The Royal College of Physicians
and Surgeons of Canada
Examinations The examinations of the Royal College are held in September of each year. Candidates wishing to sit for the examinations should note the following:
in the treatment of breast cancer are to be made, they must be done within a properly designed, meticulously controlled, investigational framework. ALEX MCPHERSON, MD SANDY PATERSON, MB, BS
Department of medicine ALAN LEES, BM, B CH
Department of radiation oncology Cross Cancer Institute Edmonton, Alta.
1. Every candidate for admission to the examinations must submit an application for assessment of training. 2. Candidates in training in Canada should apply for preliminary assessment of training at least one year before the date on which they expect to sit for the examinations, that Is to say not later than September 1st of the preceding year. Candidates who have had training outside of Canada should submit their initial application for assessment at least eighteen months before they expect to sit for the examinations, that is by March 1st of the preceding year. Only candidates whose assessment of credentials Is complete will be accepted to sit for the examinations. 3. Candidates who desire to sit for an examination, having complied with the above requirement of preliminary assessment of training, must notify the College in writing of their intent before February 1st of the year of the examination. Upon receipt of this notice of intent, the evaluation of the candidate's performance during training will be added to the previously completed assessment of credentials. Each candidate will then receive notification as to eligibility together with an application form for admission to the examination which he will complete and return. 4. The following documents may be obtained from the College office: (a) Application forms for assessment oftraining. (b) General Information booklet on training requirements and examinations. (c) Specific requirements for training and regulations relating to the examinations of each specialty. Requests should indicate the specialty or specialties of interest to the applicant. (d) Listing of specialty training programmes in Canada accreditedby the College. 5. Address all enquiries to: Division of Training and Evaluation ROYAL COLLEGE OF PHYSICIANS AND SURGEONS OF CANADA 74 Stanley Avenue Ottawa, Ontario KIM 1P4 Tel.: (613) 746-8177
References 1. BURNS
PE,
KREDENTSER
J,
GRACE
M, et al: Breast cancer in northern Alberta: pilot study in computerized registration. Can Med Assoc J 116: 1131, 1977 2. FISHER B, REDMOND C, et al: Studies of the National Surgical Adjuvant Breast Project (NSABP), in Adjuvan; Therapy of Cancer, SALMON SS, JONES SE (eds), North-Holland, Amsterdam, 1977, p 67 3. BONADONN,A G, Rossi A, VALAGUSSA
A, et al: Adjuvant chemotherapy with CMF in breast cancer with positive axillary nodes. Ibid, p 83
Research in general practice In recent years there has been an increasing awareness in Canada of the need for research in general practice. General practitioners can provide valid information about patients and their problems from a unique viewpoint, since they care for patients of all ages, with all types of illness, and treat disorders both in the early stages and on a long-term basis. Individual practitioners can make original and useful observations. An outstanding example, as described by Dr. Gordon Johnson in his article in this issue of the Journal (starting on page 1245), was Will Pickles,1 who, in the late 1920s and early 1930s, studied the transmission of infectious diseases in his isolated village, Wensleydale, in Yorkshire, England. About 20 years later, in the village of Peaslake, Surrey, Dr. Ian Watson2 established an epidemic observation unit to collect reports on diseases of current interest from general practitioners throughout Great Britain. Watson's idea stimulated the establishment of "sentinel stations" in the Netherlands, as well as the national recording system of the College of Family Physicians of Canada, which is now in its third year of a national influenza surveillance study.3 Although it seems that much of the early work was done by general practitioners in rural communities, some practitioners in cities have provided stimulus and basic techniques that are being used in Canada. Dr. T.S. Eimerl, from his practice in Warrington, Cheshire, developed the E-book method of recording morbidity data.' This simple way of keeping a record
1198 CMA JOURNAL/MAY 19, 1979/VOL. 120
of patient problems has been used widely and has shown the need for a classification of diseases that would enable general practitioners from various countries to compare results. In Birmingham, Drs. Robin Pinsent and Donald Crombie, both of whom were in private practice, developed expertise in a wide variety of research projects and contributed greatly to the work of the Royal College of General Practitioners.5'6 The Birmingham Research Unit, the world centre of general practice research, provides advice and technical help for both small and large studies.7 Many other general practitioners have recognized the need for interest in research, as indicated by their many contributions to the Journal of the Royal College of General Practitioners. In Great Britain research by general practitioners has received substantial support from the government and private foundations. Large grants have been given, for example, to the Royal College of General Practitioners for its oral contraception study, which was begun more than 10 years ago and has involved 1200 general practitioners and 46 000 patients.8 This unique study was possible only because of the combined efforts of physicians who were willing to give a little of their time to provide information to a central unit, where it was collected and processed. The result is the best large study ever conducted on oral contraception. General practitioners in Canada have also recognized the value of their research. In Duncan, BC, Dr.
