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Evening primrose oil and atopic eczema
50
bioincompatibility with little effect on its electrical properties. The improvement in signal quality is striking (figure, lower trace). Electrodes of this kind would improve the reliability of fetal heart rate records and also greatly increase the range of possible analyses and interpretation of the individual fetal ECG waveforms.
These are the first data suggesting a protective effect of breastfeeding against UTI. Two medical students in two weeks came up with a clinically and biologically interesting hypothesis: will it be a challenge for "burnt-out" investigators who, you say, are fit only for the administration of confirmatory randomised trials?
Institute of Obstetrics and Gynaecology, Royal Postgraduate Medical School, Queen Charlotte’s and Chelsea Hospital, London W6 OXG, UK
D. G. PENMAN J. A. D. SPENCER
Department of Paediatrics, University of Naples, 80131 Naples, Italy
Laboratory of Applied Physiology, St Thomas’s Hospital Medical School, London SE1
D. R. S. GIBBONS D. M. BAND
1. Hon EH. Instrumentation of fetal heart rate and fetal electrocardiography. Am J Obstet Gynecol1963; 76: 772-84. 2. Arulkumaran S, Lilja H, Lindecrantz K, Ratnam SS, Thavarasah AS, Rosen KG. Fetal ECG waveform analysis should improve fetal surveillance in labour. J. Perinat Med 1990; 18: 13-22.
ALFREDO PISACANE
LIBERATORE GRAZIANO GREGORIO ZONA
Gabrielli O, Giorgi P, et al. Preliminary study of breastfeeding and bacterial adhesion to uroepithelial cells. Lancet 1990; 335: 569-71. 2. Kovar MG, Serdula MK, Marks JS, Fraser DW. Review of the epidemiologic evidence for an association between infant feeding and infant health. Pediatrics 1984; 74 (suppl): 702-27. 3. Siegel SR, Sokoloff B, Siegel B. Asymptomatic and symptomatic urinary tract infection in infancy. Am J Dis Child 1973; 125: 45-47. 4. Kunin CM. Epidemiology and natural history of urinary tract infection in school age children. Pediat Clin North Am 1971; 18: 509. 1.
Coppa GV,
Breastfeeding and urinary tract infection SIR,-Your May 12 editorial about case-control studies and the creativity of "hundreds of small research studies" prompts us to record an example of what may be further evidence of the potential of the case-control approach. Discussion with medical students, engaged in basic epidemiology training, of a Lancet paper on breastfeeding and bacterial adhesion to uroepithelial cells1 led to a case-control study of exposure to breastfeeding and urinary tract infection (UTI) in infants. It is not known if human milk protects against UTL.2 The 62 cases were all infants aged 0-6 months who were admitted to the university department of paediatrics between Jan 1,1980, and Dec 31,1988, and whose diagnosis was UTI, confirmed by at least one urine culture, done in our hospital, that yielded more than 100 000 organisms/ml of a single species. The children had one or more of the following: failure to thrive, vomiting, diarrhoea, and fever. Two groups of controls-matched by sex, age (within 15 days), father’s occupation, geographical area of residence, birth order, type of delivery, and month of admission-were chosen by systematic sampling. 62 controls were seen at our well-baby clinic; they were healthy and no urine cultures were done (in healthy infants asymptomatic bacteriuria is very unusuaP). The other 62 controls had been admitted to our hospital with an acute illness and had negative urine cultures. None of the males, cases or controls, had been circumcised. Data on breastfeeding were complete from the clinical records of both cases and controls. The proportion of infants who had been put to the breast at all was 47% in the cases and 82% and 87% in the controls (p < 0’001), and the mean duration of breastfeeding was 60, 61, and 61 days. For the purpose of analysis we defined an infant as breast-fed if he or she had had breast milk up to the day of the admission or outpatient visit (or at least until 3 days before). The factors for which we matched cases and controls are not confounders for UTI4 so the table gives the results for the unmatched analysis; matched and unmatched relative risk estimates were almost identical. CHARACTERISTICS OF CASES AND CONTROLS
Evening primrose oil and atopic eczema SiR,—Dr Sharpe and Dr Farr (May 26, p 1283) suggest that because, by an accident of randomisation, the groups assigned to
evening primrose oil (’Epogam’) in some trialsl,2 were more seriously affected than thoseassigned to placebo, the statistical analyses were inappropriate. In two examples given, patients assigned to epogam started off worse ded up better than those assigned to placebo. The change in res onse to epogam was significantly greater than the change in response to placebo.
