414
Vol. 7 No. 7 October1992
Journal of Pain and SynQtom Management
dliative Care: versus 1988
ts in
Sebastian0 Mercadante, MD, Giuseppe Genovese, MD&far Agcha Kargar, MD, Salvatore Maddaloni, MD, Salvina Roccella, MD, Ieonardo Salvaggio, MD, and Maria Teresa Simonetti, MD An&hesioIo~ Sewice (S. M.), HospitalBuccherila F&a,-Pain Therajlrand HomePalliative Care (G.G.,JA.K., S.M., S.R, L.S., M.T.S.), SAMOI;PaZermo, Ztaly
AbsWct Home care k greatlyexpanding becauseof the savings it offers by avoiding unnecessary hospitalizationand also becausepatients benefitfrom being in their own home environmats. Since 1988, SocietaAssistenzaMa&o OncologicoTerminale (SAMOT} has organizeda pain relief and homepalliative care unit for terminal cancer patients. Objectives,dzffkulties,~otocols, and achievementsof 4years of experiencewereexamined, and thefindings of the variousyearswerecompared. Our resultssuggest that considerable pqyess has been maok in homepalliativecare. There are still social and cultural ds@ulties to overcome,howev0.J Pain Symptom Manage 1992;7:414-418. Home care, pain control, terminal cancer
Introduction Control of symptoms, including pain, is the fundamental aim of the palliative care of advanced cancer patients, who usually require continuing care for varying periods of time (2-3 months on average) .l Hospitalization in such cases is discomforting for the patients and expensive for society. Home care is greatly expanding because of the savir,ga PL offer. by av&,dir,g =Z_X^^ u,,‘lc_essary hospitalization, and also because patients benefit from being in their own home environments, surrounded by the affection of their families.2 AaUress reprint requests to: Sebastian0 Mercadante, MD, Pain Relief and Palliitive Care, SAMOT, v. Villahxa 99,90141 Palermo, Italy. Acceptedforpublicatian: May 29,1992. Q U.S. Cancer Pain Relief Committee, 1992 Published by Ehevier, New York, New York
Palliative care in terminal cancer patients thus satisfies the requirement of home care in the general sense. Economic advantages are combined with psychophysical benefits for the patients. Recognizing this potential, Societa Assistenza Malato Oncologico Tenninale (SAMOT), which has been active in Palermo since 1988, has been offering home care to such patients. It is the only service of this kind in Sicily.3 This article examines the objectives, difficulties, protocols, and achievements of these 4 years of experience, and compares the findings of the various years.
In 1988, SAMOT organized a pain relief and home palliative care unit for terminal cancer patients in the city of Palermo (popu08853924/92/$5.00
Vol. 7 No. 7 October 1992
Honae palliative Care
415
1 General manager Secretary 1 Psychiatrist 1 Chief for psychosocial activities 1 Social worker Volunteers 1 Director (Pain clinic) 1 Coordinator 7 Physicians (homecare)
uration of treat-
7 Nurses(homecarp)
dose/daysxlOO (used only for treatment lasting more than 15 days); and (f) pain level, was defined as “good” when pain was maintained at the level of “slight” or “moderate” (less than analogue scale (VAS) of rior to treatment was th its degree of efficacy, locks or any treatments and parented use of opioids, induding subcutaneous or intramuscular administration. Statistical analysis was erformed using x2 test and Student’s t test.
lation,l ,~~O,~OO~. thisinitiative was p and by private donanons. e management was nonprofit and private. consisted of a secretaryatrist, an oncologist, an anesthesiologist, three nurses, and a social worker. In 11989, the staff was extended and uhimateiy reached the final form &own in Table 1. Financial support also increased (about $300,000 per yr). At the beginning of 1991, a continuous on-call system was s and each home physician was issu beeper. Home visits are performed on nate days by physician and nurses so that nearly all the days of the week are covered. Data are collected and are recorded on special files indicating sym toms, drug doses, and general information about the patient.
A total of 745 patients were followed up during a 4yr period. Patient characteristics are listed in Table 2. The mean duration of Table 2
Patient
Year Treatment
1988
1989
1990
1991
121 53/47 61 11
248 66/34 37” 8
350 64/36 41” 7
.. Ex (m/Q (%I Home care (days) Incidence of dropout (%) Site of tumor (%) Head and neck Breast Lung Gastrointestinal Genitourinary Liver Pancreas Hematologic Other The values are expressed as mean. of c 0.05 when compared with 1989.
