2000

INTRODUCTION

By the start of 2000 I had been retired from the NHS for three  years.  I continued with my voluntary work with the Cystic Fibrosis Trust as Chairman of their Research and Medical Advisory Committee until 2003 when I accepted the invitation to become their Chairman when the present chairman Duncan Bluck retired.   I was Chairman of the CF Trust from 2003 to 2011 (when I required a coronary artery stent and stepped down); later in  the year I was honoured to be made Hon. President of the CF Trust.

18.1. 2000 Meeting of the Publications Committee at CFT headquarters in Bromley

I enjoy these well-organised meetings which Sandra Kennedy, the CFT Publications Manager,  arranges.  A great deal of my time is now taken up with writing on behalf of the Cystic Fibrosis Trust – which I really enjoy, working with `Sandra Kennedy

The “Antibiotic Treatment for Cystic Fibrosis” (69 pages) is now being printed and soon will be sent to all major CF Centres and CF clinics in the UK.
In the evening I attended a dinner at the Royal College of Physicians in London prior to a meeting there the next day which is described below

19. 1. 2000.    Seminar “The Next Ten Years in CF care” at the Royal College of Physicians, Regents Park 

This meeting was organised by Professor Nick Bosanquet, Professor of Health Policy at Imperial College London. 

Overall it was a good meeting chaired by Professor Duncan Geddes, of the Brompton Hospital,  and attended by many of the  UK clinicians involved in CF care. Unfortunately, there were few hospital managers there so the speakers were often talking to the converted. Nick Bosanquet is supportive of CF care in the broadest sense and has agreed to attend the CF Trust workshop in London on neonatal screening on 20th. At this meeting two  managers appeared with us on the panel but really said nothing new. The most senior manager had been “in oil”  until recently but was now “getting to grips with the NHS”. It surprises me how of our  captains of industry seem to move from one senior job to another; usually the functions of the new organisation having a little or nothing to do with that of their previous job!.  I’m afraid it doesn’t seem to work with the NHS and it is very irritating for those of us working for a lifetime in the NHS.  I know that even the NHS senior executive has just resigned before his contract expired, it is said “to seek new challenges in academia” – as if  the NHS is not a sufficient challenge?  
I suppose the recurring theme of this present meeting was how do we fund the NHS whose problems would be greatly diminished by a massive injection of money. 

Professor Nick Bosanquet made some suggestions in an article in the Daily Mail on the 18th of January which are summarised as follows –

• The NHS to develop contracts with the private sector for elective non-emergency treatment and focus on more serious disorders
• The NHS organises contracts with private nursing homes for early discharge and intermediate care freeing hospital beds
• Encourage the return of nurses and doctors who have recently taken early retirement possibly on a part-time basis
• Encourage investment by the private sector in the health service; the government promises of 50 cataract treatment centres seems unrealistic through NHS resources and could be contracted out
• The Prime Minister should call a Downing Street healthcare summit not just the NHS people but all the other potential voluntary and private partners
• To long-term proposals whether the government should build partnerships with both international and UK companies for innovation in healthcare and research also there should be a new partnership between the state and its citizens who must begin to  recognise that they will have to pay more for their routine care while the NHS concentrates on providing a high-quality service for those with serious illnesses such as cystic fibrosis.

Nick Bosanquet subsequently  joined Telematic and Biomedical Services as a director in 2006. and we had little further contact with him that I recall.

Addendum. 25 years later in 2025  the NHS was yet again is at crisis point and severely under-funded.

3.1.2000   `Meeting of the CFT Infection Control Group.  ~   I  invited Duncan Geddes and Margaret Hodson both physicians at  the Brompton  onto this group as they were  the most senior and best  informed critics of our provisional Pseudomonas document that received such ill-informed criticism at the recent CF Centre Directors meeting. In contrast,  this was a very successful meeting. The Group modified our document to suit everyone including the new members and the final version was agreed more easily than  I  had expected. It is now a very good document and will be available for the medical CF meeting in London on the 30th of March.

3.2.2000   Helen Cunliffe is our pharmacist at St James’s. in Leeds .   Helen  attends the weekly CF unit meetings and advises on all aspects of drug use. She is now an essential member of our CF Team.

This was the first meeting of this new group for CF pharmacists. Pharmax Ltd sponsored the meeting and some 30 delegates attended.
I described the CF Trust’s new “Antibiotic Treatment for Cystic Fibrosis” document and distributed copies of the final draft.  There was a general approval of the final  version. Three of the pharmacists had who attended th meeting had been very helpful in preparing the pharmacopoeia section of the document – Paula Hayes (Liverpool), Helen Cunliffe (Leeds) and Amanda Bevan (Southampton).   At St James’s Helen Cunliffe, a senior pharmacist is an essential member  of our CF team.

15.1.2000 Ann and I were invited to attend Prof. Ros Smyth’s inaugural Lecture at Liverpool University. It was a good lecture dealing with aspects of paediatrics with which she has been concerned and also made major contributions to particularly the CF Cochrane group for which she is responsible.

16.1. 2000  Travel to Holland to give a lecture at a CF Conference  in Amersfort tomorrow.  The lecture was entitled “Good care for cystic fibrosis  – the importance of centre treatment”.  The talk went well but some adult physicians were not in favour of shared care for adults . All the other lectures were in Dutch. I kept hearing my name mentioned relating to subjectsa on which I had published, people looked at me and smiled, but I had not a clue what was going on. Double Dutch is a very good expression!

Amersfort is a medieval city and municipality in the province of Utrecht, Netherlands        As of 31 January 2023, the municipality had a populatioa of 160,902, making it the second-largest of the province and fifteenth-largest of the country.

18.1.2000  We fly back to Leeds Bradford Airport after having had a look round the pleasant town of Amersfort.  

We had a bit of excitement at Skipol Airport.  Standing at the counter in the check-in. There was a huge bang and smoke appeared from the end of the huge departure lounge. Surprisingly the staff continued working until the smoke became almost unbearable! At this stage. The whole of the huge building was evacuated.  Apparently it was not a bomb but an explosion in one of the fast food outlets on the floor below we traped over to the adjacent terminal and managed to catch our plane to Leeds.

25.1. 2000. In the evening flew with Ann from Heathrow to Utrecht for a CF Meeting the next day.
I was ask to speak on fibrosing colonoparthy. The  conference, which was held in a magnificent conference centre in the very impressive new hospital on the outskirts of Utrecht.  I gave a detailed review of fibrosing colonopathy. I kept off the subject of the now notorious Dr Van Velsen previously of the Alder Hey hospital in Liverpool and now referred to in the press as “the organ doctor.”    However, he was the main pathologist involved in the original description of fibrosing colonopathy from Liverpool in 1994. Luckily the condition was so obviously new and the pathology is so  gross and characteristic that there is no fear his description was a fraud.  It is important in my opinion to avoid all pancreatic enzymes containing methacrylic acid copolymer which is likely to be an important factor in causing colonopathy – for example Pancreas HL Nutrizym 22, and Nutrizym  GR which is still on the market (as I write) and can be prescribed the children. Creon  25,000   and 10,000 and standard Pancrease appear to be quite safe and have never been associated with colonopathy.

The new hospital was frankly awesome and made one realise how far behind we are in the National Health Service.

UMC Utrecht is one of the top-ranked academic medical centers in Europe with the core tasks of care, research and education. With more than 12,000 employees, UMC Utrecht, of which the Wilhelmina Children’s Hospital is a part, is one of the largest public healthcare institutions in the Netherlands and the largest employer in the Utrecht region.

With Ann,  spent a day looking round Utrecht before flying home to Leeds.

 

With Dr Martin Scott, Scientific  Director of the CF Trust, I visit the CF unit at the North Staffordshire Hospital

Consultants at the Stoke on Trent unit are Dr Pantin (adults), Dr Warren Lenney (paediatrics) and Dr Campbell (paediatrics). This unit is developing into a major CF Centre, which is certainly needed in the area. We had encouraging presentations at a meeting which was attended by the staff of the unit. They seem to provide an excellent service and already undertaking shared care with some of the smaller hospitals.  They agreed  to contact us at the CF Trust with more detailed proposals for their future development.

