- Email: [email protected]
TROUBLE IN THE POTTING SHED
151
POSITIVE DISCRIMINATION FOR SURGERY? The lament that surgical interventions are unjustly spared the rigours of evaluation by randomised controlled trials has been heard before.’ Often the contrast is made with all the premarketing fuss that surrounds the introduction of a new drug, from which a surgeon proposing a new technique seems to be exempt. The theme was repeated lately in a "call for patients" concerning a trial of hysterectomy vs ablation of endometrium via transcervical resection as a treatment for
menorrhagia.2 Undoubtedly
there
are
grand examples of surgical
randomised controlled trials—eg, the sagas of coronary bypass surgery and extracranial/intracranial bypasses-but the overall impression is that the risks and benefits of less often formally evaluated. If one refuses to entertain the hypothesis that the surgical sciences initially are less amenable to the finer points of logic, there must be something intrinsically different and more difficult in surgical trials by comparison with pharmacological studies. In a drug trial, the use of placebo and blinding permits precise quantification of the true pharmacological effect of a chemical, at least in principle. The total placebo effect, induced by the swallowing of pills and its accompanying tender loving care, is made expressly the same in both treatment arms, so that it cancels out. Not so in surgery. Short of a sham operation, it is impossible to devise a true placebo procedure. Thus, the effects of surgery canot be separated from all the other aspects of surrounding care. The effect of surgery will almost always remain confounded3 with the effect of the surgeon. The proposed trial of hysterectomy vs transcervical resection of the endometrium is a case in point. Hysterectomy stops all future dysfunctional bleeding effectively whereas partial or total ablation aims to reduce bleeding to at least an acceptable menstrual pattern. Blinding by a sham operation is not feasible. How will risks and benefits be counted? The immediate risk count might be straightforward-more harm might be done by the more invasive procedure. What about the benefit? Is it consumer satisfaction? Should the benefit strictly be measured in terms of an equal lack of recurrence of menorrhagia? Proving equality of treatments is in itself a hard job statistically4’s and will be even more difficult here-a slight recurrence of dysfunctional bleeding might be perfectly acceptable to a woman in exchange for a less invasive operation with retention of the uterus. If it stands to reason that the new procedure is indeed less risky, it might suffice to show acceptable recurrence rates without the necessity of going through the motions of a randomised trial. But how reasonable is an informal comparison of the risks of the competing procedures? What are acceptable recurrence rates? Moreover, the availability of an easier procedure might widen the indication-women who would never have been candidates for hysterectomy might now opt for partial ablation. When it comes to informed consent how do we convince a truly informed and articulate patient that it is necessary to sacrifice her womb on the altar of science when a less mutilating alternative is available?6 Whilst our surgical colleagues might face headier challenges if they attempt to apply the gold standard of therapeutic evaluation-the randomised trial-to their innovations, perhaps they should not impose such standards indiscriminately but only "by indication". Surgeons could set an example by giving far more careful thought to their trials than is needed in the planning of a pharmacological surgery
evaluation, in which routine protocols for randomised trials can be and are applied almost blindly. 1. Pocock SJ. Clinical trials, a practical approach. Chichester: Wiley, 1983: 64-65. 2. Stirrat GM, Dwyer N, Browning J. Planned trial of transcervical resection of the endometrium versus hysterectomy. Br J Obstet Gynaecol 1990; 97: 459. 3. Fisher RA. The design of experiments. 7th ed. Edinburgh: Oliver and
Boyd, 1960: 109-36. 4. Mau J. A statistical assessment of clinical equivalence. Stat Med 1988; 7: 1267-77. 5. Rodary Ch, Com-Nogue C, Toumade MF. How to establish equivalence between treatments: a one-sided clinical trial in paediatric oncology. Stat Med 1989; 8: 593-98. 6. Payer L. Medicine and culture: varieties of treatment in the United States, England, West Germany and France. New York: Henry Holt &
Co, 1988: 21-22.
