1278
form in which it is found in many types of cells.’ The Bethesda group also studied two patients longitudinally during the course of their illness, and were able to show high levels of collagenase and neutral protease activity in bronchoalveolar washings taken over many months. These observations leave little doubt that collagen in IPF is under sustained enzymatic attack. Since the total amount of collagen in diseased lung is similar to normal, enhanced enzymatic degradation must be fully compensated by increased collagen synthesis, but the newly synthesised collagen is redistributed in type, location, and form. Under normal circumstances there is a slow turnover of alveolar interstitial collagen, which is probably synthesised by several types of normal lung cell and broken down by collagenases released in the main from alveolar macrophages. It seems that in idiopathic pulmonary fibrosis the turnover is greatly speeded, with production of relatively more type I collagen which in turn becomes disorganised by coexisting high levels of active collagenase. Most cases of idiopathic pulmonary fibrosis show increased cellularity of lung tissue, providing plenty of candidate cells both to increase synthesis and to provide active collagenase for degradation of collagen. Neutrophils8 and macrophages, for example, are rich in collagenase. Where does this work on collagen lead in our understanding of IPF? It points to chronically enhanced activation of a destructive enzyme, probably through a sustained and self-perpetuating inflammatory process mediated by several types of cell. There is some parallel in active rheumatoid arthritis, where both collagenase and neutral protease activities are high in synovial fluid from inflamed bursar Unfortunately, we are no closer to knowing how the process is initiated-immune complexes have been evoked, with some experimental backing,1O but as yet the nature of any antigen responsible for such complexes remains obscure. In patient management, measurement of collagenase activity in bronchoalveolar washings may have something to offer in providing a method for following disease activity. For example, it would be particularly interesting to study the effect upon collagenase activity of treatment with corticosteroids and immunosuppressives. Regrettably, the technique can hardly be used to screen for early rises in enzyme activity, which may precede the stage of irreversible progressive fibrosis.
SICKNESS ABSENCE IN HOSPITAL STAFF
SICKNESS absence, more properly described as absence from work attributed to incapacity, is troublesome to managers in most organisations, and hospitals are no exception. A study in nurses at two Leicester hospitals1 Collagenases in human synovial fluid. J Clin Invest 1969; 48: 2104-13. 8. Lazarus GS, Brown RS, Daniels JR, Fullmer HM. Human granulocyte colla-
7. Harris ED, DiBona DR, Krane SM.
genase. Science 1968; 159: 1483-85. 9. Lazarus GS, Decker JL, Oliver H, Daniels JR, Multz CV, Fullmer HM. Collagenolytic activity of synovium in rheumatoid arthritis. N Eng J Med 1968;
279: 914-19. 10. Dreisin RB, Schwarz MI, mune
Theofilopoulous AN, Stanford RE. Circulating imcomplexes in idiopathic interstitial pneumonias. N Eng J Med 1978;
S, Hussey DG. Sickness absence amongst tals. J Soc Occup Med 1979; 29: 126-30.
nursing staff at two
hospi-
confirms earlier
small for firm conclusions to be drawn. Nevertheless absence causes serious difficulties in staffing and, of course, additional costs. The published work on this theme is now extensive and interest has varied with scarcity of manpower, as in the world wars, or with high costs of labour and sick pay, as in more recent years. Many of the reports, however, are merely descriptive and contribute little to our understanding of what is certainly a complex phenomenon of multifactorial aetiology. If comparisons are to be made within, or between, organisations, there are at least. three factors for which allowance must be made-sex, age, and occupation.5 Furthermore absence, as a repetitive event of variable duration, must be measured in terms of frequency as well as severity, since unpredictable high frequency but relatively brief absences are the main problem in industry today. The frequency distribution of absence in every working group is highly skewed, particularly when severity (time lost) is considered as was the case in the Leicester study. One consequence is that between 5% and 10% of any group accounts for at least half of all absence. In such a situation the use of a mean rate can easily be misleading since it will be heavily biased by the lengthy absence of a few people. Froggatt6 and more recently Behrend’ have emphasised the need to look at distributions, and medians or quartiles may be more informative than means alone. It is one of the ironies of all modern industrialised societies that more and more time is being taken off work attributed to incapacity despite objective improvements in health status, social circumstances, and the availability of health care. This underlines the point that sickness absence is not a reliable index of morbidity. Few people are healthy in terms of the World Health Organisation definition, and, for the rest, it is the individual who decides whether or not to consult a doctor and whether or not to take time off work. Similar considerations apply to the timing of a return to work after illness or injury. Doctors all over the world are required to certify fitness or unfitnesto work but few, if any, 2. Brown IM. Hospital staff sickness absence. Hospital 1968; March issue, 94-98. 3. Rushworth V. ’Not in today’: absence survey. Nursing Times 1975; Dec. 11, 121-24. 4. Redfern SJ. Absence and wastage in trained nurses. J Advanced Nursing
1978; 3: 231-49.
