1594
`
`logical triggers, such as a hormonal pregnancy test15 or a viral
`infection.1' The study by Smithels et al,17 although it was not a
`controlled trial and used multivitamin supplementation, would
`seem to indicate the possible success of dietary improvement.
`We conclude, therefore, that dietary counselling was effective
`in south Wales. All eight recurrences were in mothers whose
`diet was poor during the early stages of the project pregnancy.
`Counselling may have reduced the incidence of recurrence by
`60%, but even more effective counselling may be possible.
`Advice on diet should be part of a health education pro-
`gramme that should start in school. Women should be taught
`what is an adequate and balanced diet and how important such
`a diet is, especially before and during pregnancy. As the dietary
`habits of a woman are determined largely by what she learns
`in the parental home,'8 however, to be effective any dietary
`advice would have to be reinforced by the press and the media.
`In the case of women at increased risk of pregnancy complicated
`by neural-tube defects because of a history of such pregnancies
`or because a close relation has a neural-tube defect, special
`dietary counselling may be required well before any pregnancy
`is begun.
`
`We thank the women who took part in this study. This study was
`supported by Action Research for the Crippled Child, the Manpower
`Services Commission, and Tenovus.
`Requests for reprints should be addressed to Professor K M
`Laurence, Department of Child Health, Welsh National School of
`Medicine, Heath Park, Cardiff CF4 4XN.
`
`References
`1 Record, RG, McKeown T. Congenital malformations of the central
`nervous system 1-survey of 930 cases. Br J Prev Soc Med 1949;3:
`183-219.
`2 Williamson EM. Incidence and family aggregation of major congenital
`
`BRITISH MEDICAL JOURNAL VOLUME 281
`
`13 DECEMBER 1980
`
`malformations of the central nervous system (a survey of 100 families
`in Southampton). J Med Genet 1965;2:161-72.
`3 Laurence KM, Carter CO, David PA. Major central nervous system
`malformations in South Wales. II. Pregnancy factors, seasonal variation,
`and social class effects. Br J Prev Soc Med 1968;22:212-22.
`4Carter CO, Evans K. Spina bifida and anencephalus in Greater London.
`J Med Genet 1973;1O:209-34.
`5Elwood JM, Elwood JH. Epidemiology of anencephalus and spina bifida.
`Oxford: Oxford University Press, 1980.
`6Smithells RW, Sheppard S, Schorah CJ. Vitamin deficiencies and neural
`tube defects. Arch Dis Child 1976;51 :944-50.
`7 Richards IDG. Congenital defects in South Wales. PhD thesis. University
`of Wales. 1971.
`8 Department of Health and Social Security. Recommended intake of
`nutrients for the United Kingdom. Reports on Public Health and
`Medical Subjects; Great Britain. 1969; No 120.
`9 Carter CO, David PA, Laurence KM. A family study of central nervous
`system malformations in South Wales. Jf Med Genet 1968;5:81-106.
`50 Carter CO. Clues to the aetiology of neural tube malformations. Dev
`Med Child Neurol 1974;16,suppl 32:3-15.
`11 Thiersch JB. Therapeutic abortions with folic acid antagonist 4-amnio-
`pteroylglutamic acid (4 amino PGA) administered by the oral route.
`Am J' Obstet Gynecol 1952;63:1298-304.
`12 Andrews J, McGarry JM. A community study of smoking in pregnancy.
`J7ournal of Obstetrics and Gynaecology of the British Commonwealth 1972;
`79:1057-73.
`13 Choi NW, Klaponski J. Neural tube defects: an epidemiological elicitation
`of etiological factors. Neurology (Minneap) 1970 ;20 :399-400.
`14 Kelsey JL, Dwyer T, Holford TR, Bracken MB. Maternal smoking and
`congenital malformations. Y Epidemiol Community Health 1978 ;32:
`102-7.
`15 Gal I, Kiman B, Sterm J. Hormonal pregnancy tests and congenital
`malformation. Nature 1967;216:83.
