- Email: [email protected]
NEEDLESS DIGOXIN
96 DISTRIBUTION OF PLASMA DIGOXIN CONCENTRATIONS
There has been considerable discussion of the relative merits of surgical and medical management of certain clinical conditions, especially coronary disease: clearly, medical management is only valid if it does not interfere with the patient’s intellectual processes, as I suspect it often does. ,
-
Centre for Research
in Experimental Space Science, York University, Downsview, Toronto, Canada M3J 1P3
H. O. PRITCHARD
LYMPHOMAS OF AIDS and last
samples
of the series for
patients
with
more
than
one
measurement.
Only 5 7’6% of single samples fell within the wide therapeutic range for the drug. There was no increase in this proportion at the end of a series of digoxin measurements, casting doubt on whether measurements had influenced patient management. There was a small movement test, p<0’05) away from potentially toxic levels. However, since at least 12% of first samples were inappropriately timed (less than 6 h post-dose), a subsequent fall in
(X2
concentration may not reflect actual dosage reduction. The only valid reason for measuring the circulating concentration of digoxin, or indeed of any drug, is to answer a clinical questioneg, why is there poor response to treatment or does dosage need to be adjusted in the light of altered renal function? Clague and colleagueshave reported widespread failure to define the reasons for serum digoxin measurement and to take action on the results. Our data suggest that alteration in digoxin dosage resulted from digoxin measurement in few patients, and it is difficult to avoid the conclusion that a large proportion of the requests were unnecessary. Provision of this quality of service costs £ 4000 per year in reagents alone. The unnecessary performance of "routine" investigations in large numbers of patients represents a major drain on NHS resources. An effective therapeutic drug monitoring service requires more than the ability to provide accurate concentration measurements on all specimens received.5 If therapeutic drug monitoring is not to go the way of "urea and electrolytes" careful appraisal of requesting procedures is necessary to ensure benefit to the patient and to improve cost-effectiveness. Department of Pathological Biochemistry, and Clinical Pharmacology Unit, University Department of Medicine, Western Infirmary, Glasgow G11 6NT
MICHAEL J. HALLWORTH MARTIN J. BRODIE
DB. Plasma digoxin. an over-used test? Ann Clin Biochem 1984; 21: 449-52 JK. Indications for the measurement of plasma digoxin concentration. Drugs 1983, 26: 230-42 3 Aronson JK, Grahame-Smith DG, Wigley FM. Monitoring digoxin therapy: The use of plasma digoxin concentration measurements in the diagnosis of digoxin toxicity. Quart J Med 1978; 47: 111-22 4. Clague HW, Twum-Barima Y, Carruthers SG. An audit of requests for therapeutic drug monitoring of digoxin problems and pitfalls. Therap Drug Monit 1983; 5: 1
Morgan
2 Aronson
249-54. 5
Brodie MJ, McIntosh ME, Hallworth MJ Therapeutic drug monitoring. the need for audit? Scott Med J 1985, 30: 75-82.
SIR,—The case definition of AIDS has lately been revised by the Centers for Disease Control to include several additional diseases, amongst which is non-Hodgkin’s lymphoma.During the past two years, the incidence oflymphomas in homosexual males has shown a continuous increase. At this New York hospital, 21 cases of lymphoma in patients at risk for AIDS were diagnosed by January, in homosexual males 1985.2 8 months later, the total who also manifested clinical or immunological symptoms of AIDS has risen to 35. These cases, the several published case-reports and the one series of 90 cases originating from six major medical centres present common characteristics features that differ from those of lymphomas in the general population and are similar to the lymphomas seen in organ transplant recipients.3-6 The mean age of our patients was 40, 8 years than that in The ratio of nonpatients with AIDS-related Hodgkin’s to Hodgkin’s lymphomas was 29:6, the reverse of that commonly recorded in this population of young adults. The ratio between nodal and extranodal non-Hodgkin’s lymphomas was much decreased, with 15 of 31 located at diagnosis in extranodal organs showing a marked predilection for the gastrointestinal tract and the brain. Lymphomas were highly aggressive and uniformly involved multiple organs. Histologically, they were not uniform; however, almost all cases belonged to high-grade categories, predominantly diffuse, large, non-cleaved cell type. The phenotype was B cell without exception. Non-neoplastic lymphadenopathies preceded the lymphomas in most cases and showed the typical AIDS-related morphological changes, in most cases the involuted germinal centres with high vascular proliferation.Of the patients tested, all 9 had circulating HTLV-III antibodies, 14 of 18 had a T-cell helper/suppressor ratio of less than 0-8, and 11 of 14 had circulating anti-T-lymphocyte antibodies.9 Reflecting the immature tumour cell types and the defective immune response, the course of lymphomas in AIDS-related patients has been highly malignant, with the only survivors those diagnosed within the past 6 months. Despite a variety of chemotherapy regimens and generally a positive initial response, almost all patients have relapsed. Because of the poor results obtained in their treatment, AIDS-related lymphomas should be considered a separate group and not be included in general clinical or chemotherapy studies.
of lymphomas
lymphadenopathies.more
Departments of Pathology and Medicine, Lenox Hill Hospital, New York, NY10021, USA
1. Centers
for
Disease
HARRY L. IOACHIM MARVIN C. COOPER Control
Revision
of the
case
definition
of
acquired
immunodeficiency syndrome for national reporting-United States. MMWR 1985; 34: 373-75.