are
TROUBLE IN THE POTTING SHED has been an outbreak of infection with Legionella longbeachae serogroup (SG) U This organism, originally cultured from a patient with pneumonia, is an infrequent cause of infection and has only occasionally been isolated from the environment, although it has been found in the UK.2 Antibody to L longbeachae of SG1 and 2 has been
In
Australia, there
found in some patients with respiratory infection, although in one series3 the response was sometimes to both serogroups and was usually associated with antibody to L jordanis. Since the organisms were not isolated from any of these patients, the importance of the antibody findings is unclear. Starting in October, 1988, there were 23 cases of L longbeachae SG1 infection in South Australia over three months. Additional single cases occurred in February, April, and June, 1989, and there were a few between May, 1987, and October, 1988, making a total of 30 patients. 11 patients yielded L longbeachae SG1 on culture, 8 of whom seroconverted. 8 other patients showed seroconversion alone and the remaining 11 a high level of antibody (256; only late serum samples obtained). Detailed epidemiological investigations suggested that gardening was a major risk factor for the infection, so water supplies from the homes of cases were studied. When this examination did not yield any positive cultures the South Australian Communicable Diseases Control Unit turned its attention to soil samples from the gardens of 4 patients whose infection had occurred either during or after December, 1988, the diagnosis having been confirmed by culture or seroconversion. All 4 patients were active gardeners who had used commercially available potting mixes shortly before they became ill. L longbeachae SG was isolated from a potting mix from the homes of 3 patients, from soil from a potted plant in 1 of these, and from soil from a potted plant alone in the remaining patient. Numbers of organisms in soil ranged from 102 to 105 cfu/g. Two of the undried potting mix brands remained culture positive on testing for seven months, whereas legionellae were not isolated from known positive soil samples that had been dried for seven days. L longbeachae SG1 was also isolated from water at the bottom of a potted plant that had been left outdoors for eighteen weeks and watered only with
legionella-free water. The presence of legionellae has been documented in many parts of the world in association with diverse natural waters and it is well known that legionellae are found in cooling towers, evaporative condensers, humidifiers, and domestic water systems. Legionellae have also been described in association with mud, and the soil in that
152
instance may well have been contaminated from a water supply, as is possible for the potting mixes investigated in Australia. Garden soil and water at the homes of patients did not yield L longbeachae SG1, the organism being isolated only from the soil of the potted plant and the three mixes. The potting mixes were not examined for the presence of free-living amoebae. This is an important omission because such organisms may be important in the ecology of legionellae in water. 4,5 After the original work of Rowbotham,4 others have confirmed his findings that legionellae can multiply inside amoebae, and Fields et al6 showed that amoebae may be an important factor in the survival of legionellae in stored water. When potable water in which L pneumophila was able to multiply was passed through a 0.45 µm filter the legionellae were no longer able to grow because the filtration had removed amoebae in which the legionellae could multiply. Earlier observations7 had shown that legionellae persist in tap water, even in the presence of a low level of chlorine, and it was suggested that chlorine resistance of the organisms might have been enhanced. However, Kilvington and Price8 have lately shown that legionellae can survive inside amoebic cysts and thereby resist killing by chlorine at levels of up to 50 mg/l. The possible relation between trophozoites or even cysts of amoebae and the survival of legionellae in the potting mix could be important, although the fact that legionellae were not found in the soil after drying suggests that at least in these circumstances legionellae were not protected from the effects of drying, which one might have expected had they been inside amoebic cysts. Nevertheless, it would be well worth while to examine potting mix samples to see whether amoebae are present. These Australian investigations are of additional interest because in one of the early accounts of an outbreak of legionnaires’ disease, at a psychiatric hospital in Washington,9 the researchers commented that shortly before the outbreak of infection, in which patients with access to the grounds or sleeping near the windows were especially affected, there had been excavation work for a new water sprinkling system for the grounds of the hospital with consequent soil disturbance. If there had been legionellae in the soil, either in amoebic cysts or in amoebae, and they had been carried in an aerosol or even in the dust observed at the hospital, it is possible that the amoebae could have been the vectors of infection.4,8 1. Steele TW, Lanser J, Sangster N. Isolation of Legionella longbeachae serogroup 1 from potting mixes. Appl Environ Microbiol 1990; 56: 49-53. 2. Fallon RJ.