`16 Saxdn K, Hjelt L, Sjostedt JE, Hakgsalo J, Hakosalo H. Asian influenza
`during pregnancy and congenital malformations. Acta Pathol Microbiol
`Scand 1960;49:114-26.
`17 Smithels RW, Sheppard S, Schorah CJ, et al. Possible prevention of
`neural tube defects by periconceptional vitamin supplementation.
`Lancet 1980;i:339-40.
`18 Emanuel I, Sever LE. Questions concerning the possible association of
`potatoes and neural tube defects and an alternative hypothesis relating
`to maternal growth and development. Teratology 1974;8:317-20
`
`(Accepted 20 October 1980)
`
`Adjuvant chemotherapy for breast cancer: side effects and
`quality of life
`
`B V PALMER, G A WALSH, J A McKINNA, W P GREENING
`
`Summary and conclusions
`In a trial of postoperative adjuvant chemotherapy
`women with primary breast cancer and spread to one
`or more axillary nodes were randomised to receive a
`six-month course of either the single agent chlorambucil
`or the five-drug combination of chlorambucil, metho-
`trexate, fluorouracil, vincristine, and adriamycin. On
`completing the treatment 47 patients were asked to
`f11 in questionnaires at home on the side effects of
`treatment and its influence on the quality of their life.
`Side effects including nausea, vomiting, malaise, and
`alopecia had been severe enough to interfere with their
`lifestyle in 9 (42%) of the patients who had received
`the single agent and 19 (79%) of those who had received
`
`Breast Unit, Royal Marsden Hospital, London SW3 6JJ
`B V PALMER, FRCS, senior surgical registrar (present address: Royal
`Sussex County Hospital, Brighton)
`G A WALSH, secretary of unit
`J A McKINNA, FRcs, consultant surgeon
`W P GREENING, FRcs, consultant surgeon
`
`multiple-drug treatment. Various other side effects
`were reported by a few patients. Seven (29%) of the
`patients who had received the multiple-drug schedule
`voluntarily added that the treatment had been "un-
`bearable" or "could never be gone through again."
`The proportion of patients who had experienced
`severe side effects while receiving the treatment was
`considerable; hence such adjuvant chemotherapy is
`justifiable only if it will substantially improve a patient's
`prognosis.
`
`Introduction
`Results of using adjuvant chemotherapy after mastectomy for
`patients with primary breast cancer encouraged the hope that
`chemotherapy might be a major advance in the treatment of
`these patients.1-4 Various trials were set up to establish the
`most effective regimens and assess which patients might be
`helped. Thus Bonadonna et a15 and Fisher et al' showed little
`benefit in postmenopausal patients. Results of most studies
`indicated that the toxicity of the various drug regimens was
`not troublesome.
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`BRITISH MEDICAL JOURNAL VOLUME 281
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`
`A trial of adjuvant chemotherapy was started at this hospital
`in 1975 and a survey undertaken to discover the true incidence
`and severity of the various side effects experienced by women
`in the trial.
`
`Patients and methods
`Patients at this hospital who had undergone mastectomy for
`carcinoma of the breast with spread to one or more axillary lymph
`nodes were entered into the trial and randomised to receive one of
`two schedules of adjuvant chemotherapy so that single- and multiple-
`drug treatment could be compared. Results of screening tests for
`metastases were negative in all cases. Patients allocated to schedule 1
`received only chlorambucil, 25 mg by mouth at night for five nights.
`Patients allocated to schedule 2 received adriamycin, vincristine,
`fluorouracil, methotrexate, and chlorambucil. On day 1 they received
`in the outpatient department adriamycin 40 mg, vincristine 1 mg, and
`5-fluorouracil (5-FU) 500 mg intravenously and methotrexate 100 mg
`intramuscularly and at 2000 took chlorambucil 25 mg and chlor-
`promazine 50-100 mg by mouth; and at 0800 on day 2 they took
`metoclopramide (Maxolon) 10 mg, 5-FU 500 mg, and folinic acid
`30 mg by mouth.
