Soil acidity is challenging agricultural production in Ethiopia. Above 43% of the farmland is under soil acidity problem and it leads to low crop yields and production losses. Ag-lime is widely considered as an effective remedy for amending soil acidity. This study assesses the current structure of ag-lime value chain and its functionality focusing on central parts of Ethiopia where lime is produced and channeled to acidity affected areas. The study uses Ethiopia as a case study and applies qualitative methods such as key informant interviews and focus group discussions to collect data from different actors in the ag-lime value chain. Key findings indicate that both public and private ag-lime producing factories are operating below their capacity. Due to limited enabling environments, the engagement of private sector in ag-lime value chain is minimal. In addition, farmers have a good awareness of soil acidity problem on their farms, and its causes and mitigation strategies in all regions. However, the adoption of ag-lime by smallholders was minimal. Overall, the current structure of the ag-lime value chain appears fragmented and needs improvement. Addressing soil acidity challenge through efficient ag-lime value chain could narrow lime supply-demand mismatches and increase widespread adoption by farmers to enhance crop productivity and food security in acidity-prone areas of the country. Agricultural transformation in Ethiopia requires the appropriate use of soil resources. About 43% of Ethiopia's agricultural land is affected by soil acidity and 28% is estimated to be strongly acidic with soil pH ranging between 4.1 to 5.5 ; 2021. SSome technologies and practices have been recommended to reclaim soil acidity and upgrade the productivity of strongly acidic soils. These include the cultivation of acid-tolerant plants, covering the surface with non-acidic soil, the use of organic fertilizers, and liming. Among these practices, liming and the application of organic fertilizers appear the best measures, because of their more persistent agronomic effects . Ag-limeThe application of agricultural lime (ag-lime hereafter) is one of the main strategies for reducing soil acidity and increasing crop productivity. Consequently, Ethiopia has initiated an acid soil reclamation strategy that can address different segments along the ag-lime value chain e.g., . The goaImproving the efficiency of the ag-lime value chain requires the active participation of both public and private sector actors. However, there is limited information on the current structure of the ag-lime value chain in Ethiopia. The production, transportation and distribution of lime are not well coordinated in most cases. Therefore, understanding the underlying technological and institutional hurdles surrounding the ag-lime value chain would help provide adequate ag-lime to farmers in time and at a reasonable price. It would also create investment opportunities for the private sector actors and job creation for the public sector along the value chain to spur economic growth in the country.The objective of this study is to analyze the current production, distribution, and utilization of ag-lime in major administrative regions of Ethiopia. The specific objective is to explore the main actors, their roles, and functions as well as opportunities and challenges along the ag-lime value chain for the development of an efficient value chain. Together with other few studies , the stuThe rest of the paper is organized as follows: the next sections present the methodology followed and different qualitative methods used to collect and analyze data. The third section provides a summary of major findings and discussion. The paper concludes with some reflections and policy implications.The study was conducted in four major crop-dominated regional states of the country. These were the Oromia, Amhara, Southern Nations, Nationalities and Peoples (SNNP), and Sidama regional states. These regional states were selected because of two major reasons. First, the state-owned/public ag-lime factories are established in these regions except for the Sidama regional state. These public lime factories are producing, supplying ag-lime, and promoting related improved agricultural practices and knowledge to farmers. Second, there is high coverage of soil acidity in these regions. Small and large-scale lime demonstrations have also been conducted in these regions and encouraging ag-lime use practices have been reported.This study uses Ethiopia as a case study to provide useful information about ag-lime production, distribution, and utilization for acid soil management in the smallholder farming systems. The government of Ethiopia has established ag-lime factories in Oromia, Amhara, and SNNP regional states to increase ag-lime production and supply to enhance crop productivity in areas affected with severe soil acidity. The study also focused on three state-owned (public) lime crushing factories: Guder, Dejen, and Kella lime factories in Oromia, Amhara, and SNNP regional states, respectively. These factories were established to reclaim acidic soil zones in the country. In addition, we assessed a few private lime processing factories (Dashen and Muger cement factories) which have started producing ag-lime. Important information and data were obtained from the Bureau of Agriculture (BoA) and farmers utilizing ag-lime technology in the West Shoa, East Gojjam, and Sidama zones. We also assessed the status of ag-lime awareness and utilization in the study areas. Insights from this ag-lime value chain analysis contribute to the ongoing broader efforts in guiding acid soil management investments in Africa .We reviewed literature and reports related to ag-lime use in Ethiopia. Qualitative research methods were used to collect data from major actors and facilitators of the ag-lime value chain. We used a purposive sampling procedure to select the main stakeholders/actors involved in the ag-lime value chain for data collection . The maiThe qualitative data were recorded in handwritten notes and immediately transcribed or typed into the computer for further content and thematic analysis. The qualitative data collected from various actors in the ag-lime value chain was categorized and organized using a spreadsheet. The information was then organized within each research question according to a predetermined theme or category. This helped to document relevant information and spot issues that are frequently raised by the various actors in the value chain. Text information was also thoroughly analyzed using both content and thematic analysis to pinpoint certain themes and emergent patterns. We narrated the information following the themes created to generate the report. Finally, we identified the voices of the various actors in the value chain to enrich the dynamics, validity, and reliability of findings .We estimated costs and margins of ag-lime business along the production and distribution nodes of the value chain starting from core-limestone suppliers to distributors. The cost information was gathered from major actors including core-limestone suppliers, ag-lime factories, transporters, and distributors. Furthermore, we assessed farmers’ cost of production at the Gozamen district in the East Gojjam zone using key informant interviews. We also analyzed the effect of ag-lime adoption on the yield and revenue of farmers in the selected district. The average wheat yield (productivity) was sourced from Gozamen district BoA. Data related to wheat productivity of land treated with lime was collected from the key informant farmers in the district. Wheat was considered for the analysis because of its dominance in the study areas.We summarized the main results using figures, tables, and charts. Ag-lime production, distribution and utilization trends were also shown. Descriptive statistics were used to summarize the ag-lime cost of production and gross margins along the value chain. We present the major findings and discussions in subsequent sections.According to farmers, soil acidity and fertility challenges were previously treated using local soil management practices such as fallowing cropland to improve the productivity of their land. However, the practice of fallowing cropland has limited prospect because of land scarcity and unsustainability to address the problem of soil acidity in the long-term .'sinar' and plant eucalyptus trees on non-responsive farmlands because of severe soil acidity. These crops are considered tolerant to soil acidity. Farmers are also aware that the severity of soil acidity affects even the growing period of eucalyptus trees. Concerning this, a key informant farmer from the Oromia region said:"The severity of soil acidity is increasing from time to time in our area. Our land is becoming out of production, and we are changing annual crops into eucalyptus trees. Even the harvesting time of eucalyptus trees are affected by the problem. Moderately acidic soil takes four years and highly acidic soil takes six years for harvesting even the eucalyptus trees planted on these fields”.Our qualitative results indicate that farmers are aware of soil acidity problems and mitigation strategies. Farmers learn about soil acidity from development agents (DA) and researchers. Tailored training on soil acidity was also provided to some farmers and then passed to fellow farmers. Farmers can also detect soil acidity on their land through poor crop growth, and low productivity even if inorganic fertilizer is applied. Complete crop failures due to soil acidity are also observed by farmers. Farmers perceive soil erosion and over-plowing (continuous cropping without leaving crop residues) as the main causes of soil acidity. Different soil acidity mitigation strategies are also used by farmers as reflected during the focus group discussion. These include the use of compost and manure, crop rotation with legumes and ag-lime application. Farmers produce wild oats locally known as During the FGD, farmers at Amhara region indicated low use of lime technology due to different reasons. Amongst, high price of ag-lime and cost of application were the major ones. They added, initially, government and non-government organizations introduced the ag-lime technology free of charge for popularization purpose. However, currently farmers have stated that they are paying huge amounts of money to get lime needed for their land. They confirmed that there is access to a credit service for ag-lime, despite the high interest rate. The lack of small innovative farm implements to apply lime is also a constraint for the adoption of lime technologies, added the farmers.