NEEDLESS DIGOXIN
abstract returned; it has remained with
me ever
HL, Cooper MC, Hellman GC. Lymphomas in males at high risk for the acquired immune deficiency syndrome (AIDS): a study of 21 cases. Cancer (in press) Centers for Disease Control. Diffuse, undifferentiated non-Hodgkin’s lymphoma
2. Ioachim
SIR,—Your Nov 9 editorial on digoxin prompts me to describe my own experience. I underwent a triple coronary bypass operation in 1977, and upon discharge from hospital was put on 0 - 25 mg digoxin daily. During the succeeding months, I began to recognise that I was left with several after-effects, the most important being a dulling of the mental processes, to the extent that I could not manipulate even the simplest algebraic expressions in my head; as a mathematical scientist, I thus began to consider my options in respect of early retirement, or long-term disability, at the age of 49. A year after the operation, I was told to discontinue the digoxin (which I did with some apprehension because, by then, I had come to believe that my life somehow depended upon not forgetting to take the little pill), and within two days, my ability to think in the since.
3. 4.
5.
among homosexual men-United States. MMWR 1982; 31: 277 Ziegler JL, et al. Non-Hodgkin’s lymphoma in 90 homosexual men: Relationship to generalized lymphadenopathy and acquired immunodeficiency syndrome (AIDS) N Engl J Med 1984; 311: 565-71. Hanto WH, Frizzera G, Purtillo DT, et al. Clinical spectrum of lympho-proliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus
6 Penn I.
Cancer Res 1981; 41: 4253-61.
Lymphomas complicating transplantation patients. Transpl
Proc 1983; 15:
2790-97.
7. Ioachim men:
HL, Lerner CW, Tapper ML Lymphadenopathies in homosexual with the acquired immune deficiency syndrome. JAMA 1983,
relationships
250: 1306-09. 8. Ioachim HL, Lerner CW, Tapper ML. The lymphoid lesions associated with the acquired immunodeficiency syndrome Am J Surg Pathol 1983; 7: 543-53. 9. Dorsett B, Cronin W, Chuma V, Ioachim HL Anti-lymphocyte antibodies in patients with the acquired immune deficiency syndrome. Am J Med 1985; 78: 621-26.
There has been considerable discussion of the relative merits of surgical and medical management of certain clinical conditions, especially coronary disease: clearly, medical management is only valid if it does not interfere with the patient’s intellectual processes, as I suspect it often does. ,
-
Centre for Research
in Experimental Space Science, York University, Downsview, Toronto, Canada M3J 1P3
H. O. PRITCHARD
LYMPHOMAS OF AIDS and last
samples
of the series for
patients
with
more
than
one
measurement.
Only 5 7’6% of single samples fell within the wide therapeutic range for the drug. There was no increase in this proportion at the end of a series of digoxin measurements, casting doubt on whether measurements had influenced patient management. There was a small movement test, p<0’05) away from potentially toxic levels. However, since at least 12% of first samples were inappropriately timed (less than 6 h post-dose), a subsequent fall in
(X2
concentration may not reflect actual dosage reduction. The only valid reason for measuring the circulating concentration of digoxin, or indeed of any drug, is to answer a clinical questioneg, why is there poor response to treatment or does dosage need to be adjusted in the light of altered renal function? Clague and colleagueshave reported widespread failure to define the reasons for serum digoxin measurement and to take action on the results. Our data suggest that alteration in digoxin dosage resulted from digoxin measurement in few patients, and it is difficult to avoid the conclusion that a large proportion of the requests were unnecessary. Provision of this quality of service costs £ 4000 per year in reagents alone. The unnecessary performance of "routine" investigations in large numbers of patients represents a major drain on NHS resources. An effective therapeutic drug monitoring service requires more than the ability to provide accurate concentration measurements on all specimens received.5 If therapeutic drug monitoring is not to go the way of "urea and electrolytes" careful appraisal of requesting procedures is necessary to ensure benefit to the patient and to improve cost-effectiveness. Department of Pathological Biochemistry, and Clinical Pharmacology Unit, University Department of Medicine, Western Infirmary, Glasgow G11 6NT
MICHAEL J. HALLWORTH MARTIN J. BRODIE
DB. Plasma digoxin. an over-used test? Ann Clin Biochem 1984; 21: 449-52 JK. Indications for the measurement of plasma digoxin concentration. Drugs 1983, 26: 230-42 3 Aronson JK, Grahame-Smith DG, Wigley FM. Monitoring digoxin therapy: The use of plasma digoxin concentration measurements in the diagnosis of digoxin toxicity. Quart J Med 1978; 47: 111-22 4. Clague HW, Twum-Barima Y, Carruthers SG. An audit of requests for therapeutic drug monitoring of digoxin problems and pitfalls. Therap Drug Monit 1983; 5: 1
Morgan
2 Aronson
249-54. 5
Brodie MJ, McIntosh ME, Hallworth MJ Therapeutic drug monitoring. the need for audit? Scott Med J 1985, 30: 75-82.