5. Taylor PJ. Aspects of sickness absence. approaches to occupational medicine.
In: Gardner AW, ed. Current Bristol: John Wright, 1979:
322-38. P. Research in industrial morbidity. Trans Soc Occup Med 1968; 18: 89-92. 7. Behrend H. How to monitor absence from work. London: Institute of Personnel Management, 1978. 8. Report of the Committee on Abuse of Social Security Benefits (Cmnd. 5228). London: H. M. Stationery Office, 1973.
6.
298: 353-57. 1. Clarke
reports2-4 that such absence rates are considerably higher among part-time than full-time staff, and that rates are generally inversely related to status in the nursing as in industrial hierarchies. Nurses in the Leicester Maternity Hospital took twice as much time off sick as those in the Royal Infirmary, and staff midwives, particularly those working in the postnatal ward, had exceptionally high rates. The study, which was for the year ending in March, 1976, covered only 158 person-years in the Maternity Hospital and 479 in the Royal Infirmary, and thus for subgroups such as midwives the populations at risk were probably too
now
Froggatt
1279
have been trained to do this. There seems little prospect, in the United Kingdom at least, of this obligation being removed from a reluctant profession. The Fisher Committee recognised that family doctors may find themselves in a difficult position in relation to certification, but concluded that there was no justification for abolishing the requirement. The report also observed "some claimants may be reluctant to tell lies to their doctor face to face, first, because in many cases he will be a person they know and respect and, second, because they over-estimate the doctor’s capacity to detect their deceit". As research by occupational health services in industry has repeatedly shown, the causes of sickness absence lie as much in the sphere of management as in the sphere of medicine.
MONITORING BLOOD-PRESSURE ONE of the most remarkable features of hypertension is that the clinician has access to a precise actuarial assessment of the prognosis for any given blood-pressure level. This knowledge is based on life-insurance statistics derived from groups of patients far greater than any multicentre study could ever hope to recruit.’ Despite the hazards of particularising from the general, insurance data can be very helpful in the management of high blood-pressure. Fortunately for the physician who adjusts his treatment on the basis of readings obtained in the hurly-burly of outpatients, the actuarial data are derived from casual blood-pressure measurements. This is not to say that such readings are the most informative : basal blood-pressure is probably a better predictor of subsequent mortality.2 Unfortunately the measurement of basal blood-pressure demands overnight sedation and habituation to the procedure by repeated measurement in a quiet room,2 which is not feasible with a large clinic population. If cardiovascular morbidity and mortality reflect the cumulative burden imposed upon the circulation by high blood-pressure, a continuous record of blood-pressure over a period of normal activity should provide a good method of assessing risk. Complete recording of bloodpressure in ambulant subjects requires arterial cannulation and elaborate apparatus both to measure and record pressure and to maintain patency of the cannula. Earlier methods, although cumbersome and unreliable, clearly demonstrated wide fluctuations in blood-pressure with varying physical and mental activity.3 At a recent workshop, results with more advanced techniques for measurement and analysis were discussed: the result is a small book4 which summarises the opportunities and problems. Apparently the more advanced technology has not fundamentally altered the picture described by theOxford group.5 A debate in these and other columns6-8 on a possible circadian rhythm of blood-pressure was
Build and blood pressure study, vol. 1. Chicago: Society of Actuaries, 1959. 2. Smirk FH. Casual, basal and supplemental blood pressures in 519 first degree relatives of substantial hypertensive patients and in 350 population controls. Clin Sci Mol Med 1976; 51: suppl 3, 13s-17s. 3. Bevan AT, Honour AJ, Stott FD. Direct arterial pressure recordings in unrestricted man. Clin Sci 1969; 36: 329-44. 1.
