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Jamison DT, Breman JG, Measham AR, et al., editors. Disease Control Priorities in Developing Countries. 2nd edition. Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2006. Co-published by Oxford University Press, New York.

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Disease Control Priorities in Developing Countries. 2nd edition.

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Chapter 52Pain Control for People with Cancer and AIDS

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The undertreatment of chronic pain is a global problem, especially for people in the final stages of cancer and, increasingly, AIDS. The pain of dying is often severe, but it can be controlled for most people by a simple and inexpensive intervention: oral analgesic drugs, including morphine and other opioids. Although it was long known that opioid drugs were essential for the relief of moderate to severe pain, even in the 1980s the amounts being used globally were so low that only a minority of those dying could have had adequate pain relief. Since then progress has been made, mainly in resource-rich countries, widening the gap between rich and poor. The absence of opioids in developing countries is not merely a problem of supply or costs, however. This chapter lays out the institutional and political barriers that restrict their availability in most low- and middle-income countries.

Burden of Pain from Cancer and AIDS

Pain is"an unpleasant sensory and emotional experience associated with either actual or potential tissue damage or described in terms of such damage"(Task Force on Taxonomy 2004). Pain, in its various manifestations, is the most common symptom leading patients to seek medical assistance (box 52.1).

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Box 52.1

Classification of Pain. Pain is classified according to two main characteristics: temporal and physiologic. Temporal categories are acute pain characterized by a well-defined onset and self-limited end allows clear description of location, character, (more...)

Measurement of Pain

Pain is a subjective experience, but it can be described by patients and assessed using validated questionnaires and scales (Cleeland 1990). In categorical scales, the patient describes the pain using specific words, for example, mild, moderate, severe, or excruciating. With numerical scales, patients rate their pain by choosing a number—for example, from 0 (no pain) to 10 (worst pain). Visual analog scales often take the form of a ruled line, anchored on the left by the words no pain and on the right by worst possible pain.

Pain measurement instruments have been validated in clinical trials of analgesic therapies and subsequently used in national and international surveys, repeatedly demonstrating sensitivity and reliability for both cancer and AIDS patients. These instruments include the Brief Pain Inventory (Bernabei and others 1998; Cleeland and others 1996; Daut, Cleeland, and Flanery 1983), the Memorial Pain Assessment Card (Fishman and others 1987), the Memorial Symptom Assessment Scale (Portenoy and others 1994), and the Edmonton Symptom Assessment Scale (Chang, Hwang, and Feuerman 2000).

Effects of Pain

Pain dramatically affects quality of life. Patients with persistent serious pain cease participating in social activities and may be unable to work or care for their families (Daut, Cleeland, and Flanery 1983). Psychological effects, including depression and anxiety, increase with pain intensity (Rosenfeld and others 1996).

The suffering of an individual radiates throughout households, neighborhoods, and villages. Caregivers suffer distress, anxiety, and depression. They may have to give up their own employment to care for a dying relative. The loss of income of the patient and the caregiver may dramatically lower the family's social status (Murray and others 2003).

Pain in Patients with Cancer and AIDS

Several well-defined acute and chronic pain syndromes are associated with cancer, with HIV/AIDS, and with their treatment (Breitbart 2003; Foley 1979). In low-income countries, where patients usually present late in the course of illness, pain from the disease itself is more common than treatment-related pain.

Researchers consistently report that 60 to 90 percent of patients with advanced cancer experience moderate to severe pain, regardless of age and gender and whether ambulatory or hospitalized (Cleeland and others 1988; Cleeland and others 1996; Daut and Cleeland 1982; Foley 1979; Foley 1999; Stjernsward and Clark 2003). The intensity, degree of pain relief, and effect of pain vary according to the type of cancer, treatment, and personal characteristics, but prevalence and severity of pain usually increase with disease progression. No population-based studies of AIDS-related pain have been published, but several researchers report that up to 80 percent of patients in the last phase of illness experience significant pain requiring analgesics (Larue, Fontaine, and Colleau 1997; Schofferman and Brody 1990; Singer and others 1993).

