- Email: [email protected]
Is mortality rate what it is all about in congestive heart failure?
be able to personally defend their decisions-in the if necessary. Unless CDS systems can offer this level of confidence, clinicians and patients are unlikely to place much faith in them. It seems that, at their current state of development, CDS systems are better suited to computerassisted learning, and for this it must be possible for a trainee to interrogate the system to explore how a particular diagnosis or decision has been derived. In this way both experience and understanding are improved. It is noteworthy that the computer aided diagnosis system proposed by de Dombal and colleagues3 started life as a teaching system4 and was subsequently shown to improve the diagnostic performance of the clinicians5 but is still not in general use. Such evidence might be presented as a ranking of possibilities together with their likelihoods, confidence intervals, and diagnostic thresholds such that the clinician can (1) assess the reliability of the advice, and (2) be able to accept the responsibility for the clinical decision to act immediately or request further information. Unless it can be shown that neural nets can provide this level of decision support then it is unlikely that they will be accepted by clinicians any more readily than their predecessors. must
courts
S R Dodds Department of Vascular Surgery, Royal South Hants Hospital, Southampton SO14 0YG, UK
1 Croft DJ. Is computerized diagnosis possible?
Comput Biomed Res
1972; 5: 351-67. 2 MacCartney FJ. Diagnostic logic. BMJ 1987; 295: 1325-31. 3 de Dombal FT, Leaper DJ, Staniland JR, McCann AP, Horrocks JC. Computer-aided diagnosis of acute abdominal pain. BMJ 1972; 2: 9-13. 4 de Dombal FT, Hartley JR, Sleeman DH. A computer-assisted system for learning clinical diagnosis. Lancet 1969; i: 145-48. 5 de Dombal FT, Leaper DJ, Horrocks JC, Staniland JR, McCann AP. Human and computer-aided diagnosis of abdominal pain: further report with emphasis on performance of clinicians. BMJ 1974; iv: 376-80.
SiR-We would add to the number of clinical conditions for which ANNs have been used to investigate the process of diagnosis, outlined by Baxt (Oct 28, p 1135). We used data from a retrospective study of 1444 patients aged 40-70 years in a group general practice to investigate the use of ANNs in the diagnosis of asthma.’ The study included all patients who had respiratory symptoms (eg, cough, wheeze, and phlegm) and those who did not. The ratio of those with respiratory symptoms to those without, was about one to three. The general practitioner’s diagnosis was used to train the neural network. The data set contained 35 variables including age, sex, respiratory function tests, severity of condition, social class, and smoker status. Baxt’s data for myocardial infarction are affected by physicians erring on the side of safety, pushing their diagnostic sensitivity as high as possible. The variability in the diagnosis of asthma is shown by the asthma neural network having a sensitivity of 90% and a specificity of only 65%. Although we recognise the truth of Baxt’s statement that physicians are unenthusiastic about decision aids and that this will undoubtedly affect the professional acceptance of ANNs, we believe that it is important to emphasise that neural networks are an infinitely more friendly technology than any earlier computer science decision aid, statistical technique, or artificial intelligence technology such as expert systems. This so-called friendliness could lead to a different development approach-not one in which the physician is dependent on other experts or computer scientists to develop decision aids, but a situation in which practising physicians will develop the network themselves. A technology that can build a decision aiding model from
one’s
previous work and experience, with no computer programming (which was essential with earlier technologies, including expert systems) must be appealing to the practitioner. It is this friendliness that may overcome the difficulties of acceptability and lead to its usefulness as a screening tool. Baxt suggests that in life-threatening situations, physicians "push their diagnostic sensitivity as high as possible, leading to ..." over diagnosis. A similar approach could be used with ANNs in many clinical settings by training neural networks to a high sensitivity for screening patients, to identify those at risk. *Victor Lane, Peter
Littlejohns
*The IT Group, South Bank Business School, London SE1 0AA, UK; and Health Care Evaluation Unit, St George’s Hospital Medical School, London
1
Littlejohns P, Ebrahim S, Anderson R. Treatment the diagnosis relevant? Thorax 1989; 44: 797-802.