Society of Actuaries.
at the workshop. The claim that blood-pressure rises in the early morning independently of awakening9 was not substantiated in a critical analysis from Oxford, when blood-pressure was measured every 2 rather than every 60 min. 10 It is easy to become blinded to the problems of scientific interpretation by technical ingenuity. Major changes in blood-pressure, whether associated with activity or with an intrinsic biorhythm, are of biological interest, but their clinical importance is hard to evaluate. Even if a peak incidence of cardiovascular accidents seems to coincide with the morning blood-pressure rise,9 this may represent the last straw for severely damaged blood-vessels : the basic clinical need is to control hypertensive vascular damage rather than prevent the immediate precipitating cause of a catastrophe. This emphasises the fundamental difficulty in direct blood-pressure monitoring. There is a small but real risk in sending a patient home with an arterial catheter in situ, so we can hardly expect huge numbers of patients to be studied in this way for long periods. There is certainly no possibility of acquiring morbidity and mortality data on the scale now available for single casual blood-pressure measurements. The fundamental question remains, therefore, what does a particular abnormality in a blood-pressure record mean in terms of risk? It would be all too easy to leap to conclusions based upon an intuitive reaction to what looks like an unhealthy record. One need only look at an analogous sphere--electrocardiographic monitoring of arrhythmias in coronary-care units-to appreciate the problems of attaching importance to apparent gross abnormalities. On the other hand, in certain limited respects direct blood-pressure measurement has proved clinically useful: it has helped to elucidate the response to medication over the complete 24 hour period," and it can clarify matters in patients who have outpatient blood-pressure readings which are inconsistent with their clinical state-one study showed that often in such patients casual blood-pressure readings are unrepresentative of blood-pressure during normal activity. 12 However, more widely applicable techniques are required if we are to learn more of the prognostic importance of abnormalities in ambulatory blood-pressure. There is a hint here from work reported in the workshop proceedings (regrettably without detailed data) that useful information may be obtained with a non-invasive ambula-
pursued
.
4. Blood Pressure
Variability. Edited by D. L. CLEMENT. Lancaster: MTP. 1979. Pp. 111. £7·95. 5. Pickering G. Hypertension: causes, consequences and management. Edinburgh: Churchill Livingstone, 1974: 14-25. 6. Millar-Craig MW, Bishop CN, Raftery EB. Circadian variation of blood pressure. Lancet 1978; i: 795-97. 7. Floras JS, Jones JV, Johnston JA, Brooks DE, Hassan MO, Sleight P. Arousal and the circadian rhythm of blood pressure. Clin Sci Mol Med 1978; 55: suppl 4, 395s-97s. 8. Millar-Craig MW, Mann S, Balasubramanian V, Raftery EB. Blood pressure circadian rhythm in essential hypertension. Clin Sci Mol Med 1978; 55: suppl 4, 391s-93s. 9. Raftery EB, Millar-Craig MW. Information denved from direct 24 hour recordings. Ref. 4, p. 67-79. 10. Sleight P, Floras J, Jones JV. Automatic analysis of continuous intra-artenal blood pressure recordings. Ref. 4, p. 61-66. 11. Watson RDS, Stallard TJ, Littler WA. Influence of once-daily administration of &bgr;-adrenoceptor antagonists on arterial pressure and its variability. Lancet 1979; i: 1210-13. 12. Littler WA, Honour AJ, Pugsley DJ, Sleight P. Continuous recording of direct arterial pressure in untreated patients: its role in the diagnosis and management of high blood pressure. Circulation 1975; 51: 1101-06.