10.2.000.  Visit the Department of Health to meet Jane Verity.   Martin Scott, our scientific director,   Graham Barker, of the CF Trust,  and myself visited the Department of Health to meet Jane Verity who has recently taken over the responsibility for cystic fibrosis.  We had a pleasant couple of hours and a coffee but did not seem to achieve anything more – except we now know what Jane Verity looks like when we ring her!    She fully admitted that the government has failed to keep its promise to abolish of prescription charges for people with cystic fibrosis and it was unlikely to abolish them in the near future.         Payment for prescriptions was a “running sore “ with the CF population for as long as I can remember. We agreed to keep her closely informed of CF developments. Lack of detailed knowledge of what is actually happening on the “shop floor” is really worrying. We are particularly keen that she sees our Guidelines to ensure they are in a suitable form to be “kite marked” by the DOH and NICE.      I do not recall any subsequent further contacts with  Jane Verity!!

5.2.2000 Fly from Leeds/Bradford to Glasgow for a visit to the Yorkhill  Children’s Hospital with Rosie Barnes, our Director.  In the evening  Rosie conducted a very good meeting with about 30 parents with whom there was a very open discussion on the staffing and accommodation problems at the hospital.  It was good  that the parents were able to voice their concerns about the CF service at the hospital; Rosie  managed to reassure them that the  CF Trust was there to improve the situation, both for the staff and the families.

6.2.2000. We had lunch with  Dr John McCLure, a senior paediatrician from Kilmarnock.     He was very keen  to introduce a CF regional network for Southwest Scotland hub and spoke the hub a fully staffed and well accommodated Specialist CF Centre at York Hill  in Glasgow – which unfortunately has neither at present.   After lunch we had a meeting with the CF staff at York Hill, about 15 to 20 assorted managers and commissioners to discuss the present and proposed service.  The meeting went well but we were not clear as to the next step the local officials would be taking.  The Yorkhill  paediatricians were surprisingly cooperative after the meeting when Rosie listed in great detail the parents concerns that we had heard the previous day.  It is likely that Rosie will be arranging another meeting of the parents and CF staff in the near future .
Definitely a successful couple of days.  `The refusal and inability of the Yorkhill hospital managers to provide adequate staffing and accommodation for the CF Unit was in stark contrast to the superb accommodation and liberal staffing I had seen in Holland a few days earlier.  It is unfortunate that as a nation we have come to accept secondary standards in the NHS.  On the bright side that evening waiting at Glasgow Airport for the flight back to Leeds Bradford we had Fish and chips at a Harry Ramsden’s – a name known to all Yorkshireman. it was the best Harry’s I had tasted for some  years.

14. 2.000    Meeting of the CF Trust’s Nutrition Group in Sheffield
 Yet another of our CF Trust special interest groups, this one chaired by Prof. Chris Taylor of Sheffield Children’s Hospital where he runs a major paediatric CF unit. The group is making slow progress but the guidelines should be ready by the autumn.  I remain optimistic and enjoy the meetings – particularly as the meetings are arranged in a local pub near the hospital where they provide excellent cheeseburgers and chips for lunch. Surely a good omen for a nutrition group!

Prof. Chris Taylor is the leading paediatric  gastroenterologist in the UK involved with CF. With the Hardcastles, his scientific colleagues in Sheffield, Chris has undertaken both clinical and fundamental scientific research relating to gut function and other aspects of CF since 1987.  Chris and the Hardcastles  were the first group to show abnormal secretion in the small bowel of children with CF.

C J Taylor CJ, Baxter PS, ˙Hardcastle J, hardcastle PT.  Absence od secretory response jejunal biopsy samples from children with cystic fibrosis Lancet 1987 `jul 1121;107-8 1987.    https://pubmed.ncbi.nlm.nih.gov/2885564/                                                                                        

C J Taylor, P S Baxter, J Hardcastle, P T Hardcastle. Failure to induce secretion in jejunal biopsies from children with cystic fibrosis. Gut 1988 29:957-https://pubmed.ncbi.nlm.nih.gov/2840366/

15.2.2000  We have a week’s holiday  in the Lakes at the Holiday Property Bond at Braithwaite
Mostly excellent weather so we had the opportunity to do some interesting walks. This was our first visit to the HPB at Braithwaite which was good and well up to the usual  Holiday Property Bond (HPB) excellent standards.

“The Holiday Property Bond is a practical and affordable alternative to those dreaming of buying their own holiday home. It offers you exclusive access to a portfolio of over 1,400 top-quality villas, cottages and apartments in over 30 locations across the UK and Europe. You can use them for the whole of your life – without the problems and worries of ownership such as organising repairs, cleaning and gardening.” (HPB Website)

Ann arranged of us to join many years ago soon after the organisation started since when we have had numerous  holidays at many of their excellent high quality properties in the UK and abroad. Best thing we ever did re. holidays.

25.2.2000  We travel to Exeter for the South West Regional Meeting of the CF Trust with Dr Martin Scott the, CF Trust Scientific Director.   The local service was well spoken of by those families attending there;  cooperation between the paediatrician (Dr Patrick Oades) and the chest physician (Dr Chris Sheldon) was particularly appreciated by the families.

But there are problems e.g. although Chris Sheldon, the Exeter  consultant sees Torbay patients on a shared-care basis, the  patients can only attend once a year. Which is unsatisfactory if they sr going through s bad patch.

Also  many patients in the Peninsula do not have the benefit of a CF nurse specialist, particularly necessary when home intravenous antibiotic treatments are given. It depends entirely on where you live. The reluctance of some paediatricians to accept the need for major CF Centre’s involvement and the belief of some chest physicians that CF is just another condition, which can be dealt with at a normal chest clinic, have not helped matters.

I’m afraid these attitudes are by no means restricted to the south-west.  In the discussion, one mother of a CF child observed that a detailed document was needed for doctors stating precisely the best antibiotic for every eventuality in CF patients. I was delighted to tell her that the CF Trust’s “Antibiotic treatment for cystic fibrosis” was being printed and soon would be available for all doctors, patients and parents

29.2.2000. A meeting was organised for us at St James’s by PathoGenesis reporting the results of the trial of their new inhaled tobramycin preparation – TOBI
This meeting in Leeds was one of a series around the UK. The intravenous preparations of tobramycin, gentamicin and colomycin have been used for many years in the UK as inhaled treatment for cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, but not in the USA where the use of inhaled anti-Pseudomonal antibiotics was very slow to be introduced. In the UK the intravenous preparation of tobramycin is used for inhalation usually with no problems.
TOBI is a new preparation of tobramycin free of preservatives which was developed in the USA over a number of years. In an excellent large multicentre study in the USA (costing $60 million) inhaled TOBI given as nebulised 300mg twice daily, on alternate months improved respiratory function tests by about 10% – some patients responded better than others. The preparation was licensed in the USA and came into use there for people chronically infected with Pseudomonas..

1999 Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, Williams-Warren J, Vasiljev-K M, Borowitz D, Bowman CM, Marshall BC, Marshall S, Smith AL.. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med 1999; 340:23-30.      https://pubmed.ncbi.nlm.nih.gov/9878641/

This was one of the most important clinical trials of the decade, thanks to the drive and enthusiasm of Dr Bruce Montgomery, for which he received a special award from the CF Foundation showing a significant benefit of inhaled preservative free tobramycin (TOBI) given during alternate four week cycles for 24 weeks to patients chronically infected with Pseudomonas aeruginosa. Treated patients had an average increase of FEV1 of 10% predicted at 20 weeks where as those on placebo had a 2% decline; also the treated patients had 23% fewer hospital admissions.

The introduction of TOBI, supported by this excellent clinical trial, was one of the major clinical advances of the decade and the culmination of much preliminary work started in the late Eighties by Dr Arnold Smith and others in the USA (Smith al et al. 1989).