Legionella pneumophila infections in Scotland 1987. CD(S) U Weekly Rep 1988 22 No26 7-9. 3. Fallon RJ, Abraham WH. Experience with heat-killed antigens of L longbeachae serogroups 1 and 2, and L jordanis in the indirect fluorescence antibody test. Zbl Bakt Hyg I Abt Orig 1983; A255: 8-14. 4. Rowbotham TJ. Preliminary report on the pathogenicity of Legionella pneumophila for fresh water and soil amoebae. J Clin Pathol 1980; 33: 1179-83. 5. Fallon RJ, Rowbotham TJ. Microbiological investigations into an outbreak of Pontiac fever due to Legionella micdadei associated with use of a whirlpool. J Clin Pathol 1990; 43: 479. 6. Fields BS, Sander GN, Barbaree JM, et al. Intracellular multiplication of Legionellae pneumophila from amoebae isolated from hospital hot water tanks. Current Microbiol 1989; 18: 131-37. 7. Kuchta JM, Slates SJ, McGlaughlin JE, et al. Enhanced chlorine resistance of tap water-adapted Legionella pneumophila as compared with agar medium-passaged strains. Appl Environ Microbiol 1985; 50: 21-26. 8. Kilvington S, Price J. Survival of Legionella pneumophila within cysts of Acanthamoeba polyphaga following chlorine exposure. J Appl Bacteriol 1990; 68: 519-25. 9. Thacker SB, Bennet JV, Tsai TF, et al. An outbreak in 1965 of severe respiratory illness caused by the legionnaires’ disease bacterium. J Infect Dis 1978; 138: 512-19.
ADVISING PATIENTS WITH ARTIFICIAL HEART VALVES All patients with implanted prosthetic heart valves are at risk from certain complications, some of which are lifethreatening and can occur without warning--eg, valve thrombosis, cerebral or coronary embolism, and mechanical valve failure. Media publicity about cases of mechanical failure of the Bjork-Shiley 60° CC valve has lately alarmed many recipients of this and other types of valve replacement. These patients naturally turn to their doctor for advice and reassurance. What should they be told? The risk of mechanical failure of Bjork-Shiley 60° CC valves (sizes 29, 31, and 33 mm) manufactured between Feb 1,1981, and June 30,1982, is 0.295% per year. The risk with other sizes and valves manufactured before or after these dates is less than 0-087% per year.1 Expressed actuarially, the hazard rate decreases with time. The yearly hazard rate, for the batch of valves most at risk, declined from 0-4% in the first year to 0-125% at 6 years after implant.z2 In deciding how to counsel patients with implanted 60° CC valves, the ongoing (but decreasing) risk of lifethreatening mechanical failure must be set against the risk of elective reoperation to replace the valve, which in the UK carries a case-fatality of 13% according to the Society of Cardiothoracic Surgeons. Thus reoperation is associated with a substantially greater risk and cannot be recommended on the basis of these figures. In a few patients, other factors may modify this recommendation. The more difficult question to answer unequivocally is whether all patients with a 60° CC valve should be informed of the possible risk. In health services centred on primary care, the patient’s general practitioner should be given all the relevant details and will often be in the best position to initiate a thorough discussion. Since most patients will be reassured rather than frightened by the figures, doctors must have strong reasons for withholding such information. In the event of mechanical valve failure, outcome depends on prompt diagnosis and emergency surgery. For this reason it is important that the patient carries information detailing the prosthetic valve type and model number and that doctors are aware of the mode of presentation of sudden valve failure, which can easily be confused with myocardial infarction. Patients with acute valve failure will be in cardiogenic shock with hypotension and pulmonary oedema. Severe dyspnoea rather than chest pain is the prominent symptom. On examination, the valve-clicks cannot be heard. A penetrated radiograph will reveal absence of the disc and one valve strut; an echocardiogram will also show that the valve disc is not in the prosthesis. The time between valve failure and death or reparative surgery varies from minutes to 15 hours, depending on the patient’s myocardial reserve and pulmonary vasculature. So, patients with artificial heart valves can be reassured that the overall frequency of complications is very low. The probability of freedom from failure of the Bjork-Shiley 60° CC valve in the mitral position at 10 years is 96-7% The probability of freedom from valve failure causing death is 99% according to one UK series. 1.
2.
Figures from Shiley up-date circular, Shiley Inc, Irvine, California. June 4, 1990. Hiratzka LF, Kouchoukos NT, Grunkemeier GL, Miller C, Scully HE, Wechsler AS. Outlet strut fracture of the Bjork-Shiley 60° convexoconcave
valve:
current
care. JACC 1988;
information and recommendations for patient
11: 1130-37.
