- Email: [email protected]
Phoenix, not white elephant, at Northwick Park?
Hip, hip, hooray
Phoenix,
About 800 000 total hip replacements have been done in North America, where the current rate is about 120 000 per year. Participants at the consensus development conference on total hip replacement at the US National Institutes of Health on Sept 12-14 described the operation as successful, and an excellent bargain in terms of quality-adjusted life-years per dollar, relative to other interventions in chronic disabling disease. : With advances in prosthesis design and anchorage, including both cemented and porous-coated non-cemented techniques, and advances in asepsis and antibiotic prophylaxis, the new hips typically last from 5 to 20 years. Over 90% of prostheses are not revised. Although revisions are more difficult and less successful than primary total hip replacements, this : should not (and does not) deter young people from having the operation. Over half of the operations are for osteoarthritis, and another nearly 20% are for : femoral neck fractures. There are few contraindications, except active local or systemic infection; any patient with pain, disability, and radiographic evidence of joint damage, for whom an extended trial of non-surgical management has failed, is a candidate. The panel considers the bench mark for success rates to be a cemented acetabular component combined with a non-cemented femoral component, but this is by no means a rigid recommendation. : Most failures involve osteolysis and aseptic loosening, brought on by local granulomatous reaction to sub-micron wear particles. The near-term generation of particulates from failing cement has been reduced, and concern has shifted to long-term wear of the ultra-high molecular weight polyethylene socket. Further improvements in the polyethylene, or replacement of the alloy ball component with ceramic, may reduce this difficulty. Modularity can be a problem, because every crevice in the prosthesis has the potential for mechanically-assisted corrosion, also yielding particulates. Another important source of failure is stress-shielding and disuse atrophy of the proximal femur, associated with the more rigid stems of uncemented femoral components, which transfer stress more distally. The panel recommended regular radiological follow-up every few weeks to detect osteolysis before catastrophic fracture, and they called for randomised trials of various prosthesis designs, with doubleblind follow-up, to assess the relative merits of the many approaches available, and to relate the various designs and techniques to outcomes in specific types of
highly
i
i
not white
elephant,
When the Medical Research Council built its Clinical Research Centre at Harrow, on the outskirts of London, about 25 years ago, there was talk of its being a white elephant (see Lancet 1969; ii: 787-88). That prediction could have proved apt when the Council moved its clinical research initiative to Hammersmith Hospital in 1990. With the title deeds restricting use of the building to biomedical purposes, competition for the space was bound to be limited. Enter a group of scientists at the Harrow complex convinced of the potential for setting up a new research institute. This centre, the Northwick Park Institute for Medical Research, will be officially opened on Oct 4 by Nobel prizewinner Sir James Black, best known for his discovery of HZ histamine antagonists. The group believed that the Northwick Park general hospital that had been built alongside the CRC and the stable but ethnically diverse population that it served was an excellent source of the material for a wide range of epidemiological clinical research, and that existing and potential clinical and research strengths at the hospital/laboratory complex could be exploited to attract world-class scientists. Furthermore, the 45 acres of land belonging to the complex would allow expansion of facilities. First the group encouraged Northwick Park Hospital and North West Thames regional health authority to bid for the 78-year-lease for the CRC, which was obtained for jC3’2 million. This sum paid for some 25 000 m2 of purpose-built laboratories. About a third of this will be occupied by the new institute, a third will
at Northwick Park?
be let out on short leases, and, as part of the rationalisation of London’s hospitals, the final third is being converted to accommodate St Mark’s Hospital, from April next year. The strength that this specialist hospital for bowel diseases will be bringing to Northwick Park (along with its academic unit and its Imperial Cancer Research Fund Colorectal Cancer Unit) quite naturally makes gastroenterology one of the four main themes chosen for the NPIMR’s research programme. Another of the main themes selected is immunology, infections, and tropical medicine. The research group, led by Prof Geoffrey Pasvol, head of infectious diseases at Imperial College of Science, Technology, and Medicine/St Mary’s Hospital Medical School (IC/SMH) and NPIMR’s assistant director in charge of clinical studies, is already on site, occupying the CRC’s Lister Unit. The unit, which is one of the Wellcome Trust’s four tropical diseases clinical centres in the UK, is interested in mechanisms of disease. In the case of malaria, for example, the group is investigating cellular interactions in pathogenesis of the disease, the molecular mechanisms by which the parasite enters the red cell, how infected cells bind to tissue (brain especially), whether the rosette of uninfected cells around infected cells contributes to pathogenesis, and the production of toxins by the
parasite. The
other main themes are medical which will be based on an genetics, version of the Kennedy Galton expanded Centre (the regional centre for clinical two
i
i
i
patients.