`Both schedules were repeated every three weeks subject to satis-
`factory haematological control. Both were administered on an out-
`patient basis over six months, eight courses being given at three-weekly
`intervals. Nausea and vomiting were anticipated and antiemetics
`prescribed to accompany both drug schedules. Of the antiemetics
`prescribed, metoclopramide appeared to be less effective than drugs
`such as prochlorperazine (Stemetil) and perphenazine (Fentazin).
`For geographical and social reasons a few women receiving the
`multiple-drug regimen were admitted overnight.
`When they had completed the eight courses of treatment the
`patients were asked to answer a detailed questionnaire to elicit the
`side effects of their treatment and their overall reactions. One of us
`(GAW) passed out the questionnaires and explained their format.
`Patients were asked to complete the form at home and return it by
`post. No obvious difficulties were encountered in answering the
`questions. The forms were handed to 47 patients, of whom 23 had
`received schedule 1 and 24 schedule 2. All 47 forms were completed
`and returned, but some patients did not answer every question.
`Patients were asked whether they had experienced a particular
`symptom and, if so, when it had started, how long it had lasted, and
`whether it had changed with successive courses of treatment. To each
`question four or five answers were possible: the patient indicated
`which answer she thought was most relevant by marking a box
`opposite that answer. After each question a space was left in which
`the patients were asked to write any additional specific comments.
`
`Results
`
`MAJOR SIDE EFFECTS
`Nausea-Table I shows the severity of nausea experienced, its
`time of onset, and whether it had improved with subsequent courses
`of the drugs. On average, nausea lasted for the five days of treatment
`with the single agent and for three to five days when the combined
`drugs were used.
`Vomiting-Table II gives details of the severity and time of onset
`of vomiting. Vomiting was not always associated with nausea. Some
`patients vomited for several days after each course and "any exertion"
`and the "slightest smell" were common precipitating factors. One
`woman who had taken schedule 1 commented, "The vomiting was
`so unpredictable and so severe it was not possible to go out socially
`for nine days out of each twenty-one."
`Alopecia was by far the most emotive side effect associated with
`the treatment and had to be fully discussed with those patients
`randomised into schedule 2 before they started treatment (table III).
`Appreciable hair loss had occurred in the group receiving schedule 2
`from one to eight weeks after the start of treatment. All the women
`in this group had been offered NHS wigs before starting treatment
`and most had accepted, although several, especially the younger
`women, preferred to purchase their own as they did not like the
`range of colours and styles. Many did not find it easy wearing a wig;
`one stated: "I found it was hot and felt everyone knew I was wearing
`a wig." Several complained that, although the wig had fitted before
`treatment, with appreciable hair loss it became too loose and was
`therefore liable to blow off or slip around. Regrowth of hair usually
`
`1595
`
`occurred within six months after stopping treatment, and, although
`it was sometimes of a different texture and colour, the women were
`generally pleased with their "new" hair.
`Feeling "off colour"-A peculiar malaise had affected most patients
`to some extent at each course of treatment (table IV). One eloquent
`patient, who had received schedule 2, wrote: "No words describe
`the sensation you euphemistically call 'off colour,' which starts
`about an hour or less after the injection. The unpleasant sensation
`crawls round the body. It feels as though one has had an anaesthetic
`that has not properly worked, only it is worse than that-vile."
`
`TABLsE I-Number (%) ofpatients with varying degrees of
`nausea, its time of onset, and whether its severity changed
`with subsequent courses of treatment
`
`Schedule 1
`Severity of nausea
`6 (26)
`(4)
`.
`Nil .
`.
`1
`Slight...6 (26)
`4 (17)
`6 (26)
`5 (21)
`Moderate
`5 (22)
`14 (58)
`Severe
`Time of onset after start of treatment
`Before .
