1515
applied to CVS and second trimester amniocentesis. What we need now is a clinical trial of early amniocentesis, perhaps international to obtain the necessary results as quickly as possible. First trimester amniocentesis should not be introduced into routine clinical practice before the results of such an evaluation are known. 1. Hahneman
N, Mohr J. Genetic diagnosis in the embryo by means of biopsy from extra-embryonic membrane. Bull Europ Soc Hum Genet 1968; 2: 23-29.
2. Prenatal diagnosis of genetic disease in Canada: report of a collaborative study. Can Med Assoc J 1976; 115: 739-46. 3. NICHHD. National Registry for Amniocentesis Study Group. JAMA
1976; 236: 1471. party on amniocentesis: an assessment of the hazards of amniocentesis. Br J Obstet Gynaecol 1978; 85 (suppl): 2. 5. Tabor A, Philip J, Madsen M, Bang J, Obe EB, Norgaard-Pedersen B. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women. Lancet 1986; i: 1287-92. 6. Canadian Collaborative CVS-Amniocentesis Clinical Trial Group. Multicentre randomised clinical trial of chorion villus sampling and amniocentesis: first report. Lancet 1989; i: 1-6. 7. Rhoads GG, Jackson LG, Schlesselman SE, et al. The safety and efficacy of chorionic villus sampling for early prenatal diagnosis of cytogenetic abnormalities. N Engl J Med 1989; 320: 609-17. 8. Firth HV, Boyd PA, Chamberlain P, MacKenzie IZ, Lindenbaum RH, Huson SM. Severe limb abnormalities after chorion villus sampling at 56-66 days’ gestation. Lancet 1991; 337: 762-63. 9. Hsieh F-J, Chen D, Tseng L-H, Lee C-N, Ko T-M, Chuang S-M, Chen H-Y. Limb-reduction defects and chorion villus sampling. Lancet
4. Working
1991; 337: 1091-92. 10. Mastroiacovo P, Cavalcanti DP. Limb-reduction defects and chorion villus sampling. Lancet 1991; 337: 1091. 11. Monni G, Ibba RM, Lai R, Olla G, Cao A. Limb-reduction defects and chorion villus sampling. Lancet 1991; 337: 1091. 12. Mahoney MJ. Limb abnormalities and chorionic villus sampling. Lancet 1991; 337: 1422-23. 13. Froster-Iskenius UG, Baird PA. Limb reduction defects in over one million consecutive livebirths. Teratology 1989; 39: 1278-35. 14. Donnai P, Charles N, Harris R. Attitudes of patients after "genetic" termination of pregnancy. Br Med J 1981; 282: 621-22. 15. Blumberg BD, Golbus MS, Hanson KH. The physiological sequelae of abortion performed for a genetic indication. Am J Obstet Gynecol 1975; 122: 799-808. 16. Faden RR, Chwalow AJ, Quaid K, et al. Prenatal screening and pregnant women’s attitudes towards the abortion of defective fetuses. Am J Publ Health 1987; 77: 288-90.