1989 Smith AL, Ramsey BW, Hedges DL, Hack B, Williams-Warren J, Weber A, Gore EJ, Redding GJ. Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis. Pediatr Pulmonol 1989; 7:265-271. [PubMed]

Arnold Smith had noted tobramycin in urine samples after nebulised administration hence the present study to assess safety of 12 weeks of thrice daily inhalations of 0.6gm of preservative free tobramycin. There was no detectable laboratory evidence of nephrotoxicity, neither a decrease in auditory acuity (range 250-20,000 Hz) nor vestibular dysfunction. Pulmonary function tests significantly improved during the first month in all subjects but returned to enrolment values by the end of the 12th week of administration of the tobramycin aerosol. Sputum P. aeruginosa density initially decreased and remained significantly below the enrolment value throughout. Coincident with the reduced bacterial density, a reduction in cough frequency and sputum production, as well as a weight gain was observed. However, seventy-three percent of the patients with sputum P. aeruginosa isolates susceptible to tobramycin on enrolment yielded resistant organisms during aerosol administration although 1 year later all sputum P. aeruginosa isolates were susceptible to tobramycin. The authors concluded that thrice daily aerosol tobramycin administration for three months was safe although transient emergence of tobramycin resistant P. aeruginosa may occur.

Although inhaled antibiotics for chronic Pseudomonas infection were surprisingly late to arrive in the USA by 2011  65.9% of eligible people with CF in the US CFF Registry were receiving nebulised TOBI. 
Although the cost (£10K per annum in the UK) has restricted the use of the TOBI preparation in the UK, inhaled anti-Pseudomonal antibiotics (colistin, tobramycin for injection and gentamicin) have been widely used in the UK for CF patients with chronic Pseudomonas infection since Margaret Hodson’s important 1981 paper (Hodson et al, 1981).  Inhaled gentamicin is now avoided due to the risk of auditory toxicity

1981 Hodson ME, Penketh ARL, Batten JC. Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa in patients with cystic fibrosis. Lancet 1981; i: 1137-1139. https://pubmed.ncbi.nlm.nih.gov/6118579/

This was another definite landmark paper from the Adult CF Unit at the Royal Brompton Hospital, London by Dr. Margaret Hodson, later Professor of Cystic Fibrosis there. Professor Hodson was to make many major contributions to the treatment of people with CF from her vast experience at the Brompton Hospital treating many hundreds of adult patients with CF. Regular use of inhaled antibiotics was widespread during the Eighties, whereas in the USA   their use was delayed until the 1999 trial mentioned above.
A subsdequent UK trial  compared TOBI 300 mg twice daily and Colomycin I mega unit twice daily, for one month in patients with chronic Pseudomonas infection. 

Hodson M E et al. A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis, Our Respir J 2002; 20(3):658-64  https://pubmed.ncbi.nlm.nih.gov/12358344/

In this trial the patients on TOBI had a 6% improvement  in respiratory function and those on colomycin remained the same. Problems were the trial was short, the dose of colomycin was half that which is usually used in the UK and finally the annual cost of TOBI is three times that of conventional tobramycin (£9400 versus £3000 per patient per year). Also, intravenous tobramycin was one of the most valuable intravenous drugs for P. aeruginosa and definitely led to some increase in the resistance of the organism in contrast to colomycin where resistance is very rare indeed.

Even though by 2000 TOBI was licensed in the UK, there were funding problems as inhalation of  the standard intravenous tobramycin preparation or Colomycin seemed to do the job for most patients.  The use of nebulised antibiotics is dealt with in great detail in our  CFT antibiotic document, it is likely we will require a working party for a consensus on the use of TOBI as we had for the use of Pulmozyme. It is of relevance to remember all the initial problems in funding Pulmozyme at £7,500 pa – a very effective drug for which there was no alternative, in contrast to TOBI where both conventional IV tobramycin and colomycin are satisfactory and widely used  alternatives for inhalation in the UK.

The National Institute for Clinical Excellence (NICE), contrary to my advice,  decided not to consider funding TOBI for the foreseeable future; if it is used the funds will need  to be found from local budgets.

1.3.2000 Clinical Trial Advisory Group. (CTAG). London

This group CTAG goes from strength to strength, now chaired by the very capable and pleasant Prof. Ros Smyth of Liverpool and later of the Institute of Child Health London.

A parent recently commented that the CF Trust spends a major part of its income on basic research, particularly that relating to gene or pharmacological means of correcting the defective CFTR, yet there are still many patients with CF who  are still recieving  substandard care due to inadequate accommodation or inadequate staffing.  She questioned the point of finding a cure if the patients will not be well enough to benefit. I suspect many patients and parents may feel this way even though when asked directly, they almost all support the search for a “cure”.

Until recently I’ve always taken the view that the NHS should provide adequate staffing and accommodation and not rely  on charities, but it is becoming quite obvious that the  NHS cannot and never will be able to provide all that is required. Thus, perhaps the CF Trust will have to reconsider whether more of its resources should be spent on caring for patients e.g. providing more CF nurse specialists and dedicated CF staff, to bring the service up to the standard in those areas which do not have adequate staffing.

7. 3. 2000. I wrote an urgent letter to Dr Muir-Gray. the  Director of the National Screening Committee

Rosie and I were due to have a video conference with him. The request for this meeting appears to have been prompted by the recent adjournment debate in the House of Commons in which Tess Kingham MP for Gloucester spoke on neonatal CF screening. Rosie and Tess Kingham took up the minister’s (Yvette Cooper)  suggestion of a meeting. I enclosed detailed comments on the National Screening Committee’s document outlining why they did not recommend national neonatal screening. My document runs to some 20 pages of single space text includes all the recent data including a key study from Wisconsin. We thought the meeting went well and the new evidence which considerably changed things was mentioned a number of times.

8.3.2000. Rosie (in Bromley), Dr Miur-Gray and Stephen Pugh of the DHS (in London) and myself (In Leeds) had a good video conference. Dr Muir-Gray seemed very impressed by the new supportive evidence from Phillip Farrell’s unit in Wisconsin, from France and some from our own UK database prepared by Anil Mehta. He indicated the matter would be reviewed in the near future and “the door was by no means closed”.
Dr Muir-Gray was knighted in 2005 for the development of the foetal, maternal and neonatal screening programme and the creation of the National Library of Health

3.3.00 . We are invited to the Sixty-Five Roses Ball. London

Duncan Bluck, our C F Trust Chairman, and his wife Stella kindly invited Ann and myself to this impressive function. We had a really excellent evening which also seemed to be a great financial success for the CF Trust. A very skilled professional auctioneer managed to extract over £27,000 from the guests for the CF Trust – more than Jeffrey Archer’s total last year!  It was good for us to see the great efforts that are made by so many people to raise funds for the CF Trust so that we in RAMAC can keep their efforts in mind when recommending to the Executive which grant application should be funded.

16. 3.2000 I visit  Benton Park School, Guisely, near Leeds  

I arrived at the school at 8am to attend main assembly to receive a cheque on behalf of the CF Trust.   I said a few words about children with cystic fibrosis and accepted the cheque. Afterwards we had some photos taken with the cheque and the children.

Over the years I travelled to a wide variety of places, indeed hundreds of places and venues,  to receive cheques for the CF Trust and say a few words about CF and of thanks – schools, bars, working mens clubs, formal dinners, sports events etc.

 

28.3.2000   An historic evening meeting in London to discuss formation of a “Gene Therapy Consortium”.

In retrospect this was an historic meeting as it marked the start of the UK Gene Therapy Consortium.  It had been over ten years since the CF gene was identified  in 1989 and as yet,  there had been no new treatment as a result of the discovery; the lack of progress was disappointing.

It was Rosie Barnes, our dynamic excellent chief executive, who suggested the three main UK research groups working on gene therapy in London, Oxford and Edinburgh should combine their efforts as a “UK Gene Therapy Consortium”.   If they agreed the CF Trust would agree to provide regular preferential funding.   This seemed to be a very exciting and timely development. The preparation of the plan clarified the general direction of gene therapy research over the next five years. The CF Trust would appoint a supervisory committee to meet regularly with the members of the Consortium.  The consortium of UK research groups would make this the strongest group in the world working in this field.

Addendum: Disappointingly, as I write in 2025, although the CF gene was identified in 1989, and the Gene Therapy Consortium (GTC) was formed back in 2000  on the initiative of the CF Trust to speed research, there was still no gene therapy available for cystic fibrosis. The members are still very active by 2025 and have produced a vast amount of relevant scientific research over the past 20 years. They have recently combined with Boehringer Ingelheim in 2018. Under the terms of the option and license agreement with Boehringer Ingelheim, originally announced in August 2018, Boehringer Ingelheim will pay “IP Group, on behalf of the GTC, an option exercise fee, near term, success based development, regulatory and sales milestone payments as well as royalties on net sales. OXB will receive an option exercise fee of £3.5 million and will be entitled to payments in an aggregate amount of up to £27.5 million upon achievement of various development, regulatory and sales milestones, in addition to a tiered low single digit royalty on net sales of a cystic fibrosis gene therapy product”.