“Transportation from the distribution center to home and to farmland costs us money. This additional cost of ag-lime purchase, interest rate, transportation, and application cost inflates our cost of production and reduces our profit margin since the price of grain we sell is not increasing accordingly. Due to this, some farmers used to plant eucalyptus trees on their land which is crop and land damaging harmful tree. This could create conflict between neighborhood farmers who have adjacent farmlands”.A key informant farmer from the Amhara region also shared the points raised during the FGD. He said,kebeles.Regarding the intensity of soil acidity, the key informant farmers perceive that 60–75% of land in their village is affected by soil acidity. Yet, few farmers 10–15%) use ag-lime to reclaim their land in their respective 0–15% useFarmers in the Oromia region sow barley, wheat, and teff on lime-treated lands. Farmers in the Sidama region sow barley, wheat, potato, and beans. The choice of these crops depends on their importance to food security or cash as well as advice by DAs. Farmers perceive that ag-lime alone could not increase much crop yield unless it is complemented by other inputs such as improved seed, fertilizers, and proper land preparation. This farmers’ perception is consistent with recent studies recommending targeted lime application as part of a greater policy of integrated soil fertility management that includes fertilizer and farm management strategies .kebeles. Farmers do not apply ag-lime on rented-in land because of uncertainty to use the rented-in land for subsequent seasons when the soil acidity is reduced. Farmers suggest timely supply of lime, access to spreading machines, credit, and subsidies for a widespread use of ag-lime. These support services have also been noted and suggested by different studies , labor-intensive nature of the lime application, untimely (late) supply of lime, and low supply to remote  studies .Ag-lime is produced by both private- and public-owned lime processing plants. However, both the public and private ag-lime processing factories are operating below their potential capacity . GovernmLack of autonomy on financial management and key decisions by the government-owned lime crushers were reported by the public lime factory managers as a major cause for low amount of production even when there is some level of demand. Guder, Dejen, and Kella lime factories were established by the government of Ethiopia to support ag-lime supply for the acid soil treatment initiatives. According to the lime factory managers, these factories get their operational budget from the respective District Finance Offices they are in, and any income generated from the lime sale also goes to the same offices. Any procurement decisions (including spare parts for machinery maintenance) are passed through the government offices. Managers of these factories indicated the inefficiency created especially where there is any maintenance problem during the peak lime processing seasons . We also observe that storage problems for produced ag-lime and electric power interruptions to be critical in all the public lime factories.The private lime factory managers indicated that private lime processors need a guaranteed product market and yet are not ready to take any risk in lime marketing. As the market for ag-lime is not yet well developed, the private lime processors are reserved from taking any marketing risks and stick to the contract agreement they have with the regional governments for the quantity of agricultural lime they produce. We noted that these private factories are not taking any costs in promoting and marketing ag-lime. They just respond to the regional governments’ procurement plan and produce what is agreed upon between them. That could be one of the critical reasons for the disparity between their maximum annual production capacity and their actual production in a season.Overall, our results indicate that the lime crushing plants we visited are producing much less than their potential capacity because of limited demand, lack of storage capacity, power supply shortage, etc. Our key findings corroborate with the view that effective policies are required to incorporate effective incentive mechanisms  for incrThe regional and zonal level agricultural extension experts we interviewed indicate that several extension methods are used to popularize ag-lime technologies in Ethiopia. This is expected to create demand for ag-lime by farmers. For example, the MoA Soil Resources Development Desk provides training of trainers (ToT) to regional states once a year on the management of acid soils. Furthermore, the Directorate uses public media for transmitting tailored programs regarding acid soil management and the ag-lime technology. In all regions, the major popularization methods were large-and small-scale demonstrations, field days, public media, leaflets, cluster farming and training on soil acidity and its management strategies including liming as reflected by the key informant agricultural extension experts.We noted that these ag-lime technology popularization efforts are done by a range of stakeholders including research institutes, Bureaus of Agriculture (BoAs), and NGOs particularly, the Germen Technical Cooperation (GIZ). The Ethiopian Institute of Agricultural Research (EIAR) also promotes ag-lime through small-scale and large-scale demonstrations, field-days, training, and cluster-farming. Different electronic media are also used for the extension of ag-lime technologies to farmers. NGOs such as GIZ also support the demonstration of lime technologies to farmers and popularize ag-lime through field days, mass media, farmers' field schools, posters, and pamphlets. Different radio and TV programs, news and documentaries have been transmitted regarding the use of ag-lime in collaboration with the BoA. Despite these efforts, lack of demand is the major limiting factor contributing to the low adoption of ag-lime in the country, said the experts. In addition, for smallholder farmers, lime is a new and unusual production input that was not common before some years. Farmers were struggling to even use the commonly known production inputs such as improved seeds and fertilizers. Unlike fertilizer and seed, the volume of ag-lime needed per unit of area is quite huge which makes the purchase and transportation difficult. Due to such reasons, convincing farmers to purchase ag-lime is a difficult process, added the experts.An expert at GIZ working on acid soil management remarked that farmers’ dependency is the major constraint towards the low adoption of lime technology in the country. Research and development partners popularize any technology for free on fields of few farmers to supplement effective extension. Then, government extension takes the lead to scale out the technology for the masses. Farmers must be aware of this as there is ‘no free lunch’, added the expert.Mass popularization is not the case for all regions. Unlike in the Amhara and Oromia regions where lime technology is widely popularized, lack of lime popularization was raised as the main constraint in the Sidama region. For instance, the manager of Elto Union stated that the Union faced 40% carryover which was due to low demand for ag-lime. They were ordered by BoA to supply ag-lime but the demand was low due to limited popularization and mobilization done in the Sidama zone by the relevant stakeholders. The carryover increases the cost of storage and could further inflate the price of lime. In addition, access to credit was a problem in the region as stated by the manager.We stress that consolidated efforts in ag-lime popularization are also vital in future through the integration of key actors in the value chain to enhance this sluggish demand. This is because the benefits from the investments of lime are not always clear (or immediate) to resource-poor farmers as it takes few years for the benefits to accrue, and yet the awareness campaigns and extension services have not been able to materialize this notion. For example, Lime transportation and distribution are critical at the mid-stream node of the value chain. Different supply chain modalities were found in the regional states covered under this study. In the Amhara Region, the main lime supplier is the private lime factory (70%) and the public supply accounts for 30% . Though However, in Oromia Region, the regional government is fully subsidizing the production and distribution of lime where farmers get lime free of charge through the district BoA. The public sector supplies 85% of the lime while the private sector accounts for only 15% . The BoA2We observe that free handing of lime could help for promotional purposes and awareness creation among farmers operating on acid soils. However, prolonged free handing could discourage lime business development by deterring the involvement of the private sector. It appears that the current ag-lime value chain is quite traditional. We find that the ag-lime value chain in all public crushing sites is highly fragmented with short actor chains. This result was consistent with Nevertheless, there is a gradual increase in the number of farmers applying lime on their farms, the quantity of lime used, and land area treated by lime each year in the major study areas . The majThe production activity of ag-lime in our factory is throughout the year. However, demand is limited to a few months ranging from April to June. Thus, our warehouse is filled with the product, and we store it in open areas outside the warehouses as lime is bulky and needs a huge space for storage. Failing to distribute on time caused lime produced to be damaged by rain. We stopped some machines from working to reduce the production volume due to a lack of demand, low capacity of warehouses, and untimely distribution”.