SIR,—The case definition of AIDS has lately been revised by the Centers for Disease Control to include several additional diseases, amongst which is non-Hodgkin’s lymphoma.During the past two years, the incidence oflymphomas in homosexual males has shown a continuous increase. At this New York hospital, 21 cases of lymphoma in patients at risk for AIDS were diagnosed by January, in homosexual males 1985.2 8 months later, the total who also manifested clinical or immunological symptoms of AIDS has risen to 35. These cases, the several published case-reports and the one series of 90 cases originating from six major medical centres present common characteristics features that differ from those of lymphomas in the general population and are similar to the lymphomas seen in organ transplant recipients.3-6 The mean age of our patients was 40, 8 years than that in The ratio of nonpatients with AIDS-related Hodgkin’s to Hodgkin’s lymphomas was 29:6, the reverse of that commonly recorded in this population of young adults. The ratio between nodal and extranodal non-Hodgkin’s lymphomas was much decreased, with 15 of 31 located at diagnosis in extranodal organs showing a marked predilection for the gastrointestinal tract and the brain. Lymphomas were highly aggressive and uniformly involved multiple organs. Histologically, they were not uniform; however, almost all cases belonged to high-grade categories, predominantly diffuse, large, non-cleaved cell type. The phenotype was B cell without exception. Non-neoplastic lymphadenopathies preceded the lymphomas in most cases and showed the typical AIDS-related morphological changes, in most cases the involuted germinal centres with high vascular proliferation.Of the patients tested, all 9 had circulating HTLV-III antibodies, 14 of 18 had a T-cell helper/suppressor ratio of less than 0-8, and 11 of 14 had circulating anti-T-lymphocyte antibodies.9 Reflecting the immature tumour cell types and the defective immune response, the course of lymphomas in AIDS-related patients has been highly malignant, with the only survivors those diagnosed within the past 6 months. Despite a variety of chemotherapy regimens and generally a positive initial response, almost all patients have relapsed. Because of the poor results obtained in their treatment, AIDS-related lymphomas should be considered a separate group and not be included in general clinical or chemotherapy studies.
of lymphomas
lymphadenopathies.more
Departments of Pathology and Medicine, Lenox Hill Hospital, New York, NY10021, USA
1. Centers
for
Disease
HARRY L. IOACHIM MARVIN C. COOPER Control
Revision
of the
case
definition
of
acquired
immunodeficiency syndrome for national reporting-United States. MMWR 1985; 34: 373-75.
NEEDLESS DIGOXIN
abstract returned; it has remained with
me ever
HL, Cooper MC, Hellman GC. Lymphomas in males at high risk for the acquired immune deficiency syndrome (AIDS): a study of 21 cases. Cancer (in press) Centers for Disease Control. Diffuse, undifferentiated non-Hodgkin’s lymphoma
2. Ioachim
SIR,—Your Nov 9 editorial on digoxin prompts me to describe my own experience. I underwent a triple coronary bypass operation in 1977, and upon discharge from hospital was put on 0 - 25 mg digoxin daily. During the succeeding months, I began to recognise that I was left with several after-effects, the most important being a dulling of the mental processes, to the extent that I could not manipulate even the simplest algebraic expressions in my head; as a mathematical scientist, I thus began to consider my options in respect of early retirement, or long-term disability, at the age of 49. A year after the operation, I was told to discontinue the digoxin (which I did with some apprehension because, by then, I had come to believe that my life somehow depended upon not forgetting to take the little pill), and within two days, my ability to think in the since.
3. 4.
5.
among homosexual men-United States. MMWR 1982; 31: 277 Ziegler JL, et al. Non-Hodgkin’s lymphoma in 90 homosexual men: Relationship to generalized lymphadenopathy and acquired immunodeficiency syndrome (AIDS) N Engl J Med 1984; 311: 565-71. Hanto WH, Frizzera G, Purtillo DT, et al. Clinical spectrum of lympho-proliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus
6 Penn I.
Cancer Res 1981; 41: 4253-61.
Lymphomas complicating transplantation patients. Transpl
Proc 1983; 15:
2790-97.
7. Ioachim men:
HL, Lerner CW, Tapper ML Lymphadenopathies in homosexual with the acquired immune deficiency syndrome. JAMA 1983,
relationships
250: 1306-09. 8. Ioachim HL, Lerner CW, Tapper ML. The lymphoid lesions associated with the acquired immunodeficiency syndrome Am J Surg Pathol 1983; 7: 543-53. 9. Dorsett B, Cronin W, Chuma V, Ioachim HL Anti-lymphocyte antibodies in patients with the acquired immune deficiency syndrome. Am J Med 1985; 78: 621-26.