POSITIVE DISCRIMINATION FOR SURGERY? The lament that surgical interventions are unjustly spared the rigours of evaluation by randomised controlled trials has been heard before.’ Often the contrast is made with all the premarketing fuss that surrounds the introduction of a new drug, from which a surgeon proposing a new technique seems to be exempt. The theme was repeated lately in a "call for patients" concerning a trial of hysterectomy vs ablation of endometrium via transcervical resection as a treatment for
menorrhagia.2 Undoubtedly
there
are
grand examples of surgical
randomised controlled trials—eg, the sagas of coronary bypass surgery and extracranial/intracranial bypasses-but the overall impression is that the risks and benefits of less often formally evaluated. If one refuses to entertain the hypothesis that the surgical sciences initially are less amenable to the finer points of logic, there must be something intrinsically different and more difficult in surgical trials by comparison with pharmacological studies. In a drug trial, the use of placebo and blinding permits precise quantification of the true pharmacological effect of a chemical, at least in principle. The total placebo effect, induced by the swallowing of pills and its accompanying tender loving care, is made expressly the same in both treatment arms, so that it cancels out. Not so in surgery. Short of a sham operation, it is impossible to devise a true placebo procedure. Thus, the effects of surgery canot be separated from all the other aspects of surrounding care. The effect of surgery will almost always remain confounded3 with the effect of the surgeon. The proposed trial of hysterectomy vs transcervical resection of the endometrium is a case in point. Hysterectomy stops all future dysfunctional bleeding effectively whereas partial or total ablation aims to reduce bleeding to at least an acceptable menstrual pattern. Blinding by a sham operation is not feasible. How will risks and benefits be counted? The immediate risk count might be straightforward-more harm might be done by the more invasive procedure. What about the benefit? Is it consumer satisfaction? Should the benefit strictly be measured in terms of an equal lack of recurrence of menorrhagia? Proving equality of treatments is in itself a hard job statistically4’s and will be even more difficult here-a slight recurrence of dysfunctional bleeding might be perfectly acceptable to a woman in exchange for a less invasive operation with retention of the uterus. If it stands to reason that the new procedure is indeed less risky, it might suffice to show acceptable recurrence rates without the necessity of going through the motions of a randomised trial. But how reasonable is an informal comparison of the risks of the competing procedures? What are acceptable recurrence rates? Moreover, the availability of an easier procedure might widen the indication-women who would never have been candidates for hysterectomy might now opt for partial ablation. When it comes to informed consent how do we convince a truly informed and articulate patient that it is necessary to sacrifice her womb on the altar of science when a less mutilating alternative is available?6 Whilst our surgical colleagues might face headier challenges if they attempt to apply the gold standard of therapeutic evaluation-the randomised trial-to their innovations, perhaps they should not impose such standards indiscriminately but only "by indication". Surgeons could set an example by giving far more careful thought to their trials than is needed in the planning of a pharmacological surgery
evaluation, in which routine protocols for randomised trials can be and are applied almost blindly. 1. Pocock SJ. Clinical trials, a practical approach. Chichester: Wiley, 1983: 64-65. 2. Stirrat GM, Dwyer N, Browning J. Planned trial of transcervical resection of the endometrium versus hysterectomy. Br J Obstet Gynaecol 1990; 97: 459. 3. Fisher RA. The design of experiments. 7th ed. Edinburgh: Oliver and
Boyd, 1960: 109-36. 4. Mau J. A statistical assessment of clinical equivalence. Stat Med 1988; 7: 1267-77. 5. Rodary Ch, Com-Nogue C, Toumade MF. How to establish equivalence between treatments: a one-sided clinical trial in paediatric oncology. Stat Med 1989; 8: 593-98. 6. Payer L. Medicine and culture: varieties of treatment in the United States, England, West Germany and France. New York: Henry Holt &
Co, 1988: 21-22.