Peter Postuk9 recorded morbidity data from his group practice for 8 years before he organized the first large-scale morbidity survey in British Columbia in 1965. Dr. Jim Collyer10'" conducted studies in Ontario, first in Leamington and then in London, on workload and time, morbidity and psychosocial aspects of his solo practice. He also organized group studies.12 Dr. John Garson, who gained experience in research while in Great Britain, carried out many studies on family practice in Saskatoon.13'14 Bob Westbury15 and Michael Tarrant,18 in Calgary, compiled long-term studies of their practices that showed clinical content and operational factors. Their work contributed greatly to the new "International Classification of Health Problems in Primary Care",17 which was prepared by a committee set up by the World Organization of National Colleges and Academies of General Practitioners/Family Physicians. In an important study of perinatal morbidity carried out by the Nova Scotia chapter of the College of Family Physicians of Canada,18 with Dr. Mike Hebb as project director, highrisk factors were identified by means of an antenatal scoring system. As a result, there was substantial improvement in the morbidity in that province. Research in family practice is needed in a wide range of areas, such as clinical studies, therapeutic studies, epidemiology, patient attitudes, methods of providing care and determination of the relevance of medical education to community practice. Family physicians can provide a unique perspective in several aspects of medicine, especially the natural history of disease, family relations, longterm care, early diagnosis and multiple diagnoses. There are many topics on which more knowledge is needed; however, 'they must be studied one at a time. To be effective in research we must proceed systematically. The area of study must be clearly defined and not too large, and the method of study must be well planned, so that the results can be valid. Sources of
consultation are available to the planner who wants to avoid bias or confusion. Each provincial chapter of the College of Family Physicians of Canada, for example, has a research committee that might be able to provide help. If not, the chapter can refer the planner to resources at universities or government agencies. Advice can also be obtained from the family practice research units that have recently been started by the college in cooperation with the University of British Columbia, or from the Toronto offices of the college. For those who wish to do research, there are deterrents. Probably the biggest one is the fact that the needs of one's patients deserve priority. Partners in group practices must also be considered, for their support is necessary, whether they are participating in the project or helping to provide time and resources. Another big deterrent is inertia. Most physicians have not been trained to develop an inquiring mind or the basic skills needed for research. They must therefore make an active effort to break out of their usual routine. Finances can be a problem. Small projects may be managed personally, without the bother of applying for grants, especially if the research can be regarded as a hobby; the cost may be much less than the membership fee at a golf or squash club. Larger projects will require careful and timeconsuming preparation of applications for grants, an effort that may prove futile. Granting agencies have had little experience with general practitioners and may be hard to convince that general practitioners are capable of doing good research. Family practitioners who become involved in research should be compensated for the time lost from their usual work. Physicians in private practice may be overwhelmed or discouraged by the tendency of granting agencies to give greater support to university departments with salaried personnel. Much has already been accomplished by cooperation between private and university-based family physicians, and many individuals at
a university developed their initial interest and ability while in private practice. The cooperation should be maintained and strengthened, so that optimum use is made of resources in both areas, and to ensure that the research represents all the relevant aspects of community practice. To provide the best service to patients and the best information for policy decisions in education and politics, general practitioners must continue to develop a solid base of research to justify their claim that they can make a unique contribution to knowledge in the health field. WILLIAM A. FALK, MD
References
Associate professor Division of family practice Faculty of medicine University of Calgary Calgary, Alta.
1. PICKLES WN: Epidemiology in Country Practice, Wright, Bristol, 1939 2. WATSON GI: Letter from the honorary director of the epidemic observation unit. J R Coil Gen Pract 19: 233, 1970 3. Canadian Influenza Surveillance Working Party: First report: methods of the national recording system. Can Fain Physician 23: 64, September, 1977 4. EIMERL TS, LAIDLAW AJ: A Hand-
book for Research in General Practice, 2nd ed, Livingstone, Edinburgh, 1969, pp 39-62 5. Dr. R.J.F.H. Pinsent (E). J R Coil Gen Pract 27: 707, 1977 6. CROMBIE DL, PINSENT RJFH: Com-
parison of the first and second national morbidity surveys. J R Coll Gen Pract 25: 874, 1975 7. The Birmingham Research Unit (E). I R Coll Gen Pract 23: 386, 1973 8. KAY CR: British experience of the pill. Can Fain Physician 16: 57, May 1970 9. POSTUK PD: A Report of an Analysis of General Practice in British Columbia from a Study of the Practices of 54 Physicians, 1964, monograph, BC chapter, Coll Fain Phys Can, Vancouver
10. COLLYER JA: A measure of a family doctor's work. Part I: setting up a
one-practice study. Can Med Assoc J 112: 1256, 1975 of a family doctor's practice. Part II: drugs, time, changes, morbidity. Ibid, p 1357 12. Idem: An evaluation of treatment in family practice; a group research project. Can Fain Physician 15: 44, September 1969 13. GARSON JZ, BooR 5, MCASKILL J, et
al: The checkup centre as part of an ongoing medical practice. Can Fain
Physician 18: 93, February 1972 14. GARSON JZ, WOLFE RR: Social problems of the hospitalized elderly.