`.
`0
`Immediately after
`..
`4
`1-6 hours after
`..
`2
`7-12 hours after
`..
`9
`Change with subsequent courses
`3
`8
`4
`
`Schedule 2
`
`5
`4
`6
`8
`
`1
`11
`11
`
`Better
`No change
`Worse ..
`
`TABLE Ii-Numbers (%) of patients who vomited, time of
`onset of vomiting, and whether its severity changed with
`subsequent courses of treatment
`
`Schedule 2
`
`Schedule 1
`Severity of vomiting
`2 (8)
`Nil . . 12 (57)
`Slight
`2 (8)
`3 (14)
`..
`..
`(8)
`2 (10)
`Moderate
`..
`..
`2
`..
`..
`18 (76)
`4 (19)
`Severe
`Time of onset after start of treatment
`Before
`2
`Immediately after
`3
`2
`..
`1-6 hours after
`6
`7-12 hours after
`..
`5
`8
`13-24 hours after
`3
`..
`2
`Change with subsequent courses
`4
`2
`.2
`
`Better
`No change
`Worse
`
`1
`9
`12
`
`TABLE Iii-Number (%) of patients with alopecia and
`time of onset after start of treatment
`
`Schedule 1
`Severity of alopecia
`None . .16 (70)
`Slight
`7 (30)
`Considerable
`Total
`
`2-3 weeks
`4-S5 weeks
`6-7 weeks
`>8 weeks
`
`..
`..
`..
`..
`
`Time of onset
`1
`2
`2
`
`..
`..
`..
`..
`
`Schedule 2
`
`(4)
`1
`3 (13)
`16 (70)
`3 (13)
`
`5
`4
`5
`6
`
`MINOR SIDE EFFECTS
`Mouth ulcers had been a troublesome symptom for many patients
`receiving schedule 2 (see table V); the ulcers developed within
`24 hours of treatment and lasted, on average, for seven days after
`each course. Most patients had had mouth ulcers with each course,
`the severity changing little with successive courses, although some
`complained of ulceration with only one or two courses.
`Taste-Only three patients who had received schedule 1 compared
`with 12 who had received schedule 2 had noticed an abnormal
`sense of taste. Several patients remarked specifically that the taste
`of tea or coffee was "horrible" or "made them feel ill." One patient
`commented that "everything became tasteless"; another that "food
`and drink tasted sweet"; and a third that "all liquids tasted vile."
`Smell-Ten of the patients who had received schedule 2 remarked
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`1596
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`on an abnormal sense of smell, of whom five had noticed an increased
`sensitivity. Only one patient who had received schedule 1, however,
`had been aware of any change. One patient who had received schedule
`2 stated that her sense of smell had become so acute that it had made
`life difficult: for two out of three weeks she could not drive a car
`because of the fumes, and she could not bear anyone smoking near her
`for a few days after each course of treatment.
`
`TABLE Iv-Number (%) of patients feeling "off colour,"
`duration of malaise, and changes with subsequent courses
`of treatment
`
`Schedule 1
`Severity of malaise
`Nil .. . 4 (17)
`Slight .. . 8 (35)
`Moderate
`7 (31)
`Severe
`4 (17)
`Duration
`1 day ... 3
`2-3 days
`1
`4-5 days
`4
`>5 days
`4
`Changes with subsequent courses
`4
`6
`6
`
`Better
`No change
`Worse .
`
`.
`
`Schedule 2
`
`(4)
`1
`4 (17)
`6 (25)
`13 (54)
`
`3
`6
`5
`5
`
`1
`10
`12
`
`TABLE v-Numbers (%) ofpatients with minor side effects
`of varying severity
`
`Schedule 1
`Mouth ulcers
`None...18 (79)
`Slight .
`.
`.
`3 (13)
`Moderate
`(4)
`1
`Severe
`(4)
`1
`Diarrhoea
`None...20 (88)
`Slight .