Figure: Paul M Rowe
The
hospital/laboratory complex
The former MRC Clinical Research Centre
is in
at Northwick the white
Park, Harrow
rectangle.
943
genetics), and cardiovascular diseases, versity teaching hospital associated with an emphasis on nuclear cardiology Imperial College. IC/SMH has estaband vascular medicine. : lished a new chair of community genetics,
with
Several other research teams already on site will continue with their research programmes because they are well regarded or funded, or will interact with the four main groups or develop alongside fresh Northwick Park and St Mark’s initiatives, such as the proposed North Thames trauma centre. One of these is the IC/SMH antigen-presentation group headed by Dr Stella Knight, NPIMR’s assistant director in charge of pre-clinical studies. The group’s AIDS research is funded by the MRC and concentrates on the early part that dendritic cells play in HIV infections. It will continue its clinical links with Dr Anthony Pinching of St Bartholomew’s Hospital in examining the number of dendritic cells infected as a prognostic indicator, but will now also be able to draw on patients from Pasvol’s infectious diseases unit. And, together with Dr Cecil Reid from the haematology unit at Northwick Park Hospital, the group is trying to culture stem cells that will differentiate into : functioning dendritic cells. Another team that will be continuing its programme is the surgical sciences group led by Prof Colin Green, NPIMR’s director. The focus is on tissue repair, wound healing, reconstructive surgery, and organ transplantation. The group has close links with scientists and plastic surgery teams at Mount Vernon Hospital in Northwood, Middlesex, and University College Hospital in London, and the Blond Mclndoe Centre in East Grinstead, Sussex. : The Institute also aims to assist the hospital with its undergraduate and postgraduate teaching programme. Links between Northwick Park and IC/SMH have been built up over the past few years and the hospital is now a recognised uni.
.
Savings from the superfluous in Germany Sales of the 10th (1994) edition of the Arzneiverordnungs-Report (Medicines Prescription Report) are hot. Buyers are more likely to be salesmen and pharmacists than doctors, who need to know how their competitors are faring and what is worth stocking. Industry and pharmacists have taken the brunt of the strict medicines budget imposed on the German sick fund physicians by the 1993 Health Structure Law. For each of the past 12 years the Scientific Institute of the Sick Funds (WIDO) has analysed a 1 in 1000 sample of all prescriptions for Sick Fund members for the 2000 most commonly prescribed medicines-ie, close to 90% of all prescriptions. It gives also the defined daily doses (not always identical with WHO’s) for the 20 leading indication groups, which cover 75% of all prescriptions.
944
be based at the Kennedy Galton Centre. NPIMR-whose board of trustees is chaired by Prof Sir Stanley Peart, and includes Sir Terence English, past president of the Royal College of Surgeons, Sir Walter Bodmer, director general of the ICRF-hopes to formalise its teaching and research links with IC/SMH. The arrangement would allow for exchange of research teams, shared posts between sites, joint grant applications, shared facilities (eg, JANET computer network), expansion of its teaching programmes at Northwick Park for the St Mary’s stuto
dents, joint supervision of postgraduate students, and shared administrative skills. The institute’s third aim is to collaborate closely with the health-care industry in the research and development of pharmaceutical products and new technologies. Glaxo and Pfizer have for several years had use of ward and laboratory space and more is available for expansion for suitable collaborative work. The bold venture could fail if it does not attract sufficient funding. The institute has secured funds to maintain the infrastructure for 3 years. With research groups expected to support themselves through programme grants, part of which could be used for administrative and infrastructure costs, and with an annual income of c600000 promised from other sources, the institute calculates that, in addition to C2200 000 for various start-up costs, at least £ 1-5 million per year would have to be raised to provide the infrastructure for the 250 research workers it hopes to recruit by the end of 1996. Vivien Choo
This time, sick fund physicians managed not to exceed the budget of DM 23-9 billion. The booklet tells us where they economised and where not. The losers (in % of prescriptions) were: varicose vein remedies (-28-3), gallbladder remedies (-27), mineral supplements (-23-8), immunotherapeutics (-23), "blood flow enhancers" (-22.8), lipid- lowering agents (-22-1), "urologicals" (-21-8), mouth and throat remedies (-20-9), vitamins (-20.6), and antihypotensives (-19-9). Thus the losses concern mostly medicines rarely prescribed in other developed countries. Increasingly prescribed were certain sex hormones and their inhibitors, mostly menopausal preparations (+11-7), and ACE inhibitors (+5-8), antibiotics (+2-6), corticosteroids (mostly systemic) (+1-9), thyroid medicines (+1-4), and antidiabetics
scribing
(+0-1). The rate of generic preincreased from 11-8% in 1981 to
Gangliosides
hold
The European Union Committee for Proprietary Medicinal Products has recommended the withdrawal of marketing authorisations for mixtures of ganglio-
sides. Concerns about a link to GuillainBarre syndrome led the CPMP to conclude that "a positive risk/benefit ratio has not been demonstrated". The CPMP also called for a one-year suspension of marketing authorisations for the monosialoganglioside GM-1 (Sygen [Fidia],
monosialotetrahexosylganglioside), pending completion of ongoing clinical trials. Fidia, the Italian company that manufactured the ganglioside mixture (Cronnassial) implicated in the cases complicated by Guillain-Barré syndrome, has also been asked to submit a progress report to competent authorities in all EU member states after a year. Cronnassial is marketed as a therapy for peripheral or diabetic neuropathy and GM-1 for vascular cerebral