CMA JOURNAL/MAY 19, 1979/VOL. 120 1199
'Zylop rime allopurinol l.ilcutie.c: ZYLOPRIM is intended for the treatment of gout as well as primary and secondary hyperuricaemia. ZYLOPRIM is indicated in the treatment of primary orsecondary uric acid nephropathy. ZYLOPRIM is especially useful in patients with gouty nephropathy, in those who form renal urate stones, and those with unusually severe disease. ZYLOPRIM is effective in preventing the occurrence and recurrence of uric acid stones and gravel. ZYLOPRIM is useful in the therapy and prophylaxis of tissue urate deposition, renal calculi and for acute urate nephropathy in patients with neoplastic disease who are particularly susceptible to hyperuricaemia and uric acid stone formation, especially after radiation therapy or the use of antineoplastic drugs. hiniraiiniiutieinc: Zyloprim should not be given to patients who are hypersensitive or who have had a severe reaction to this drug. Premileuc end Warnings: Acute gouty attacks may be at the start of treatment with Zyloprim and these may continue even after serum uric acid levels begin to fall. Prophylactic administration of colchicine and a low dosage of Zyloprim are advisable, particularly in new patients and in those where the previous attack rate has been high. Zyloprim is not recommended for use during pregnancy or in women of child-bearing potential unless in the jud gement of the physician, the potential benefits outweigh the possible risks to the fetus. Zyloprim should not be given to children except those with hyperu ricaemia secondary to malignancy or with Lesch-Nyhan syndrome. Patients with impaired renal or hepatic functions should be carefully observed during the early stages of Zyloprim administration and the drug withdrawn if increased abnormalities in hepatic or renal functions appear. liriceecriec cud Zylepri.: Combined therapy of Zyloprim and uricosurics will result often in a reduction in dosage of both agents. Purimihel ur mural with Zyleprim: In patients receiving PURINETHOL* (mercaptopurine) or IMURAN* (azathioprine), the concomitant administration of 300. 600 mg of ZYLOPRIM per day will require a reduction in dose to approximately 'A to ¼ of the usual dose of mercapto p urine or azathioprine. Subsequent adjust. ment of doses of PURINETHOL or IMURAN should be based on therapeutic response and any toxic effects. OhierPre..cmide with Zyleprim: In the presence of allopumay be competition in the renal tubule for excretion of chiorpropamide. When renal function is poor, the recognised risk of prolonged hypoglycasmic activity of chiorpropamide may be increased if ZYLOPRI M is given concomitantly. Ceumeri. c.iieecgulc.te with Zyleprim: It has been reported that under experimental conditions allopurinol prolongs the half-life of the anticoagulant, dicumarol. The clinical significance of this has not been established, but this interaction should be kept in mind when allopurinol is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed. Adveree reculiema: Skin reactions associated with exfoliation, fever, chills, nausea and vomiting, lymphadenopathy, arthralgia and/or eosinophilia are the most common and may occur at any time during treatment. Gastrointestinal disorders were reported but may diminish if Zyloprim Is taken after meals. STqiems cii reclined ci everdeange: Overdosage of a lopuri no is usually manifested by nausea and vomiting. No treatment is normally required, provided the drug is withdrawn and adequate hydration Ii maintained to facilitate excretion of the drug. If, however, other forms of acute distress are observed, gastric lavage should be considered, otherwise the treatment is symptomatic. Pharmeclegy: When taken orally allopurinolis rapidly metabolized. The main metabol he is oxypurinol, which is itself a xanthine oxidase inhibitor. Allopurinol and its metabolites are excreted by the kidney, but the renal handling is such that allopurinol has a plasma half-life of about one hour, whereas that of ox y purinol exceeds 18 hours. Thus, the therapeutic effect can be achieved by a once-a-day dosage of ZYLOPRIM In patients taking 300 mg or less per day. Decage cii cd.iidclrctie.: ZYLOPRIM, administered orally should be divided into 1 to 3 daily doses. Daily doses up to and including 300 mg may be taken once daily after a meal. Divided doses should not exceed 300 mg. The minimum effective dose Is 100 to 200 m¶.. The average is 200 to 300 mg/day for patients wit mild gout, 400 to 600 mg/day for moderately severe tophaceous gout, and 700 to 800 mg/day in severe conditions. The maximal recommended dose is 800 mg per day in patients with normal renal function. Treatment with 600 to 800 mg daily fortwo or three days prior to chemotherapy or x-irradlation is advisable to preventuricacid neph ropathy. Treatmentshould becontinued at a dosage adjusted to the serum uric acid level until there is no longer a threat of hyperuriccemia and hyperuricosuria. Itis essential thata daily urinary output of two litres or more be maintained during ZYL OPRIM therapy, and neutral or alkaline urine is desirable. *hlMru: For the treatment of secondary hy peruriccemla associated with malignancies and In the Lesch-Nyhan syndrome, ZYLOPRI M should be given in doses of 10 mg/kg/day. The response should be evaluated after approximately 48 hours by monitoring serum uric acid and/or urinary uric acid levels and adjusting the dose if necessary. P.eceictleu: ZYLOPRIM 100 mg scored white tablets. Bottles of 100 and 500 tablets; Code: Welicome U4A. ZYLOPRIM 300 mg scored peach coloured tablets. Bottles of 100 tablets. Code: Wellcome C9B. Preded Mecegraph availableec requeci. W-8006 *Trade Mark FF.ii1 IccPpI
.