Pain Days

No standard metric has been developed to describe the pain burden for people at the end of life. We have adopted a transparent and direct measure—the pain day—defined as a day of moderate or severe pain requiring an opioid drug for relief. The elements that determine the number of cancer and AIDS pain days in a population are the numbers dying from each condition and the average prevalence and duration of severe pain associated with dying.

Patterns of pain from specific cancers and from AIDS at given stages appear to be similar everywhere. However, because different cancers produce different symptoms, the mix of cancers in a country will influence the overall pattern and burden of pain reflected in the total number of pain days.

About 2.1 million deaths from cancer and about 3 million from AIDS occur annually in low- and middle-income countries (LMICs) worldwide, and these numbers are increasing. Using expert opinion, we estimate that about 80 percent of people dying from cancer and 50 percent of those dying from AIDS experience moderate or severe pain, lasting for an average of 90 days.

Interventions for Pain Relief

The goal of pain control is not to cure disease, but to allow patients to function as effectively as possible and to minimize pain. Interventions for pain relief include drugs, radiotherapy, and anesthetic, neurosurgical, psychological, and behavioral approaches (see table 52.1). However, analgesic drugs are the mainstay of treatment and the focus of this chapter. According to the World Health Organization (WHO), "A palliative care programme cannot exist unless it is based on a rational national drug policy," and this includes "regulations that allow ready access of suffering patients to opioids" (WHO 2002, 87).

Table 52.1. Procedures Used to Control Specific Types of Cancer Pain.

Table 52.1

Procedures Used to Control Specific Types of Cancer Pain.

WHO Three-Step Analgesic Ladder and Its Effectiveness

WHO has developed a "three-step analgesic ladder" (figure 52.1) for cancer pain and its treatment (WHO 1986), which includes a strong opioid (morphine) (table 52.2). The ladder is equally appropriate for patients with HIV/AIDS (O'Neill, Selwyn, and Schietinger 2003).

Figure 52.1

Figure 52.1

The Three-Step Analgesic Ladder

Table 52.2. Basic Drug List for Cancer and AIDS Pain Relief: Analgesics and Adjuvant Drugs.

Table 52.2

Basic Drug List for Cancer and AIDS Pain Relief: Analgesics and Adjuvant Drugs.

The steps in the ladder represent increasing pain severity and the drugs that should be used in each case:

  • Step 1 is limited to nonopioids, including drugs that are widely available (for example, acetaminophen, aspirin, or nonsteroidal anti-inflammatory drugs, or NSAIDs).
  • Step 2 describes moderate pain that requires a combination of a nonopioid and opioid for relief.
  • Step 3 is for pain requiring a strong opioid. No specific dosages are recommended for opioid drugs because the concept of a standard dose does not apply: effective doses of oral morphine range from as little as 5 mg to more than 1,000 mg every four hours. Adjuvant drugs are also essential to treat side effects of analgesics or to provide additive analgesia (table 52.2).

Controlled field testing and clinical experience has demonstrated that 70 to 90 percent of cancer patients can achieve pain control using the ladder (Goudas, Carr, and Bloch 2001). Although the ladder has not been validated in formal studies for patients with AIDS, recent clinical reports describe its successful application (Anand, Carmosino, and Glatt 1994; Kimball and McCormick 1996; McCormack and others 1993; Newshan and Lefkowitz 2001; Newshan and Wainapel 1993; Schofferman and Brody 1990).

In an ideal world, a trained professional would prescribe pain medication throughout the course of illness, in accordance with the ladder. However, most patients self-medicate pain with analgesics and traditional medicines that they buy over the counter until they have late-stage disease and severe pain that can be treated only with a strong opioid. That is when they are most likely to seek formal medical care, which would start on step 3 of the ladder. Unfortunately, the opioid they need is unlikely to be unavailable in LMICs, even from health professionals.

Adequacy of and Barriers to Pain Control and Palliative Care in Developing Countries

The adequacy of pain control in populations is not easily measured. A useful and available surrogate is the per capita consumption of morphine (Joranson 1993), a figure based on mandatory annual reports by national governments to the International Narcotics Control Board (INCB). Of the 27 million grams of morphine used legally in 2002, 78 percent went to six countries—Australia, Canada, France, Germany, the United Kingdom, and the United States. The rest went to the other 142 countries that reported. Morphine is largely unavailable in Africa, the eastern Mediterranean, and Southeast Asia (figure 52.2).