Sharpe and Farr refer your readers to a paper by Altman and Dore on the importance of baseline values3 which states that if there are differences in baseline that might be important "the analysis should be modified by, for instance, regression modelling or analysis of change from initial values". The latter is what Bordoni et all and Schalin-Karrila et aF did. Sharpe and Farr also ignore the significant reduction in steroid use by patients on epogam in one of the two trials.2 In view of the possible side-effects of long-term topical steroid use this reduction is important. Your correspondents also miss the point of Wright and Burton’s trial4 and of four others described in the meta-analysis papery These trials were crossover in design so that differences in baseline between patients are irrelevant. In these trials improvement on epogam, whether given first or second, were consistently and significantly greater than those on placebo. There was a substantial carryover effect of epogam and crossover trials are probably inappropriate for the assessment of such a long-acting agent. However, carryover does not happen in the absence of a real effect, and its presence leads to an underestimate of the efficacy of active treatment.
Sharpe and Farr’s criticisms are directed against the only agent among the seven top-selling drugs for atopic eczema in the UK which has been tested in published, double-blind, placebocontrolled trials in the disease. Untested in this way are ’Betnovate’, ’Dermovate’, ’Eumovate’, ’Locoid’, ’Oilatum’, and ’Synalar’. In view of the possible risks of long-term steroids doctors should ask why the drugs they are prescribing so freely for atopic eczema have not been tested rigorously. Scotia Pharmaceuticals Ltd, Guildford, Surrey GU1 1 BA, UK
DAVID F. HORROBIN CHARLES STEWART
1. Bordoni A, Biagi PL, Masi M, et al. Evening primrose oil (Efamol) in the treatment of children with atopic eczema. Drugs Exp Clin Res 1987; 14: 291-97.
2. Schalin-Karrila M, Manila L, Jansen CT, Uotila P. Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987; 117: 11-19. 3. Altman DG, Doré CJ Randomisation and baseline comparisons in clinical trials. Lancet 1990; 335: 149-53. 4.
Wnght S, Burton JL. Oral evening primrose seed oil improves atopic eczema. Lancet 1982; ii: 1220-22.
5 Morse PF, Horrobin DF, Manku MS, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema: relationship between plasma essential fatty acid changes and clinical response. Br J Dermatol
1989; 121: 75-90.
bioincompatibility with little effect on its electrical properties. The improvement in signal quality is striking (figure, lower trace). Electrodes of this kind would improve the reliability of fetal heart rate records and also greatly increase the range of possible analyses and interpretation of the individual fetal ECG waveforms.
These are the first data suggesting a protective effect of breastfeeding against UTI. Two medical students in two weeks came up with a clinically and biologically interesting hypothesis: will it be a challenge for "burnt-out" investigators who, you say, are fit only for the administration of confirmatory randomised trials?
Institute of Obstetrics and Gynaecology, Royal Postgraduate Medical School, Queen Charlotte’s and Chelsea Hospital, London W6 OXG, UK
D. G. PENMAN J. A. D. SPENCER
Department of Paediatrics, University of Naples, 80131 Naples, Italy
Laboratory of Applied Physiology, St Thomas’s Hospital Medical School, London SE1
D. R. S. GIBBONS D. M. BAND
1. Hon EH. Instrumentation of fetal heart rate and fetal electrocardiography. Am J Obstet Gynecol1963; 76: 772-84. 2. Arulkumaran S, Lilja H, Lindecrantz K, Ratnam SS, Thavarasah AS, Rosen KG. Fetal ECG waveform analysis should improve fetal surveillance in labour. J. Perinat Med 1990; 18: 13-22.
ALFREDO PISACANE
LIBERATORE GRAZIANO GREGORIO ZONA
Gabrielli O, Giorgi P, et al. Preliminary study of breastfeeding and bacterial adhesion to uroepithelial cells. Lancet 1990; 335: 569-71. 2. Kovar MG, Serdula MK, Marks JS, Fraser DW. Review of the epidemiologic evidence for an association between infant feeding and infant health. Pediatrics 1984; 74 (suppl): 702-27. 3. Siegel SR, Sokoloff B, Siegel B. Asymptomatic and symptomatic urinary tract infection in infancy. Am J Dis Child 1973; 125: 45-47. 4. Kunin CM. Epidemiology and natural history of urinary tract infection in school age children. Pediat Clin North Am 1971; 18: 509. 1.