of adult asthma: is
mortality rate what it is all about in congestive heart failure? Is
SiR-Congestive heart failure (CHF) has become an increasingly important medical problem, with a poor prognosis in mild to severe disease. Mortality has been related to the severity of disease according to the New York Heart Association (NYHA). For patients with NYHA IV (symptoms at rest), the 1-year mortality is 50% or greater,’ whereas in NYHA III (symptoms on mild exertion) the rate is 35-40%. It is therefore not surprising that CHF has been compared to incurable cancer, with similar mortality rates and inevitable outcome. However, the therapeutic approach and especially the treatment possibilities offered to patients are quite different. Large CHF trials have mainly focused on mortality, and drugs with short-term efficacy were withdrawn because of unfavourable long-term effects on mortality.’-°3 Furthermore, effects on mortality are overemphasised in these trials, which measure reduction in mortality. It is of much more interest to report increases in survival time. Many clinicians might be surprised and disappointed by the modest increase in survival time by converting enzyme inhibitors-ie, 4-8 months-in patients with CHF Alternative vasodilator therapy, which has shown to be more effective with respect to exercise capacity,’ has gained little attention in clinical practice in the Netherlands. Since effects on mortality seem to be the gold standard, other endpoints are no longer considered. Therefore, drugs with potential short-term efficacy are not considered for further development and, ergo, are not available for patients who might prefer an increase of short-term exercise tolerance rather than a longer life. Published data on effects of drug regimens in large (disparate) patient groups may not be identical or relevant to the effect in an individual. Clinicians should decide with their patients the treatment that suits them best. For example, considerations with respect to survival will be different in an octogenarian than in a 40-year-old. And large trials do not always provide the answer for a specific patient, although, certainly, controlled prospective trials are very helpful in clinical decisions. In treating malignant diseases, however, discussions with patients are common, centering on the short-term benefit versus long-term and short-term risks, to achieve a chance of better survival. In first relapse of acute myeloid leukaemia, for example, treatment choices can be discussed: this may vary from supportive care in the outpatient clinic, or from intensive reinduction chemotherapy, to bone marrow transplantation. In many older patients these choices have to 1501
be discussed from the start of the disease. A shorter life expectancy, but being at home, might be preferred to a small chance of a longer life at the cost of a sometimes long hospital stay and considerable morbidity. The patient should have an important (and final) vote in the choice of therapy and the choice of what he considers important for his life. Since the ideal drug for the treatment of CHF that prolongs life and increases the quality of life, together with increased exercise tolerance is still a remote possibility, such discussions will probably be impossible for the CHF patient, especially since mortality outcome only seems to be the important issue-which is not justified in our view.
follow-up of at least 14 months, neurological abnormalities (hemiparesis three cases, pharmacoresistant
After
epilepsy in disturbance
3
4
5
together
polyneuropathy
movement
in
2,
case
*G Kluger, A Schöttler, K Waldvogel, D Nadal, W Hinrichs, G F Wündisch, M C Laub
The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med 1987; 316: 1429-35. Promise Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991; 325: 1468-75. Jondeau G, Dubourg O, Delorme G, et al. Oral enoximone as a substitute for intravenous catecholamine support in end-stage congestive heart failure. Eur Heart J 1994; 15: 242-46. The SOLVD investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293-302. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991; 325: 303-10.
*Neuropaediatric Department, Behandlungszentrum, Krankenhausstrasse 20, D-83569 Vogtareuth, Germany; Intensive Care and Infectious Diseases Units, Children’s Hospital, Zürich, Switzerland; Cnopf’sche Kinderklinik, Nurnberg, Germany; Children’s Hospital, Bayreuth, Germany 1
Zoulek G, Roggendorf M, Deinhardt F, Kunz C. Different immune responses after intradermal and intramuscular administration of vaccine against tick-borne encephalitis virus. J Med Virol 1986; 19:
2
Kunz C, Hofmann H, Kundi M, Mayer K. Zur Wirksamkeit von FSME—Immunglobulin. Wien Klin Wochenschr 1981; 93: 665-67. Morens DM. Antibody-dependent enhancement of infection and the pathogenesis of viral disease. Clin Infect Dis 1994; 19: 500-12.
55-61.
3
in
Hiking sticks Tickborne
encephalitis despite specific immunoglobulin prophylaxis
SiR-Tickborne Europe. Severe
2, and extrapyramidal
with
All three patients developed severe TBE despite passive immunisation after exposure at doses and within the time frame recommended by the manufacturer. In the last 10 years we have not observed severe TBE in children not passively immunised. Administration of hyperimmune globulin after a tick bite may have had a detrimental effect on the course of the illness in our patients. This would be in agreement with the notion of antibody-dependent enhancement of infection and contribution to pathogenesis in other arboviral diseases.3
Netherlands
2
1 and
remained.