Weilcome Medcai Division Burroughs Welicome Ltd. LaSalle, Qua.
Can Fain Physician 21: 85, November 1975 15. WESThURY RC: The Content of a Calgary Family Practice, 1967-1971, MD thesis, Cambridge U, Cambridge, England (submitted) 16. TARRANT M: What price admitting privileges? A study of hospital admis-
sions by two family physicians. Can Fain Physician 23: 837, July 1977 17. International Classification of Health Problems in Primary Care, American Hospital Association, Chicago, 1975 18. HEBB AMO: Reports on Nova Scotia Fetal Risk Project, 197 1-76, national health grant 602-7-147
Adverse drug reactions: uncommon or unrecognized? Clinically important drug interactions that are predictably beneficial to the patient are the mainstay of optimal drug therapy for such disorders as malignant disease, hypertension, arrhythmias and infections. Harmful drug interactions have been unduly emphasized with respect to overall importance, and their mechanisms are considerably misunderstood.1 The reported frequency of interactions is dependent on the definitions and criteria applied. For example, when drug interactions were "diagnosed" by comparing patients' prescriptions with a computer bank of 24 000 drug interactions reported in the literature, it was found that every day 9% of patients had an adverse interaction.2 When strict criteria for what is a potentially serious interaction were applied, the maximum predicted frequency was 1.2%. In contrast, in the Boston collaborative drug surveillance program only 0.28% of patients had a clinically recognized adverse interaction.2 For almost all specific adverse drug interactions the true frequency is not known since the frequency of coadministration of two drugs without interaction is not known; conversely, the frequency with which undetected interactions occur is also unknown. Even if the frequency of interaction is known, the concurrent prescription of two drugs with a potential for serious adverse interactions does not have any predictive value as to the likelihood of such an interaction in a particular patient. In the absence of more specific information, combinations of frequently implicated drugs should be avoided; for example, coumarin anticoagulants (e.g., warfarin), orally administered hypoglycemics (e.g., tolbutamide), antiseizure medications (e.g., pheny-
tom) and anti-inflammatory agents (e.g., phenylbutazone). However, drugs that are proven to frequently induce clinically important adverse drug interactions can safely be given, when it is essential, with dose adjustment or extra observation of the patient or both. In this issue of the Journal (beginning on page 1261), Cass, Kadar and Stein focus attention on a large number of potential and often predictable interactions among drugs that affect the autonomic nervous system. Interactions among /3blockers, sympathomimetic agonists (e.g., ephedrine, phenylephrine and salbutamol), tricyclic antidepressants, phenothiazines and antihypertensive agents must occur commonly, and occasionally will be important. When drugs with such pharmacologic potential are given together, the patient should be watched carefully when administration of the second drug is started or stopped. For example, if phenylephrine is given to a patient taking reserpine or guanethidine, both a-adrenergic receptor sensitivity and blood pressure will increase.3 The fatal outcome in the case reported by Cass and colleagues was due to the presence of an aneurysm, which made any increase in blood pressure dangerous for the patient. The administration of eye drops containing 10% phenylephrine can alone raise the blood pressure a little in some patients.4 The magnitude of the increase and the probability that it will be clinically important are determined by the dose of phenylephrine, the technique used to instil the eye drops, whether there is conjunctival inflammation, whether the drops reach the nasal mucosa and whether the responsiveness of the cardiovascular system is altered. In the patient
and Surgeons of Canada
Examinations The examinations of the Royal College are held in September of each year. Candidates wishing to sit for the examinations should note the following:
in the treatment of breast cancer are to be made, they must be done within a properly designed, meticulously controlled, investigational framework. ALEX MCPHERSON, MD SANDY PATERSON, MB, BS
Department of medicine ALAN LEES, BM, B CH
Department of radiation oncology Cross Cancer Institute Edmonton, Alta.