Drawing the curtain
on
malaria
The public health impact of falciparum malaria remains colossal-in parts of west Africa, childhood deaths from this condition approach 10% each year. World Health Organisation recommendations emphasise the need to control malaria through primary health care measures. The malariatransmitting female Anopheles mosquito commonly bites during the night and, with the subsequent blood protein meal, is able to produce eggs that it deposits in a suitable water source before returning to seek another meal. If blood is contaminated with malarial gametocytes, infective sporozooites reach the salivary glands of the mosquito within twelve days. Thus for community protection it is important to prevent collections of standing water from becoming stagnant. Individual protection relies on suitable clothing, mosquito nets or curtains, and
chemoprophylaxis. The value of
nets or
curtains
impregnated
with
synthetic pyrethroid antimalarial agents has been debated for some time. Although permethrinimpregnated bed nets are toxic to mosquitoes, the important clinical end-point is not direct toxicity to anophelines but whether malarial transmission at the population level can be reduced. Moreover, confounding factors must be avoided-in one study, use of nets during the night was influenced by the extent of television viewing. Researcher-observed rather than subject-reported assessment of bed net use is therefore essential. Trials of bed nets test two variables: acceptability of nets among the general population and their efficacy in protecting against malaria. In Papua New Guinea controlled studies indicated that bed nets gave 70 % protection against Plasmodium falciparum infection in children aged ü-4 years.2 However, trials in Gambian children aged 1-9 years showed that, although there were significantly fewer episodes of malaria after introduction of permethrintreated bed nets, there was no difference in the frequency of splenomegaly or parasitaemia between treatment and control groups.3 The lack of effect on such signs of malarial infection is reversed if all nets in a locality are treated with insecticide.4 The beneficial properties of nets may be confined to periods of moderate parasite transmission.5 There may also be a difference between bed nets and curtains. Sexton et al found that, although bed net users in Kenyan families had fewer episodes of P falciparum infection per person week at risk than controls (5-42 vs 3-77), curtains gave even greater protection than nets (3 - 77 vs 2-35).In this issue, Alonso et al (p 1499) report on mortality in Gambian children; 92% were confirmed to have slept under nets. They found that in children aged 1-4 years, mortality was nearly a third lower than in controls. Thus, infection, symptomless clinical sequelae, and mortality have all been shown to be reduced when bed nets are adopted in the homes of those at risk. How do they work? Curiously, the researchers do not tell us-a combination of a deterrent effect and insecticide-induced death of
mosquitoes seems likely. . Impregnation of other
household items with insecticides may also be worthwhile. Controlled trials with jute ropes impregnated with deltamethrin, which smoulder through the night once set alight, showed that at maximum doses of insecticide an 80 % reduction in total numbers of anophelines could be expected.7 Topically applied permethrin from repellent/insecticidal bars could prove helpful since mosquitoes have a preference for exposed areas of the body such as arms and legs.88 Meanwhile, this simple approach to malaria control by use of impregnated bed nets should be welcomed The wholeheartedly. increasing difficulties encountered with drug resistance highlight the importance of this low-tech means of reducing the morbidity and mortality associated with the disease.
1516
1. Leake DW, Hii JLK. Giving bed nets "fair" tests in field trials against malaria. Southeast Asian J Trop Med Public Health 1989; 20: 379-84. 2. Graves PM, Brabin BJ, Charlwood JD, et al. Reduction in incidence and prevalence of Plasmodium falciparum in under 5-year-old children by permethrin impregnation of mosquito nets. Bull WHO 1987; 65: 869-77. 3. Snow RW, Rowan KM, Greenwood BM. A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children. Trans R Soc Trop Med Hyg 1987; 81: 563-67. 4. Snow RW, Lindsay SW, Hayes RJ, Greenwood BM. Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children. Trans R Soc Trop Med Hyg 1988; 82: 838-42. 5. Procacci PG, Lamizana L, Kumlien S, Habluetzel A, Rotigliano G. Permethrin-impregnated curtains in malaria control. Trans R Soc Trop Med Hyg 1991; 85: 181-85. 6. Sexton JD, Rueburgh TK, Brandling-Bennett AD, et al. Permethrinimpregnated curtains and bed nets prevent malaria in Western Kenya. Am J Trop Med Hyg 1990; 443: 11-18. 7. Sharma VP, Ansari MA, Mittal PK, Razdan RK. Insecticide impregnated ropes as mosquito repellent. Ind J Malariol 1989; 26: 179-85. 8. Chiang GL, Tay SL, Eng KL, Chan ST. Effectiveness of repellent/ insecticide bars against malaria and filariasis vectors in peninsular Malaysia. Southeast Asian J Trop Med Public Health 1990; 21: 412-17.