*Armand R J Girbes, Joost Th M de Wolf Surgical Intensive Care Unit, University Hospital Groningen, 9713 EZ Groningen,
1
cases
(TBE) is widespread in of TBE with permanent neurological damage are rare, especially in children. Active immunisation with a killed-virus vaccine is recommended in endemic areas, and offers 90% protection.’ Passive immunisation before or after exposure with a specific immunoglobulin is available but little information exists as to the efficacy of this treatment." According to the manufacturer’s recommendation, the dosage of immunoglobulin should vary according to the time since exposure, and be administered no longer than 4 days after the tick bite. We report on three girls who had severe TBE with residual symptoms despite passive immunisation (table). In all three cases, intrathecal TBE virus-specific antibody was detected and immunodeficiency was ruled out. In cases 1 and 2 TBE-specific IgM was still found in cerebrospinal fluid after 8 months and in one case TBE-PCR was also positive. During the acute-phase of the encephalitis, enhanced signals in T2-weighted magnetic resonance imaging in the thalamus were demonstrated in all cases.
encephalitis
cases
mountaineering
SiR-Many hikers, mountaineers, and climbers use telescopic sticks, because these aid walking uphill or downhill and ease the strain of the spine and the leg joints, especially the knee.’ Telescopic sticks, however, must be used with the correct technique. Two sticks should always be used, and should be height-adjustable and have handles that
are
constructed in
a
way that the user’s hands-when
firm
support. pressing down-gain importance to use two sticks as close body’s line of fall.
It as
is
of
utmost
possible
to
the
1
To test whether hikers follow this advice by the Unione Internazionale delle Associazioni Alpinistiche Medical Commission we observed 860 hikers who used telescopic sticks. This study was undertaken in the Austrian Alps near Innsbruck during the summer of 1995. We found that more than 95% of our participants did not use telescopic sticks with the correct technique. Therefore, ways have to be found to pass down the correct advice’ to hikers and mountaineers. *Christian Haid, Arnold Koller Departments of *Orthopaedic Surgery, and Sports and Circulatory Medicine, University Hospital, A-6020 Innsbruck, Austria 1
Official Standards of the UIAA Medical Commission. Hiking sticks in vol 3. Medical Commission of UIAA, 1994.
mountaineering,
DEPARTMENT OF ERROR Tackling liver cancer with mterferon (Oct 21, p 1049)-In this Commentary by Schluger and Bodenheimer, the authors incorrectly stated that Nishiguchi and colleagues in the accompanying article (p 1051) used interferon CX2b’ which is recombinant mterferon, when the human lymphoblastoid interferon.
preparation used
was
Pertussis
Table: Severe tickborne
immunisation
1502
encephalitis after passive
in adults: frequency of transmission after household exposure-In this article by Wirsing von König and colleagues (Nov 18, p 1326), the two sex ratios in table 2 should be replaced by, respectively, 2-3 (41/18) and 1-1 (13/12).
courts
S R Dodds Department of Vascular Surgery, Royal South Hants Hospital, Southampton SO14 0YG, UK
1 Croft DJ. Is computerized diagnosis possible?
Comput Biomed Res
1972; 5: 351-67. 2 MacCartney FJ. Diagnostic logic. BMJ 1987; 295: 1325-31. 3 de Dombal FT, Leaper DJ, Staniland JR, McCann AP, Horrocks JC. Computer-aided diagnosis of acute abdominal pain. BMJ 1972; 2: 9-13. 4 de Dombal FT, Hartley JR, Sleeman DH. A computer-assisted system for learning clinical diagnosis. Lancet 1969; i: 145-48. 5 de Dombal FT, Leaper DJ, Horrocks JC, Staniland JR, McCann AP. Human and computer-aided diagnosis of abdominal pain: further report with emphasis on performance of clinicians. BMJ 1974; iv: 376-80.