`.
`.
`(4)
`1
`Moderate
`(4)
`1
`Severe
`(4)
`1
`Headache
`None...14 (61)
`Slight .
`.
`.
`4 (17)
`Moderate
`(9)
`2
`Severe
`3 (13)
`Paraesthesia
`None...16 (70)
`Slight .
`.
`.
`6 (26)
`Moderate
`(4)
`1
`Severe
`
`..
`
`Schedule 2
`
`6 (25)
`5 (21)
`(4)
`1
`12 (50)
`
`16 (67)
`5 (21)
`3 (12)
`
`15 (62)
`4 (17)
`(4)
`1
`4 (17)
`
`14 (58)
`6 (26)
`(8)
`2
`(8)
`2
`
`TABLE vi-Responses of patients to the question
`"How much did the full course of treatment
`interfere with your life ?" (Figures are numbers
`(%) of patients responding)
`Schedule 1
`6 (29)
`6 (29)
`7 (33)
`2 (9)
`
`Not at all
`Slightly
`Moderately
`Severely
`
`..
`..
`.. ..
`..
`..
`.. ..
`
`Schedule 2
`(4)
`1
`4 (17)
`10 (42)
`9 (37)
`
`Appetite-Twelve of the women who had received schedule 1 had
`noted a change in appetite; of these, eight had had a reduced and
`four an increased appetite. Thirteen who had received schedule 2 had
`noticed a reduction and three an increase in appetite.
`Indigestion had been noted by 11 women in each group but had
`been severe in only two, both receiving schedule 2. One of these
`stated: "My stomach felt like a ball of fire two days after treatment."
`Diarrhoea (see table V)-Two patients who had received schedule
`1 had had diarrhoea, which occurred within 12 hours after starting
`treatment and continued for a few days. Four women who had
`received schedule 2 complained of diarrhoea: it occurred within
`12 hours after starting treatment and was of only a few hours' duration.
`Three women noted that it started before treatment. One-patient
`who had received schedule 1 and three who had received schedule 2
`complained of constipation during the six months of treatment.
`
`BRITISH MEDICAL JOURNAL VOLUME 281
`
`13 DECEMBER 1980
`
`Menstruation-Of the 10 women still menstruating when given
`schedule 1, three had become amenorrhoeic. Of the 16 premenopausal
`women who had received schedule 2, seven noted no change; in
`four the periods had become irregular, and in five they had stopped
`completely.
`Cystitis-Frequency and dysuria had been noted by two patients
`when receiving schedule 1 but had been slight in both. Six patients
`who had received schedule 2 noted these symptoms, which had been
`severe in only one.
`Bone pain-Six women who had received schedule 1 and four
`who had received schedule 2 complained of skeletal discomfort
`within a few hours after drug administration; this symptom had been
`severe in only one patient in each group. In none was there any
`evidence of osseous deposits on bone scanning or x-ray examination.
`Headache (see table V) was not a prominent feature of treatment. In
`patients receiving schedule 1 headaches had tended to last for five
`days and their intensity appeared to vary little with successive
`courses. In the group receiving schedule 2 headaches had lasted
`for only one to two days but half the patients thought the severity
`had increased with each course.
`"Pins and needles" (table V) had been noted most frequently in
`the hands: it was usually transient but was maximal some days
`after treatment.
`Blurred vision, which was distinct from conjunctivitis, had been
`noted by five patients taking schedule 1 and 10 taking schedule 2.
`Conjunctivitis-"Sore" eyes were a major source of complaint
`of patients who had received schedule 2, being noted by 18 patients.
`Conjunctivitis had been severe in four of these patients, two of whom
`had stopped treatment after six courses because of its severity.
`Conjunctivitis had been present in four patients receiving schedule 1.
`Profuse watering and irritation would start seven to 10 days after
`treatment and last for seven days or more. It prevented one woman
`wearing her contact lenses.