Figure 52.2

Figure 52.2

Global Morphine Consumption, by Country (Per Capita, 2002)

The major barriers to palliative care in LMICs are scarce resources, lack of national policies or low priority for pain relief, lack of awareness by health professionals and the public that cancer and AIDS pain can be relieved, concern that medical use of opioids will lead to drug abuse and addiction, and legal restrictions on opioids. Medical, religious, gender, social, and cultural factors also present barriers (see box 52.2). With AIDS, social and self-stigmatization work against adequate care of any kind. In addition, most of the emphasis in poor countries has been on prevention and, more recently, on antiretroviral drugs. In all cases, even less care is in place for children than for adults (Joranson, Rajagopal, and Gilson 2002).

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Box 52.2

Living with and Dying from Cancer in Scotland and Kenya. Physical suffering dominates the lives of people with advanced cancer in rural Kenya. In contrast, the concerns of cancer patients in Scotland, whose physical needs are met, focus on the prospect (more...)

Legal Controls on Opioid Drugs

The Single Convention on Narcotic Drugs of 1961, amended by the 1972 Protocol (United Nations 1961), is an international treaty that aims both to prevent the illicit production of, trafficking in, and use of narcotic drugs and to ensure their availability for medical and scientific needs. The INCB, established in 1968 by the Single Convention, is the independent, quasi-judicial organization that implements the Single Convention.

The Single Convention requires that all countries (even nonsignatories) intending to make opioids available for medical use estimate national opioid needs and report annually on imports, exports, and distribution to the retail level. It also sets out the following principles on which countries can develop their own policies and regulations:

  • Individuals must be authorized to dispense opioids by virtue of their professional license or be specially licensed to do so.
  • Opioids may be transferred only between authorized parties.
  • Opioids may be dispensed only with a medical prescription.

Many governments have imposed even tighter restrictions, such as limiting the number of days for which an opioid prescription can be written.

Costs and Cost-Effectiveness

This section describes the costs and benefits of providing oral morphine and essential adjuvant drugs to terminally ill cancer and AIDS patients who require it. It assumes the drugs are used according to the WHO analgesic ladder. We recognize that other analgesics can also contribute significantly to patients' costs and pain relief, but at least some such drugs (acetaminophen, for example) are available relatively cheaply in most places. Although not everyone has access to such drugs, we are unaware of any data that could be used to estimate that proportion. Costs are estimated for three countries at differing income levels and with different patterns of cancer and AIDS deaths: Chile, Romania, and Uganda (see box 52.3).

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Box 52.3

Pain Control in Romania and Chile. Palliative care has developed in Romania since the early 1990s, largely through the Romanian Association for Palliative Care. Support has come predominantly from U.K. charities and from the Open Society Institute. Services (more...)

Costs Included in the Estimates

The quantitative analysis presented here is restricted to the costs, before such drugs reach the patient, of oral morphine and the adjuvant drugs needed to treat its side effects. We mention other costs associated with delivering oral morphine to terminal AIDS and cancer patients later in this section, but for reasons we discuss, we have not assigned dollar values to them.

Costs of Oral Morphine

The appropriate measure of drug cost is the sum of costs to all payers—governments, insurers, charities, and patients—for the drug itself, but that sum does not include the costs of personnel to administer the drug or otherwise care for the patient.

Oral morphine can be purchased in bulk powder or finished form and administered as a tablet or liquid (De Lima and others 2004; Rajagopal and Venkateswaran 2003). The cost to the final payer is influenced by import taxes, if any; requirements to document the chain of custody of the product; costs to local manufacturers of excipients, salts, diluents, and other materials required to produce finished forms; and price markups. The actual cost of oral morphine in LMICs is difficult to document because it is unavailable in so many places or is manufactured for finished use at different points in the distribution chain. The price of a 30-day supply of immediate-release oral morphine in 2003 ranged from US$10 in India to US$254 in Argentina, among the few countries for which prices were reported (De Lima and others 2004).