SiR-We would add to the number of clinical conditions for which ANNs have been used to investigate the process of diagnosis, outlined by Baxt (Oct 28, p 1135). We used data from a retrospective study of 1444 patients aged 40-70 years in a group general practice to investigate the use of ANNs in the diagnosis of asthma.’ The study included all patients who had respiratory symptoms (eg, cough, wheeze, and phlegm) and those who did not. The ratio of those with respiratory symptoms to those without, was about one to three. The general practitioner’s diagnosis was used to train the neural network. The data set contained 35 variables including age, sex, respiratory function tests, severity of condition, social class, and smoker status. Baxt’s data for myocardial infarction are affected by physicians erring on the side of safety, pushing their diagnostic sensitivity as high as possible. The variability in the diagnosis of asthma is shown by the asthma neural network having a sensitivity of 90% and a specificity of only 65%. Although we recognise the truth of Baxt’s statement that physicians are unenthusiastic about decision aids and that this will undoubtedly affect the professional acceptance of ANNs, we believe that it is important to emphasise that neural networks are an infinitely more friendly technology than any earlier computer science decision aid, statistical technique, or artificial intelligence technology such as expert systems. This so-called friendliness could lead to a different development approach-not one in which the physician is dependent on other experts or computer scientists to develop decision aids, but a situation in which practising physicians will develop the network themselves. A technology that can build a decision aiding model from
one’s
previous work and experience, with no computer programming (which was essential with earlier technologies, including expert systems) must be appealing to the practitioner. It is this friendliness that may overcome the difficulties of acceptability and lead to its usefulness as a screening tool. Baxt suggests that in life-threatening situations, physicians "push their diagnostic sensitivity as high as possible, leading to ..." over diagnosis. A similar approach could be used with ANNs in many clinical settings by training neural networks to a high sensitivity for screening patients, to identify those at risk. *Victor Lane, Peter
Littlejohns
*The IT Group, South Bank Business School, London SE1 0AA, UK; and Health Care Evaluation Unit, St George’s Hospital Medical School, London
1
Littlejohns P, Ebrahim S, Anderson R. Treatment the diagnosis relevant? Thorax 1989; 44: 797-802.
of adult asthma: is
mortality rate what it is all about in congestive heart failure? Is
SiR-Congestive heart failure (CHF) has become an increasingly important medical problem, with a poor prognosis in mild to severe disease. Mortality has been related to the severity of disease according to the New York Heart Association (NYHA). For patients with NYHA IV (symptoms at rest), the 1-year mortality is 50% or greater,’ whereas in NYHA III (symptoms on mild exertion) the rate is 35-40%. It is therefore not surprising that CHF has been compared to incurable cancer, with similar mortality rates and inevitable outcome. However, the therapeutic approach and especially the treatment possibilities offered to patients are quite different. Large CHF trials have mainly focused on mortality, and drugs with short-term efficacy were withdrawn because of unfavourable long-term effects on mortality.’-°3 Furthermore, effects on mortality are overemphasised in these trials, which measure reduction in mortality. It is of much more interest to report increases in survival time. Many clinicians might be surprised and disappointed by the modest increase in survival time by converting enzyme inhibitors-ie, 4-8 months-in patients with CHF Alternative vasodilator therapy, which has shown to be more effective with respect to exercise capacity,’ has gained little attention in clinical practice in the Netherlands. Since effects on mortality seem to be the gold standard, other endpoints are no longer considered. Therefore, drugs with potential short-term efficacy are not considered for further development and, ergo, are not available for patients who might prefer an increase of short-term exercise tolerance rather than a longer life. Published data on effects of drug regimens in large (disparate) patient groups may not be identical or relevant to the effect in an individual. Clinicians should decide with their patients the treatment that suits them best. For example, considerations with respect to survival will be different in an octogenarian than in a 40-year-old. And large trials do not always provide the answer for a specific patient, although, certainly, controlled prospective trials are very helpful in clinical decisions. In treating malignant diseases, however, discussions with patients are common, centering on the short-term benefit versus long-term and short-term risks, to achieve a chance of better survival. In first relapse of acute myeloid leukaemia, for example, treatment choices can be discussed: this may vary from supportive care in the outpatient clinic, or from intensive reinduction chemotherapy, to bone marrow transplantation. In many older patients these choices have to 1501
be discussed from the start of the disease. A shorter life expectancy, but being at home, might be preferred to a small chance of a longer life at the cost of a sometimes long hospital stay and considerable morbidity. The patient should have an important (and final) vote in the choice of therapy and the choice of what he considers important for his life. Since the ideal drug for the treatment of CHF that prolongs life and increases the quality of life, together with increased exercise tolerance is still a remote possibility, such discussions will probably be impossible for the CHF patient, especially since mortality outcome only seems to be the important issue-which is not justified in our view.
follow-up of at least 14 months, neurological abnormalities (hemiparesis three cases, pharmacoresistant
After
epilepsy in disturbance
3
4
5
together
polyneuropathy
movement
in
2,
case
*G Kluger, A Schöttler, K Waldvogel, D Nadal, W Hinrichs, G F Wündisch, M C Laub
The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med 1987; 316: 1429-35. Promise Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991; 325: 1468-75. Jondeau G, Dubourg O, Delorme G, et al. Oral enoximone as a substitute for intravenous catecholamine support in end-stage congestive heart failure. Eur Heart J 1994; 15: 242-46. The SOLVD investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293-302. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991; 325: 303-10.