`Skin changes had been noted by nine women receiving schedule 1
`and 11 receiving schedule 2. Most complained of excessively dry
`and sometimes flaky skin but one in each group had developed
`rashes that were exacerbated by sunlight. Two women who had
`received schedule 2 volunteered the information that minor cuts
`and abrasions had healed slowly and become easily infected.
`Nails had been brittle and easily broken in five patients receiving
`schedule 1 and nine receiving schedule 2.
`Other symptoms-One patient added that she had been prone to
`infections and had had persistent coryza. She had developed pneu-
`monia, throat infections, enteritis, and styes and had had several
`septic cuts while taking schedule 2.
`
`INTERFERENCE WITH QUALITY OF LIFE
`Patients were asked to what extent the treatment had disturbed
`their lives. Table VI shows their replies.
`At the end of the survey form a space had been left for further
`comments, and, as was to be expected, reactions were far stronger
`from the group who had received schedule 2. Seven patients (29 %)
`stated that "treatment was unbearable" or "never again," with a
`further eight (33 %) volunteering that the experience had been
`"most unpleasant" or that they had "dreaded" the treatment "but
`would have it again if it were recommended for their health's sake."
`
`Discussion
`This survey shows the severity of some patients' reactions
`to cytotoxic drugs. Undoubtedly side effects were accentuated
`by the anxiety and depression experienced by many of the
`patients, who had recently undergone a major mutilating
`operation, had a possibly fatal tumour, and had been attending
`hospital every three weeks to receive drugs with upsetting
`side effects. Importantly, of the 24 women receiving Schedule 2
`five (22%) experienced nausea and two (9%) actually vomited
`before the drugs were administered.
`Adjuvant chemotherapy may be unpleasant and for the patient
`has no immediate objective benefit. The side effects are due
`to the differing drugs used and the methods of administration.
`The manner in which information on toxicity is obtained is
`highly relevant in assessing the severity of side effects: it had
`been apparent that a few questions asked by a doctor in a busy
`
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`BRITISH MEDICAL JOURNAL VOLUME 281
`
`13 DECEMBER 1980
`
`outpatient clinic did not elicit a true picture of morbidity. The
`possibility that the doctor and being in a clinic inhibit a patient's
`inclination to report side effects led us to produce a question-
`naire and to arrange for a sympathetic, non-medical member
`of the team to distribute and explain it. The women were
`asked to complete the form at home in the hope that they
`would then express their reactions to the treatment more
`accurately.
`We recommend that this method is a more appropriate one
`of assessing side effects, and similar experiences were reported
`by H Bush at a symposium of the Royal College of Physicians,
`London, in May 1980. If such questionnaires were more
`widely used the toxicity of various chemotherapy regimens
`could be compared more objectively.
`Troublesome side effects were much more common and
`severe in those women receiving the five-drug regimen, and the
`therapeutic case for using such a combination has to be a
`strong one. Side effects were also seen in an appreciable number
`of patients receiving single-agent chemotherapy, and claims
`that single-agent chemotherapy (using chlorambucil in this
`dosage) should be used as an adjuvant because it is "non-toxic"
`should therefore be regarded with caution.
`The proportion of patients who had experienced severe side
`effects in the trial was considerable; hence such treatment is
`justifiable only if it will result in a substantial increase in
`prognosis. A major ambition of doctors should be to improve
`the wellbeing of patients. Any treatment which causes distress
`or illness should be given only when there is good evidence of
`
`1597
`
`future benefit. The results of this survey contributed to our
`decision to stop this study of adjuvant chemotherapy.
`
`We are grateful to Miss Rosemary Fisher for her valuable advice
`in designing the questionnaire and thank the patients for their help
`and interest.
`Requests for reprints should be sent to Miss G A Walsh, Secretary,
`Breast Unit, Royal Marsden Hospital, Fulham Road, London
`SW3 6JJ.