Coppa GV,
Breastfeeding and urinary tract infection SIR,-Your May 12 editorial about case-control studies and the creativity of "hundreds of small research studies" prompts us to record an example of what may be further evidence of the potential of the case-control approach. Discussion with medical students, engaged in basic epidemiology training, of a Lancet paper on breastfeeding and bacterial adhesion to uroepithelial cells1 led to a case-control study of exposure to breastfeeding and urinary tract infection (UTI) in infants. It is not known if human milk protects against UTL.2 The 62 cases were all infants aged 0-6 months who were admitted to the university department of paediatrics between Jan 1,1980, and Dec 31,1988, and whose diagnosis was UTI, confirmed by at least one urine culture, done in our hospital, that yielded more than 100 000 organisms/ml of a single species. The children had one or more of the following: failure to thrive, vomiting, diarrhoea, and fever. Two groups of controls-matched by sex, age (within 15 days), father’s occupation, geographical area of residence, birth order, type of delivery, and month of admission-were chosen by systematic sampling. 62 controls were seen at our well-baby clinic; they were healthy and no urine cultures were done (in healthy infants asymptomatic bacteriuria is very unusuaP). The other 62 controls had been admitted to our hospital with an acute illness and had negative urine cultures. None of the males, cases or controls, had been circumcised. Data on breastfeeding were complete from the clinical records of both cases and controls. The proportion of infants who had been put to the breast at all was 47% in the cases and 82% and 87% in the controls (p < 0’001), and the mean duration of breastfeeding was 60, 61, and 61 days. For the purpose of analysis we defined an infant as breast-fed if he or she had had breast milk up to the day of the admission or outpatient visit (or at least until 3 days before). The factors for which we matched cases and controls are not confounders for UTI4 so the table gives the results for the unmatched analysis; matched and unmatched relative risk estimates were almost identical. CHARACTERISTICS OF CASES AND CONTROLS
Evening primrose oil and atopic eczema SiR,—Dr Sharpe and Dr Farr (May 26, p 1283) suggest that because, by an accident of randomisation, the groups assigned to
evening primrose oil (’Epogam’) in some trialsl,2 were more seriously affected than thoseassigned to placebo, the statistical analyses were inappropriate. In two examples given, patients assigned to epogam started off worse ded up better than those assigned to placebo. The change in res onse to epogam was significantly greater than the change in response to placebo.
Sharpe and Farr refer your readers to a paper by Altman and Dore on the importance of baseline values3 which states that if there are differences in baseline that might be important "the analysis should be modified by, for instance, regression modelling or analysis of change from initial values". The latter is what Bordoni et all and Schalin-Karrila et aF did. Sharpe and Farr also ignore the significant reduction in steroid use by patients on epogam in one of the two trials.2 In view of the possible side-effects of long-term topical steroid use this reduction is important. Your correspondents also miss the point of Wright and Burton’s trial4 and of four others described in the meta-analysis papery These trials were crossover in design so that differences in baseline between patients are irrelevant. In these trials improvement on epogam, whether given first or second, were consistently and significantly greater than those on placebo. There was a substantial carryover effect of epogam and crossover trials are probably inappropriate for the assessment of such a long-acting agent. However, carryover does not happen in the absence of a real effect, and its presence leads to an underestimate of the efficacy of active treatment.
Sharpe and Farr’s criticisms are directed against the only agent among the seven top-selling drugs for atopic eczema in the UK which has been tested in published, double-blind, placebocontrolled trials in the disease. Untested in this way are ’Betnovate’, ’Dermovate’, ’Eumovate’, ’Locoid’, ’Oilatum’, and ’Synalar’. In view of the possible risks of long-term steroids doctors should ask why the drugs they are prescribing so freely for atopic eczema have not been tested rigorously. Scotia Pharmaceuticals Ltd, Guildford, Surrey GU1 1 BA, UK
DAVID F. HORROBIN CHARLES STEWART
1. Bordoni A, Biagi PL, Masi M, et al. Evening primrose oil (Efamol) in the treatment of children with atopic eczema. Drugs Exp Clin Res 1987; 14: 291-97.
2. Schalin-Karrila M, Manila L, Jansen CT, Uotila P. Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987; 117: 11-19. 3. Altman DG, Doré CJ Randomisation and baseline comparisons in clinical trials. Lancet 1990; 335: 149-53. 4.
Wnght S, Burton JL. Oral evening primrose seed oil improves atopic eczema. Lancet 1982; ii: 1220-22.
5 Morse PF, Horrobin DF, Manku MS, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema: relationship between plasma essential fatty acid changes and clinical response. Br J Dermatol
1989; 121: 75-90.