Morphine is likely to cost less where it is produced locally and used in easy-to-reach, urban locations. Liquid preparations made by mixing morphine powder will cost less than tablets. Even with these variations, if barriers to access to oral morphine are removed, a total drug cost of 1 cent per milligram or less for immediate-release oral morphine should be achievable for most countries. A realistic and conservative estimate of the cost of oral morphine is 0.5 cent to 1.0 cent per milligram in the countries in our analysis.

The cost of morphine per patient depends on the number of days that opioids are required and the average daily dose, recognizing that the required dosage typically increases with increasing pain nearer to death. An average daily dose in palliative care programs in developing countries is roughly 60 to 75 mg per day, and patients require this dose for an average of three months. (Merriman 2002; personal communication, L. De Lima, International Association for Hospice and Palliative Care, June 2004; personal communication, M. R. Rajagopal, Amrita Institute of Medical Sciences, Kochi, Kerala, India, June 2004).

Using the inputs above, we estimate the cost of oral morphine for a cancer or AIDS patient with severe pain near the end of life at about 30 to 75 cents per day, or US$9.00 to US$22.50 per month, which is needed for an average of three months.

Costs of Other Necessary Drugs

Morphine's most common side effects are constipation, nausea, and (less frequently) psychosis. Representative drugs to treat these conditions are senna, a laxative, available to some government purchasers for about 3 cents per day; prochlorperazine, an antiemetic, about 8 cents per day; and haloperidol, an antipsychotic, about 15 cents per day (Management Sciences for Health 2003). Retail prices after markups would add 20 to 30 percent.

Under the assumptions of this analysis, oral morphine for all dying cancer and AIDS patients would cost between 3 cents and 21 cents per capita per year (table 52.3) in Chile, Romania, and Uganda. The cost per pain day avoided by oral morphine is the same in all three countries, assuming that each country can acquire and dispense morphine equally efficiently.

Table 52.3. Background Data, Assumptions, and Results of Cost Analysis.

Table 52.3

Background Data, Assumptions, and Results of Cost Analysis.


The analysis indicates that the drug costs of oral morphine come to about US$216 to US$420 per year of pain-free life gained in the three sample countries. The next question is whether the pain relief that could be achieved would be worth the cost. We know that patients value pain-free days highly. A day lived with the certainty of experiencing severe pain is of very low value, perhaps even lower than death itself (Furlong and others 2001; Le Gales and others 2002). Bryce and others (2004) find that people are willing to give up several months of healthy life for access to good end-of-life care. Patients in low-income countries place as great or even greater value on pain relief as patients in high-income countries (Cleeland and others 1988; Murray and others 2003).

Costs Not Included in the Analysis

The analysis presented includes only the most basic costs—the costs of oral opioids and associated drugs—that would be incurred in a pain control program. Clearly, there are many other costs, ranging from the costs of services at the individual patient level to the costs of changing drug laws and policies at the national level. The most significant additional costs are discussed below.

Incremental Costs of Care Delivery

In addition to requiring the drugs themselves, implementation of the three-step ladder requires trained individuals to assess and monitor patients. Where health care systems are well developed, the incremental cost of adding oral morphine will be low. If it involved one additional health center visit, the cost per patient would increase by about US$8 in Chile, US$6 in Romania, and US$4 in Uganda, amounting to less than 1 cent per capita in all three countries.

Where primary health care is weak, widespread access to oral opioids depends on the development of new systems, such as community- or hospital-based palliative care networks. Clearly, allocating the full cost of upgrading the health care system, or even the development of new palliative care programs, to oral morphine alone, would be inappropriate.

Other Costs

Security and recordkeeping related to stocking and distributing opioids, required by the Single Convention, entail additional fixed and ongoing costs. Because most hospitals handle injectable opioids (for example, pethidine), these costs would be less for hospital-based programs than for community-based programs.

Professional training and education is required for all personnel involved in the use of opioids for dying patients, in part to overcome fears and in part to ensure proper use. These costs are likely to be highest where the health care system is most deficient.