W/40 26 42” 2 6 10 22 18 21 4 t 11
7 9 23 E
3 5 25 ::
5 6 4 6
9 2 2 15
4 8 19 16 25 5 3 3 17
Vol. 7 No. 7 ckceober1992
Memdante et al.
416
Tadle 3 Analgesic Treatment Data Year
Treatment Incidence of pain (%) First step analgesic ladder (days) Starting opioid dose (mg) Maximal opioid dose (mg) Duration opioid treatment (days) Used “weak” opioicw only (%) Opioid escalation index Parenteral route (%) Pain control (%) Other techniques (%)
1988
1989
1990
1991
75 25 27 60 22 65 7 21 80 2
79 42 28 65 81b 62 5 16
80 190 38 63 32 60 lib 16
81
956
3
2
70 210 25 68 21 61 6 40 87 2
The flues are expressed as mean (for opioid daily dose). ‘PC 0.05 when compared with 1989. bk 0.05 when compared with other yean.
home care gradually reduced from a maximum of 61 days (range, l-384) in 1989 to 37
days (range, l-206) in 1990 (RO.05) and 41 days (range, l-301) in 1991 (RO.05). The percentage of patients with pain remained constant between 1990 (80%) and 1991 (70%). The mean duration of the first step of the so-called analgesic ladder (NSAID therapy j gradually reduced from a maximum of 42 days (range, l-300) in 1989 to 19 days (range, l-85) in 1990 (RO.05). A total of 85% of patients with pain received opioids before death. Of these, 57% received a so-called weak opioid. Table 3 presents the mean daily dosages in milligrams equivalent to morphine at the beginning of care, the maximum dose reached, the duration of opioid administration, and the frequency of parenteral opioid administration. Important variations in the initial and maximum opioid
dose were not observed. Only the escalation
index showed a significant increase (RO.05) in 1990. This modification did not affect overall opioid dosage, however. The parenteral administration of opioids (particularly by subcutaneous infusion in terminal phases) increased considerably in 1991 (RO.05). Pain control was possible in more than 80% of cases in all the years of study. Only a small proportion of the patients had been treated with opioids prior to treatment by our team (250/o, 33%, 34%, and 36% in 1988, 1989, 1990, and 1991, respectively). In most cases, the drugs administered previously were antiinflammatory drugs (75% in 1988, 67% in 1989, 66% in 1990, and 64% in 1991). When opioids were used, the drugs were nearly alwayspentazocine or buprenorphine. Only 2%, 2.5%, l%, and 10% of the patients during the 4 years, respectively, had previ-
Year Treatment Opioid treatment (%) Agonist opioid tres ment (%) Unsuccessful pain control (%) Use of “as needed” dosing (%) Use of antiinflammatory drugs (%) *PC 0.05 when compared with 1988 and 1989. bP < 0.05 when compared with other years.
1988
1989
1990
1991
25 2 75 80
33 2.5 68 83
34 1 60 73
75
36 10” 75 674
67
66
64
Vol, 7 No. 7 0c&0h?rI992
Pdialive
Care
417
to about six times and 75% in 1991) and was administered ai needed (80% in 1988, 83% in 1990, and 67% in 1991). significant reduction in “as needed” stration in 1991 (PcO.05) corn 1988 and 1989. In the last year, th a significant increase in the use of agonist opioids prior to the initiati Alternative or parenteral were rarely performed. including nerve blocks, alcoholization, or intraspinal injection, were performed at a 1989,2% in 899
evaluate the treatment of our patients from the time our team’s activity began until 1991. They enable us to assess variations in the type and duration of treatment, drug doses and efficacy, and treatments previously performed in o clinical settings. The mean duration of treatment steadily decreased during this period. This finding e attributed to patient selection. growing number of patients who request antineoplastic treatment result in referral of patients who are increasingly advanced. The same reason explains the reduction in duration of the first step of the “analgesic ladder.” Because pain is more likely as the disease progresses, the referral of more advanced cases will lead to more severe pain problems in a larger proportion. The incidence of pain remained constant, however, indicating that the type of patients did not change during the years studied. At least 60% of the patients with pain had been treated with only “weak” opioids until death during all 4 years. This may explain the relatively low opioid doses used in our patients. These doses did provide good pain control. There were no evident increases in maximum daily opioid dose in the various years; this value remained equivalent to approximately 60-70 mg for morphine. This finding
were less spectacular.