form in which it is found in many types of cells.’ The Bethesda group also studied two patients longitudinally during the course of their illness, and were able to show high levels of collagenase and neutral protease activity in bronchoalveolar washings taken over many months. These observations leave little doubt that collagen in IPF is under sustained enzymatic attack. Since the total amount of collagen in diseased lung is similar to normal, enhanced enzymatic degradation must be fully compensated by increased collagen synthesis, but the newly synthesised collagen is redistributed in type, location, and form. Under normal circumstances there is a slow turnover of alveolar interstitial collagen, which is probably synthesised by several types of normal lung cell and broken down by collagenases released in the main from alveolar macrophages. It seems that in idiopathic pulmonary fibrosis the turnover is greatly speeded, with production of relatively more type I collagen which in turn becomes disorganised by coexisting high levels of active collagenase. Most cases of idiopathic pulmonary fibrosis show increased cellularity of lung tissue, providing plenty of candidate cells both to increase synthesis and to provide active collagenase for degradation of collagen. Neutrophils8 and macrophages, for example, are rich in collagenase. Where does this work on collagen lead in our understanding of IPF? It points to chronically enhanced activation of a destructive enzyme, probably through a sustained and self-perpetuating inflammatory process mediated by several types of cell. There is some parallel in active rheumatoid arthritis, where both collagenase and neutral protease activities are high in synovial fluid from inflamed bursar Unfortunately, we are no closer to knowing how the process is initiated-immune complexes have been evoked, with some experimental backing,1O but as yet the nature of any antigen responsible for such complexes remains obscure. In patient management, measurement of collagenase activity in bronchoalveolar washings may have something to offer in providing a method for following disease activity. For example, it would be particularly interesting to study the effect upon collagenase activity of treatment with corticosteroids and immunosuppressives. Regrettably, the technique can hardly be used to screen for early rises in enzyme activity, which may precede the stage of irreversible progressive fibrosis.
SICKNESS ABSENCE IN HOSPITAL STAFF
SICKNESS absence, more properly described as absence from work attributed to incapacity, is troublesome to managers in most organisations, and hospitals are no exception. A study in nurses at two Leicester hospitals1 Collagenases in human synovial fluid. J Clin Invest 1969; 48: 2104-13. 8. Lazarus GS, Brown RS, Daniels JR, Fullmer HM. Human granulocyte colla-
7. Harris ED, DiBona DR, Krane SM.
genase. Science 1968; 159: 1483-85. 9. Lazarus GS, Decker JL, Oliver H, Daniels JR, Multz CV, Fullmer HM. Collagenolytic activity of synovium in rheumatoid arthritis. N Eng J Med 1968;
279: 914-19. 10. Dreisin RB, Schwarz MI, mune
Theofilopoulous AN, Stanford RE. Circulating imcomplexes in idiopathic interstitial pneumonias. N Eng J Med 1978;
S, Hussey DG. Sickness absence amongst tals. J Soc Occup Med 1979; 29: 126-30.
nursing staff at two
hospi-
confirms earlier
small for firm conclusions to be drawn. Nevertheless absence causes serious difficulties in staffing and, of course, additional costs. The published work on this theme is now extensive and interest has varied with scarcity of manpower, as in the world wars, or with high costs of labour and sick pay, as in more recent years. Many of the reports, however, are merely descriptive and contribute little to our understanding of what is certainly a complex phenomenon of multifactorial aetiology. If comparisons are to be made within, or between, organisations, there are at least. three factors for which allowance must be made-sex, age, and occupation.5 Furthermore absence, as a repetitive event of variable duration, must be measured in terms of frequency as well as severity, since unpredictable high frequency but relatively brief absences are the main problem in industry today. The frequency distribution of absence in every working group is highly skewed, particularly when severity (time lost) is considered as was the case in the Leicester study. One consequence is that between 5% and 10% of any group accounts for at least half of all absence. In such a situation the use of a mean rate can easily be misleading since it will be heavily biased by the lengthy absence of a few people. Froggatt6 and more recently Behrend’ have emphasised the need to look at distributions, and medians or quartiles may be more informative than means alone. It is one of the ironies of all modern industrialised societies that more and more time is being taken off work attributed to incapacity despite objective improvements in health status, social circumstances, and the availability of health care. This underlines the point that sickness absence is not a reliable index of morbidity. Few people are healthy in terms of the World Health Organisation definition, and, for the rest, it is the individual who decides whether or not to consult a doctor and whether or not to take time off work. Similar considerations apply to the timing of a return to work after illness or injury. Doctors all over the world are required to certify fitness or unfitnesto work but few, if any, 2. Brown IM. Hospital staff sickness absence. Hospital 1968; March issue, 94-98. 3. Rushworth V. ’Not in today’: absence survey. Nursing Times 1975; Dec. 11, 121-24. 4. Redfern SJ. Absence and wastage in trained nurses. J Advanced Nursing
1978; 3: 231-49.