David Ramsden, Chief Executive of the Cystic Fibrosis Trust said in relation to this latest development: “It is great news that Boehringer Ingelheim have committed to the next stage of the development of a gene therapy treatment for people with cystic fibrosis. This is an important step as it brings hope to the whole cystic fibrosis community and in particular to those who don’t benefit from the currently available medicines. All of those who have helped us to invest long term in the work of the UK CF Gene Therapy Consortium should be proud of what they have made possible.”

A recently revised website gives a concise account of the consortium, (www.respiratorygenetherapy.org.uk/about). 

So the CF Trust has been involved from 2000 – in fact, the funding and difficulties in funding the GTC have dominated the research aspects of the charity particularly around the time of the 2008 recession. It has been a very long 20 years, at times exciting, disappointing, and controversial. Hopefully, the recent collaboration with “biopharma” will eventually result in a product which is effective particularly for the 10% of people with CF who do not benefit from the new highly effective modulator therapies.

29.3.2000. Meeting on Neonatal CF Screening in London

I requested the CF Trust arrange a  meeting of key UK people with an interest in neonatal CF screening including those members  of the National Screening Committee Child Health Group (Prof Sir David Hall, Dr David Elliman and Dr Carol Dezateux) who would advise the National Screening Committee.

It was not a good meeting – in fact, it was ghastly!   Our visitors, all essentially community paediatricians (who had little present day practical experience of dealing with CF children and knew little about CF),  were obviously not in favour of neonatal CF screening and were overtly looking for reasons not to recommend it.        They required a great deal more data they said. Their  near belligerent general attitude was most discouraging and at times verged on frank rudeness to our unfortunate colleagues attempting to present their data.

Subsequently, in 2001 after Rosie Barnes and I, in desparation, went to see the then Health Minister, Yvette Cooper, following which the Government wisely recommended countrywide neonatal CF screening – but even then,  against the advice of their National Screening Committee!

1.4.2000   The CF Trust’s Regional Advisory Committee, in  Birmingham.  As usual, a very informative source of parents’ and patients’ views. There is no substitute to hearing parents and relatives talking about their experiences to appreciate the standard of care they are receiving. It is sometimes very depressing and in some cases reflects the desperate state of the NHS.

2.4.2000. Meeting on “Learning from the National Health Service” at St Catherine’s College Oxford               I thought I should attend this meeting as many of the “good and great” of the NHS would  be speaking. Also, I’m due to give a talk on the NHS at the CF Trust 2000 meeting in October and I thought I might pick up a few useful “morsels”.  It was a great mistake!  The air was thick with the usual NHS buzzwords with little substance – we heard  of “rolling out” programs,  “disbenefiting” people etc, etc.  I gained the feeling that these well-meaning people were somewhat remote from the staff who actually do the work in the NHS.

One bright spot was a very humorous after-dinner speech by Professor James Drife, our accomplished after dinner speaking Professor of Obstetrics from Leeds, which lifted the gloom somewhat; but it was sad that it was the NHS that was the main butt of his humour!

However, the following day things personally go from bad to worse in Oxford!      As I am now too old to totter down the corridor in outdoor shoes to the toilet as is necessary if one stays in “college accommodation”, I opted for a rather dubious hotel near Oxford station. Attempting to reach the bath taps (no shower!) I developed an acute back strain. I struggled to the meeting but had to leave early and only just managed to get back to the hotel, then taxi to the station, train to Leeds and car home and crawled into bed. What a disaster.
I learned nothing at the meeting except medicine was quite different from 44 years ago when I qualified and I suspect it will become even more different under the new “NHS commissar” Mr Alan Milburn.

Addendum: Alan Milburn was a prominent Labour politician at the time who was involved in various aspects of the NHS including Secretary of State for Health in 1999.  He introduced NHS Foundation Trusts in 2002 “described as a half way house between the private and public sectors” but he resigned “for personal reasons” in 2003.

7. 4.2000  The CF Trust’s Infection Control Group meeting at Manchester Airport
My back had recovered sufficiently to travel by train to Manchester. Fortunately the train from Leeds goes directly from Leeds to Manchester Airport.      We had a good meeting.  I chair this jovial group of national experts but we get plenty of work done.  Key members of the group were the microbiologists Professor John Govan of Edinburgh , a world expert on Pseudomonas and good friend of the CF Trust and the late Prof. Tony Hart of Liverpool another very helpful colleague.

I agreed to write a draft of guidelines which included the segregation of patients with chronic Pseudomonas (PA) infection from those not so infected.

This formed the basis of our 2001 publication “Pseudomonas infection in people with cystic fibrosis. Suggestions for prevention and infection control”

 

Many of the more progressive UK clinics were already separating PA-positive for PA-negative patients – some being moved in this direction by patient or parental pressure.   It is reassuring that adult CF clinics have increasing numbers of patients who are PA-negative.

The group were unanimous in recommending segregation of patients according to their PA status – even though one of the consultant paediatricians at the Royal Brompton (Mark Rosenthal) wrote a fierce, frankly rude,  letter to the CF Trust suggesting segregation would be impossible and suggesting we were a “group of zealots”!   There’s always one!!!!

13.4.00.  At York University for an afternoon at the Annual Meeting of the Royal College of Paediatrics and Child Health (RCPCH)

There was a session on “Guidelines” with speakers such as Sir Michael Rawlins,  Chairman of of NICE.  Not a good idea – I’d heard it all before.  

There was an interesting editorial in the British Medical Journal. 27th of March 1999.

“And what about the accountability of NICE? Who appointed the first chairman Sir Michael Rawlins – pleasant fellow that he is, and what process was used?  There is an inevitable  sense that although the government has learnt that the rhetoric of transparency, accountability and evidence-based appraisal, it would rather avoid living with it day by day”

 Another depressing feature of this RCPCH meeting was the complete absence of any presentation or poster relating in anyway to Cystic Fibrosis.  However, in all fairness, most  CF research is presented at International CF conferences.

17.4. 2000.   CF Trust Nutrition Group, Sheffield
After a long gestation period our report is nearing completion and we hope will be ready by October.  The meetings of the group were organised by the Sheffield members and one had been seriously ill, also the group lacked the driving forward skills of Sandra Kennedy and Carol Eagles at the CF Trust.

Rosie Barnes had given a very good talk at the North Yorkshire Branch  of the CF Trust the previous day. Today she attended a meeting of the West Riding Branch of CF Trust at St James ’s and gave an excellent talk but the attendance was very disappointing.  Apparently the local Yorkshire branch seems to be in a bad way with committee problems.

However, even if the local branch has problems the clinical care in Leeds area remains very good.    There are now three consultants with a major interest in Cystic fibrosis.

The latest edition of our booklet   “Cystic Fibrosis in Children an Adults. The Leeds Method of Management”   has just been printed. The first was written in 1986 and the last in 2008.

 

 

4.5.2000  Leeds Medical School Year of 1956 graduates  – 44th reunion 

One of our year, Harry Egdell, a psychiatrist, has kept in touch with all of our year –  those who were still breathing that is!  It’s really amazing and quite sad how people “wear out” at different rates. However, Harry has done a good job and organised these annual reunions up to 2015.

Harry has a record of virtually all the members of our year of 1956. He put these facts together for a university publication to which I contributed an article entitled “The year we qualified as doctors -1956”. This article is available on this present website (jimlittlewood.com) and describes some aspects of hospital medical life at the time.

 3rd -10th June. To Stockholm for the Annual European Cystic Fibrosis Society Conference

The first day, June 4th was my busiest day but it was good to get my work out of the way early.
At 08.00 hrs I chaired the first main plenary session on “CF Care”. At 10.30 gave a lecture on the “Historical development of nutritional management of CF”. I take the lunch time session on “Abdominal pain in CF” and at 14.00 hrs chair a session where a panel of experts discuss “Difficult clinical problems”.  Phew!!