*Neuropaediatric Department, Behandlungszentrum, Krankenhausstrasse 20, D-83569 Vogtareuth, Germany; Intensive Care and Infectious Diseases Units, Children’s Hospital, Zürich, Switzerland; Cnopf’sche Kinderklinik, Nurnberg, Germany; Children’s Hospital, Bayreuth, Germany 1
Zoulek G, Roggendorf M, Deinhardt F, Kunz C. Different immune responses after intradermal and intramuscular administration of vaccine against tick-borne encephalitis virus. J Med Virol 1986; 19:
2
Kunz C, Hofmann H, Kundi M, Mayer K. Zur Wirksamkeit von FSME—Immunglobulin. Wien Klin Wochenschr 1981; 93: 665-67. Morens DM. Antibody-dependent enhancement of infection and the pathogenesis of viral disease. Clin Infect Dis 1994; 19: 500-12.
55-61.
3
in
Hiking sticks Tickborne
encephalitis despite specific immunoglobulin prophylaxis
SiR-Tickborne Europe. Severe
2, and extrapyramidal
with
All three patients developed severe TBE despite passive immunisation after exposure at doses and within the time frame recommended by the manufacturer. In the last 10 years we have not observed severe TBE in children not passively immunised. Administration of hyperimmune globulin after a tick bite may have had a detrimental effect on the course of the illness in our patients. This would be in agreement with the notion of antibody-dependent enhancement of infection and contribution to pathogenesis in other arboviral diseases.3
Netherlands
2
1 and
remained.
*Armand R J Girbes, Joost Th M de Wolf Surgical Intensive Care Unit, University Hospital Groningen, 9713 EZ Groningen,
1
cases
(TBE) is widespread in of TBE with permanent neurological damage are rare, especially in children. Active immunisation with a killed-virus vaccine is recommended in endemic areas, and offers 90% protection.’ Passive immunisation before or after exposure with a specific immunoglobulin is available but little information exists as to the efficacy of this treatment." According to the manufacturer’s recommendation, the dosage of immunoglobulin should vary according to the time since exposure, and be administered no longer than 4 days after the tick bite. We report on three girls who had severe TBE with residual symptoms despite passive immunisation (table). In all three cases, intrathecal TBE virus-specific antibody was detected and immunodeficiency was ruled out. In cases 1 and 2 TBE-specific IgM was still found in cerebrospinal fluid after 8 months and in one case TBE-PCR was also positive. During the acute-phase of the encephalitis, enhanced signals in T2-weighted magnetic resonance imaging in the thalamus were demonstrated in all cases.
encephalitis
cases
mountaineering
SiR-Many hikers, mountaineers, and climbers use telescopic sticks, because these aid walking uphill or downhill and ease the strain of the spine and the leg joints, especially the knee.’ Telescopic sticks, however, must be used with the correct technique. Two sticks should always be used, and should be height-adjustable and have handles that
are
constructed in
a
way that the user’s hands-when
firm
support. pressing down-gain importance to use two sticks as close body’s line of fall.
It as
is
of
utmost
possible
to
the
1
To test whether hikers follow this advice by the Unione Internazionale delle Associazioni Alpinistiche Medical Commission we observed 860 hikers who used telescopic sticks. This study was undertaken in the Austrian Alps near Innsbruck during the summer of 1995. We found that more than 95% of our participants did not use telescopic sticks with the correct technique. Therefore, ways have to be found to pass down the correct advice’ to hikers and mountaineers. *Christian Haid, Arnold Koller Departments of *Orthopaedic Surgery, and Sports and Circulatory Medicine, University Hospital, A-6020 Innsbruck, Austria 1
Official Standards of the UIAA Medical Commission. Hiking sticks in vol 3. Medical Commission of UIAA, 1994.
mountaineering,
DEPARTMENT OF ERROR Tackling liver cancer with mterferon (Oct 21, p 1049)-In this Commentary by Schluger and Bodenheimer, the authors incorrectly stated that Nishiguchi and colleagues in the accompanying article (p 1051) used interferon CX2b’ which is recombinant mterferon, when the human lymphoblastoid interferon.
preparation used
was
Pertussis
Table: Severe tickborne
immunisation
1502
encephalitis after passive
in adults: frequency of transmission after household exposure-In this article by Wirsing von König and colleagues (Nov 18, p 1326), the two sex ratios in table 2 should be replaced by, respectively, 2-3 (41/18) and 1-1 (13/12).