The costs of changing national policy toward opioids is substantial in terms of cost, time, expertise, and leadership (see, for example, Pain and Policy Studies Group 2003 and 2004 and other annual reports at The time expended is an opportunity cost, but it may be amortized over a long time if the effort succeeds.

Potential Cost Savings

In some circumstances, making oral morphine available through a palliative care system could actually save money—for example, if it enabled some terminally ill patients who would otherwise be admitted to the hospital for pain control to die at home, or if it shortened their period of hospitalization. This outcome is more likely in places with good medical infrastructure, but even in low-income countries, patients in unbearable pain are often brought to hospitals by distressed relatives who are willing to go into debt to ease the suffering.

Implementation of Strategies to Improve Pain Control

Providing adequate oral morphine involves medical, political, legal, and societal change. Model programs, such as Hospice Uganda and efforts in India, have demonstrated the feasibility of providing good palliative care, including oral morphine, even for poor rural dwellers. WHO and the INCB have supported these efforts.

WHO Guidance on Palliative Care and Pain Relief

WHO has affirmed the need for palliative care and has defined the elements of model programs in several reports. In 2002, WHO's executive board called for the integration of pain and palliative care into national cancer control programs (box 52.4; WHO 2002). The Joint United Nations Programme on HIV/AIDS and the WHO AIDS Program consider pain and palliative care to be essential and pain management to be integral to AIDS care (Foley, Aulino, and Stjernsward 2003). WHO, in collaboration with the INCB and the WHO Collaborating Center (WHOCC), has developed guidelines for national authorities to self-diagnose their regulatory systems for problems that might lead to a lack of access to needed drugs (WHO 2000). These organizations also sponsor national and international workshops to help national authorities evaluate their policies, develop action plans, implement policy change, and evaluate outcomes. In addition to WHO and the INCB, a number of programs and organizations are making resources and expertise available to assist countries in various ways (box 52.5).

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Box 52.4

WHO Pain Relief and Palliative Care Recommendations Based on Resource Level. WHO's recommendations are as follows: Countries with low levels of resources should ensure that minimum standards for pain relief and palliative care are progressively adopted (more...)

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Box 52.5

Selected Resources for Developing National Palliative Care Programs. Resources available to countries include the following: The WHOCC for Policy and Communications in Cancer Care at the University of Wisconsin serves as a critical resource for palliative (more...)

Hospice Uganda

Hospice Uganda began in 1993 with an old Land Rover, a grant to last three months, and a mandate to become Africa's model home-based hospice for dying cancer and AIDS patients (Ramsay 2001). By July 2004, the original Kampala location had served about 4,500 nearby patients. Two additional sites—Mobile Hospice Mbarara and Little Hospice Hoima—had served about 2,500 patients (Merriman 2004). Hospice Uganda's influence has spread across Africa through its reputation and the training programs it runs (Merriman 2004).

At the beginning, morphine was largely unavailable, and the law required that a physician prescribe it. Hospice Uganda's founder, Anne Merriman, convinced the government to amend the law to allow specialist palliative care nurses and clinical officers to prescribe morphine (Merriman 2003). Now, morphine, paid for by the government, is available for dying patients in about 15 of Uganda's 56 districts (Merriman 2003). In 1998, Uganda became the first nation in Africa to list palliative care as an essential clinical service.

The cost of treating a patient in Kampala and Mbarara is about US$7 per week, including one home visit. For patients who come to the hospice, the cost is about US$4 per week (personal communication, A. Merriman, Hospice Uganda, February 2003). Even at those prices, most patients cannot afford even the medicines, which are subsidized by contributions.


For decades, the only morphine available in India was injectable and used for postoperative pain. The enactment of a strict, national narcotics law caused morphine use to decline even further, from a high of 573 kilograms in 1985 to 18 kilograms in 1997, among the lowest per capita in the world. During the period of declining use, international efforts to promote pain control and palliative care programs began to reach India. In 1992, pain relief and the availability of morphine were designated priorities in the National Cancer Control Programme (Joranson, Rajagopal, and Gilson 2002; Rajagopal, Joranson, and Gilson 2001; Rajagopal and Venkateswaran 2003).