“According to the government owned ag-lime factory managers, the poor distribution system has also challenged the production volume of ag-lime in Ethiopia. Distribution is ordered from the Regional Bureau of Agriculture and quota based for zones and districts. They should go to Addis Ababa and Bahirdar  to come with a letter of permission to purchase the lime, the managers added. This long process for distribution discourages the demand and increases the time of storage in the factory's warehouses. For instance, the manager of Guder ag-lime factory from Oromia region stated that timely distribution is one of the major problems to expand ag-lime production. He explained the problem as follows.In summary, we emphasize the importance of exploiting the strengths/opportunities and addressing the weaknesses in the ag-lime current distribution process to narrow the supply-demand disparities. Encouraging the private sector  through targeted incentives could create trust gradually and sustain the ag-lime distribution and marketing system. In the future, we expect that granular forms of ag-lime  could alWe observed that several organizations and institutions support the ag-lime value chain in the country. These organizations empower and facilitate the value chain so that farmers would have an adequate and sustainable supply of lime at a reasonable price. The main actors include the national ag-lime technology extension by the Ministry of Agriculture (MoA) and BoAs, research institutions, NGOs, cooperative unions, and the Ministry of Mines (MoM). We briefly describe the main actors and their current roles.kebeles despite differences in implementing capacities. In all regions, we learnt from the key informant agricultural extension experts that the management of acid soils was given high priority in the extension system, and they have allocated soil fertility experts in their respective zones and woredas. Soil acidity reclamation has been included in the annual training programs for farmers, DAs, and experts. NGOs such as GIZ and the Sustainable Land Management (SLM) program support these trainings. The DAs and model farmers also deliver the training to fellow farmers in their respective kebeles. According to the key informant agricultural experts, special emphasis was given to acid soil management in different soil fertility management training because of its significant effect on crop production and productivity to enhance the food security of the country.The national ag-lime technology extension is mainly done by the Ministry of Agriculture (MoA) and the BoAs in the major regional states. The MoA also prepares and distributes different manuals, pamphlets, and leaflets for regions which help build the capacity of experts and DAs. Continuous follow-ups, monitoring, and evaluations of implemented demonstration activities were also the major activities of the ministry as reflected by the key informant agricultural experts. The ministry also uses stakeholder platforms for ag-lime distribution and dissemination. The BoAs in Oromia, Amhara, SNNP and Sidama regions also undertake the ag-lime extension in their respective zones, woredas and We also noted that research institutions contribute to the development of the ag-lime value chain. The main contributions include the generation and popularization of ag-lime technologies, building the capacity of experts, DAs, and farmers, and soil acidity testing services.10.13039/100004421World Bank.NGOs support the ag-lime value chain in major acid-soil prone regions of the country. They support the BoAs through training, providing pH meters, supplying ag-lime, ag-lime crushing machines and other physical capacity building efforts. The main NGOs and projects working on acid soil management efforts include GIZ, the Alliance for a Green Revolution in Africa (AGRA), and Agricultural Growth Program (AGP) supported by the Robi Berga Union in Oromia, Elto Farmers’ Union in Sidama and Gozamen Farmers’ Union in the Amhara region. We observed that these Unions and associated primary cooperatives had experience in the distribution of inorganic fertilizers and could also handle the distribution of ag-lime. However, ag-lime demand should be created for farmers and cash liquidity constraints are addressed for well-functioning of the distribution process. With its current bulky nature, an average of 20 quintals (Qt)We noted that the cooperatives and unions are just beginning to engage in the ag-lime value chain. In general, the cooperative and unions provide little marketing and supply of ag-lime to farmers. Nonetheless, we observed the significant role of cooperatives and unions in the transportation and distribution of ag-lime. These include Ministry of Mines (MoM) provides licenses for mining industries based on different criteria and documents. Several mining companies produce non-ag-lime but are now interested in producing ag-lime if there is a substantial demand as noted by key informants from the MoM (Table A.1). For instance, Homa Construction PLC, and Derba Lime and Chemical PLC showed a great interest in producing ag-lime if there is effective demand from the government in large quantities and quality. Therefore, we note that these mining companies offer good opportunities for ag-lime supply in the country. We argue that engaging them in the ag-lime value chain would be crucial through a well-coordinated stakeholders’ platform.kebeles, and lime quality testing services for lime producing industries. National soil laboratory of Ethiopia usually tests the quality of lime produced at the ag-lime-producing factories. Soil laboratory services are provided by the national soil laboratory, regional soil laboratories and research centers’ soil laboratories. Calcium carbonate (CaCO3) equivalence is the major chemical attribute observed by the laboratory tests. The national soil laboratory sometimes suggests that the factories should not use deposits of certain locations if calcium carbonate equivalence is low at that specific location.Different soil laboratories at national and regional levels provide soil sample testing for woredas and kebeles in testing the acidity level of the soil sample for free. The samples were sent to the laboratories through the woredas, and the results would be sent back to the woredas immediately. Delayed laboratory results were the major challenge raised by woredas during this assessment. In addition, research centers of EIAR provide soil test services for woredas and kebeles. For instance, Holetta Agricultural Research Center (HARC) provides soil test services for 2–4 zones and 2–5 woredas annually. In 2018/2019, the center tested 320 soil samples for different acid soil prone zones and woredas. Frequently, service receiving zones include West Shoa, North Shoa (Oromia), and Finfinnee Special zone. Due to the limited capacity of soil laboratories and increasing demand for soil test results, delays of soil test results were encountered in most of the study areas according to a key informant from the research institute. Additional soil laboratories, at least in each of the zones, are important in addition to capacitating the existing soil laboratories. Soil testing is crucial for a targeted application of ag-lime and to avoid blanket use that has huge cost implications.Several public-owned regional soil laboratories serve woredas and 3) of limestone for 47 ETB or 5.5 ETB/Qt of limestone. According to the suppliers, 40% of the gross income goes to costs such as fuel, machines, and renting trucks.We present the costs and margins across each actor along the ag-lime supply chain. The major actors include core-limestone suppliers, ag-lime factories, transporters, and distributors. Most of the ag-lime factories supply core-limestone by themselves except the Kella ag-lime factory. The estimates of the cost of core-limestone supply is based on the information gathered from the Kella lime factory. The private core-limestone supplier won the bid to supply one cubic meter  is 23 ETB/Qt, and the unloading cost was 10 ETB/Qt. The rest, i.e., 27 ETB/Qt is the net margin of the transporters. Thus, the average margin of transporters in all regions was 42 ETB/Qt. The cost of transportation is calculated based on distances in kilometers ag-lime is moved. In the Oromia region, the transportation cost was 0.55–0.75 ETB/Qt/km and Elto Union serves at 0.30 ETB/Qt/km for the kebeles in the Sidama region. We used the average transportation costs to kebeles at 42 ETB/Qt for the gross margin calculation.The costs of transporters include the truck rental cost, fuel, and unloading cost. In Oromia, SNNP, and Sidama regions, the average transport cost of ag-lime to Primary and secondary distributors operate in the ag-lime supply chain. The primary distributors are mainly BoAs and unions. They obtain lime from ag-lime factories or NGOs and distribute it to primary cooperatives . However, BoAs sometimes distribute by themselves in some regions such as in the Oromia region. Moreover, they purchase lime for 200 ETB/Qt in Oromia, spend 10 ETB/Qt for unloading and get a margin of 20 ETB/Qt. In the Amhara region, the unions purchase at 280 ETB/Qt and sell at 300 ETB/Qt with a margin of 20 ETB/Qt. The transport cost, loading and unloading costs are covered by transporters.The final distributors are mainly primary cooperatives that receive ag-lime from primary distributors such as BoAs and/or cooperative unions. They get the lime for 300 ETB/Qt and sell it to farmers at 320 ETB/Qt. The difference of 20 ETB/Qt is the commission or margin they collect for the distribution of lime. This implies that the final distributors have no cost incurred to ag-lime storage.kebele. On average, it costs 46,230 ETB to produce wheat on a hectare of land. The cost of ag-lime purchase, transportation from cooperatives to home, ag-lime application, and mixing costs are new costs due to soil acidity which is estimated to be 2860 ETB. The average quantity of ag-lime applied for a hectare of land in the area is 20 Qt. A split application of ag-lime is used in the region for four years.We present the costs of ag-lime for wheat production in