1. Every candidate for admission to the examinations must submit an application for assessment of training. 2. Candidates in training in Canada should apply for preliminary assessment of training at least one year before the date on which they expect to sit for the examinations, that Is to say not later than September 1st of the preceding year. Candidates who have had training outside of Canada should submit their initial application for assessment at least eighteen months before they expect to sit for the examinations, that is by March 1st of the preceding year. Only candidates whose assessment of credentials Is complete will be accepted to sit for the examinations. 3. Candidates who desire to sit for an examination, having complied with the above requirement of preliminary assessment of training, must notify the College in writing of their intent before February 1st of the year of the examination. Upon receipt of this notice of intent, the evaluation of the candidate's performance during training will be added to the previously completed assessment of credentials. Each candidate will then receive notification as to eligibility together with an application form for admission to the examination which he will complete and return. 4. The following documents may be obtained from the College office: (a) Application forms for assessment oftraining. (b) General Information booklet on training requirements and examinations. (c) Specific requirements for training and regulations relating to the examinations of each specialty. Requests should indicate the specialty or specialties of interest to the applicant. (d) Listing of specialty training programmes in Canada accreditedby the College. 5. Address all enquiries to: Division of Training and Evaluation ROYAL COLLEGE OF PHYSICIANS AND SURGEONS OF CANADA 74 Stanley Avenue Ottawa, Ontario KIM 1P4 Tel.: (613) 746-8177
References 1. BURNS
PE,
KREDENTSER
J,
GRACE
M, et al: Breast cancer in northern Alberta: pilot study in computerized registration. Can Med Assoc J 116: 1131, 1977 2. FISHER B, REDMOND C, et al: Studies of the National Surgical Adjuvant Breast Project (NSABP), in Adjuvan; Therapy of Cancer, SALMON SS, JONES SE (eds), North-Holland, Amsterdam, 1977, p 67 3. BONADONN,A G, Rossi A, VALAGUSSA
A, et al: Adjuvant chemotherapy with CMF in breast cancer with positive axillary nodes. Ibid, p 83
Research in general practice In recent years there has been an increasing awareness in Canada of the need for research in general practice. General practitioners can provide valid information about patients and their problems from a unique viewpoint, since they care for patients of all ages, with all types of illness, and treat disorders both in the early stages and on a long-term basis. Individual practitioners can make original and useful observations. An outstanding example, as described by Dr. Gordon Johnson in his article in this issue of the Journal (starting on page 1245), was Will Pickles,1 who, in the late 1920s and early 1930s, studied the transmission of infectious diseases in his isolated village, Wensleydale, in Yorkshire, England. About 20 years later, in the village of Peaslake, Surrey, Dr. Ian Watson2 established an epidemic observation unit to collect reports on diseases of current interest from general practitioners throughout Great Britain. Watson's idea stimulated the establishment of "sentinel stations" in the Netherlands, as well as the national recording system of the College of Family Physicians of Canada, which is now in its third year of a national influenza surveillance study.3 Although it seems that much of the early work was done by general practitioners in rural communities, some practitioners in cities have provided stimulus and basic techniques that are being used in Canada. Dr. T.S. Eimerl, from his practice in Warrington, Cheshire, developed the E-book method of recording morbidity data.' This simple way of keeping a record
1198 CMA JOURNAL/MAY 19, 1979/VOL. 120
of patient problems has been used widely and has shown the need for a classification of diseases that would enable general practitioners from various countries to compare results. In Birmingham, Drs. Robin Pinsent and Donald Crombie, both of whom were in private practice, developed expertise in a wide variety of research projects and contributed greatly to the work of the Royal College of General Practitioners.5'6 The Birmingham Research Unit, the world centre of general practice research, provides advice and technical help for both small and large studies.7 Many other general practitioners have recognized the need for interest in research, as indicated by their many contributions to the Journal of the Royal College of General Practitioners. In Great Britain research by general practitioners has received substantial support from the government and private foundations. Large grants have been given, for example, to the Royal College of General Practitioners for its oral contraception study, which was begun more than 10 years ago and has involved 1200 general practitioners and 46 000 patients.8 This unique study was possible only because of the combined efforts of physicians who were willing to give a little of their time to provide information to a central unit, where it was collected and processed. The result is the best large study ever conducted on oral contraception. General practitioners in Canada have also recognized the value of their research. In Duncan, BC, Dr.