are
TROUBLE IN THE POTTING SHED has been an outbreak of infection with Legionella longbeachae serogroup (SG) U This organism, originally cultured from a patient with pneumonia, is an infrequent cause of infection and has only occasionally been isolated from the environment, although it has been found in the UK.2 Antibody to L longbeachae of SG1 and 2 has been
In
Australia, there
found in some patients with respiratory infection, although in one series3 the response was sometimes to both serogroups and was usually associated with antibody to L jordanis. Since the organisms were not isolated from any of these patients, the importance of the antibody findings is unclear. Starting in October, 1988, there were 23 cases of L longbeachae SG1 infection in South Australia over three months. Additional single cases occurred in February, April, and June, 1989, and there were a few between May, 1987, and October, 1988, making a total of 30 patients. 11 patients yielded L longbeachae SG1 on culture, 8 of whom seroconverted. 8 other patients showed seroconversion alone and the remaining 11 a high level of antibody (256; only late serum samples obtained). Detailed epidemiological investigations suggested that gardening was a major risk factor for the infection, so water supplies from the homes of cases were studied. When this examination did not yield any positive cultures the South Australian Communicable Diseases Control Unit turned its attention to soil samples from the gardens of 4 patients whose infection had occurred either during or after December, 1988, the diagnosis having been confirmed by culture or seroconversion. All 4 patients were active gardeners who had used commercially available potting mixes shortly before they became ill. L longbeachae SG was isolated from a potting mix from the homes of 3 patients, from soil from a potted plant in 1 of these, and from soil from a potted plant alone in the remaining patient. Numbers of organisms in soil ranged from 102 to 105 cfu/g. Two of the undried potting mix brands remained culture positive on testing for seven months, whereas legionellae were not isolated from known positive soil samples that had been dried for seven days. L longbeachae SG1 was also isolated from water at the bottom of a potted plant that had been left outdoors for eighteen weeks and watered only with
legionella-free water. The presence of legionellae has been documented in many parts of the world in association with diverse natural waters and it is well known that legionellae are found in cooling towers, evaporative condensers, humidifiers, and domestic water systems. Legionellae have also been described in association with mud, and the soil in that
152
instance may well have been contaminated from a water supply, as is possible for the potting mixes investigated in Australia. Garden soil and water at the homes of patients did not yield L longbeachae SG1, the organism being isolated only from the soil of the potted plant and the three mixes. The potting mixes were not examined for the presence of free-living amoebae. This is an important omission because such organisms may be important in the ecology of legionellae in water. 4,5 After the original work of Rowbotham,4 others have confirmed his findings that legionellae can multiply inside amoebae, and Fields et al6 showed that amoebae may be an important factor in the survival of legionellae in stored water. When potable water in which L pneumophila was able to multiply was passed through a 0.45 µm filter the legionellae were no longer able to grow because the filtration had removed amoebae in which the legionellae could multiply. Earlier observations7 had shown that legionellae persist in tap water, even in the presence of a low level of chlorine, and it was suggested that chlorine resistance of the organisms might have been enhanced. However, Kilvington and Price8 have lately shown that legionellae can survive inside amoebic cysts and thereby resist killing by chlorine at levels of up to 50 mg/l. The possible relation between trophozoites or even cysts of amoebae and the survival of legionellae in the potting mix could be important, although the fact that legionellae were not found in the soil after drying suggests that at least in these circumstances legionellae were not protected from the effects of drying, which one might have expected had they been inside amoebic cysts. Nevertheless, it would be well worth while to examine potting mix samples to see whether amoebae are present. These Australian investigations are of additional interest because in one of the early accounts of an outbreak of legionnaires’ disease, at a psychiatric hospital in Washington,9 the researchers commented that shortly before the outbreak of infection, in which patients with access to the grounds or sleeping near the windows were especially affected, there had been excavation work for a new water sprinkling system for the grounds of the hospital with consequent soil disturbance. If there had been legionellae in the soil, either in amoebic cysts or in amoebae, and they had been carried in an aerosol or even in the dust observed at the hospital, it is possible that the amoebae could have been the vectors of infection.4,8 1. Steele TW, Lanser J, Sangster N. Isolation of Legionella longbeachae serogroup 1 from potting mixes. Appl Environ Microbiol 1990; 56: 49-53. 2. Fallon RJ.