Perioperative myocardial ischaemia and non-cardiac surgery Heart attacks and their complications are the main cause of death after anaesthesia and surgery.1 The risk of surgery in the "general population", some of whom will of course have had an earlier myocardial infarction, will depend on what type of patients are studied. In a group of 1001 patients2 undergoing various major non-cardiac operations there were 19 perioperative cardiac deaths. Multifactorial analysis revealed several indpendent risk predictors, including a myocardial infarction in the previous 6 months, signs of heart failure, presence of any sustained cardiac arrhythmia, frequent ventricular extrasystoles, age over 70 years, vascular operations, aortic stenosis, and a generally poor medical condition. How risky is non-cardiac surgery in patients known have coronary disease? In a group of more than 30 000 patients who underwent surgery at the Mayo Clinic in 1967 and 1968, operations done in the
to
subgroup who had had a myocardial infarction in the preceding 3 months carried a 37% risk of reinfarction.3 In the 1970s it was reported that operations within 3 months of an infarction were associated with a 27% risk of reinfarction, whereas the risk was 11% for operations done after 3-6 months; operations done after more than 6 months carried a 4% risk of reinfarction, which seemed to remain constant.4 Findings such as these still have a profound effect on the attitude of surgeons and anaesthetists when they elective non-cardiac operations in are planning patients who have sustained a myocardial infarction, despite claims made in the 1980s that "aggressive invasive monitoring of hemodynamic status" can reduce the reinfarction rate to 5-7% even in the first 3 months after an infarction, and to 25% in the 3-6 month period.5 All these estimates may be pessimistic: patients included in the registry of the Coronary
Artery Surgery Study (CASS) who had
coronary
documented at angiography had a perioperative infarction rate of 1.1% associated with non-cardiac surgery. Nevertheless, few of these patients had sustained a myocardial infarction in the months preceding their operation. Perioperative myocardial infarction can be difficult to diagnose: patients will have postoperative pain and will be given analgesics, so cardiac pain may not be noticed. Tachycardia, hypotension, and fever may be ascribed to blood loss, pulmonary emboli, or infection rather than to a myocardial infarction. When attempts have been made to detect myocardial ischaemia associated with non-cardiac surgery, it has been found to be very common. Mangano et aF used continuous electrocardiographic (ECG) monitoring to detect ischaemic ST segment changes following non-cardiac surgery in 243 men with known coronary disease and in 231 who were thought to be at high risk of having it. 83 of these patients (18%) had postoperative events attributable to cardiac ischaemia, and there was a nine-fold increase in the risk of an ischaemic event among those shown to have ischaemia by ECG monitoring. When a similar monitoring technique was used to compare episodes of ischaemia before, during, and after elective surgery8,9 it was found that, among 100 men with or at risk from coronary disease, 28 patients had 105 episodes of ischaemia in the 2 days before surgery. During anaesthesia itself, 27 patients had 39 episodes of ischaemia. In the 2 days following surgery, 42 patients had 187 ischaemic episodes detected on their ECG; in the postoperative period the duration of ischaemia and the degree of ST segment depression were greater than in the period leading up to the operation. The excess of postoperative ischaemia appeared to be related to an increased heart disease
rate.
Perhaps the most striking finding in these detailed studies of perioperative cardiac ischaemia8,9 was that almost all the episodes were "silent": the characteristic ECG changes of ischaemia were not accompanied by cardiac pain. These silent ECG changes are known to be due to cardiac ischaemia,10 although why they are not associated with pain is unclear. 11,12 The prognostic importance of silent, as opposed to symptomatic, ischaemia is likewise uncertain. If silent ischaemia and perioperative cardiac events are related,8 it could be argued that ECG monitoring for ST segment changes is necessary before, during, and for a few days after non-cardiac surgery. This policy would be extremely expensive and is unlikely to be cost effective. Such monitoring should not become standard practice until its value has been compared with simple tests (eg, an ECG recorded at rest or under stress). Preoperative exercise testing adds little to a routine ECG in the prediction of cardiac events during or after surgery, and in a study of 200 patients a cardiac event occurred in 23% of those with an abnormal preoperative ECG compared with 2% of those whose ECG was normal.13
applied to CVS and second trimester amniocentesis. What we need now is a clinical trial of early amniocentesis, perhaps international to obtain the necessary results as quickly as possible. First trimester amniocentesis should not be introduced into routine clinical practice before the results of such an evaluation are known. 1. Hahneman
N, Mohr J. Genetic diagnosis in the embryo by means of biopsy from extra-embryonic membrane. Bull Europ Soc Hum Genet 1968; 2: 23-29.