Peter Postuk9 recorded morbidity data from his group practice for 8 years before he organized the first large-scale morbidity survey in British Columbia in 1965. Dr. Jim Collyer10'" conducted studies in Ontario, first in Leamington and then in London, on workload and time, morbidity and psychosocial aspects of his solo practice. He also organized group studies.12 Dr. John Garson, who gained experience in research while in Great Britain, carried out many studies on family practice in Saskatoon.13'14 Bob Westbury15 and Michael Tarrant,18 in Calgary, compiled long-term studies of their practices that showed clinical content and operational factors. Their work contributed greatly to the new "International Classification of Health Problems in Primary Care",17 which was prepared by a committee set up by the World Organization of National Colleges and Academies of General Practitioners/Family Physicians. In an important study of perinatal morbidity carried out by the Nova Scotia chapter of the College of Family Physicians of Canada,18 with Dr. Mike Hebb as project director, highrisk factors were identified by means of an antenatal scoring system. As a result, there was substantial improvement in the morbidity in that province. Research in family practice is needed in a wide range of areas, such as clinical studies, therapeutic studies, epidemiology, patient attitudes, methods of providing care and determination of the relevance of medical education to community practice. Family physicians can provide a unique perspective in several aspects of medicine, especially the natural history of disease, family relations, longterm care, early diagnosis and multiple diagnoses. There are many topics on which more knowledge is needed; however, 'they must be studied one at a time. To be effective in research we must proceed systematically. The area of study must be clearly defined and not too large, and the method of study must be well planned, so that the results can be valid. Sources of
consultation are available to the planner who wants to avoid bias or confusion. Each provincial chapter of the College of Family Physicians of Canada, for example, has a research committee that might be able to provide help. If not, the chapter can refer the planner to resources at universities or government agencies. Advice can also be obtained from the family practice research units that have recently been started by the college in cooperation with the University of British Columbia, or from the Toronto offices of the college. For those who wish to do research, there are deterrents. Probably the biggest one is the fact that the needs of one's patients deserve priority. Partners in group practices must also be considered, for their support is necessary, whether they are participating in the project or helping to provide time and resources. Another big deterrent is inertia. Most physicians have not been trained to develop an inquiring mind or the basic skills needed for research. They must therefore make an active effort to break out of their usual routine. Finances can be a problem. Small projects may be managed personally, without the bother of applying for grants, especially if the research can be regarded as a hobby; the cost may be much less than the membership fee at a golf or squash club. Larger projects will require careful and timeconsuming preparation of applications for grants, an effort that may prove futile. Granting agencies have had little experience with general practitioners and may be hard to convince that general practitioners are capable of doing good research. Family practitioners who become involved in research should be compensated for the time lost from their usual work. Physicians in private practice may be overwhelmed or discouraged by the tendency of granting agencies to give greater support to university departments with salaried personnel. Much has already been accomplished by cooperation between private and university-based family physicians, and many individuals at
a university developed their initial interest and ability while in private practice. The cooperation should be maintained and strengthened, so that optimum use is made of resources in both areas, and to ensure that the research represents all the relevant aspects of community practice. To provide the best service to patients and the best information for policy decisions in education and politics, general practitioners must continue to develop a solid base of research to justify their claim that they can make a unique contribution to knowledge in the health field. WILLIAM A. FALK, MD
References
Associate professor Division of family practice Faculty of medicine University of Calgary Calgary, Alta.
1. PICKLES WN: Epidemiology in Country Practice, Wright, Bristol, 1939 2. WATSON GI: Letter from the honorary director of the epidemic observation unit. J R Coil Gen Pract 19: 233, 1970 3. Canadian Influenza Surveillance Working Party: First report: methods of the national recording system. Can Fain Physician 23: 64, September, 1977 4. EIMERL TS, LAIDLAW AJ: A Hand-
book for Research in General Practice, 2nd ed, Livingstone, Edinburgh, 1969, pp 39-62 5. Dr. R.J.F.H. Pinsent (E). J R Coil Gen Pract 27: 707, 1977 6. CROMBIE DL, PINSENT RJFH: Com-
parison of the first and second national morbidity surveys. J R Coll Gen Pract 25: 874, 1975 7. The Birmingham Research Unit (E). I R Coll Gen Pract 23: 386, 1973 8. KAY CR: British experience of the pill. Can Fain Physician 16: 57, May 1970 9. POSTUK PD: A Report of an Analysis of General Practice in British Columbia from a Study of the Practices of 54 Physicians, 1964, monograph, BC chapter, Coll Fain Phys Can, Vancouver
10. COLLYER JA: A measure of a family doctor's work. Part I: setting up a
one-practice study. Can Med Assoc J 112: 1256, 1975 of a family doctor's practice. Part II: drugs, time, changes, morbidity. Ibid, p 1357 12. Idem: An evaluation of treatment in family practice; a group research project. Can Fain Physician 15: 44, September 1969 13. GARSON JZ, BooR 5, MCASKILL J, et
al: The checkup centre as part of an ongoing medical practice. Can Fain
Physician 18: 93, February 1972 14. GARSON JZ, WOLFE RR: Social problems of the hospitalized elderly.
