of each response during the — period:. In order to do this, the function lm from R-program was used. Marginal means were also computed at the different levels using the function emmeans , whereas the differences between each level was achieved through contrast analysis. All these functions are available in the free R-program R Core Team, Extension of this model to m factors is straightforward. In this context, the median household income was used to measure the socioeconomic level of each municipality and island, whereas the percentage of over 65 years old in population and population density were used as sociodemographic variables. Table 1 shows the population and demographic data at the provincial and island level. During the analyzed period, the population at the provincial level increased by 0. However, Gran Canaria is considered an urban area Reig et al. Lanzarote and Fuerteventura are considered semi-urban, but compared with Lanzarote, Fuerteventura has the lowest population density 2. Additionally, the The overall DDD per inhabitants per day variation shows different trends in opioid use, for example, Gran Canaria presented the highest value, it was even higher than that those observed at a nationwide level, by approximately eight points, whereas Lanzarote and Fuerteventura had lower values Table 2. However, the trends in both islands were different; Fuerteventura had an increasing tendency, whereas Lanzarote show a stable trends during this period, although the consumption in was negative, a decrease of Variation of the overall DDD per inhabitants per day and percentage of strong opioids, expressed as a percentage of overall DDD per inhabitants per day at different levels province and island during the period — Firstly, the prescription rate would be expected to increase with the rise in the number of aged people expressed as a percentage of over sixty-five-year olds in the population. This result is fairly misleading since the population density in Arrecife is fifteen times higher than the mean average of the rest of the island. The second step was to analyze the variability in overall DDD per inhabitants per day between-islands and municipalities during the study period, using an ANCOVA following the model proposed in Material and Methods Table 3. Firstly, the coefficient of adjusted determination R 2 was 0. This new model allowed R 2 to increase up to 0. This fact supposes that the overall DDD per inhabitants per day varied between islands during the study period. In this case, Gran Canaria and Fuerteventura had the same variation rate 1. However, Lanzarote and Fuerteventura presented the same dispensation level i. Furthermore, the data from Table 3 shows that there are differences between municipalities from different islands this is logical but also within the same island. In order to confirm this result, a second analysis was performed to determine the possible differences between municipalities for each island as well as their evolution during this period Table 5 , and the marginal means were calculated to do this. SE: Standard error with degrees of freedom. Table 6 shows the estimated marginal means for different municipalities within the same island. The residual standard error was 0. From an administrative point of view, the island of Gran Canaria has twenty-one municipalities and, the contrast analysis shows more than pairwise entries and, therefore, the data interpretation is too complex. In such a situation, the analysis of the data set has been in terms of district see Figure 1. Gran Canaria is divided into three districts: metropolitan district 4 municipalities , northern district 12 municipalities and southern district 5 municipalities. Figure 2 shows the estimated marginal means for the different municipalities within each district of Gran Canaria, indicating there are differences between municipalities within the same district. Estimated marginal means for the different municipalities within each district on the island of Gran Canaria for DDD per inhabitants per day A and percentage of strong opioid responses B. Opioids are classified in two groups: weak tramadol in monotherapy and combinations and strong opioids the remaining ones. In this case, codeine combined with other analgesics was excluded as these drugs may be used in other pathologies. Lanzarote shows the same pattern but a sharp increase was observed in , although the proportion of elderly people rate is the lowest of the three islands. Thus, the dispensation level i. The analysis of estimated marginal means shows that there are differences between municipalities within the same island Table 6. In the case of Gran Canaria, the contrast analysis was performed at the district level Figure 1. Besides which, the data analysis by municipalities within each district shows that there are no differences between the municipalities in southern district, whereas the difference between Arucas and Santa Brigida municipalities was significant in the case of the metropolitan district Figure 2. The northern district shows differences between its municipalities, although all of them are considered rural areas Figure 2. The combination of tramadol and paracetamol in tablet form was the most commonly prescribed formulation in all three islands. It was produced and packaged with a low dose and low number of units per package In the case of the first presentation, the values expressed as percentage of units sold per inhabitants and year varied between However, a trend in change was observed in , with an increase