the study area . Wheat wThe largest share of farmers' wheat production costs goes to labor (40%) followed by fertilizer (21%) and seed (20%). With split ag-lime application method, lime-related costs are estimated to be 6% which is a new cost for farmers because of the increasing soil acidity . HoweverA total of 138.35 ETB/Qt gross margin was gained from core-limestone suppliers to final ag-lime distributors. The largest share of gross margin goes to ag-lime factories which was 36.7% (50.8 ETB/Qt) followed by transporters (31.9% or 44.25 ETB/Qt). Both primary and final distributors of ag-lime gain a margin of 20 ETB/Qt or 14.5% of the total gross margin generated in the value chain. Core-limestone suppliers gain 2.4% of the gross margin (3.3 ETB/Qt) . The proFarmers in the study area predominantly grow wheat on lime-treated plots. Accordingly, the yield of wheat for ag-lime user farmers was 12.5% more than the wheat yield of non-users. Our finding is consistent with result of The objective of this study was to analyze the ag-lime value chain in Ethiopia around three major lime factory sites: Guder, Dejen, and Kella. We collected data from different stakeholders to examine how the current ag-lime value chain is structured, integrated, and functioned. Ag-lime is produced both by public and privately owned factories in the country. However, BoAs are not well handling the public lime factories to the expected levels. Consequently, there is underproduction of ag-lime and not utilizing what is produced due to poor planning and distribution process. These problems appear to be managed in the private lime factories although these still need support to exploit their maximum production capacity. Muger cement factory and private Dashen ag-lime factory have huge potential to produce required quantities due to their ample core-limestone deposit. However, these factories are also producing below 3% of their capacity due to low ag-lime demand. Thus, increasing the production capacity of public lime factories would be crucial. Engaging private cement factories in the ag-lime production could also significantly enhance widespread lime supply in the country.The structure of the value chains around the three public factory sites is quite different. The ag-lime value chain in Amhara appears well developed compared to the other regions. Likewise, the adoption of ag-lime is better in Amhara region than in other regions. This is because farmers in the Amhara region have started to buy lime through credit or cash depending on their capacities. Conversely, farmers in other regions are still freely getting limited quantities of ag-lime.Government extension, research, NGOs, universities, and cooperatives are among the key enabling institutions involved in the popularization and distribution of ag-lime. These institutions offer training, build physical capacity, conduct soil acidity tests, and provide free lime for demonstrations. Cooperative unions especially in Amhara and Sidama regions also support the ag-lime value chain in transporting and distributing ag-lime to users. However, there is no strong integration among the actors and often each actor attempts to address the problem alone. There is no joint planning and implementation to address the soil acidity problems in a well-coordinated and integrated manner. Therefore, improving the interaction, linkages, and networking among main actors in the value chain would be crucial. This requires creating and managing a well-coordinated ag-lime stakeholders’ platform to address the supply and demand challenges simultaneously.Ag-lime technology demonstrations and farmers’ advisory services are still needed. In some areas, farmers' awareness about the benefit of lime is quite low due to limited popularization work done so far. This calls for intensive awareness creation both for local agricultural experts and farmers through a tailored approach. It is also better to involve farmers in participatory ag-lime demonstration and field experience sharing. The participation of farmers in field days and on-farm demonstrations would create more awareness on the benefits of lime and enhance widespread ag-lime utilization in acid-soil prone areas.kebele level for acid-soil prone areas. In the future, granular forms of lime could help reduce the distribution and application hurdles.Farmers in the Amhara region reported that lime is expensive, and they are getting it only through purchase in cash. In this regard, it is important to actively involve and capacitate cooperative unions in the lime value chain through credit arrangements. It would also be important to build cooperatives’ capacity to enhance the lime transportation and distribution to farmers. Currently, the role of cooperatives in the ag-lime value chain is very limited, especially in Oromia and SNNP regions. Ag-lime distribution should be started like fertilizers at the Last-mile lime distribution is another challenge farmers are facing in lime use. Lime is bulky and competes with agricultural labor during peak periods such as planting. It also burdens women and children who mainly participate in the last-mile transportation and application of lime on farm plots. In reducing drudgery in the application of lime, it is also essential to improve farmers’ access to small farm implements and machinery that can save labor.Strong planning is required in the ag-lime value chain. Public ag-lime factories are challenged by a shortage of stores and limited warehouse capacity. BoAs often distribute ag-lime for farmers close to the planting season  and negatively affecting crop production. Thus, timely distribution of ag-lime is crucial. The current planning process is quite weak.Farmers should be encouraged to use ag-lime in combination with inorganic fertilizers and soil-water conservation practices such as manure and compost application, and the retention of crop residues. It should be noted that the application of ag-lime alone would not increase much production unless complemented with fertilizers and soil-water conservation measures. This is because once the lime is applied to the field, its residual effect could stay longer period especially if the plot is not exposed to erosion. We recommend policymakers to pursue a bundle of strategies promoting ag-lime and related technologies as also argued by other studies  through The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Therapeutic interchange (TI) interventions are commonly used to manage pharmacy benefit costs. While several studies have considered the effect that TI interventions have on drug costs, most have not considered the effect they have on medical management costs. The purpose of the present study was to assess drug cost and drug therapy management costs of a TI intervention following a change in the drug formulary for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) drugs, including the conversion of atorvastatin from formulary to nonformulary status.A retrospective, quasi-experimental within-subjects design was used in this study. Administrative claims data were obtained from a select northeastern segment of a multistate Medicaid managed care organization (MCO). To be included in the study, patients had to meet the following criteria: (1) they must have had a minimum of 3 atorvastatin prescriptions during a 6-month enrollment phase, (2) they must have been continuously enrolled throughout the 900-day study period, and (3) they must have switched from atorvastatin to another statin between April 1, 2003, and July 31, 2003. The day of the switch from atorvastatin marked for each patient the end of the 12-month pre-TI period and the beginning of the 12-month post-TI period. Two separate dependent variables were developed: (1) statin drug costs (statin cost + dispensing fee) and (2) the costs paid by the MCO for the medical management of statin therapy, including office visit costs and the medical laboratory costs of measuring lipids and creatine kinase, and of checking liver functions. To estimate expenditures over 24 months, a panel analytic technique was used that allows each patient to serve as his or her own control. Multivariate models were used to assess the effects of the TI policy while controlling for age, gender, adjunctive dyslipidemia therapy, comorbidity, presence of a prior coronary artery event, statin compliance, cardiologist management, and disease severity.Of the 3,636 patients who met the study inclusion criteria and were converted from atorvastatin to an alternate statin drug, 129 patients (3.5%) switched back to atorvastatin following the TI. The average statin cost per claim in the 12-month post-TI period was $70.93, 9.5% less than the average cost in the 12-month pre-TI period ($78.40). The average cost per patient per year (PPPY) for statin laboratory tests  increased by 31.5% to $16.15 in the post-TI period compared with $12.28 PPPY in the pre-TI period, and medical office visit costs increased by 44.9% to $20.70 PPPY in the post-TI period compared with $14.29 PPPY in the preperiod. These increased costs related to the medical management of statin therapy were overwhelmed by an 11.7% reduction in statin drug costs, from $793.69 PPPY in the pre-TI period to $701.01 PPPY in the post-TI period, resulting in a net 10.0% reduction for combined statin costs and related medical costs, from $820.27 PPPY in the pre-TI period to $737.87 in the post-TI period. After limiting the analysis to patients who did not convert from atorvastatin to pravastatin (which cost more than atorvastatin before the rebate) and controlling for the influence of potential confounders, statin expenditure decreased by 33% (P less than 0.001). Multivariate models indicated no statistically significant differences in the costs related to the medical management of statin therapy after the TI compared with before the TI.Total costs for medical management of dyslipidemia with statin therapy decreased following implementation of the TI intervention for atorvastatin users. An 11.7% savings in statin drug cost, before consideration of manufacturer rebate revenues, became a net savings of 10.0% after inclusion of the medical costs associated with laboratory tests and physician office visits.