My talk on history of nutrition was very long and detailed – 12 pages in the programme and 178 references. I think this was the start of my increasing interest in the historical aspects of cystic fibrosis – as I was soon becoming history myself.

The Stockholm meeting was very good and finished with a banquet in the town hall on the 8th.
The CF Trust’s new “Antibiotic treatment for Cystic fibrosis “ was available on the AstraZeneca stand (they had funded the printing) and it was well-received.
There was nothing really new from the clinical point of view in the meeting.  The CF scientists were under-represented – I suspect they were holding their fire for the more scientifically orientated meetings and for the US CF Foundation meeting in the autumn.

 One other memory of the meeting was one evening when we all attended a drug company sponsored evening lecture and dinner. We went by boat to an island where we heard a very long, rather dry  lecture which seemed to go on forever. By the time the return boat arrived we were desperate for food!  

Ann and I had a look round Stockholm on the 9th and travelled home on the 10th of June.

29.6.2000 . Invited to a CF meeting at Groningen University Hospital.  On the 30th fly to Schipol and  then travel to Groningen by train.  

This was a meeting to celebrate 10 years of their CF Unit  I gave an invited lecture on Burkholderia cepacia, discussing the UK CF Trust’s recent statement and guidelines on the subject. Later, I took part in a panel discussion on cystic fibrosis.

The Groningen University Hospital is quite superb and there appears to be none of the poverty-stricken attitude which sadly permeates our unfortunate, underfunded National Health Service. The ground floor is designed so that visitors do not feel as if they are in a hospital – the space is airy, there is a lot of green, and the glass   roofs are opened when the weather is fair. Patient wards are on the outside of the building, so that all rooms have windows with a view. Each ward has a balcony that opens to one of the main ‘streets’ of the hospital – some patients were sitting on the balconies.

The  following day we had a day off in Groningen and took a boat tour around the central part of the city. The city seemed rather subdued as Holland had been knocked out of the European football competition by Italy the previous day!!

3.7.2000.   I spent whole day sending and answering e-mails

I will be working with Anil and Gita Mehta to review the data on screened and non-screened CF infants born in 1996 and 1997. This should answer the question as to whether the 20% of infants already detected by screening have an advantage.  I am certain from anecdotal reports, medical legal work relating to sad consequences of missed diagnoses, and personal experience with over 600 patients, that some non-screened infants do very badly and  are permanently damaged before the diagnosis in made and treatment eventually started. Unfortunately, we do not know how many infants the NSC require to be damaged before they recommend neonatal CF screening for the 80% of UK infants who at present denied early diagnosis by neonatal screening.

Rosie’s letter to Alan Milburn, the then Health Minister, describing our disappointment with the NSC,  is reported to have “saddened” the National Screening Committee –  but I suspect may have given them food for thought.  Our campaign for national neonatal CF screening continues and increases in intensity!

5.6.2000  Visit Nottingham City Hospital to attend the investigators meeting of the TOPIC clinical trial which is funded by the CF Trust

This is the second year of a trial to compare the efficacy and toxicity of once versus three times daily intravenous tobramycin. Dr Alan Smyth consultant paediatrician at the hospital is the lead investigator.  There  have been problems with recruiting patients but these are being resolved. I was impressed by their account of progress. This is the first big clinical trial the CF Trust has funded for some years and it is essential it is a success.      I think it will be. (Indeed, it was completed and a great success proving once daily IV tobramycin was as effective as three times daily injections and also safe.

 I was requested to give a presentation on “Clinical Trials the Way Forward”. Two important points which I made were the importance of CF clinics entering their patients into the UK database, so that we know where and what type of patients are available for future trials of all types . As mentioned above I am now quite convinced of the need to link the Clinic Support Grants, which  all special CF centres now receive  to their entry of their patients’ annual data into the UK database.  Also clinics who receive support from the CF Trust should be obliged to collaborate with CF trials if requested to do so.   I was pleased that these suggestions did not cause an uproar but were generally accepted by clinicians at the meeting. I will raise them at the Directors of Large CF Clinics meeting in October. 

One further suggestion I made was that we should consider forming a CF Trust clinical investigation network as has recently been started in the USA by the CF Foundation. We already have a very good clinical trials advisory group chaired by Ros Smyth.  In the USA  8 of the large Specialist CF Centres are  funded for five years ($150,000 pa each) to have a permanent trials nurse and supporting infrastructure.

  The nurses are coordinated from the CF Unit in Seattle by a leading US clinical expert, Dr Bonnie Ramsey who is the CF Foundation have made responsible for the network. The purpose of the network is to bring findings in the laboratory rapidly to the clinic if the driver of the treatment looks promising.  It can be tested rapidly and safely in phase 1 and 11 trials by networks which are already geared up and experienced in CF trials. The system is already working in the USA.  I have a feeling that today I was observing an embryo network group going up a steep learning curve.

Addendum: Alan Smyth and his colleagues completed and published their trial  which proved to be very valuable in changing many patients to once from thrice daily IV tobramycin.   Alan became an expert on trials and eventually was awarded a chair in Paediatrics in Nottingham University.

2005 Smyth A, Tan K H-V, Hyman-Taylor P, Mulhearn M, Lewis S, Stableforth D, Knox A, for the TOPIC study group. Once versus three-time daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis – the TOPIC study: a randomised controlled trial. Lancet2005; 365:573-578.  https://pubmed.ncbi.nlm.nih.gov/15708100/

8.7.2000.  Regional Advisory Council Meeting.  London & South East Region at Kings College Hospital, London

This was an interesting meeting. First, why did only 1% of the families with CF in this region attend the meeting?  Some families said the purpose of the meeting had not been made clear on the invitation.  The usual subjects were raised by those who did attend including, uniform standards of care or lack of them, knowing what to expect from the clinic, arrangements for shared care, distance to travel to the clinic, communications between doctors, between doctors and patients, between specialised clinics and local hospitals, the role of GPs, annual reviews, continuity of care and the problems of seeing a different doctor each time at the clinic. Cross infection issues, isolation of child and parents, and community services – in particular, lack of CF nurse specialist for home intravenous antibiotics and the lack of specialist adult services.  It seems remarkable that a prosperous area of the country should be so lacking in a reasonable CF service.

7.7.2000  We visit the Tate Modern in London  

The Tate Modern is housed in the former Bankside Power Station, which was originally designed by Sir Giles Gilbert Scott, the architect of Battersea Power Station, and built in two stages between 1947 and 1963.

It is directly across the river from St Paul’s Cathedral. The power station closed in 1981. The re-developed building was opened by the Queen in May 2000
It really is a magnificent building. As for its contents – count me out!!

13.7.2000. Visit Lewisham Hospital with Rosie 

I had not realised it was such an impressive hospital with the obvious potential  for a specialist CF unit for both children and adults.

Lewisham DGH It is an acute district general hospital run by the Lewisham and Greenwich NHS Trust serving the London Borough of Lewisham. It is affiliated to King’s College London and forms part of the Kings Health Partners academic health science centre.  The impression for CF was there was a link with Kings.
Kings College Hospital as a Regional Specialist Paediatric Cystic Fibrosis (CF) Service providing care mainly to children and young people who live in South East London, Kent and East Sussex.  The service runs shared care clinics with local hospitals throughout the region with their multidisciplinary team visiting each of these at least twice a year. The rest of the patients receive all their CF care at King’s.

20.7.2000^. I visit the West Indies Test match in Nottingham with my son in law Nick and his father Tony Haines

This was the first time I had been to a Test Match – Nick (my son in law) and his father Tony were “old hands”. In fact, Tony was a member of the MCC.

They took the food and drink and the weather was excellent. We had a most enjoyable day – although I don’t remember if the West Indies or England won!

 

 

 

 

 

However, I do recall one very amusing incident that occurred during the afternoon.

We had finished our lunch and were sitting in the seats two or three rows back from a gangway running parallel with the rows of seats. Along this walkway came a rather fat, tough-looking character carrying some beer in plastic glasses. He had long hair and walked with his legs slightly apart in an aggressive manner; he was stripped to the waist in view of the heat, revealing his quite well developed “chest”.  Just as he passed our seats a loud voice from directly behind us said “Nice tits!” at which he stopped, swung round and glared in our direction. However, everyone was suddenly doing something else either opening their sandwiches, looking at their programmes – anything but looking in his direction. After a prolonged glare he continued on his way to everyone’s relief!