CMA JOURNAL/MAY 19, 1979/VOL. 120 1199
'Zylop rime allopurinol l.ilcutie.c: ZYLOPRIM is intended for the treatment of gout as well as primary and secondary hyperuricaemia. ZYLOPRIM is indicated in the treatment of primary orsecondary uric acid nephropathy. ZYLOPRIM is especially useful in patients with gouty nephropathy, in those who form renal urate stones, and those with unusually severe disease. ZYLOPRIM is effective in preventing the occurrence and recurrence of uric acid stones and gravel. ZYLOPRIM is useful in the therapy and prophylaxis of tissue urate deposition, renal calculi and for acute urate nephropathy in patients with neoplastic disease who are particularly susceptible to hyperuricaemia and uric acid stone formation, especially after radiation therapy or the use of antineoplastic drugs. hiniraiiniiutieinc: Zyloprim should not be given to patients who are hypersensitive or who have had a severe reaction to this drug. Premileuc end Warnings: Acute gouty attacks may be at the start of treatment with Zyloprim and these may continue even after serum uric acid levels begin to fall. Prophylactic administration of colchicine and a low dosage of Zyloprim are advisable, particularly in new patients and in those where the previous attack rate has been high. Zyloprim is not recommended for use during pregnancy or in women of child-bearing potential unless in the jud gement of the physician, the potential benefits outweigh the possible risks to the fetus. Zyloprim should not be given to children except those with hyperu ricaemia secondary to malignancy or with Lesch-Nyhan syndrome. Patients with impaired renal or hepatic functions should be carefully observed during the early stages of Zyloprim administration and the drug withdrawn if increased abnormalities in hepatic or renal functions appear. liriceecriec cud Zylepri.: Combined therapy of Zyloprim and uricosurics will result often in a reduction in dosage of both agents. Purimihel ur mural with Zyleprim: In patients receiving PURINETHOL* (mercaptopurine) or IMURAN* (azathioprine), the concomitant administration of 300. 600 mg of ZYLOPRIM per day will require a reduction in dose to approximately 'A to ¼ of the usual dose of mercapto p urine or azathioprine. Subsequent adjust. ment of doses of PURINETHOL or IMURAN should be based on therapeutic response and any toxic effects. OhierPre..cmide with Zyleprim: In the presence of allopumay be competition in the renal tubule for excretion of chiorpropamide. When renal function is poor, the recognised risk of prolonged hypoglycasmic activity of chiorpropamide may be increased if ZYLOPRI M is given concomitantly. Ceumeri. c.iieecgulc.te with Zyleprim: It has been reported that under experimental conditions allopurinol prolongs the half-life of the anticoagulant, dicumarol. The clinical significance of this has not been established, but this interaction should be kept in mind when allopurinol is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed. Adveree reculiema: Skin reactions associated with exfoliation, fever, chills, nausea and vomiting, lymphadenopathy, arthralgia and/or eosinophilia are the most common and may occur at any time during treatment. Gastrointestinal disorders were reported but may diminish if Zyloprim Is taken after meals. STqiems cii reclined ci everdeange: Overdosage of a lopuri no is usually manifested by nausea and vomiting. No treatment is normally required, provided the drug is withdrawn and adequate hydration Ii maintained to facilitate excretion of the drug. If, however, other forms of acute distress are observed, gastric lavage should be considered, otherwise the treatment is symptomatic. Pharmeclegy: When taken orally allopurinolis rapidly metabolized. The main metabol he is oxypurinol, which is itself a xanthine oxidase inhibitor. Allopurinol and its metabolites are excreted by the kidney, but the renal handling is such that allopurinol has a plasma half-life of about one hour, whereas that of ox y purinol exceeds 18 hours. Thus, the therapeutic effect can be achieved by a once-a-day dosage of ZYLOPRIM In patients taking 300 mg or less per day. Decage cii cd.iidclrctie.: ZYLOPRIM, administered orally should be divided into 1 to 3 daily doses. Daily doses up to and including 300 mg may be taken once daily after a meal. Divided doses should not exceed 300 mg. The minimum effective dose Is 100 to 200 m¶.. The average is 200 to 300 mg/day for patients wit mild gout, 400 to 600 mg/day for moderately severe tophaceous gout, and 700 to 800 mg/day in severe conditions. The maximal recommended dose is 800 mg per day in patients with normal renal function. Treatment with 600 to 800 mg daily fortwo or three days prior to chemotherapy or x-irradlation is advisable to preventuricacid neph ropathy. Treatmentshould becontinued at a dosage adjusted to the serum uric acid level until there is no longer a threat of hyperuriccemia and hyperuricosuria. Itis essential thata daily urinary output of two litres or more be maintained during ZYL OPRIM therapy, and neutral or alkaline urine is desirable. *hlMru: For the treatment of secondary hy peruriccemla associated with malignancies and In the Lesch-Nyhan syndrome, ZYLOPRI M should be given in doses of 10 mg/kg/day. The response should be evaluated after approximately 48 hours by monitoring serum uric acid and/or urinary uric acid levels and adjusting the dose if necessary. P.eceictleu: ZYLOPRIM 100 mg scored white tablets. Bottles of 100 and 500 tablets; Code: Welicome U4A. ZYLOPRIM 300 mg scored peach coloured tablets. Bottles of 100 tablets. Code: Wellcome C9B. Preded Mecegraph availableec requeci. W-8006 *Trade Mark FF.ii1 IccPpI
.