insufficiency. Problems with gangliosides were first reported to the CPMP in December, 1989, when German authorities highlighted six cases of Guillain-Barre syndrome temporally linked to Cronnassial, and countries where this drug was registered limited indications and product avail-
ability. In 1993 an Italian case-control study, the Lazio study, showed that ganglioside intake was substantially commoner among patients with Guillain-Barré syndrome than among controls. Italy subsequently suspended all gangliosides and in March, 1993, the CPMP, recommended temporary suspension of marketing authorisations until the evaluation was finalised. Greece had already suspended authorisation in January, but Spain did so on April 29 and Portugal on March 19, ironically the very day that Italy repealed its suspension order. Italy went on to suspend authorisations again in December, 1993, and completely revoked them for ganglioside mixtures in August this year. On Aug 29, Italy suspended marketing authorisation for a year for GM-1, pending completion of clinical trials. Fidia gave the CPMP an oral explanation of product safety in mid-September to back up various written reports and documentation it had provided the committee. The company also outlined its ongoing clinical trial programme for acute ischaemic stroke. Marketing authorisations for GM-1 have been suspended in Greece and Italy, and an application is pending in Portugal. Authorisations for Cronnassial have been suspended in Germany, Greece, Luxembourg, Spain, and Portugal and revoked in Italy. The other EU member state have not registered the products.
38% in 1993. Karl H Kimbel
on
Sara Lewis
Phoenix,
About 800 000 total hip replacements have been done in North America, where the current rate is about 120 000 per year. Participants at the consensus development conference on total hip replacement at the US National Institutes of Health on Sept 12-14 described the operation as successful, and an excellent bargain in terms of quality-adjusted life-years per dollar, relative to other interventions in chronic disabling disease. : With advances in prosthesis design and anchorage, including both cemented and porous-coated non-cemented techniques, and advances in asepsis and antibiotic prophylaxis, the new hips typically last from 5 to 20 years. Over 90% of prostheses are not revised. Although revisions are more difficult and less successful than primary total hip replacements, this : should not (and does not) deter young people from having the operation. Over half of the operations are for osteoarthritis, and another nearly 20% are for : femoral neck fractures. There are few contraindications, except active local or systemic infection; any patient with pain, disability, and radiographic evidence of joint damage, for whom an extended trial of non-surgical management has failed, is a candidate. The panel considers the bench mark for success rates to be a cemented acetabular component combined with a non-cemented femoral component, but this is by no means a rigid recommendation. : Most failures involve osteolysis and aseptic loosening, brought on by local granulomatous reaction to sub-micron wear particles. The near-term generation of particulates from failing cement has been reduced, and concern has shifted to long-term wear of the ultra-high molecular weight polyethylene socket. Further improvements in the polyethylene, or replacement of the alloy ball component with ceramic, may reduce this difficulty. Modularity can be a problem, because every crevice in the prosthesis has the potential for mechanically-assisted corrosion, also yielding particulates. Another important source of failure is stress-shielding and disuse atrophy of the proximal femur, associated with the more rigid stems of uncemented femoral components, which transfer stress more distally. The panel recommended regular radiological follow-up every few weeks to detect osteolysis before catastrophic fracture, and they called for randomised trials of various prosthesis designs, with doubleblind follow-up, to assess the relative merits of the many approaches available, and to relate the various designs and techniques to outcomes in specific types of
highly
i
i
not white
elephant,
When the Medical Research Council built its Clinical Research Centre at Harrow, on the outskirts of London, about 25 years ago, there was talk of its being a white elephant (see Lancet 1969; ii: 787-88). That prediction could have proved apt when the Council moved its clinical research initiative to Hammersmith Hospital in 1990. With the title deeds restricting use of the building to biomedical purposes, competition for the space was bound to be limited. Enter a group of scientists at the Harrow complex convinced of the potential for setting up a new research institute. This centre, the Northwick Park Institute for Medical Research, will be officially opened on Oct 4 by Nobel prizewinner Sir James Black, best known for his discovery of HZ histamine antagonists. The group believed that the Northwick Park general hospital that had been built alongside the CRC and the stable but ethnically diverse population that it served was an excellent source of the material for a wide range of epidemiological clinical research, and that existing and potential clinical and research strengths at the hospital/laboratory complex could be exploited to attract world-class scientists. Furthermore, the 45 acres of land belonging to the complex would allow expansion of facilities. First the group encouraged Northwick Park Hospital and North West Thames regional health authority to bid for the 78-year-lease for the CRC, which was obtained for jC3’2 million. This sum paid for some 25 000 m2 of purpose-built laboratories. About a third of this will be occupied by the new institute, a third will
at Northwick Park?