I have not been to a cricket match since although Ann and I took a very interesting tour of the cricket ground soon after we moved to the area in about 2017

Wikipedia tells us – Trent Bridge was first used as a cricket ground in the 1830s. The first recorded cricket match was held on an area of ground behind the Trent Bridge Inn in 1838.  Trent Bridge hosted its first Test match in 1899, with England playing against Australia.

The ground was first  opened in 1841 by William Clarke, husband of the proprietress of the Trent Bridge Inn and himself Captain of the All England Cricket Team. He was commemorated in 1990 by the opening of the new William Clarke Stand which incorporates the Rushcliffe Suite. The West Park Sports Ground in West Bridgford was the private ground of Sir Julien Cahn, a furniture millionaire, who often played host to touring national sides.

22.7.2000   Ben’s and Elliot’s 7^th Birthdays     Ben’s & Elliott’s birthday party. It was glorious weather so we were able to have most of the party activity outside in their excellent back garden.

27.7.000  Visit to Dr Frank Edenborough’s Adult CF unit at the Northern General Hospital, Sheffield

The adequacy of facilities and staffing of the adult unit had been questioned by Professor Chris Taylor, director of the Paediatric CF Unit at the Children’s Hospital. There had been a reluctance to transfer young adult patients from the Children’s Hospital to the Northern General. Essentially Frank Edenborough requested  the CF Trust to visit his unit, meeting the staff to confirm that the unit was satisfactory.

 Rosie Barnes, Sue Madge (senior CF nurse a Great Ormond Street at the time and chair of the UKCF Nurse Specialist Association)  and myself spent the day at the Northern General.
We were impressed with the present and potential set up there. It was reassuring that a CF Unit for adults  was developing in Sheffield –  and not before time.  We were able to provide Frank Edenborough with a detailed report confirming that his unit was quite satisfactory, had potential and would fill an obvious need, not only for adults from Sheffield also from towns around who needed a specialist adult centre. Subsequently I frequently heard that young adult patients were now being transferred from the Children’s Hospital.

3.7.2000. Visit the relatively new Conference Centre in the centre of Birmingham

From the CF Trust there was Rosie Barnes,  Sandra Kennedy (Publications manager), David Stickles (Finance Director) and Ann my wife (a veteran CF conference attendee). The purpose of the visit was to inspect facilities as a possible location for the International CF conference be held in the UK in 2004. We were impressed with the facilities also the new developments in the centre of the city around the conference centre near the canal.  In the evening there is almost a continental sense of activity.
We did eventually choose the venue for the 2004 conference.

17.8.2000  Visit the Leeds Regional CF Unit at St James’s with Rosie      

Kieth Brownlee the consultant paediatrician, Steve Conway lead clinician of both the paediatric and adult units were present with other members of the staff to meet Rosie.   

I was very proud that both Steve and Keith were amongst the most widely respected leading authorities on CF – and both had trained with me in Leeds.  Also both were very pleasant kind doctors who were popular with staff,  patients and parents.

29.8. 2000. Attend the World Congress on Lung Health in Florence

This was a combined meeting of the European Respiratory Society and other American National Respiratory Societies – a huge conference attended by over 12,000 delegates.  The CF section was rather disappointing except for the excellent presentations by Prof. Eric Alton (a overview of gene replacement therapy) and Dr Andy Bush (significant advances in treatment) – both from the Brompton Hospital in London. It was  encouraging to hear Andy’s fierce support of neonatal CF screening. 

We had dinner with the chief executive officer and medical director of PathoGenesis on one evening and the chief executive officer of  Medicaid, who make a new revolutionary light nebuliser,on another night. Both evenings were very useful in strengthening the CF Trust’s relationships with both firms.

7.9.00. CF Trust Publications Committee at Bromley
This is a very interesting and useful meeting organised by Sandra Kennedy. I found the meetings particular helpful as a large part of my work is now concerned with writing for the CF Trust. The support of Carol Eagles and Clare Pendry of the Trust is really excellent.

The Trust does produce an increasing number of really excellent publications, articles and  guidelines – most of which Sandra Kennedy and myself write and organise with the help and approval of our various expert advisory groups – usually these groups contain a number of national authorties on the particular subject under review. They all without exception give their time and expertise willingly and with good humour.

9.9.2000. Travel to San Francisco for meeting at  Genentech headquarters

There was a meeting at Genentech’s headquarters concerning an international trial of the mucolytic  Pulmozyme in mildly affected patients. I had been recruited by the firm with two other senior CF doctors  as an independent expert/monitor/advisors – one from Holland and one from Germany. The Genentech buildings are in South San Francisco and very impressive.  The meeting was interesting and the trial seemed to have progressed without problems and to have given a positive result.   I had the opportune to do a great deal of networking – meeting a number people from the North American CF world I had not met before but whose work and reputations I knew well..

It was a privilege to meet Dr Mary Ellen Wohl (1932-2011)  a distinguished N. American Respiratory Paediatrician who apparently succeeded Harry Shwachman at Boston Children’s Hospital. We went out to dinner with her after the meeting. Dr Wohl was a co-author of the subsequent publication – the subject of this meetingg

Pulmozyme had already been shown to be a most effective mucolytic in CF patients in 1994.  This trial was to examine the effects in more mildly affected patients.  This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers and 474 children. Inclusion criteria were age six to 10 years and forced vital capacity > or = 85% predicted. At 96 weeks the treated group had maintained their respiratory function levels; the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for FEV1 (P =.006), 7.9 +/- 2.3 for FEF 25-75 % (P =.0008), and 0.7 +/- 1.0 for FVC (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa. The authors concluded that treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.

Quan JM, Tiddens HAWM, Sy JP, McKenzie SG, Montgomery MD, Robinson PJ, Wohl ME, Konstan MW. Pulmozyme Early Intervention Trial Study Group. A two-year randomised placebo controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities. J Pediatr 2001; 139:813-820. https://pubmed.ncbi.nlm.nih.gov/11743506/

–   The results of this trial influenced some paediatricians to try young CF patients on Pulmozyme before they developed chronic infection which seemed a good idea; this became routine practice in at least one large UK Paediatric CF Centre. In Copenhagen the treatment was found to reduce the frequency of respiratory exacerbations and new positive respiratory tract cultures.

We had the opportunity to look round San Francisco and surrounding area – even riding on the street cars. We also went on a day trip to the Napa Valley wine area.       On our very pleasant outing to Napa Valley I purchased a rather strange souvenir  (Nunzilla) – described in the  “Sixty Years of Souvenirs” section of this website.

16.9.2000 . We fly from San Francisco to Gatwick then straight on to Amsterdam for a Scientific Planning group of the European CF Society.
The meeting was to discuss next year’s Vienna meeting. Rosie was keen that I attend  this meeting to get into “organising a big meeting mode”.; because we were due to host the international CF Worldwide Conference in 2004.  The  visit did prove useful. The scientific program was planned is in some detail by approximately 20 clinicians and scientists representing most European countries. It was agreed this would be a useful type of meeting to hold regularly and planning annual ECFS meetings and the 2004 international meeting in Birmingham UK.

20.9.2000. European database meeting organised by Margaret Hodson at Heathrow
I arranged for Dr Anil Mehta ,who with his wife Gita, to attend as they are responsible for the excellent UK CF database.  The meeting was to encourage European countries to make their data available to the European database, which hopefully will be funded during its development phase by a European community grant.

22.9.2000. Invited to lecture at Great Ormond Street on the CF Trust’s recent documents    “A statement on Burkholderia cepacia”and “Pseudomonas aeruginosa in people with cystic fibrosis – guidelines for prevention and control’ .

The CF Trust has already published  the booklet on B. cepacia and that on Pseudomonas aeruginosa is in it’s final draft. It was interesting and encouraging, that the sensible CF nurses reported that the majority of CF clinics are already segregating Pseudomonas-positive patients from Pseudomonas -negative patients.

The lectures went very well – I was impressed, as always, by how knowledgeable and caring the CF Nurses were.  In marked contrast to some medical colleagues who still argue against segregation!!