2. Prenatal diagnosis of genetic disease in Canada: report of a collaborative study. Can Med Assoc J 1976; 115: 739-46. 3. NICHHD. National Registry for Amniocentesis Study Group. JAMA
1976; 236: 1471. party on amniocentesis: an assessment of the hazards of amniocentesis. Br J Obstet Gynaecol 1978; 85 (suppl): 2. 5. Tabor A, Philip J, Madsen M, Bang J, Obe EB, Norgaard-Pedersen B. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women. Lancet 1986; i: 1287-92. 6. Canadian Collaborative CVS-Amniocentesis Clinical Trial Group. Multicentre randomised clinical trial of chorion villus sampling and amniocentesis: first report. Lancet 1989; i: 1-6. 7. Rhoads GG, Jackson LG, Schlesselman SE, et al. The safety and efficacy of chorionic villus sampling for early prenatal diagnosis of cytogenetic abnormalities. N Engl J Med 1989; 320: 609-17. 8. Firth HV, Boyd PA, Chamberlain P, MacKenzie IZ, Lindenbaum RH, Huson SM. Severe limb abnormalities after chorion villus sampling at 56-66 days’ gestation. Lancet 1991; 337: 762-63. 9. Hsieh F-J, Chen D, Tseng L-H, Lee C-N, Ko T-M, Chuang S-M, Chen H-Y. Limb-reduction defects and chorion villus sampling. Lancet
4. Working
1991; 337: 1091-92. 10. Mastroiacovo P, Cavalcanti DP. Limb-reduction defects and chorion villus sampling. Lancet 1991; 337: 1091. 11. Monni G, Ibba RM, Lai R, Olla G, Cao A. Limb-reduction defects and chorion villus sampling. Lancet 1991; 337: 1091. 12. Mahoney MJ. Limb abnormalities and chorionic villus sampling. Lancet 1991; 337: 1422-23. 13. Froster-Iskenius UG, Baird PA. Limb reduction defects in over one million consecutive livebirths. Teratology 1989; 39: 1278-35. 14. Donnai P, Charles N, Harris R. Attitudes of patients after "genetic" termination of pregnancy. Br Med J 1981; 282: 621-22. 15. Blumberg BD, Golbus MS, Hanson KH. The physiological sequelae of abortion performed for a genetic indication. Am J Obstet Gynecol 1975; 122: 799-808. 16. Faden RR, Chwalow AJ, Quaid K, et al. Prenatal screening and pregnant women’s attitudes towards the abortion of defective fetuses. Am J Publ Health 1987; 77: 288-90.