be let out on short leases, and, as part of the rationalisation of London’s hospitals, the final third is being converted to accommodate St Mark’s Hospital, from April next year. The strength that this specialist hospital for bowel diseases will be bringing to Northwick Park (along with its academic unit and its Imperial Cancer Research Fund Colorectal Cancer Unit) quite naturally makes gastroenterology one of the four main themes chosen for the NPIMR’s research programme. Another of the main themes selected is immunology, infections, and tropical medicine. The research group, led by Prof Geoffrey Pasvol, head of infectious diseases at Imperial College of Science, Technology, and Medicine/St Mary’s Hospital Medical School (IC/SMH) and NPIMR’s assistant director in charge of clinical studies, is already on site, occupying the CRC’s Lister Unit. The unit, which is one of the Wellcome Trust’s four tropical diseases clinical centres in the UK, is interested in mechanisms of disease. In the case of malaria, for example, the group is investigating cellular interactions in pathogenesis of the disease, the molecular mechanisms by which the parasite enters the red cell, how infected cells bind to tissue (brain especially), whether the rosette of uninfected cells around infected cells contributes to pathogenesis, and the production of toxins by the
parasite. The
other main themes are medical which will be based on an genetics, version of the Kennedy Galton expanded Centre (the regional centre for clinical two
i
i
i
patients.
Figure: Paul M Rowe
The
hospital/laboratory complex
The former MRC Clinical Research Centre
is in
at Northwick the white
Park, Harrow
rectangle.
943
genetics), and cardiovascular diseases, versity teaching hospital associated with an emphasis on nuclear cardiology Imperial College. IC/SMH has estaband vascular medicine. : lished a new chair of community genetics,
with
Several other research teams already on site will continue with their research programmes because they are well regarded or funded, or will interact with the four main groups or develop alongside fresh Northwick Park and St Mark’s initiatives, such as the proposed North Thames trauma centre. One of these is the IC/SMH antigen-presentation group headed by Dr Stella Knight, NPIMR’s assistant director in charge of pre-clinical studies. The group’s AIDS research is funded by the MRC and concentrates on the early part that dendritic cells play in HIV infections. It will continue its clinical links with Dr Anthony Pinching of St Bartholomew’s Hospital in examining the number of dendritic cells infected as a prognostic indicator, but will now also be able to draw on patients from Pasvol’s infectious diseases unit. And, together with Dr Cecil Reid from the haematology unit at Northwick Park Hospital, the group is trying to culture stem cells that will differentiate into : functioning dendritic cells. Another team that will be continuing its programme is the surgical sciences group led by Prof Colin Green, NPIMR’s director. The focus is on tissue repair, wound healing, reconstructive surgery, and organ transplantation. The group has close links with scientists and plastic surgery teams at Mount Vernon Hospital in Northwood, Middlesex, and University College Hospital in London, and the Blond Mclndoe Centre in East Grinstead, Sussex. : The Institute also aims to assist the hospital with its undergraduate and postgraduate teaching programme. Links between Northwick Park and IC/SMH have been built up over the past few years and the hospital is now a recognised uni.
.
Savings from the superfluous in Germany Sales of the 10th (1994) edition of the Arzneiverordnungs-Report (Medicines Prescription Report) are hot. Buyers are more likely to be salesmen and pharmacists than doctors, who need to know how their competitors are faring and what is worth stocking. Industry and pharmacists have taken the brunt of the strict medicines budget imposed on the German sick fund physicians by the 1993 Health Structure Law. For each of the past 12 years the Scientific Institute of the Sick Funds (WIDO) has analysed a 1 in 1000 sample of all prescriptions for Sick Fund members for the 2000 most commonly prescribed medicines-ie, close to 90% of all prescriptions. It gives also the defined daily doses (not always identical with WHO’s) for the 20 leading indication groups, which cover 75% of all prescriptions.