The Ministry of Health convened national workshops from 1992 to 1994 to ascertain why morphine use continued to decline. The following experience from a referral hospital, recounted by a former narcotics commissioner of India, is instructive:

the Institute has not been able to procure a single tablet [to] date, primarily due to the stringent state laws and multiplicity of licenses. After a lot of effort, the Institute had been able to obtain the licenses in 1994 and had approached [a manufacturer] for a supply of tablets . . . [but] by the time the tablets could be arranged, the licenses had expired. The doctors at the Institute and the associated pain clinic have stopped prescribing morphine tablets. (Joranson, Rajagopal, and Gilson 2002, 153).

In 1999, the INCB called on the government of India to take measures to make morphine available for medical uses. In 1994, an initiative begun by the WHOCC, the Indian Association of Palliative Care, and the Pain and Palliative Care Society systematically studied the reasons for the lack of morphine. In 1997, the WHOCC developed a proposal to reduce the number of licenses and extend their period of validity, and the following year all state governments were instructed to adopt a model rule based on the proposal. Gradually, rules have begun to change. By 2002, 7 of 28 states or territories had adopted the model rule, but it has been implemented successfully only in Kerala.

The success in Kerala can be attributed to three things: (a) the state government simplified the licensing process and stipulated that for oral morphine to be available from a center, it must have at least one doctor with at least one month of practical experience in palliative care; (b) the national drugs controller exempted palliative care programs from needing a drug license, thereby eliminating the need for a pharmacist; and (c) a palliative care network was established, which consists of about 50 small programs. Statewide, coverage has increased to about 20 percent of those needing palliative care.

Recommendations for Research and Development

Policy makers and program implementers need practical tools to improve pain control and palliative care. They need survey instruments, guidance on how to effect policy and legal changes, and palliative care models for resource-poor settings. Many tools exist, but those could be made more accessible through the use of toolkits, distance learning, Web sites, and so on. Each country also should gather information to assess its own capabilities and needs, such as the following:

  • In relation to the national level:
  • Study the incidence and prevalence of pain related to major causes of illness and death using methodologies adapted from developed countries (Breivik, Collett, and Ventafridda forthcoming).
  • Survey existing pain and palliative care programs to identify national and local leaders in pain control and palliative care and to catalog national guidelines and standards for acute and chronic pain. For hospice and palliative care services, assess the extent of available care, service delivery models, national and local policies, and professional and public knowledge about pain control and palliative care.
  • Assess national and local regulatory barriers to opioid availability using WHO (2000) guidelines and needs assessment protocols (Higginson 1997) to help countries identify the patient-related, physician-related, and institutional issues that impede drug distribution.
  • Study costs that affect opioid availability in several countries to document the costs of licensing, obtaining, storing, keeping records for, and dispensing opioid drugs.
  • Study the costs of alternative delivery models for pain control medications in LMICs.
  • Assess the offsetting savings achievable by reducing hospital days by means of better outpatient access to oral morphine, to document potential savings in representative countries, which might help reduce barriers to access.
  • In relation to model programs:
  • Construct an inventory of model programs for pain control and palliative care. Include their infrastructure and personnel needs, their operating costs, and so on, in easy-to-use formats such as toolkits and education and training programs for policy makers and implementers. Regularly add new information from ongoing and new initiatives.
  • Devise additional models, particularly for poor rural communities, for providing palliative care and pain control practically, efficiently, and sustainably.


Unrelieved acute and chronic pain is a serious public health problem worldwide, and 80 percent of cancer patients and 50 percent of AIDS patients experience severe pain during the last months of life. Relief for these patients is possible only with oral morphine or another opioid, but developing countries face many barriers in this respect. Nevertheless, model pain and palliative care programs have demonstrated the feasibility of providing opioid treatment safely, effectively, and inexpensively in resource-poor settings. To this end, national governments must resolve the legal and regulatory barriers to opioid availability, but they need the expertise and support of the global community to make pain relief a reality.


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Copyright © 2006, The International Bank for Reconstruction and Development/The World Bank Group.
Bookshelf ID: NBK11800PMID: 21250369


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