in the consumption of the latter presentation, 2. This pattern was mainly observed during the year , although the preliminary data analysis for the year seems to confirm this finding data not shown. For example, a slight increase was observed in Lanzarote during in comparison to Gran Canaria presented the same trends as Fuerteventura, although the consumption rates were different, a mean of However, it should be mentioned that the presentations of mg and 60 units per package had a consumption rate of However, differences in prescribing SO use between islands were observed, especially between Lanzarote and Fuerteventura. In the investigation of prescription opioid use, differences in measurement tools and the selection of opioids should be taken into consideration if the aims are to compare and report results on opioid use between geographical areas countries, regions, islands, municipalities, etc. Most national prescription databases report opioid consumption in DDDs, a unit recommended by the WHO for drug consumption studies. This allows the comparison of opioid use between different geographical areas. In the present study, the opioids indicated for analgesia, excluding methadone and codeine combined with other analgesics, were analyzed Oliva et al. In the present study, and for comparative purposes, the data of the nationwide report by AEMPS were re-analyzed to take this fact into account Oliva et al. The recalculated DDD per inhabitants per day varied from However, the overall DDD per inhabitants per day and year variation rate in Spain was very similar to those found in Gran Canaria and Fuerteventura, although the levels of dispensation were different. Lanzarote is completely different in all cases, where the opioid consumption rate remained stable during the studied period, but with a negative tendency; the data for the year seems to confirm this data not shown. The dispensation level of SO varied between islands, although these values remained stable because a consumption rate equal to zero was observed during the study period Table 4. Lanzarote had very similar values to those observed in Spain as a whole Spain as a whole had one of the lowest rates of opioid consumption in comparison with other European countries Hurtado et al. Hamunen et al. Chenaf et al. However, in the last 10 years, the pattern in the volume of opioid prescription has been stable in most European countries Hurtado et al. The estimated marginal means analysis shows that there are differences between islands, municipalities and districts in the case of the island of Gran Canaria. In such a situation, the municipality of Arrecife, capital of the island of Lanzarote, is considered an urban touristic have the highest DDD per inhabitants per day. In addition, the tourist activity is small in comparison with other zones. However, the municipality of Tinajo, the most rural in Lanzarote, is markedly different, with the level of SO prescription being 1. In Fuerteventura, the municipality of La Oliva, located in the north of the island, is a semi-urban area whose economic activity is linked to tourism and had the lowest value of DDD per inhabitants per day compared to the rest of the municipalities. A similar situation was observed for SO, where there is a statistically significant difference between Pajara compared to both Puerto del Rosario and Tuineje. A detailed analysis per district was carried out in Gran Canaria. These two municipalities are situated in the surrounding area of the capital and are within easy reach of the capital. Telde has a higher proportion of residents who work in manual jobs, industry and to a lesser extent in the agricultural sector, these people usually suffer work-place related physical injury and chronic pain. This fact could explain the greater DDD per inhabitants per day rates observed since Telde has the lowest proportion of elderly people, However, the DDD per inhabitants per day rate is the lowest in the metropolitan area, although the proportion of elderly people is slightly higher than the island average Although all municipalities in the northern district are considered rural areas, there are differences between them. In this context, it is possible to distinguish between two types of municipalities in terms of accessibility to urban areas. However, their DDD per inhabitants per day values are the lowest. Both municipalities have extreme SO values, In this context, the number of units sold was markedly different, with Artenara accounting for However, this data could be misleading as these three municipalities are the smallest in terms of surface area. However, the values of DDD per inhabitants per day vary considerably, from However, the SO in these three municipalities was similar to the district average, although the greatest variability was observed in Moya. However, Moya had a value of Ingenio is a rural area, where agriculture is the main economic activity, although there is a growing services sector. However, it has the highest value of DDD per inhabitants per day value These three municipalities are urban areas with tourism is the most important economic activity. However, despite having very different demographic and socio-economic characteristics, the differences between them do not reach significance for the SO. Mordecai et al. The findings showed that DDD per inhabitants per day were 10 times higher in the areas with the highest use than in those with the lowest. The socio-economic and demographic characteristics of the areas could explain these differences. In