Drawing the curtain
on
malaria
The public health impact of falciparum malaria remains colossal-in parts of west Africa, childhood deaths from this condition approach 10% each year. World Health Organisation recommendations emphasise the need to control malaria through primary health care measures. The malariatransmitting female Anopheles mosquito commonly bites during the night and, with the subsequent blood protein meal, is able to produce eggs that it deposits in a suitable water source before returning to seek another meal. If blood is contaminated with malarial gametocytes, infective sporozooites reach the salivary glands of the mosquito within twelve days. Thus for community protection it is important to prevent collections of standing water from becoming stagnant. Individual protection relies on suitable clothing, mosquito nets or curtains, and
chemoprophylaxis. The value of
nets or
curtains
impregnated
with
synthetic pyrethroid antimalarial agents has been debated for some time. Although permethrinimpregnated bed nets are toxic to mosquitoes, the important clinical end-point is not direct toxicity to anophelines but whether malarial transmission at the population level can be reduced. Moreover, confounding factors must be avoided-in one study, use of nets during the night was influenced by the extent of television viewing. Researcher-observed rather than subject-reported assessment of bed net use is therefore essential. Trials of bed nets test two variables: acceptability of nets among the general population and their efficacy in protecting against malaria. In Papua New Guinea controlled studies indicated that bed nets gave 70 % protection against Plasmodium falciparum infection in children aged ü-4 years.2 However, trials in Gambian children aged 1-9 years showed that, although there were significantly fewer episodes of malaria after introduction of permethrintreated bed nets, there was no difference in the frequency of splenomegaly or parasitaemia between treatment and control groups.3 The lack of effect on such signs of malarial infection is reversed if all nets in a locality are treated with insecticide.4 The beneficial properties of nets may be confined to periods of moderate parasite transmission.5 There may also be a difference between bed nets and curtains. Sexton et al found that, although bed net users in Kenyan families had fewer episodes of P falciparum infection per person week at risk than controls (5-42 vs 3-77), curtains gave even greater protection than nets (3 - 77 vs 2-35).In this issue, Alonso et al (p 1499) report on mortality in Gambian children; 92% were confirmed to have slept under nets. They found that in children aged 1-4 years, mortality was nearly a third lower than in controls. Thus, infection, symptomless clinical sequelae, and mortality have all been shown to be reduced when bed nets are adopted in the homes of those at risk. How do they work? Curiously, the researchers do not tell us-a combination of a deterrent effect and insecticide-induced death of
mosquitoes seems likely. . Impregnation of other
household items with insecticides may also be worthwhile. Controlled trials with jute ropes impregnated with deltamethrin, which smoulder through the night once set alight, showed that at maximum doses of insecticide an 80 % reduction in total numbers of anophelines could be expected.7 Topically applied permethrin from repellent/insecticidal bars could prove helpful since mosquitoes have a preference for exposed areas of the body such as arms and legs.88 Meanwhile, this simple approach to malaria control by use of impregnated bed nets should be welcomed The wholeheartedly. increasing difficulties encountered with drug resistance highlight the importance of this low-tech means of reducing the morbidity and mortality associated with the disease.
1516
1. Leake DW, Hii JLK. Giving bed nets "fair" tests in field trials against malaria. Southeast Asian J Trop Med Public Health 1989; 20: 379-84. 2. Graves PM, Brabin BJ, Charlwood JD, et al. Reduction in incidence and prevalence of Plasmodium falciparum in under 5-year-old children by permethrin impregnation of mosquito nets. Bull WHO 1987; 65: 869-77. 3. Snow RW, Rowan KM, Greenwood BM. A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children. Trans R Soc Trop Med Hyg 1987; 81: 563-67. 4. Snow RW, Lindsay SW, Hayes RJ, Greenwood BM. Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children. Trans R Soc Trop Med Hyg 1988; 82: 838-42. 5. Procacci PG, Lamizana L, Kumlien S, Habluetzel A, Rotigliano G. Permethrin-impregnated curtains in malaria control. Trans R Soc Trop Med Hyg 1991; 85: 181-85. 6. Sexton JD, Rueburgh TK, Brandling-Bennett AD, et al. Permethrinimpregnated curtains and bed nets prevent malaria in Western Kenya. Am J Trop Med Hyg 1990; 443: 11-18. 7. Sharma VP, Ansari MA, Mittal PK, Razdan RK. Insecticide impregnated ropes as mosquito repellent. Ind J Malariol 1989; 26: 179-85. 8. Chiang GL, Tay SL, Eng KL, Chan ST. Effectiveness of repellent/ insecticide bars against malaria and filariasis vectors in peninsular Malaysia. Southeast Asian J Trop Med Public Health 1990; 21: 412-17.