y could be attributed ts of pain and, above all, to different environmental (e.g., hoss) and sociocultural conditions, includearly exposure to opioids. Few of our patients bad received any opioid treatment, and in nearly all cases of those who opioids bad been badly used (administr renteral route use ects the resistant proper prescription 0 relate to the fear of awareness of methods of treating of cancer aingJO ioids as recomm
our center.l Until 4 years ago, pentazocine, buprenorphine, and parenteral morphine were prescribed by family or hospital doctors for several only after a patient guidelines days. Lack of know1 for cancer pain management often resulted in intolerable suffering for patients with pain associated with cancer. These findings support others reported by authors in the West German medical community.g Despite the appearance of meetings devoted to pain management and the slow diision of information about cancer pain, no great variations have been observed in the approach of family doctors or hospital facilities during the last few years. lo The analgesic therapy practiced before home care proved to be ineffective in 60%-75% of cases. Opioids were used in only one-third of the cases, and the opioids administered were rarely the pure agonists. Analgesics were administered only as needed in 67%-33% of cases. Although 1990 saw the highest opioid
418
Mercadante et al.
escalation indices, it was not observed that there was less pain control than other years, without the need to employ alternative techniques. On the contrary, when the mean duratiori of opioid administration was higher, but the maximum dosage was not significantly increased compared with other years, the lowest escalation index was observed (e.g., 1989). This index does not appear to be useful when treatments are too short (less than 15 days), but for others, it is helpful to label the patient’s response to opioids. Parenteral opioid administration clearly increased in 1990 compared with other years. This greater frequency can be attributed to the inclusion in the team’s equipment of portable pumps for the subcutaneous infusion of these drugs. This route was used when the oral route was no longer possible (e.g., inability to swallow, vomiting, intestinal obstruction, and reduced state of consciousness), in particular in the last days of life. Oral administration was maintained until death in 60% of cases. In previous years, opioids were administered by single subcutaneous or intramuscular injections. The home-care dropout percentage remained constant, even though it increased numerically. The main cause in most cases was the diffkulty in approaching the family, due to a misunderstanding of the purpose of the team’s intervention (seen as yet another consultation for an oncological assessment and therefore as a possibility of recovery). All other patients were followed at home until death. Our results suggest that considerable progress has been made in home palliative care, NOW, over 300 patients per year are able to benefit from a structure that enables them to
El. 7 No. 7 &lober 1992
control their symptoms, particularly pain, in the final stages of life; however, there are still considerable diiculties to overcome if results are to be further improved. Difficulties are not only technical, but also social and cultural. In our opinion, it is necessary to establish international links among the various forces committed to this activity in order to improve medical and social education in palliative care.
1. Mercadame S, Calaflore A, Sunset-i G, Trizzino C, Salvaggio L. The first home care program in south Italy. Pain 199O(suppl5):S375. 2. Ventafridda V Continuing care: a major issue in cancer pain management. Pain 1989;36:137-143. 3. Mercadante S, Mangione S. Home palliative care: a challenge in Palermo. J Palliat Care 1990;6:56-58. 4. Mercadante S, Lanza V A computerized file for collection of data in palliative care. In: ler Congres, Association Europeenne de Soins Palliatifs, Paris, 17-19 October 1990:154. 5. Cancer pain: a monograph on the management of cancer pain. Health and Welfare Canada; Minister of Supply and Services Canada H42-2/51984E. 6. Bruera E, MacMillan K, Hanson H, MacDonald RN. Palliative care in cancer center: results in 1984 versus 1987. J Pain Symptom Manage 1990;5:1-5. 7. Mount B. Medical applications Med Assoc J 1979;120:405-107.
of heroin. Can
8. Twycross R. Narcotics. In: Wall P, Melzack R, eds. Textbook of pain. Edinburgh: Churchill Livingstone, 1984:518. 9. Schug SA, Zech D, Dorr U. Cancer pain management according to WHO analgesic guidelines. J Pain Symptom Manage 1990;5:27-32. 10. Mercadante S, Maddaloni S, Roccella S, Salvaggio L, Simonetti MT Family doctor and palliative care team: 1988 versus 1990. J Palliat Care 1990;6:56-58.