5. Taylor PJ. Aspects of sickness absence. approaches to occupational medicine.
In: Gardner AW, ed. Current Bristol: John Wright, 1979:
322-38. P. Research in industrial morbidity. Trans Soc Occup Med 1968; 18: 89-92. 7. Behrend H. How to monitor absence from work. London: Institute of Personnel Management, 1978. 8. Report of the Committee on Abuse of Social Security Benefits (Cmnd. 5228). London: H. M. Stationery Office, 1973.
6.
298: 353-57. 1. Clarke
reports2-4 that such absence rates are considerably higher among part-time than full-time staff, and that rates are generally inversely related to status in the nursing as in industrial hierarchies. Nurses in the Leicester Maternity Hospital took twice as much time off sick as those in the Royal Infirmary, and staff midwives, particularly those working in the postnatal ward, had exceptionally high rates. The study, which was for the year ending in March, 1976, covered only 158 person-years in the Maternity Hospital and 479 in the Royal Infirmary, and thus for subgroups such as midwives the populations at risk were probably too
now
Froggatt
1279
have been trained to do this. There seems little prospect, in the United Kingdom at least, of this obligation being removed from a reluctant profession. The Fisher Committee recognised that family doctors may find themselves in a difficult position in relation to certification, but concluded that there was no justification for abolishing the requirement. The report also observed "some claimants may be reluctant to tell lies to their doctor face to face, first, because in many cases he will be a person they know and respect and, second, because they over-estimate the doctor’s capacity to detect their deceit". As research by occupational health services in industry has repeatedly shown, the causes of sickness absence lie as much in the sphere of management as in the sphere of medicine.
MONITORING BLOOD-PRESSURE ONE of the most remarkable features of hypertension is that the clinician has access to a precise actuarial assessment of the prognosis for any given blood-pressure level. This knowledge is based on life-insurance statistics derived from groups of patients far greater than any multicentre study could ever hope to recruit.’ Despite the hazards of particularising from the general, insurance data can be very helpful in the management of high blood-pressure. Fortunately for the physician who adjusts his treatment on the basis of readings obtained in the hurly-burly of outpatients, the actuarial data are derived from casual blood-pressure measurements. This is not to say that such readings are the most informative : basal blood-pressure is probably a better predictor of subsequent mortality.2 Unfortunately the measurement of basal blood-pressure demands overnight sedation and habituation to the procedure by repeated measurement in a quiet room,2 which is not feasible with a large clinic population. If cardiovascular morbidity and mortality reflect the cumulative burden imposed upon the circulation by high blood-pressure, a continuous record of blood-pressure over a period of normal activity should provide a good method of assessing risk. Complete recording of bloodpressure in ambulant subjects requires arterial cannulation and elaborate apparatus both to measure and record pressure and to maintain patency of the cannula. Earlier methods, although cumbersome and unreliable, clearly demonstrated wide fluctuations in blood-pressure with varying physical and mental activity.3 At a recent workshop, results with more advanced techniques for measurement and analysis were discussed: the result is a small book4 which summarises the opportunities and problems. Apparently the more advanced technology has not fundamentally altered the picture described by theOxford group.5 A debate in these and other columns6-8 on a possible circadian rhythm of blood-pressure was
Build and blood pressure study, vol. 1. Chicago: Society of Actuaries, 1959. 2. Smirk FH. Casual, basal and supplemental blood pressures in 519 first degree relatives of substantial hypertensive patients and in 350 population controls. Clin Sci Mol Med 1976; 51: suppl 3, 13s-17s. 3. Bevan AT, Honour AJ, Stott FD. Direct arterial pressure recordings in unrestricted man. Clin Sci 1969; 36: 329-44. 1.