944
be based at the Kennedy Galton Centre. NPIMR-whose board of trustees is chaired by Prof Sir Stanley Peart, and includes Sir Terence English, past president of the Royal College of Surgeons, Sir Walter Bodmer, director general of the ICRF-hopes to formalise its teaching and research links with IC/SMH. The arrangement would allow for exchange of research teams, shared posts between sites, joint grant applications, shared facilities (eg, JANET computer network), expansion of its teaching programmes at Northwick Park for the St Mary’s stuto
dents, joint supervision of postgraduate students, and shared administrative skills. The institute’s third aim is to collaborate closely with the health-care industry in the research and development of pharmaceutical products and new technologies. Glaxo and Pfizer have for several years had use of ward and laboratory space and more is available for expansion for suitable collaborative work. The bold venture could fail if it does not attract sufficient funding. The institute has secured funds to maintain the infrastructure for 3 years. With research groups expected to support themselves through programme grants, part of which could be used for administrative and infrastructure costs, and with an annual income of c600000 promised from other sources, the institute calculates that, in addition to C2200 000 for various start-up costs, at least £ 1-5 million per year would have to be raised to provide the infrastructure for the 250 research workers it hopes to recruit by the end of 1996. Vivien Choo
This time, sick fund physicians managed not to exceed the budget of DM 23-9 billion. The booklet tells us where they economised and where not. The losers (in % of prescriptions) were: varicose vein remedies (-28-3), gallbladder remedies (-27), mineral supplements (-23-8), immunotherapeutics (-23), "blood flow enhancers" (-22.8), lipid- lowering agents (-22-1), "urologicals" (-21-8), mouth and throat remedies (-20-9), vitamins (-20.6), and antihypotensives (-19-9). Thus the losses concern mostly medicines rarely prescribed in other developed countries. Increasingly prescribed were certain sex hormones and their inhibitors, mostly menopausal preparations (+11-7), and ACE inhibitors (+5-8), antibiotics (+2-6), corticosteroids (mostly systemic) (+1-9), thyroid medicines (+1-4), and antidiabetics
scribing
(+0-1). The rate of generic preincreased from 11-8% in 1981 to
Gangliosides
hold
The European Union Committee for Proprietary Medicinal Products has recommended the withdrawal of marketing authorisations for mixtures of ganglio-
sides. Concerns about a link to GuillainBarre syndrome led the CPMP to conclude that "a positive risk/benefit ratio has not been demonstrated". The CPMP also called for a one-year suspension of marketing authorisations for the monosialoganglioside GM-1 (Sygen [Fidia],
monosialotetrahexosylganglioside), pending completion of ongoing clinical trials. Fidia, the Italian company that manufactured the ganglioside mixture (Cronnassial) implicated in the cases complicated by Guillain-Barré syndrome, has also been asked to submit a progress report to competent authorities in all EU member states after a year. Cronnassial is marketed as a therapy for peripheral or diabetic neuropathy and GM-1 for vascular cerebral
insufficiency. Problems with gangliosides were first reported to the CPMP in December, 1989, when German authorities highlighted six cases of Guillain-Barre syndrome temporally linked to Cronnassial, and countries where this drug was registered limited indications and product avail-
ability. In 1993 an Italian case-control study, the Lazio study, showed that ganglioside intake was substantially commoner among patients with Guillain-Barré syndrome than among controls. Italy subsequently suspended all gangliosides and in March, 1993, the CPMP, recommended temporary suspension of marketing authorisations until the evaluation was finalised. Greece had already suspended authorisation in January, but Spain did so on April 29 and Portugal on March 19, ironically the very day that Italy repealed its suspension order. Italy went on to suspend authorisations again in December, 1993, and completely revoked them for ganglioside mixtures in August this year. On Aug 29, Italy suspended marketing authorisation for a year for GM-1, pending completion of clinical trials. Fidia gave the CPMP an oral explanation of product safety in mid-September to back up various written reports and documentation it had provided the committee. The company also outlined its ongoing clinical trial programme for acute ischaemic stroke. Marketing authorisations for GM-1 have been suspended in Greece and Italy, and an application is pending in Portugal. Authorisations for Cronnassial have been suspended in Germany, Greece, Luxembourg, Spain, and Portugal and revoked in Italy. The other EU member state have not registered the products.
38% in 1993. Karl H Kimbel
on
Sara Lewis