Vol. 7 No. 7 October1992
Journal of Pain and SynQtom Management
dliative Care: versus 1988
ts in
Sebastian0 Mercadante, MD, Giuseppe Genovese, MD&far Agcha Kargar, MD, Salvatore Maddaloni, MD, Salvina Roccella, MD, Ieonardo Salvaggio, MD, and Maria Teresa Simonetti, MD An&hesioIo~ Sewice (S. M.), HospitalBuccherila F&a,-Pain Therajlrand HomePalliative Care (G.G.,JA.K., S.M., S.R, L.S., M.T.S.), SAMOI;PaZermo, Ztaly
AbsWct Home care k greatlyexpanding becauseof the savings it offers by avoiding unnecessary hospitalizationand also becausepatients benefitfrom being in their own home environmats. Since 1988, SocietaAssistenzaMa&o OncologicoTerminale (SAMOT} has organizeda pain relief and homepalliative care unit for terminal cancer patients. Objectives,dzffkulties,~otocols, and achievementsof 4years of experiencewereexamined, and thefindings of the variousyearswerecompared. Our resultssuggest that considerable pqyess has been maok in homepalliativecare. There are still social and cultural ds@ulties to overcome,howev0.J Pain Symptom Manage 1992;7:414-418. Home care, pain control, terminal cancer
Introduction Control of symptoms, including pain, is the fundamental aim of the palliative care of advanced cancer patients, who usually require continuing care for varying periods of time (2-3 months on average) .l Hospitalization in such cases is discomforting for the patients and expensive for society. Home care is greatly expanding because of the savir,ga PL offer. by av&,dir,g =Z_X^^ u,,‘lc_essary hospitalization, and also because patients benefit from being in their own home environments, surrounded by the affection of their families.2 AaUress reprint requests to: Sebastian0 Mercadante, MD, Pain Relief and Palliitive Care, SAMOT, v. Villahxa 99,90141 Palermo, Italy. Acceptedforpublicatian: May 29,1992. Q U.S. Cancer Pain Relief Committee, 1992 Published by Ehevier, New York, New York
Palliative care in terminal cancer patients thus satisfies the requirement of home care in the general sense. Economic advantages are combined with psychophysical benefits for the patients. Recognizing this potential, Societa Assistenza Malato Oncologico Tenninale (SAMOT), which has been active in Palermo since 1988, has been offering home care to such patients. It is the only service of this kind in Sicily.3 This article examines the objectives, difficulties, protocols, and achievements of these 4 years of experience, and compares the findings of the various years.
In 1988, SAMOT organized a pain relief and home palliative care unit for terminal cancer patients in the city of Palermo (popu08853924/92/$5.00
Vol. 7 No. 7 October 1992
Honae palliative Care
415
1 General manager Secretary 1 Psychiatrist 1 Chief for psychosocial activities 1 Social worker Volunteers 1 Director (Pain clinic) 1 Coordinator 7 Physicians (homecare)
uration of treat-
7 Nurses(homecarp)
dose/daysxlOO (used only for treatment lasting more than 15 days); and (f) pain level, was defined as “good” when pain was maintained at the level of “slight” or “moderate” (less than analogue scale (VAS) of rior to treatment was th its degree of efficacy, locks or any treatments and parented use of opioids, induding subcutaneous or intramuscular administration. Statistical analysis was erformed using x2 test and Student’s t test.
lation,l ,~~O,~OO~. thisinitiative was p and by private donanons. e management was nonprofit and private. consisted of a secretaryatrist, an oncologist, an anesthesiologist, three nurses, and a social worker. In 11989, the staff was extended and uhimateiy reached the final form &own in Table 1. Financial support also increased (about $300,000 per yr). At the beginning of 1991, a continuous on-call system was s and each home physician was issu beeper. Home visits are performed on nate days by physician and nurses so that nearly all the days of the week are covered. Data are collected and are recorded on special files indicating sym toms, drug doses, and general information about the patient.
A total of 745 patients were followed up during a 4yr period. Patient characteristics are listed in Table 2. The mean duration of Table 2
Patient
Year Treatment
1988
1989
1990
1991
121 53/47 61 11
248 66/34 37” 8
350 64/36 41” 7
.. Ex (m/Q (%I Home care (days) Incidence of dropout (%) Site of tumor (%) Head and neck Breast Lung Gastrointestinal Genitourinary Liver Pancreas Hematologic Other The values are expressed as mean. of c 0.05 when compared with 1989.