`
`References
`Fisher B, Carbone P, Economou SG, et al. L-Phenylalanine mustard
`(L-Pam) in the management of primary breast cancer. N Engl J Med
`1975 ;292 :117-22.
`2 Bonadonna G, Brusamolino E, Valagussa P, et al. Combination chemo-
`therapy as an adjuvant treatment in operable cancer. N Engl J Med
`1976;294:405.
`3 Anonymous. Major advance in breast cancer therapy. N Engl J Med
`1976;294:440.
`4 Anonymous. Treating breast cancer-true light or false dawn? Br Med J
`1976;ii:263.
`5 Bonadonna G, Rossi A, Valagussa P, et al. The CMF program for
`operable breast cancer with positive axillary nodes: updated analysis
`on the disease-free interval, site of relapse and drug tolerance. Cancer
`1977;39:2904-15.
`6 Fisher B, Glass A, Redmond C, et al. L-Phenylalanine mustard (L-Pam)
`in the management of primary breast cancer: an update of earlier
`findings and a comparison with those utilizing L-PAM plus 5-fluoroura-
`cil (5-FU). Cancer 1977;39:2883-3903.
`
`(Accepted 22 October 1980)
`
`Prophylaxis of infection after appendicectomy: a survey
`of current surgical practice
`
`W B CAMPBELL
`
`Summary and conclusions
`Two hundred and eighty questionnaires were sent to
`junior surgical staff throughout England inquiring about
`their use of systemic antibiotic prophylaxis, topical
`antibacterial agents, and surgical drainage in appen-
`dicectomy. One hundred and seventy-five (63%) replies
`were received from 81 of the 87 hospitals included in the
`survey. Prophylactic systemic antibiotics were used by
`78 surgeons (46%) when operating on a normal appendix
`but by 168 (99%) when the organ had perforated. Most
`surgeons started antibiotics before operation, but pro-
`portionately fewer did so when the appendix was gan-
`grenous or perforated. Patients with severe contamina-
`tion tended to receive longer courses of antibiotics,
`although the duration of administration varied consider-
`ably. Metronidazole was included in over 95% of all the
`prophylactic regimens and was often combinedwithother
`drugs when the appendix was -gangrenous and perfor-
`ated. Topical antibacterial agents were applied to the
`wound routinely by only 45 surgeons (26%), although 106
`
`Department of General Surgery, Frenchay Hospital, Bristol BS16
`1LE
`W B CAMPBELL, MRCP, FRcs, registrar in surgery (present appointment:
`surgical registrar, University Department of Surgery, Bristol Royal
`Infirmary, Bristol BS2 8HW)
`
`(61%) used them sometimes. Povidine-iodone was the
`agent most commonly used. Only 98 surgeons (56%) ever
`drained appendicectomy wounds, while 135 (77%) some-
`times drained the peritoneal cavity.
`Evidence suggests that present methods of giving
`systemic antibiotic prophylaxis should continue, but that
`agents and surgical drainage are perhaps
`topical
`unnecessary when surgeons are confident of the efficacy
`of the systemic treatment used.
`
`Introduction
`Over the past 20 years many reports have assessed different
`methods of reducing infection after appendicectomy. The
`techniques examined have included surgical drainage, the
`application of topical agents to the wound, and the administra-
`tion of prophylactic systemic antibiotics. Although the general
`principle of systemic prophylaxis is now well established,
`opinion seems to vary widely regarding which patients require
`antibiotics, the optimum time to start the drugs, and the
`duration of administration. Furthermore, topical agents are still
`commonly used, although whether they confer much benefit
`compared with systemic drugs is not entirely clear.
`The impact on everyday surgical practice of results of studies
`on antibiotics in appendicectomy has not been assessed. I there-
`fore sent 280 questionnaires to junior surgical staff asking
`for details of the prophylactic measures used in their unit to
`prevent infection after appendicectomy.
`
`IMMUNOGEN 2184, pg. 4
`Phigenix v. Immunogen
`IPR2014-00676
`
`