Monkeypox, a viral zoonotic ailment originating in the Central and West African regions, has escalated into a global health issue of growing concern. The current analysis offers an exhaustive examination of monkeypox, emphasizing its historical progression, etiology, epidemiological patterns, pathophysiological mechanisms, clinical manifestations, diagnostic methodologies, treatment modalities, and preventive strategies. The worldwide discontinuation of smallpox vaccination has contributed to an increased incidence of monkeypox, driven by the expansion of vulnerable host populations. Significant strides in diagnostic procedures, prospective antiviral treatments, and vaccine development exhibit potential in managing this affliction, yet obstacles remain in terms of disease control, prevention, and treatment. Additionally, the international propagation of monkeypox underscores the need for robust public health initiatives and the significant role played by global health institutions in disease containment. Prospective research endeavors should strive to enhance our comprehension of the natural reservoirs of monkeypox and its transmission dynamics, evaluate sustained immune responses to novel vaccines, and investigate the potential impact of One Health strategies. This analysis underscores the pressing necessity for increased research and synchronized global efforts to tackle this emergent infectious malady. Monkeypox, a viral zoonotic ailment, is emerging as a mounting concern for global health . Its rooMonkeypox is the product of the monkeypox virus, part of the orthopoxvirus genus, which also includes variola virus , vaccinia virus , and cowpox virus . The disThe successful global eradication of smallpox in 1980 and the subsequent termination of routine smallpox vaccination have led to a growing pool of unvaccinated individuals, thus paving the way for a susceptible host reservoir for the monkeypox virus . Over thThis review is designed to offer a thorough examination of monkeypox as an escalating threat to global health. We aim to dissect various aspects of the disease, encompassing its history, etiology, epidemiology, pathophysiology, clinical manifestations, diagnostic procedures, treatment options, and preventive measures. Additionally, we will address the ongoing challenges and debates concerning monkeypox management and highlight recent advancements and future outlooks in research. Through this review, our objective is to enlighten and instruct clinicians, researchers, and policymakers about the escalating peril of monkeypox and the necessity for robust public health interventions to curb its proliferation .Disease overviewHistorical Account and Discovery of MonkeypoxThe term "monkeypox" was first coined in 1958 following outbreaks of a disease resembling pox among monkeys housed in research laboratories in Denmark and the United States . These iThe first recorded case of monkeypox in humans was reported in 1970 in the Democratic Republic of Congo during a heightened campaign to eliminate smallpox . ClinicaEtiology and Taxonomic Classification of Monkeypox VirusPoxviridae family [The monkeypox virus is a member of the orthopoxvirus genus, which falls under the broader e family . This gee family . It's imCharacteristically, like its counterparts in the poxvirus group, the monkeypox virus possesses a large and intricate structure, containing a linear, double-stranded DNA genome . DemonstFurthermore, the monkeypox virus is divided into two main clades: West African and Central African. These clades exhibit variances in their virulence levels when infecting humans. Notably, infections stemming from the Central African clade tend to result in more severe manifestations of the disease .EpidemiologyPrevalence and Geographic DistributionMonkeypox is primarily observed in remote regions of Central and West Africa, in proximity to tropical rainforests . A surgeBeyond Africa, occasional instances of monkeypox have been noted globally, attesting to the disease's potential for worldwide dispersion. For example, the United States witnessed a monkeypox outbreak in 2003, traced back to imported pet rodents from Ghana . More reModes of TransmissionThe monkeypox virus primarily spreads to humans when they are bitten by an infected animal or come into direct contact with the animal's blood, bodily fluids, or open sores . NotablyAdditionally, the virus can be transmitted from one human to another. This human-to-human transmission typically occurs when an individual is in close proximity to or directly touches the skin lesions or bodily fluids of an infected person. Moreover, the virus can propagate via respiratory droplets, especially during prolonged face-to-face interactions or close contact with an infected individual, often within household settings .Risk FactorsSeveral risk factors can increase the likelihood of contracting monkeypox. Foremost among these is close contact with animals or humans who are infected . In certPathophysiologyMechanisms of DiseaseOnce the monkeypox virus enters the body, it primarily invades the regional lymph nodes, where it begins to replicate . FollowiThe second phase, or secondary viremia, specifically targets certain cells within the body, including skin cells. This leads to the characteristic rash and pox lesions that are associated with monkeypox . ApproxiIt's important to highlight that the monkeypox virus has developed mechanisms to evade the host's immune response. This evasion allows the virus to continue its replication and systemic spread within the host body .Progression of Disease and StagesMonkeypox is a viral disease whose clinical progression can be understood through three distinct phases: the invasion phase, the eruptive phase, and the convalescent phase .The invasion phase, which typically lasts between 1 to 3 days, marks the onset of the disease. During this period, affected individuals often experience a range of symptoms. Fever, headache, muscle pain, backache, and swollen lymph nodes are common, often accompanied by chills and a general sense of fatigue. These initial symptoms serve as the body's immediate response to the viral invasion and can be quite debilitating for the patient .Following the invasion phase, patients enter the eruptive phase. This is most notably characterized by the emergence of a distinctive rash. Initially appearing on the face, this rash gradually spreads to other parts of the body. As the days progress, these skin lesions undergo a series of transformations. They begin as flat spots, or macules, which then elevate into papules. These papules subsequently fill with fluid, becoming vesicles, and later turn into pustules. Over time, these pustules dry out, forming crusts or scabs. The entire process, from the appearance of macules to the formation of scabs, provides a visual representation of the body's battle against the Monkeypox virus .The final stage in the clinical progression of monkeypox is the convalescent phase. This phase signifies the body's recovery from the illness. It begins as the crusts from the lesions start to fall off and can extend for several weeks. While the body's natural defenses typically manage to overcome the virus, making the disease self-limiting, complications can arise. Individuals with compromised immune systems are especially at risk. For these individuals, monkeypox can escalate in severity and, in rare cases, can even prove lethal .Clinical manifestationsClinical CharacteristicsThe clinical presentation of monkeypox bears similarities to, but is generally less severe than, smallpox. Following an incubation period of 7-14 days, the disease onset is marked by fever, headache, myalgia, backache, lymphadenopathy, chills, and fatigue . SubsequThe monkeypox rash transitions through various stages: macules, papules, vesicles, pustules, and, ultimately, crusts or scabs . Unlike ComplicationsMonkeypox can cause complications, some severe and long-lasting. These include secondary bacterial infections from compromised skin due to pox lesions and life-threatening pneumonia. Sepsis, a systemic reaction to infection, can lead to organ failure and death. Additionally, monkeypox may cause encephalitis, leading to neurological problems or death.Ocular infections are particularly concerning as they can lead to vision loss. The eyes can become infected either directly by the virus or secondarily by bacteria, leading to complications that can impair vision .Individuals with weakened immune systems are at a heightened risk of developing these complications. For them, monkeypox can be especially severe and can even result in fatal outcomes .Furthermore, even after recovery from the acute phase of the disease, patients are not entirely free from its effects. The pox lesions, which are a hallmark of the disease, can leave behind significant scarring. This scarring can be particularly pronounced if the lesions become superinfected with bacteria, leading to deeper and more extensive tissue damage .Diagnostic techniquesConventional Diagnostic MethodsHistorically, the diagnosis of monkeypox has been predicated on clinical manifestations, patient history, and epidemiological context, including any known exposure to reservoir species or human cases . LaboratAdvancements in Diagnostic TechniquesThe advent of advanced molecular methodologies has profoundly revolutionized the diagnostic landscape for