Weilcome Medcai Division Burroughs Welicome Ltd. LaSalle, Qua.
Can Fain Physician 21: 85, November 1975 15. WESThURY RC: The Content of a Calgary Family Practice, 1967-1971, MD thesis, Cambridge U, Cambridge, England (submitted) 16. TARRANT M: What price admitting privileges? A study of hospital admis-
sions by two family physicians. Can Fain Physician 23: 837, July 1977 17. International Classification of Health Problems in Primary Care, American Hospital Association, Chicago, 1975 18. HEBB AMO: Reports on Nova Scotia Fetal Risk Project, 197 1-76, national health grant 602-7-147
Adverse drug reactions: uncommon or unrecognized? Clinically important drug interactions that are predictably beneficial to the patient are the mainstay of optimal drug therapy for such disorders as malignant disease, hypertension, arrhythmias and infections. Harmful drug interactions have been unduly emphasized with respect to overall importance, and their mechanisms are considerably misunderstood.1 The reported frequency of interactions is dependent on the definitions and criteria applied. For example, when drug interactions were "diagnosed" by comparing patients' prescriptions with a computer bank of 24 000 drug interactions reported in the literature, it was found that every day 9% of patients had an adverse interaction.2 When strict criteria for what is a potentially serious interaction were applied, the maximum predicted frequency was 1.2%. In contrast, in the Boston collaborative drug surveillance program only 0.28% of patients had a clinically recognized adverse interaction.2 For almost all specific adverse drug interactions the true frequency is not known since the frequency of coadministration of two drugs without interaction is not known; conversely, the frequency with which undetected interactions occur is also unknown. Even if the frequency of interaction is known, the concurrent prescription of two drugs with a potential for serious adverse interactions does not have any predictive value as to the likelihood of such an interaction in a particular patient. In the absence of more specific information, combinations of frequently implicated drugs should be avoided; for example, coumarin anticoagulants (e.g., warfarin), orally administered hypoglycemics (e.g., tolbutamide), antiseizure medications (e.g., pheny-
tom) and anti-inflammatory agents (e.g., phenylbutazone). However, drugs that are proven to frequently induce clinically important adverse drug interactions can safely be given, when it is essential, with dose adjustment or extra observation of the patient or both. In this issue of the Journal (beginning on page 1261), Cass, Kadar and Stein focus attention on a large number of potential and often predictable interactions among drugs that affect the autonomic nervous system. Interactions among /3blockers, sympathomimetic agonists (e.g., ephedrine, phenylephrine and salbutamol), tricyclic antidepressants, phenothiazines and antihypertensive agents must occur commonly, and occasionally will be important. When drugs with such pharmacologic potential are given together, the patient should be watched carefully when administration of the second drug is started or stopped. For example, if phenylephrine is given to a patient taking reserpine or guanethidine, both a-adrenergic receptor sensitivity and blood pressure will increase.3 The fatal outcome in the case reported by Cass and colleagues was due to the presence of an aneurysm, which made any increase in blood pressure dangerous for the patient. The administration of eye drops containing 10% phenylephrine can alone raise the blood pressure a little in some patients.4 The magnitude of the increase and the probability that it will be clinically important are determined by the dose of phenylephrine, the technique used to instil the eye drops, whether there is conjunctival inflammation, whether the drops reach the nasal mucosa and whether the responsiveness of the cardiovascular system is altered. In the patient