Perioperative myocardial ischaemia and non-cardiac surgery Heart attacks and their complications are the main cause of death after anaesthesia and surgery.1 The risk of surgery in the "general population", some of whom will of course have had an earlier myocardial infarction, will depend on what type of patients are studied. In a group of 1001 patients2 undergoing various major non-cardiac operations there were 19 perioperative cardiac deaths. Multifactorial analysis revealed several indpendent risk predictors, including a myocardial infarction in the previous 6 months, signs of heart failure, presence of any sustained cardiac arrhythmia, frequent ventricular extrasystoles, age over 70 years, vascular operations, aortic stenosis, and a generally poor medical condition. How risky is non-cardiac surgery in patients known have coronary disease? In a group of more than 30 000 patients who underwent surgery at the Mayo Clinic in 1967 and 1968, operations done in the
to
subgroup who had had a myocardial infarction in the preceding 3 months carried a 37% risk of reinfarction.3 In the 1970s it was reported that operations within 3 months of an infarction were associated with a 27% risk of reinfarction, whereas the risk was 11% for operations done after 3-6 months; operations done after more than 6 months carried a 4% risk of reinfarction, which seemed to remain constant.4 Findings such as these still have a profound effect on the attitude of surgeons and anaesthetists when they elective non-cardiac operations in are planning patients who have sustained a myocardial infarction, despite claims made in the 1980s that "aggressive invasive monitoring of hemodynamic status" can reduce the reinfarction rate to 5-7% even in the first 3 months after an infarction, and to 25% in the 3-6 month period.5 All these estimates may be pessimistic: patients included in the registry of the Coronary
Artery Surgery Study (CASS) who had
coronary
documented at angiography had a perioperative infarction rate of 1.1% associated with non-cardiac surgery. Nevertheless, few of these patients had sustained a myocardial infarction in the months preceding their operation. Perioperative myocardial infarction can be difficult to diagnose: patients will have postoperative pain and will be given analgesics, so cardiac pain may not be noticed. Tachycardia, hypotension, and fever may be ascribed to blood loss, pulmonary emboli, or infection rather than to a myocardial infarction. When attempts have been made to detect myocardial ischaemia associated with non-cardiac surgery, it has been found to be very common. Mangano et aF used continuous electrocardiographic (ECG) monitoring to detect ischaemic ST segment changes following non-cardiac surgery in 243 men with known coronary disease and in 231 who were thought to be at high risk of having it. 83 of these patients (18%) had postoperative events attributable to cardiac ischaemia, and there was a nine-fold increase in the risk of an ischaemic event among those shown to have ischaemia by ECG monitoring. When a similar monitoring technique was used to compare episodes of ischaemia before, during, and after elective surgery8,9 it was found that, among 100 men with or at risk from coronary disease, 28 patients had 105 episodes of ischaemia in the 2 days before surgery. During anaesthesia itself, 27 patients had 39 episodes of ischaemia. In the 2 days following surgery, 42 patients had 187 ischaemic episodes detected on their ECG; in the postoperative period the duration of ischaemia and the degree of ST segment depression were greater than in the period leading up to the operation. The excess of postoperative ischaemia appeared to be related to an increased heart disease
rate.
Perhaps the most striking finding in these detailed studies of perioperative cardiac ischaemia8,9 was that almost all the episodes were "silent": the characteristic ECG changes of ischaemia were not accompanied by cardiac pain. These silent ECG changes are known to be due to cardiac ischaemia,10 although why they are not associated with pain is unclear. 11,12 The prognostic importance of silent, as opposed to symptomatic, ischaemia is likewise uncertain. If silent ischaemia and perioperative cardiac events are related,8 it could be argued that ECG monitoring for ST segment changes is necessary before, during, and for a few days after non-cardiac surgery. This policy would be extremely expensive and is unlikely to be cost effective. Such monitoring should not become standard practice until its value has been compared with simple tests (eg, an ECG recorded at rest or under stress). Preoperative exercise testing adds little to a routine ECG in the prediction of cardiac events during or after surgery, and in a study of 200 patients a cardiac event occurred in 23% of those with an abnormal preoperative ECG compared with 2% of those whose ECG was normal.13