monkeypox. Techniques such as the polymerase chain reaction (PCR) have emerged as pivotal tools, enabling rapid and precise identification of the disease, even in its nascent stages of infection . NotablyFurthermore, the integration of next-generation sequencing techniques offers a comprehensive insight into the entire genomic structure of the virus. Such in-depth genomic analyses are invaluable, especially during outbreaks, as they facilitate the accurate tracing of the infection source. Moreover, they provide a deeper understanding of the evolutionary trajectory and genetic variations of the monkeypox virus .Treatment and management strategiesContemporary Treatment ModalitiesThe mainstay of treatment for monkeypox primarily encompasses supportive care aimed at symptom alleviation and complication management. This could entail the use of antipyretics to combat fever, analgesics for pain mitigation, and fluids to maintain optimal hydration .Several antiviral drugs, such as cidofovir and its lipid conjugate, brincidofovir, have demonstrated activity against the monkeypox virus in in-vitro conditions and animal models . HoweverFor the containment of outbreaks, smallpox vaccine, antiviral drugs, and vaccinia immune globulin can be deployed. The smallpox vaccine has been shown to ameliorate the severity of or even thwart the disease if administered before or shortly after exposure to the virus .Constraints of Existing Treatment ApproachesDespite these available options, the treatment of monkeypox is beset with significant limitations. Firstly, there is an absence of a specific antiviral treatment approved for monkeypox, which implies that care is predominantly supportive .Moreover, although the smallpox vaccine can offer cross-protection against monkeypox, its application is curtailed due to potential side effects and contraindications in specific population groups such as individuals with eczema, pregnant women, and those with compromised immunity . Lastly,Measures for prevention and managementImmunizationThe smallpox vaccine, despite the cessation of its routine administration following the eradication of smallpox, has demonstrated effectiveness in offering cross-protection against monkeypox. It continues to be employed in particular scenarios, such as in protecting healthcare workers exposed to the disease at work and during monkeypox outbreaks to curtail further transmission .Despite the potentially severe side effects of the smallpox vaccine, efforts are underway to develop and test a new generation of vaccines that are safer and induce fewer reactions. These could be especially beneficial in managing Monkeypox .Healthcare Policies and ActionsCrucial to the control of monkeypox's spread are public health interventions, which comprise swift detection and isolation of cases, contact tracing, surveillance, and educating the public about risk factors and preventive strategies .In regions where monkeypox is prevalent, attempts should be made to avoid direct interaction with wildlife, particularly with ill or deceased animals, and to ensure all meat is fully cooked before eating . In areaCurrent challenges and controversiesComplications in Disease Management and PreventionManaging and preventing monkeypox pose several hurdles. Notably, there are restricted resources for monitoring and responding to the disease, especially in remote regions of Central and West Africa, where the virus is most common .The limited comprehension of the carrier species and specific transmission methods of the monkeypox virus in natural settings complicates the development and application of focused preventive measures .Additionally, the discontinuation of smallpox vaccination has resulted in a growing pool of unvaccinated individuals, hence increasing the susceptible population. The administration of the smallpox vaccine for monkeypox prevention is a contentious issue due to its potential adverse effects and the ethical questions raised by using a vaccine meant for a disease that has been eradicated .Challenges in DiagnosisCorrectly diagnosing monkeypox presents significant challenges. Its clinical resemblance to other infectious illnesses, such as chickenpox and even smallpox, can lead to incorrect diagnoses .While molecular techniques have significantly enhanced diagnostic precision, these technologies' limited availability in monkeypox-endemic areas reduces their practicality . MoreoveControversies Surrounding TreatmentAs of now, no specific antiviral treatment for monkeypox has been approved. The usage of antiviral medications such as cidofovir and brincidofovir is not widespread due to their adverse effects and the absence of large-scale clinical trials proving their effectiveness in humans .Recent developments and future perspectivesInnovations in Vaccine DevelopmentIn response to the potential threats posed by monkeypox, substantial progress has been achieved in creating safer, less reactogenic vaccines. One such promising candidate is the modified vaccinia Ankara (MVA). MVA is a considerably attenuated variant of the vaccinia virus that can't replicate in human cells, rendering it safer for people with compromised immune systems. Clinical trials have demonstrated that it elicits robust immune responses against orthopoxviruses, including monkeypox .Potential Antiviral TherapiesEfforts are also ongoing to develop specific antiviral medicines for monkeypox. Tecovirimat is an example of such a development; it's the first medication approved by the FDA for smallpox treatment and has demonstrated activity against the monkeypox virus in laboratory conditions. Clinical trials assessing its effectiveness in treating monkeypox could lay the groundwork for a disease-specific antiviral treatment .Future Avenues for ResearchDespite recent progress, many aspects of monkeypox remain mysterious. Future research endeavors should strive to clarify the ecology of the monkeypox virus, specifically its natural hosts and transmission methods. Such insights could guide the creation of more efficient and targeted public health measures .Additionally, investigations are needed to examine the long-term immune responses to new vaccines, the practicality of their wide-scale deployment in regions where the disease is endemic, and strategies to handle potential side effects .Finally, considering the potential of monkeypox to spread worldwide, the disease should be prioritized in One Health initiatives, which acknowledge the interrelation of human, animal, and environmental health .Global health implicationsImpact on Public HealthThe rising incidence of monkeypox, particularly in areas with low smallpox vaccination rates, highlights its emerging importance as a global public health concern . The disResponse StrategiesTo address the global menace of monkeypox, a comprehensive and multifaceted response strategy is essential. This encompasses enhancing surveillance systems, improving laboratory diagnostic capabilities, and strengthening infection prevention measures in healthcare facilities .Additionally, planning for preparedness and prompt response to outbreaks are key aspects of this strategy. This approach includes swift identification of cases, isolation, contact tracing, and suitable clinical management .The Role of International Health OrganizationsGlobal health bodies like the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) are critical in steering worldwide efforts to counter monkeypox. They offer technical assistance and advice to countries, carry out disease surveillance, and coordinate international research initiatives .These organizations also assist in formulating prevention strategies, such as immunization programs, and raise awareness about the disease among healthcare providers and the general public . Their rMonkeypox has become an increasing concern in the global health landscape. The disease is caused by the monkeypox virus and is primarily found in Central and West Africa, but its capacity for worldwide spread has been demonstrated with cases reported in countries like the United States, the United Kingdom, Israel, and Singapore. The discontinuation of routine smallpox vaccinations has resulted in a growing number of susceptible individuals and a corresponding increase in monkeypox cases.Despite bearing clinical resemblances to smallpox, monkeypox poses unique difficulties in terms of diagnosis, treatment, and prevention. This highlights the urgency for dedicated research efforts and public health strategies. Notable progress has been made in creating safer vaccines and potential antiviral treatments, yet there is a need for a more detailed examination of their long-term efficacy, potential side effects, and the feasibility of large-scale administration in endemic regions.Additional investigations are required to better understand the natural reservoirs and transmission pathways of the monkeypox virus. Moreover, research endeavors should be directed toward the creation and evaluation of new vaccines and antiviral treatments. Monkeypox should be a priority in One Health initiatives, which emphasize the interconnected nature of human, animal, and environmental health. In light of the potential for global transmission of monkeypox, international cooperation is paramount. This involves bolstering global and regional disease surveillance systems, the sharing of research data, and coordinating public health responses.