23.9.2000    First “All Ireland CF meeting” in Dublin
I was invited to give a lecture on “The use of antibiotics in Cystic Fibrosis”. I was able to provide all the 80 or so delegates with a copy of the CF Trust’s new Antibiotic document. As always the trip to Dublin was very enjoyable.

There was some added interest in that the popular singer Alison Moyet was rehearing in a lower room of the same building for her concert that evening. She is known for her very “powerful bluesy contralto voice
“Geneviève Alison Jane Ballard MBE is an English singer noted for her powerful bluesy contralto voice. She came to prominence as half of the duo Yazoo, but has since mainly worked as a solo artist. Her worldwide album sales have reached a certified 23 million, with over two million singles sold. (2022) Wikipedia

 

26.9.000  Dinner at the Royal College of Physicians, London 

I had an interesting evening. I was fortunate to be sitting next Sir George Alberti, the President of the College (pure luck as the other seats were all taken). I was able to mention the words “cystic fibrosis” periodically during the evening!

Sir Kurt George Matthew Mayer Alberti, FRCP, FRCPE, FRCPath, FKC is a British doctor. His long-standing special interest is diabetes mellitus, in connection with which he has published many research papers and served on many national and international committees.

 

28.8.00 to 5.9.00 Meeting of the European Respiratory Society, Florence
Steve Conway and his wife Ella also attended this meeting.  We stayed in two typical apartments in a typical Florence street. We hired a car and did some sight seeing after the meeting, including a visit to Sienna.

Florence is a very pleasant interesting city.  Subsequently we visited there on a number of occasions during the 2000s for the   Artimino CF meetings organised by Gerd Döring, the President of the ECFS. We Also called to see the Tower of Pisa on the way home to the airport.       Altogether a very enjoyable stay with our good friends Steve and Ella

22,&23,9.2000. Lecture at a CF Meeting at City West Hotel and Golf Resort, Dublin 

This meeting was at the very fine City West Hotel and Golf Resort. As usual I was talking on cystic fibrosis and didn’t manage a round of golf! Flew home to Leeds Bradford in the evening.

Have been to Ireland, both North and South, many times as part of my involvement with CF. I have always enjoyed our trips. Did not see much of this country club on this very short visit.

 

11,10.00 CF Trust Clinical Standards Committee, London

This meeting is to finalise the clinical guidelines for care of people with cystic fibrosis and it went very well.

We had Dr Leigh Griffin from the Department of Health attending as he is now leading CF commissioning for the Department of Health in the north-west region; he made a very useful contribution. I was relieved the committee was pleased with their final document and agreed that it should go to the Directors of Large Clinics meeting later in the month.

To convey some idea of the expertise that was available to us for the writing this document   The CFT Clinical Standards and Accreditation Group was a formidable group of experts and consisted of the following-

Dr Jim Littlewood  (Chair).         Paediatrician & CF Trust 

Dr Ian Balfour-Lynn                      Respiratory Paediatrician London
Mrs Rosie Barnes                           CEO Cystic Fibrosis Trust
Dr Di Bilton                                      Respiratory Physician Cambridge
Dr Robert Dinwiddie                    Respiratory Paediatrician London and Royal College of Paediatrics and Child health
Dr Iolo Doull Respiratory           Paediatrician Cardiff
Mrs Carol Eagles                           Research Manager CF Trust
Prof. Duncan Geddes                  Respiratory Physician London
Dr L Griffin                                      NW Regional Officier NHS Executive
Dr D Heaf                                         Respiratory Paediatrician Liverpool
Prof Margaret Hodson                 Respiratory Paediatrician London
Mrs T Jacklin                                   Patient Representative Chair Association of CF Adults
Ms Sue Madge                                CF Nurse Specialist London
Mrs Alison Morton                        CF Dietitian Leeds Chair UK Dietitians CF Interest Group
Mrs A Parker                                    CF Physiotherapist Taunton Association of Chartered Physiotherapists in 
Dr Eddie Simmonds                        Paediatrician Coventry
Dr B Stack                                          Respiratory Physician Glasgow British Thoracic Society                                                                                 Dr Sarah Walters                             Epidemiologist Birmingham

This was a very distinguished group most of whom I knew well over a number of years. They gave unstintingly of their time and expertise. After a number of quite “forceful” meetings we ended up with a document which was subsequently taken up as a basis for the European Guidelines. We were very proud of the final document which was generally well received in the UK and abroad – even as far as Australia!

18.10.000    Visited Miss Judy Sanderson at Quarry House, Leeds. 

Graham Barker, from the CF Trust, and I visited the relatively new huge Department of Health at Quarry House in Leeds.

Quarry House originally opened in 1993 as the new headquarters of the Department of Health and Social Security and at the time included a gym, swimming pool and landscaped gardens.

There was considerable concern about the expense of the facilities and lavish interiors. In fact, a notoriously rebellious Leeds thoracic surgeon, Mr Duncan Walker, entered the building disguised as a workman to inspect and report on the inappropriate luxury!
Duncan left Leeds in 1997, after various stormy incidents with colleagues and the administration to later become Karl Marx Professor of Thoracic Surgery with Leathley Walker in Edinburgh, advising on professional matters and business administration . On LinkedIn Duncan described his job in Leeds as “Surgical treatment of patients and humouring mediocre administrators”!

We were there to see Miss Sanderson who had taken over the responsibility for CF at the Department of Health. We had a useful discussion and Graham raised all the usual points such as prescription charges etc. Frankly, I was not impressed by the DOH grasp of CF problems. Frequently, we were reminded of the numerous other diseases for which Miss Sanderson was responsible. The impression was that they saw their main function as helping ministers to answer questions in the House. It is important that we never forget that the DOH knowledge of CF is probably less than the average parent’s. However, Graham did a good job in putting the problems to Miss Sanderson.

Also around this time I spent a great deal of time ringing CF parents to see if they would agree to appearing on TV “That’s Life” to describe the really dreadful experiences they had had before their children were eventually diagnosed. The purpose was of course to support the case for neonatal CF screening. As usual the mothers were so corporative but the bad news was we heard nothing further from the TV people!  There was a good piece in the Observer on screening the week before which possibly had prompted the initial transient interest and short attention span of the TV people

27.10.00 Directors of Large Clinics Meeting London
This was the most boisterous directors meeting I’ve chaired largely due to the reaction of a minority of consultants to our Infection Control Group’s document “The prevention and control of Pseudomonas aeruginosa infection”. The controversial item in this document was a recommendation that patients with chronic P. aeruginosa should be segregated from those who did not have chronic infection. I would mention, at this stage, that many CF clinics, including our own, have been doing this for years. However some clinics, notably the Royal Brompton in London were opposed to this suggestion implying that not only was it unnecessary but it would be quite impracticable. Fortunately, there is now a wealth of expert evidence in favour of segregation of patients according to their microbiological status.

However, despite a number of really unpleasant and rather personal letters to me at  the CF Trust, even though I was only chairman of the group, we do seem to be making a great deal of progress. A number of clinics are asking Prof. John Govan to review the microbiology of their patients – including Great Ormond Street and even the Royal Brompton paediatric clinic!! We are now to have another meeting of the Control of Infection Group to which we have invited Margaret Hodson and Duncan Geddes to tone down our document a little, but we are still determined to advise segregation as the best option for most clinics. It is interesting that this is also a hot topic in the USA and CF Foundation is having a conference on the subject in February. We will be discussing the subject again at our medical meeting for professional staff on the March 30th in London. Kevin Webb will be presenting the slightly revised Pseudomonas document

20.10.00 CF Trust’s “CF 2000” meeting in London.
A really excellent meeting that the CF Trust put on which was attended by many parents and relatives. Feedback from those who attended has been very good. As if to rub salt in the wounds of the “non-segregators” regarding Pseudomonas, two highly respected speakers Stuart Elborn and Steve Conway spoke at length on the importance of segregating Pseudomonas positive and negative patients! There is no doubt this segregation policy was quite in keeping with the views  of most parents many of whom have been concerned about cross infection for years.  In fact, there were a few parents who would deliberately arrive late at the of the CF clinic to reduce the likelihood of their child meeting other patients.