Legionella pneumophila infections in Scotland 1987. CD(S) U Weekly Rep 1988 22 No26 7-9. 3. Fallon RJ, Abraham WH. Experience with heat-killed antigens of L longbeachae serogroups 1 and 2, and L jordanis in the indirect fluorescence antibody test. Zbl Bakt Hyg I Abt Orig 1983; A255: 8-14. 4. Rowbotham TJ. Preliminary report on the pathogenicity of Legionella pneumophila for fresh water and soil amoebae. J Clin Pathol 1980; 33: 1179-83. 5. Fallon RJ, Rowbotham TJ. Microbiological investigations into an outbreak of Pontiac fever due to Legionella micdadei associated with use of a whirlpool. J Clin Pathol 1990; 43: 479. 6. Fields BS, Sander GN, Barbaree JM, et al. Intracellular multiplication of Legionellae pneumophila from amoebae isolated from hospital hot water tanks. Current Microbiol 1989; 18: 131-37. 7. Kuchta JM, Slates SJ, McGlaughlin JE, et al. Enhanced chlorine resistance of tap water-adapted Legionella pneumophila as compared with agar medium-passaged strains. Appl Environ Microbiol 1985; 50: 21-26. 8. Kilvington S, Price J. Survival of Legionella pneumophila within cysts of Acanthamoeba polyphaga following chlorine exposure. J Appl Bacteriol 1990; 68: 519-25. 9. Thacker SB, Bennet JV, Tsai TF, et al. An outbreak in 1965 of severe respiratory illness caused by the legionnaires’ disease bacterium. J Infect Dis 1978; 138: 512-19.
ADVISING PATIENTS WITH ARTIFICIAL HEART VALVES All patients with implanted prosthetic heart valves are at risk from certain complications, some of which are lifethreatening and can occur without warning--eg, valve thrombosis, cerebral or coronary embolism, and mechanical valve failure. Media publicity about cases of mechanical failure of the Bjork-Shiley 60° CC valve has lately alarmed many recipients of this and other types of valve replacement. These patients naturally turn to their doctor for advice and reassurance. What should they be told? The risk of mechanical failure of Bjork-Shiley 60° CC valves (sizes 29, 31, and 33 mm) manufactured between Feb 1,1981, and June 30,1982, is 0.295% per year. The risk with other sizes and valves manufactured before or after these dates is less than 0-087% per year.1 Expressed actuarially, the hazard rate decreases with time. The yearly hazard rate, for the batch of valves most at risk, declined from 0-4% in the first year to 0-125% at 6 years after implant.z2 In deciding how to counsel patients with implanted 60° CC valves, the ongoing (but decreasing) risk of lifethreatening mechanical failure must be set against the risk of elective reoperation to replace the valve, which in the UK carries a case-fatality of 13% according to the Society of Cardiothoracic Surgeons. Thus reoperation is associated with a substantially greater risk and cannot be recommended on the basis of these figures. In a few patients, other factors may modify this recommendation. The more difficult question to answer unequivocally is whether all patients with a 60° CC valve should be informed of the possible risk. In health services centred on primary care, the patient’s general practitioner should be given all the relevant details and will often be in the best position to initiate a thorough discussion. Since most patients will be reassured rather than frightened by the figures, doctors must have strong reasons for withholding such information. In the event of mechanical valve failure, outcome depends on prompt diagnosis and emergency surgery. For this reason it is important that the patient carries information detailing the prosthetic valve type and model number and that doctors are aware of the mode of presentation of sudden valve failure, which can easily be confused with myocardial infarction. Patients with acute valve failure will be in cardiogenic shock with hypotension and pulmonary oedema. Severe dyspnoea rather than chest pain is the prominent symptom. On examination, the valve-clicks cannot be heard. A penetrated radiograph will reveal absence of the disc and one valve strut; an echocardiogram will also show that the valve disc is not in the prosthesis. The time between valve failure and death or reparative surgery varies from minutes to 15 hours, depending on the patient’s myocardial reserve and pulmonary vasculature. So, patients with artificial heart valves can be reassured that the overall frequency of complications is very low. The probability of freedom from failure of the Bjork-Shiley 60° CC valve in the mitral position at 10 years is 96-7% The probability of freedom from valve failure causing death is 99% according to one UK series. 1.
2.
Figures from Shiley up-date circular, Shiley Inc, Irvine, California. June 4, 1990. Hiratzka LF, Kouchoukos NT, Grunkemeier GL, Miller C, Scully HE, Wechsler AS. Outlet strut fracture of the Bjork-Shiley 60° convexoconcave
valve:
current
care. JACC 1988;
information and recommendations for patient
11: 1130-37.