Background: Schizophrenia is a serious mental disorder that has greater negative consequences on role functioning than many other severe chronic diseases.Objective: We evaluated the economic impact of long-acting injections of paliperidone palmitate (PP) vs daily oral antipsychotics to treat chronic schizophrenia from a societal perspective over a 2-year period.Methods: A static budget impact model was developed to compare PP with daily oral antipsychotics  in the treatment of patients with chronic schizophrenia. Our study included treatments used during relapse and hospitalization, validated by an expert panel. The clinical parameters were extracted from the PRIDE trial. Direct medical costs and indirect costs were measured. The unit cost of drug acquisition for all medications was extracted from the public sector. One-way sensitivity analyses were conducted.Results: The target population in our model was estimated to be 142 incident patients. In the first year, the total drug costs in Egyptian pounds (EGP) for PP and oral antipsychotics were £2.7 million and £724 004, respectively, while the total medical costs for PP and oral antipsychotics were £3 million and £5.6 million, respectively. In the second year, the total drug costs for PP and oral antipsychotics were £2.7 million and £724 004, respectively, while the total medical costs for PP and oral antipsychotics were £3 million and £5 million, respectively. The total costs for PP (£11.6 million) over 2 years were less than those of oral antipsychotics without PP (£12.7 million). PP produced an estimated budget savings of £1 046 561 . In addition, PP resulted in the avoidance of 18 hospitalizations per year compared with the without-PP arm. Sensitivity analyses showed that the percent of hospitalizations for both oral antipsychotics and PP had the greatest impact on the results.Conclusion: The lower hospitalization rates associated with PP offset the increase in drug costs. PP may potentially be cost-saving compared with the standard of care in chronic schizophrenia in Egyptian representative healthcare settings. Policy makers may consider this approach to improve patient outcomes and budget sustainability. Mental disorders, including depressive disorders, bipolar disorder, schizophrenia, anxiety disorders, and autism spectrum disorder, are major causes of disability-adjusted life-years (DALYs), affecting more than 1 billion people worldwide.Schizophrenia is a serious mental disorder that has greater negative consequences on role functioning than many other severe chronic diseases.People with schizophrenia require lifelong treatment. The disease exerts a tremendous negative impact on health care in terms of cost, service provision, and support systems.It is often difficult to achieve success with pharmacological treatment mainly due to poor adherence, which has been observed in an average of 41% of schizophrenia cases.The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study compared the effectiveness of once-monthly PP with daily oral antipsychotics on treatment failure in 450 adults with schizophrenia and a history of incarceration. This was a 15-month, randomized, multicenter study. Time to first treatment failure was determined by a blinded event-monitoring board. They found that in real-world management of schizophrenia, PP was associated with a significant delay in time to first treatment failure compared with oral antipsychotics due to the reduced arrest/ incarceration and psychiatric hospitalization rates associated with PP.Currently, the economic impact of LAIs of PP to treat chronic schizophrenia in real-world practice has not yet been determined in Egypt. Thus, our main objective is to compare the economic impact of LAIs of PP in chronic schizophrenia with that of daily oral antipsychotics from a societal perspective over a period of 2 years to guide policy makers and decision makers to provide the best available therapy for the Egyptian population.A static economic impact model was developed to compare LAIs of PP with daily oral antipsychotics  for the treatment of patients with chronic schizophrenia. Our study included treatments used during relapse and hospitalization, validated by the local clinical practice, applied in the Health Insurance Organization (HIO) and Al-Azhar University hospitals and obtained from our expert panel. Individual responses were analyzed, gathered, and presented to reach a consensus through virtual meetings and phone interviews. This expert panel was composed of 3 psychiatrists affiliated with Al-Azhar University hospitals and HIO hospitals in Egypt. We collected insights from experts through a focus group by using the quasi-Delphi panel approach. The experts’ insights included the current local clinical practice and treatment patterns of these patients within the Egyptian representative healthcare settings . We used a well-structured questionnaire to extract the insights from the panel. No ethics committee approval was required since this research did not include human subject data. Individual patient-level information was not used, and the research relied purely on secondary data. This model was developed using Microsoft Excel 365. Economic model validation, including both clinical and programming validation, was performed by using the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) principles of good research practices for budget impact analysis.The PubMed and MEDLINE databases were comprehensively searched to identify English-language publications including clinical and economic data regarding the model structure, probabilities of the health states, and the treatment line options and doses. Articles that addressed the management of patients with chronic schizophrenia were selected on the basis of terms related to the clinical conditions and the budget impact of PP; these terms included “budget impact,” “schizophrenia,” “paliperidone palmitate,” “oral antipsychotics,” “randomized controlled trial,” “randomized,” “controlled trial,” “meta-analysis,” and “systematic review.” Twelve relevant articles and reports were identified by this electronic search and were reviewed; 5 articles were excluded as irrelevant.Several assumptions were taken into consideration. It was assumed that the share of risperidone in the standard of care treatment was 35%, while for both olanzapine and aripiprazole, it was 32.5%. Furthermore, it was assumed that the risperidone standard of care is the use of generic oral products. It was also assumed that the same suicide prevalence was used in both arms but was linked with the nonadherence rate in each treatment arm, in accordance with the PRIDE study.We conducted a budget impact analysis to compare the costs and consequences of LAI of PP with risperidone, olanzapine, and aripiprazole as one comparator arm . The results of this analysis were expressed as a budget impact per patient per year and a cumulative budget impact over 2 years that included the total direct costs such as disease management , treatment-related costs (acquisition and monitoring), and indirect costs. The analysis was performed from the perspective of the HIO over a period of 2 years. A 2-year period was selected as the tender list was re-evaluated every 2 years in Egypt to inform and guide decision makers over a longer period. The total costs of both treatment arms were calculated by computing the unit costs calculated in Egyptian pounds (EGP) and multiplying it by the resource utilization  according to the following equation:Figure 1 shows the target population of this study, which comprised adults 18 to 65 years old with chronic schizophrenia, a history of relapse, and a history of readmission/hospitalization as reported in the PRIDE study.The incidence of chronic schizophrenia was extracted from the literature and validated by the expert panel to reflect real-life clinical practice settings.Table 1 presents the model parameters. A static model  was conducted; we measured all the costs and consequences associated with the 2 treatment arms, including hospitalization and follow-up. The clinical parameters for hospitalization and adherence to all treatments were extracted from the PRIDE trial,Table 1 was multiplied by its resource utilization to generate the total costs in each treatment arm (Table 2).Direct medical costs and indirect costs were measured in our study over a 2-year period. Direct nonmedical costs were not considered because they are variable in Egypt, and there were no accurate data on their unit costs. We did not capture the intangible costs because no local data were available. The included direct medical costs are acquisition costs of medication, monitoring, and hospitalization costs. The unit cost of drug acquisition for all medications was extracted from the public sector, Egyptian Authority for Unified Procurement, Medical Supply and Management of Medical Technology (UPA) and multiplied by the utilization of each drug . The dosage of PP was 150 mg intramuscular injection, as an initial injection, then 100 mg intramuscular injection, continued on a monthly maintenance dose. The length of stay in acute wards was assumed to be 90 days for both oral and LAI based on published articles and validated by local clinical practice.Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III-R) psychiatric disorders and work impairment in major occupational groups in the labor force.Drug costs constitute only a small fraction of the economic burden of schizophrenia, as most of the total costs are hospitalization and indirect costs due to productivity loss, unemployment, and early retirement. Indirect costs, including mortality and productivity loss, were measured. The productivity loss was measured by multiplying the Egyptian patient average wage per day by the psychiatric work loss days and the hospitalization rates for both treatment arms. The patient average hourly wage was captured by using the most recently published gross domestic product by the World Bank in 2020.t tests for normally distributed variables to measure the statistical significance between the total costs of both treatment arms. A significance level of P .05 was used.Statistical analyses and all calculations were performed using Microsoft Excel 365. Two-sample comparisons were performed using 2-sided Student’s One-way sensitivity analyses were performed to assure the robustness of the results. Various parameters were varied with 10% to 20% above or below their base case values. The parameters tested were the population, clinical, and cost data for each treatment arm. Two-way sensitivity analyses were not conducted because there is no clear correlation between the parameters tested.Table 2). In the second year, the total drug costs for LAI of PP and oral antipsychotics were £2.7 million and £724 004 , respectively , while the total medical and indirect costs of LAI of PP and oral antipsychotics were £3 million and £5.6 million , respectively .The target population in our model was estimated to be 142 patients. In the first year, the total drug costs when LAI of PP was compared with oral antipsychotics were £2.7 million and £724 004 , respectively, while the total medical and indirect costs of LAI of PP and oral antipsychotics were £3 million and £5.6 million , respectively . Table 3 showed all the cost components  in both treatment arms.The total costs of LAI of PP (£11.6 million) over 2 years were less than those of oral antipsychotics without PP (£12.7 million). LAI of PP produced an estimated budget savings of £1 046 561 , as shown in On the other hand, LAIs of PP resulted in 18 hospitalizations avoided per year in comparison to the without-PP arm. Thus, it is estimated that 36 total hospitalizations were avoided with PP over 2 years and hence less burden on hospitals and healthcare staff.Figure 3). The diagram revealed that the percentage of hospitalizations for both oral antipsychotics and PP had the greatest impact on the total costs. Thus, real-world data need to be collected from local hospitals to ensure the robustness of the results.Deterministic sensitivity analyses were conducted to explore the effect of changes in model parameters on the direct medical and indirect costs over the time horizon. The tornado diagram showed the most sensitive parameters  and may foster more regular contact with caregivers. Moreover, they have better bioavailability, avoid first-pass metabolism, establish more stable concentrations and a more predictable correlation between dosages and plasma levels, and reduce the risk of voluntary overdose.Our study results were consistent with a budget impact model conducted in Austria to estimate the budget effects of the introduction of PP in schizophrenia. This study concluded that the introduction of PP in Austria was budget neutral.This study has several notable strengths. First, we extracted the clinical parameters from real-world, randomized multicenter studies that used strong evidence and were free of bias. Second, it is the first budget impact model conducted in Egypt measuring all cost consequences of PP compared with the standard of care in chronic schizophrenia in Egyptian representative healthcare settings. Third, we measured the direct and indirect costs to demonstrate the real value of the medications in schizophrenia and how their patient and economic impact from a societal perspective.Our study also had some limitations. First, cost data of informal care for people with schizophrenia were not measured because they are not available in Egypt. Second, we have not evaluated the utilization of outpatient health services, although there might be some additional cost savings in this sector as well. Third, our results might be underestimated because the reduced risk of self-harm, a factor that improves long-term clinical outcomes, was not measured.Certain key drivers of the total costs were identified, and sensitivity analysis was performed to estimate the overall impact on costs and savings. Therefore, the major drivers of the budget impact are the percentage of hospitalizations for both arms due to relapse, PP price, and percentage of patient adherence to PP. The use of PP to treat chronic schizophrenia provides a clear picture of how it can influence patient outcomes and reduce the burden on medical communities and hospitals.The lower hospitalization rates with PP offset the increase in drug costs. PP may potentially be cost-saving compared with the standard of care in chronic schizophrenia in the Egyptian representative healthcare settings. This result is robust to variations in all parameters. Policy makers should consider this approach to improve patient outcomes and budget sustainability.