W/40 26 42” 2 6 10 22 18 21 4 t 11
7 9 23 E
3 5 25 ::
5 6 4 6
9 2 2 15
4 8 19 16 25 5 3 3 17
Vol. 7 No. 7 ckceober1992
Memdante et al.
416
Tadle 3 Analgesic Treatment Data Year
Treatment Incidence of pain (%) First step analgesic ladder (days) Starting opioid dose (mg) Maximal opioid dose (mg) Duration opioid treatment (days) Used “weak” opioicw only (%) Opioid escalation index Parenteral route (%) Pain control (%) Other techniques (%)
1988
1989
1990
1991
75 25 27 60 22 65 7 21 80 2
79 42 28 65 81b 62 5 16
80 190 38 63 32 60 lib 16
81
956
3
2
70 210 25 68 21 61 6 40 87 2
The flues are expressed as mean (for opioid daily dose). ‘PC 0.05 when compared with 1989. bk 0.05 when compared with other yean.
home care gradually reduced from a maximum of 61 days (range, l-384) in 1989 to 37
days (range, l-206) in 1990 (RO.05) and 41 days (range, l-301) in 1991 (RO.05). The percentage of patients with pain remained constant between 1990 (80%) and 1991 (70%). The mean duration of the first step of the so-called analgesic ladder (NSAID therapy j gradually reduced from a maximum of 42 days (range, l-300) in 1989 to 19 days (range, l-85) in 1990 (RO.05). A total of 85% of patients with pain received opioids before death. Of these, 57% received a so-called weak opioid. Table 3 presents the mean daily dosages in milligrams equivalent to morphine at the beginning of care, the maximum dose reached, the duration of opioid administration, and the frequency of parenteral opioid administration. Important variations in the initial and maximum opioid
dose were not observed. Only the escalation
index showed a significant increase (RO.05) in 1990. This modification did not affect overall opioid dosage, however. The parenteral administration of opioids (particularly by subcutaneous infusion in terminal phases) increased considerably in 1991 (RO.05). Pain control was possible in more than 80% of cases in all the years of study. Only a small proportion of the patients had been treated with opioids prior to treatment by our team (250/o, 33%, 34%, and 36% in 1988, 1989, 1990, and 1991, respectively). In most cases, the drugs administered previously were antiinflammatory drugs (75% in 1988, 67% in 1989, 66% in 1990, and 64% in 1991). When opioids were used, the drugs were nearly alwayspentazocine or buprenorphine. Only 2%, 2.5%, l%, and 10% of the patients during the 4 years, respectively, had previ-
Year Treatment Opioid treatment (%) Agonist opioid tres ment (%) Unsuccessful pain control (%) Use of “as needed” dosing (%) Use of antiinflammatory drugs (%) *PC 0.05 when compared with 1988 and 1989. bP < 0.05 when compared with other years.
1988
1989
1990
1991
25 2 75 80
33 2.5 68 83
34 1 60 73
75
36 10” 75 674
67
66
64
Vol, 7 No. 7 0c&0h?rI992
Pdialive
Care
417
to about six times and 75% in 1991) and was administered ai needed (80% in 1988, 83% in 1990, and 67% in 1991). significant reduction in “as needed” stration in 1991 (PcO.05) corn 1988 and 1989. In the last year, th a significant increase in the use of agonist opioids prior to the initiati Alternative or parenteral were rarely performed. including nerve blocks, alcoholization, or intraspinal injection, were performed at a 1989,2% in 899
evaluate the treatment of our patients from the time our team’s activity began until 1991. They enable us to assess variations in the type and duration of treatment, drug doses and efficacy, and treatments previously performed in o clinical settings. The mean duration of treatment steadily decreased during this period. This finding e attributed to patient selection. growing number of patients who request antineoplastic treatment result in referral of patients who are increasingly advanced. The same reason explains the reduction in duration of the first step of the “analgesic ladder.” Because pain is more likely as the disease progresses, the referral of more advanced cases will lead to more severe pain problems in a larger proportion. The incidence of pain remained constant, however, indicating that the type of patients did not change during the years studied. At least 60% of the patients with pain had been treated with only “weak” opioids until death during all 4 years. This may explain the relatively low opioid doses used in our patients. These doses did provide good pain control. There were no evident increases in maximum daily opioid dose in the various years; this value remained equivalent to approximately 60-70 mg for morphine. This finding
were less spectacular.