Society of Actuaries.
at the workshop. The claim that blood-pressure rises in the early morning independently of awakening9 was not substantiated in a critical analysis from Oxford, when blood-pressure was measured every 2 rather than every 60 min. 10 It is easy to become blinded to the problems of scientific interpretation by technical ingenuity. Major changes in blood-pressure, whether associated with activity or with an intrinsic biorhythm, are of biological interest, but their clinical importance is hard to evaluate. Even if a peak incidence of cardiovascular accidents seems to coincide with the morning blood-pressure rise,9 this may represent the last straw for severely damaged blood-vessels : the basic clinical need is to control hypertensive vascular damage rather than prevent the immediate precipitating cause of a catastrophe. This emphasises the fundamental difficulty in direct blood-pressure monitoring. There is a small but real risk in sending a patient home with an arterial catheter in situ, so we can hardly expect huge numbers of patients to be studied in this way for long periods. There is certainly no possibility of acquiring morbidity and mortality data on the scale now available for single casual blood-pressure measurements. The fundamental question remains, therefore, what does a particular abnormality in a blood-pressure record mean in terms of risk? It would be all too easy to leap to conclusions based upon an intuitive reaction to what looks like an unhealthy record. One need only look at an analogous sphere--electrocardiographic monitoring of arrhythmias in coronary-care units-to appreciate the problems of attaching importance to apparent gross abnormalities. On the other hand, in certain limited respects direct blood-pressure measurement has proved clinically useful: it has helped to elucidate the response to medication over the complete 24 hour period," and it can clarify matters in patients who have outpatient blood-pressure readings which are inconsistent with their clinical state-one study showed that often in such patients casual blood-pressure readings are unrepresentative of blood-pressure during normal activity. 12 However, more widely applicable techniques are required if we are to learn more of the prognostic importance of abnormalities in ambulatory blood-pressure. There is a hint here from work reported in the workshop proceedings (regrettably without detailed data) that useful information may be obtained with a non-invasive ambula-
pursued
.
4. Blood Pressure
Variability. Edited by D. L. CLEMENT. Lancaster: MTP. 1979. Pp. 111. £7·95. 5. Pickering G. Hypertension: causes, consequences and management. Edinburgh: Churchill Livingstone, 1974: 14-25. 6. Millar-Craig MW, Bishop CN, Raftery EB. Circadian variation of blood pressure. Lancet 1978; i: 795-97. 7. Floras JS, Jones JV, Johnston JA, Brooks DE, Hassan MO, Sleight P. Arousal and the circadian rhythm of blood pressure. Clin Sci Mol Med 1978; 55: suppl 4, 395s-97s. 8. Millar-Craig MW, Mann S, Balasubramanian V, Raftery EB. Blood pressure circadian rhythm in essential hypertension. Clin Sci Mol Med 1978; 55: suppl 4, 391s-93s. 9. Raftery EB, Millar-Craig MW. Information denved from direct 24 hour recordings. Ref. 4, p. 67-79. 10. Sleight P, Floras J, Jones JV. Automatic analysis of continuous intra-artenal blood pressure recordings. Ref. 4, p. 61-66. 11. Watson RDS, Stallard TJ, Littler WA. Influence of once-daily administration of &bgr;-adrenoceptor antagonists on arterial pressure and its variability. Lancet 1979; i: 1210-13. 12. Littler WA, Honour AJ, Pugsley DJ, Sleight P. Continuous recording of direct arterial pressure in untreated patients: its role in the diagnosis and management of high blood pressure. Circulation 1975; 51: 1101-06.