Mononykus olecranus, a member of the family Alvarezsauridae, has previously been investigated. However, the method used to investigate range of motion at the shoulder in M. olecranus did not follow the standardized procedure used in subsequent studies. The latter procedure yields more reliable results, and its standardization provides that its results are directly comparable to the results of similar studies in other species. I therefore reinvestigated the range of motion at the shoulder in M. olecranus, using the latter procedure.Range of motion in the forelimb of the Upper Cretaceous theropod dinosaur M. olecranus were posed on a horizontal surface, supported from beneath with modeling clay, with the medial surface of the scapula facing toward the horizontal surface. A cast of the left humerus was posed at the limits of motion through the transverse and parasagittal planes. Photos of the poses in orthal views were superimposed and used to measure range of motion, which was measured as the angle between lines drawn down the long axis of the humerus in each position.Casts of the left scapula and coracoid of M. olecranus could be elevated to a subhorizontal position and depressed to a subvertical position. It could move through the parasagittal plane from a subvertical position at full protraction to a position above the horizontal at full retraction. These results correct the previous mischaracterization of shoulder motion in M. olecranus as restricted to a small arc with the arms held in a permanent sprawl. The range of humeral motion in M. olecranus is much greater than that found by the previous method and allowed the animal to tuck its arms in at the sides, in addition to allowing them to sprawl so as to orient the palm downward. The wide range of humeral motion allowed M. olecranus to forage for insects by employing hook-and-pull digging at surfaces with a wider range of orientations than the previous study showed to be possible.Through the transverse plane, the humerus of  Mononykus olecranus.The primary literature of paleontology includes a plethora of studies in which previous studies are redone with improvements. For example, phylogenetic analyses are routinely redone with new data, often from newly discovered specimens, which enable each new phylogenetic analysis to be more informative than its previous counterparts. Likewise, morphological descriptions of fossil specimens are often redone when reexamination provides new insights e.g. . SimilarSeveral previous investigations of the paleobiology of theropod dinosaurs have addressed the range of motion (ROM) in the forelimb or some part of it. For such studies, it is advantageous to have a repeatable protocol for numerically measuring ROM at given joints, which provides rigor and makes the results of one ROM study directly comparable to that of another. Unfortunately, early studies of theropod forelimb ROM did not involve the use of such a protocol. In some early investigations of theropod forelimb ROM, researchers illustrated poses that theropod forelimbs could achieve but did not report numerical measurements of ROM at specific joints  or reporAcrocanthosaurus atokensis, a colleague and I introduced and described a repeatable set of protocols for measuring ROM at specific joints (Acrocanthosaurus ROM protocol”), was repeated with minor variations in several subsequent studies on forelimb ROM in theropods and other non-avian dinosaurs  and retraction (extension) within that plane, and the humerus is moved in a hinge-like motion through the transverse plane to measure its range of elevation and depression within that plane. Previous studies have determined that the proximal limb bones of tetrapods may use all six degrees of freedom, the use of which may include such movements as translation and long-axis rotation . AccordiDeinonychus antirrhopus had previously been studied by Dilophosaurus wetherilli had previously been studied by Mononykus olecranus.Two previous studies applied the ARP to species for which forelimb ROM had previously been illustrated or measured without the ARP. Forelimb ROM in Mononykus olecranus is a small theropod dinosaur from Mongolia  in real space. In recent years, digital techniques have become available that enable the digital use of images on a computer screen to perform equivalent or related tasks, and some such techniques have provided useful insights into limb motion in animals . A compuMononykus olecranus (GI N107/6) to determine humeral ROM, using the ARP. First, I positioned the scapula and coracoid upon the horizontal surface of a wooden box, with the medial surface of the scapula facing downward, so that the horizontal surface of the box approximated the animal’s midsagittal plane. The two bones were held together in articulation with a narrow strip of masking tape and were supported from beneath by a blob of modeling clay, which allowed the anterior scapula and coracoid to curve toward the table, just as they would have curved medially in the living animal  of the left scapula, coracoid, and humerus of the holotype of g animal . I posedAs in previous studies using the ARP, the photographic images were digitally superimposed, a line was drawn down the long axis of the humerus in each position, and ROM was measured as the angle between the lines. In cranial view, the shaft of the humerus is straight, and the line representing its long axis was drawn down the middle of the humerus, parallel with the shaft. In lateral view, the humerus is curved (convex posteriorly); the line representing its long axis was drawn as a line connecting the center of the humeral head with the center of the lateral epicondyle.M. olecranus has a strongly projecting internal tuberosity, which made it easy to pose in this manner. The one position in which the internal tubercle was not pressed into the clay was full elevation of the humerus through the transverse plane, in which position the internal tubercle was clear of the clay. In this position, the humerus was held in place by gently pressing the humeral head onto the clay to create a shallow, form-fitting depression that supported the humerus from beneath.There was no need to support the cast of the humerus from beneath with horizontal rods, because the use of modeling clay provided a unique opportunity to support the cast in a different and simpler way. The humerus was held in place in all but one position by gently pressing the internal tuberosity into the clay. The humerus of M. olecranus does not fit precisely into the glenoid cavity , in all dimensions, is similar to but slightly greater than that found with bare bones  to a subhorizontal position   . If the al view) —applies M. olecranus is much greater than previously reported  but is shifted toward the deltopectoral crest  for this condition and the term skalodactyl for the specialized finger with the prominent claw. Extant skalodactylous animals use the skalodactyl for hook-and-pull digging, a means to crack into plants and tough insect nests to gain access to ants and termites within , vampire bats , and avocets . However, the presence of the entire suite of traits together is strongly indicative of myrmecophagy. M. olecranus is similar in absolute size to that of the silky anteater (Cyclopes didactylus), which uses its skalodactyl to break into twigs and woody vines to feed on the insects within (M. olecranus would therefore not have prohibited such use. Priodontes maximus) and all extant species of anteaters    Fig. 2)e.g. manaactylus)  than is actylus) .Orycteropus afer), sloth bears (Melursus ursinus), and armadillos other than Priodontes. However, all extant skalodactylous animals are myrmecophagous hook-and-pull diggers, and skalodactyly has no known functional significance other than hook-and-pull digging as a part of myrmecophagous behavior. The inference that alvarezsaurids were myrmecophagous is therefore supported by their forelimb morphology.Not all myrmecophagous animals are skalodactylous. Some are scratch-diggers with fingers of more uniform size. Examples include aardvarks (The use of the specialized hands of Late Cretaceous alvarezsauroids for hook-and-pull digging does not preclude their use to crack into eggshells. Some previous researchers have hypothesized that alvarezsaurids fed on eggs, because one specimen was associated with a broken shell from an egg that was too big for it to have laid, and another was associated with two eggs . In the M. olecranus resembles that of other theropods. In theropods generally, parasagittal movement of the humerus allows it to be protracted to a subvertical position and retracted to a subhorizontal position or further, with the elbows tucked in at the sides (The range of humeral motion through the parasagittal plane in he sides . The abiMononykus olecranus brings the study of forelimb ROM in M. olecranus into alignment with the protocols used in previous studies that used the ARP, thereby ensuring that measurements of shoulder ROM in this species are directly comparable to those found for other species. This investigation also confirms that humeral motion in M. olecranus was greater than previously known. It therefore elucidates aspects of the paleobiology of Mononykus olecranus that were previously obscured by the mistaken characterization, from the prior study (This restudy of shoulder ROM in or study , that th