y could be attributed ts of pain and, above all, to different environmental (e.g., hoss) and sociocultural conditions, includearly exposure to opioids. Few of our patients bad received any opioid treatment, and in nearly all cases of those who opioids bad been badly used (administr renteral route use ects the resistant proper prescription 0 relate to the fear of awareness of methods of treating of cancer aingJO ioids as recomm
our center.l Until 4 years ago, pentazocine, buprenorphine, and parenteral morphine were prescribed by family or hospital doctors for several only after a patient guidelines days. Lack of know1 for cancer pain management often resulted in intolerable suffering for patients with pain associated with cancer. These findings support others reported by authors in the West German medical community.g Despite the appearance of meetings devoted to pain management and the slow diision of information about cancer pain, no great variations have been observed in the approach of family doctors or hospital facilities during the last few years. lo The analgesic therapy practiced before home care proved to be ineffective in 60%-75% of cases. Opioids were used in only one-third of the cases, and the opioids administered were rarely the pure agonists. Analgesics were administered only as needed in 67%-33% of cases. Although 1990 saw the highest opioid
418
Mercadante et al.
escalation indices, it was not observed that there was less pain control than other years, without the need to employ alternative techniques. On the contrary, when the mean duratiori of opioid administration was higher, but the maximum dosage was not significantly increased compared with other years, the lowest escalation index was observed (e.g., 1989). This index does not appear to be useful when treatments are too short (less than 15 days), but for others, it is helpful to label the patient’s response to opioids. Parenteral opioid administration clearly increased in 1990 compared with other years. This greater frequency can be attributed to the inclusion in the team’s equipment of portable pumps for the subcutaneous infusion of these drugs. This route was used when the oral route was no longer possible (e.g., inability to swallow, vomiting, intestinal obstruction, and reduced state of consciousness), in particular in the last days of life. Oral administration was maintained until death in 60% of cases. In previous years, opioids were administered by single subcutaneous or intramuscular injections. The home-care dropout percentage remained constant, even though it increased numerically. The main cause in most cases was the diffkulty in approaching the family, due to a misunderstanding of the purpose of the team’s intervention (seen as yet another consultation for an oncological assessment and therefore as a possibility of recovery). All other patients were followed at home until death. Our results suggest that considerable progress has been made in home palliative care, NOW, over 300 patients per year are able to benefit from a structure that enables them to
El. 7 No. 7 &lober 1992
control their symptoms, particularly pain, in the final stages of life; however, there are still considerable diiculties to overcome if results are to be further improved. Difficulties are not only technical, but also social and cultural. In our opinion, it is necessary to establish international links among the various forces committed to this activity in order to improve medical and social education in palliative care.
1. Mercadame S, Calaflore A, Sunset-i G, Trizzino C, Salvaggio L. The first home care program in south Italy. Pain 199O(suppl5):S375. 2. Ventafridda V Continuing care: a major issue in cancer pain management. Pain 1989;36:137-143. 3. Mercadante S, Mangione S. Home palliative care: a challenge in Palermo. J Palliat Care 1990;6:56-58. 4. Mercadante S, Lanza V A computerized file for collection of data in palliative care. In: ler Congres, Association Europeenne de Soins Palliatifs, Paris, 17-19 October 1990:154. 5. Cancer pain: a monograph on the management of cancer pain. Health and Welfare Canada; Minister of Supply and Services Canada H42-2/51984E. 6. Bruera E, MacMillan K, Hanson H, MacDonald RN. Palliative care in cancer center: results in 1984 versus 1987. J Pain Symptom Manage 1990;5:1-5. 7. Mount B. Medical applications Med Assoc J 1979;120:405-107.
of heroin. Can
8. Twycross R. Narcotics. In: Wall P, Melzack R, eds. Textbook of pain. Edinburgh: Churchill Livingstone, 1984:518. 9. Schug SA, Zech D, Dorr U. Cancer pain management according to WHO analgesic guidelines. J Pain Symptom Manage 1990;5:27-32. 10. Mercadante S, Maddaloni S, Roccella S, Salvaggio L, Simonetti MT Family doctor and palliative care team: 1988 versus 1990. J Palliat Care 1990;6:56-58.