the case studied here, factors such as the proportion of older people, socioeconomic status, population density or access to healthcare services help to explain the opioid prescription rates and prescription pattern in all the islands and their municipalities. The results show that there is no significant correlation between the prescription opioid use rate, expressed as DDD per inhabitants per day and SO, and the population-aging rate at the municipal level. A similar result was found for income and population density variables data no shown. With regard to the main drugs contributing to the upward trend, buprenorphine and fentanyl are the greatest contributors among the strong opioids, while in the case of weak opioids tramadol alone or in combination with acetaminophen are the greatest contributors, although with differences between islands. The strong opioids accounted for All of the above mentioned are prescribed for the treatment of pain with precise indications. Buprenorphine is indicated for treatment of moderate to severe cancer pain and severe pain that does not respond to non-opioid analgesics as well as in patients with pain who have an active opioid use disorder Dowell et al. This increase in prescription in Spain as well in other European countries could be related to the ease of administrating transdermal formulations Bosetti et al. A possible explanation could be that physicians prescribed the high unit per package presentations to avoid unnecessary patient visits due to COVID restrictions. The dispensation level was two times higher in Lanzarote than in Fuerteventura All these formulations are indicated for the treatment of moderate to severe intensity pain, especially in older-people since it is prescribed in preference to NSAID drugs because of concerns over complications. In addition, the use of newer additions to the therapeutic arsenal, such as tapentadol or oxycodone plus naloxone were found to have very low consumption rates, whereas in Spain as a whole, the data seems to be suggesting an increase AEMPS, Hider-Mlynarz et al. France ranked third in weak opioid consumption whereas the use of strong opioids in France was among the lowest. The UK had the highest consumption of weak and strong opioids among the six European countries analyzed. The difference in analgesic preferences observed between European countries may reflect the role of national guidelines, prescription policies and the marketing strategies of pharmaceutical companies, which can differ between these countries, but it can also be explained by cultural backgrounds and local traditions in managing chronic pain. The results of the present study should be considered with the following limitations. However, with these data it was possible to reliably analyze the geographical distribution of prescription opioid use. Secondly, the overall picture of prescription opioid use was different for each island and municipalities, even between districts as was the case in Gran Canaria. Two observations can be made at the municipality level: the most ruralized zones are located in the interior areas and far away from urban centers longer access time. In these zones, most municipalities have lower population densities, higher rates of old age, low socio-economic status, geographical isolation with fewer public services. The urban areas are located in coastal areas and the capitals of each island are characterized by the existence of large population concentrations, their income levels are above the island average and they enjoy greater access to public services. Thirdly, the datasets used in this study included dispensing data from community pharmacies under prescription and excluded hospital prescriptions, with the risk of underestimating true opioid use. However, these would mainly concern acute care, managed by primary care physicians and would therefore be captured in our database at some point in time. A similar situation was described by Xie et al. At the municipal level, the annual variation in prescription could be overestimated, although the bias is difficult to quantify since the prescription is associated to pharmacy postal code ZIP where the patient lives but they could get their medication in a pharmacy in another municipality. For this, DDD per inhabitants per day data at island and province level are more accurate since they included all population who live in that zone. The findings here are, in general, consistent with those obtained in other European countries, where a general pattern of growth in opioid consumption has been observed in the two last decades. However, there are some notable variations in the relative levels of consumption between different geographical areas and some distinct, context-specific patterns of use for some drugs. However, there are differences in prescription patterns of weak and strong opioids, as well as in the doses and units per package according to each island. In this respect, Lanzarote and Fuerteventura are characterized by having specialist doctors located in the capital i. The authors believe that this factor plays an important role in determining opioid prescription rates. This type of pattern was also observed in the two smallest islands of the Canary Islands Oliva et al. However, Gran Canaria has two reference hospitals located in the capital where the patients from all over the island are referred depending on where their first residence is and not on their illness. However, other factors such urbanicity level, population age, socioeconomic status do not help to explain the differences in prescription opioid use across rural and urban areas. Our findings call for stronger action to promote best practices in prescription opioids use and to reduce socio-economic and demographic variation between geographical areas. The model proposed by this study could be used for the routine monitoring of the prescription of opioids in order to promote interventions able to reduce the consumption in the islands, especially in Gran Canaria, and is certainly not intended to criticize legitimate medical uses. The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation. AO and SA drafted the first and final version of the manuscript. AO and PG designed the database used in this study. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Front Pharmacol. Find articles by Alexis Oliva. Find articles by Susana Abdala. 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A boat loaded with more than six tons of hashish intercepted south of the Canary Islands
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A transnational criminal organization has been dismantled and five people have been arrested, including the head of an international network who had been on the run for months after evading a police operation carried out by different countries. The network's infrastructure in Spain was led by a major drug trafficker who controlled a logistics network that distributed large quantities of drugs between different European countries. Six raids and searches have been carried out in the provinces of Alicante, Murcia, Las Palmas and Madrid, in which, among other things, more than 35, euros in cash, two boats and a vehicle were seized. In one of the searches carried out, a clandestine laboratory for the design of synthetic drugs was dismantled, which was located in an industrial warehouse in a town in Murcia. August 30, As a result of the operation, a transnational criminal organization has been dismantled and five people have been arrested, including the head of an international network who had been on the run for months after evading a police operation carried out by different countries. The network's infrastructure in Spain was led by a major drug trafficker known for his international links to transport large quantities of drugs between different European countries. Six raids and searches were carried out in the provinces of Alicante, Murcia, Las Palmas and Madrid, resulting in the seizure of, among other items, more than 35, euros in cash, two boats and a vehicle. In one of the searches carried out, a clandestine laboratory for the design of synthetic drugs located in an industrial warehouse in a town in Murcia was dismantled. The investigation was launched in by the Central Narcotics Brigade when the presence of a sailboat docked on the island of Lanzarote was detected, which could be used for a maritime drug trafficking operation. After several investigations, the agents established possible international connections, so the information was shared with international organizations, as well as with other European police units. As a result of this cooperation, the Dutch authorities indicated that there could be a criminal organisation of Dutch origin related to the vessel found in our country. As a result of the investigation, the police discovered that an international criminal organisation based in the Netherlands was using a town in Alicante as its centre of operations. The criminal network's logistics and infrastructure in Spain was led by a major drug trafficker known for his international links, controlling a logistics network capable of transporting large quantities of drugs between different European countries. The members of the organization operated under tight security measures and used a very sophisticated modus operandi, with a high degree of preparation and planning. They travelled in person between different countries to discuss the details of the illicit businesses they were carrying out, which made police work difficult. After several months of monitoring the movements of the network, investigators detected that a boat had been taken to Alicante and that members of the organisation were preparing it to embark on a journey to the Atlantic Ocean. Continuing with the investigation, the investigators carried out six raids and searches in the provinces of Alicante, Murcia, Madrid and Gran Canaria, in which, among other things, more than 35, euros in cash, a multitude of mobile and satellite phones, various documents on boats used by the organisation and a vehicle were seized. During a search of a warehouse in a town in Murcia, officers located and dismantled a clandestine laboratory for the design of synthetic drugs, where they found a large quantity of substances used to make pills and industrial machinery for making and counting the tablets. In addition, a twelve-metre-long inflatable boat was also seized. On the other hand, in one of the searches carried out at the home of one of the detainees in Alicante, the police seized small quantities of tusi pink cocaine , hashish, marijuana and crystal, as well as items for retail distribution. Five people were arrested during the operation, including the leader of an international criminal organisation dedicated to drug trafficking and money laundering, who was on the run from the German authorities and is facing a year prison sentence. Boat loaded with more than six tons of hashish intercepted south of the Canary Islands 88 KB - pdf.
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