3.11.00. Opening of the new “state of the art” Neonatal Screening Laboratory at St James’s University Hospital, Leeds
I have known the biochemists at St James’s as good colleagues for many years and they have always been prepared to help paediatrics.  For example, in the late Seventies, the chief biochemist Dr Robert Evans agreed to help with my first newborn CF screening study at St Mary’s Maternity hospital Bramley, on the other side of Leeds, by examining the meconium specimens if we sent them across to his lab’ at St James.     Robert was also first author of our subsequent publication – which incidentally was the only successful study on CF neonatal screening using the BM Meconium method. The reason was that specimens were examined in the St James’s laboratory with proper control rather than on the maternity wards by overworked midwives as was the case in other previously published studies.

Evans RT, Little AJ, Steel AE, Littlewood JM. Satisfactory screening for cystic fibrosis with the BM meconium procedure. J Clin Path 1981; 34:911-913. [PubMed] 72z76211    

I was pleased that this early study of a method regarded by many paediatricians as unsatisfactory was described in 2020  by three of Europe’s leading screening biochemists, Georges Travert, Mary Heeley and Anthony Heeley. as follows –     “Due to its lack of specificity and sensitivity, screening trials with this test (the BM Meconium procedure) were not widely implemented; the exception being where the meconium specimens could be delivered directly from the maternity ward to a laboratory, usually closely associated with a CF clinical centre, where more elaborate testing could take place [Evans R T  et al. 1981]

 Georges Travert , Mary Heeley, Anthony Heeley^.  History of Newborn Screening for Cystic Fibrosis-The Early Years. Int J Neonatal Screen   2020 Jan 31;6(1):8.  Free PMC article [Pubmed]

To return to the present. The main attraction at this opening ceremony was a lady called Mel B, one of the Spice Girls;  she had recently had a baby.  I didn’t have an opportunity to speak to her but was able to ask the junior minister who attended the ceremony whether the National Screening Committee would soon decide who would be screened. She did not seem to understand what I was getting at.  I left before the tea and biscuits!

4-1o.000  North American CF Conference in Baltimore
The  NACFC was a very good meeting, as usual. Also, we had meetings with a number of individuals from drug companies including Dr Marie Bakowski from Solvay and Carol Sanderson from PathoGenesis.

8-7.11.000. Attended a meeting of the International Trials Group with Ros Smyth – our trials expert.   It was organised by the CF foundation. Each country presented the  trials they had in progress and these are registered with the CF foundation. We in the UK are well organised compared to most of the countries. The CFF clinical trials network is impressive and we should consider the possibility of a similar facility in the UK, rather than “re-inventing the wheel” every time we do a multi-centre clinical trial in the UK.

9th-13th.000. The Baltimore meeting was quite a good meeting despite the emphasis on seafood!  There was nothing really new on the CF front although the meeting was interesting with plenty of opportunity for networking. We are pleased that the work of the UK Cochrane CF group organised by Prof. Ros Smyth was given a special mention.

Baltimore is not a very impressive city. There are many very poor black people there, as we discovered when we travelled by the local bus to a nearby shopping outlet! The bus travelled through increasingly more deprived areas of the city to reach the shopping mall.
The old warship in the harbour is the US Constellation built in 1854.  On this visit we had a trip around the harbour in an amphibious vehicle and visited the old Fort McHenry guarding the harbour  The fort was named after an early American statesman, James McHenry  (1753 – 1816), a Scots-Irish immigrant and surgeon-soldier. He was a delegate to the Continental Congress from Maryland and also a signer of the United States Constitution. 

17.11.00. Fly to Heathrow for meeting with PathoGenesis with Rosie and David Stickels
Pathogenesis markets the new preservative free tobramycin preparation TOBI nebulised treatment for CF patients with chronic P. aeruginosa infection. Most CF patients do well on inhaled colistin but clinicians are becoming uneasy about using the intravenous tobramycin preparation for inhalation, as they have done for years in the UK. Particularly,  in view of the increasing tendency for litigation by patients. It is interesting that most North American patients and those in Europe who need it are likely to get TOBI.  The financial restrictions of the NHS are having a bad affect on the use of this type of drug.

23.11.000.  Meeting  about the  CALICO trial in Liverpool
This is a major multicentre trial the CF Trust is funding on the use of oral dietary supplements. It seems to be going well and I will be attending all the investigators meetings

The trial was led by Vanessa Poustie a Liverpool dietitian and was eventually published in 2006.   The conclusion was that “long term use of oral protein energy supplements did not result in an improvement in nutritional status or other clinical outcomes in children with cystic fibrosis who were moderately malnourished. Oral protein energy supplements should not be regarded as an essential part of the management of this group of children”.

Poustie VJ, Russell JE, Watling RM, Ashby D, Smyth RL. CALICO Trial Collaborative Group. Oral protein energy supplements for children with cystic fibrosis: CALICO multicentre randomised controlled trial. BMJ 2006; 332(7542):632-636. [PubMed]

23.11.000.  Invited Lecture at the headquarters of Pharmax in Bexley.  ”CF – where are we now?”
Have always had a good relationship with this drug firm (now called Forest Labs) as their main product in the UK is the antibiotic colomycin. It would be false modesty if I did not mention the importance of my short letter to the Lancet way back in 1985 reporting successful eradication of Pseudomonas aeruginosa from  children with CF by the use of early nebulised colomycin treatment. This was the most important article I ever published.

Littlewood JM, Miller MG, Ghoneim AT, Ramsden CH. Nebulised colomycin for early Pseudomonas colonisation in cystic fibrosis. Lancet 1985; I: 865.

Previously it had been considered impossible to eradicate the organism once it had appeared in sputum cultures. This report caused a great deal of interest and some people started using the drug for this purpose. It is generally acknowledged this letter started the gradual introduction of early eradication treatment of P. aeruginosa. One wit in the audience at Pharmax observed that my portrait in oils should be on the boardroom wall! 

(Extract from my comments in cysticfibrosis.online/history)  “This was the first report of the use of nebulised colomycin to eradicate early Pseudomonas infection from people with CF and, although only a modest letter, was undoubtedly the most important publication of my career! Previously it had been thought to be impossible to eradicate P. aeruginosa once the organism appeared in throat cultures. Subsequently, and according to Niels Hoiby of Copenhagen, as a result of our short letter to the Lancet, they started a controlled trial of early eradication therapy (Valerius et al, 1991) and found their results “confirm and extend the preliminary report by Littlewood and colleagues”. We had been using nebulised colomycin in Leeds CF patients since about 1983/84 when Pseudomonas was first isolated to attempt eradication and after treating only seven patients it was quite obvious that in most cases the organism was eradicated quite contrary to current teaching; so we reported this interesting finding in this letter to the Lancet”.

 30.11.000  Invited to be a Trustee of the CF Trust i.e. a full member of the Board
Up to that time, since 1995, I had attended all Board Meetings of the CF Trust in an ex officio capacity in my role as Chair of the Research and Medical Advisory Committee. Now the Board invited me to be a bona fide Trustee. I was assured that, if I agreed, I wouldn’t go broke if the Trust failed financially as would have been the case for a Trustee some years ago. So I accepted the invitation and on 1.1.2001 became a Trustee of the Cystic Fibrosis Trust.

5.12.000 . Spent much of the past few days recovering from yet another bad back.
Was able to make many phone calls to arrange the March 30th Medical Meeting in London.  We now have all the speakers organised. I suggest that this should be an annual event that will replace the old “Hon Medical Advisors Meetings” which are now  an anachronism. The new meeting is for all those in the UK who treat CF patients many of whom never get to European or North American CF meeting rather than one consultant from each centre.  We have a list of excellent speakers and there will be plenty of sessions to discuss the new consensus guidelines that would be supplied to the attendees before the meeting.
As I had hoped, the specialist groups of dietitians, physiotherapist etc. have arranged to have their own meetings the day before in London.

So Looking back on the year 2000

Although somewhat mentally bruised I feel a sense of real progress this year end.   A number of projects with which we are involved are now completed or are nearing completion and others are showing definite progress.

–  Unfortunately the exception is neonatal CF screening.        In practical terms three doctors (Prof David Hall, Dr David Elliman and Dr Carol Desataux) of the Child Health Subgroup of the National Screening committee are essentially community paediatricians or epidemiologists and not involved with people and CF. They are “not convinced” of the value of neonatal CF screening, regard the “evidence as weak”. Consequently they will not advise the National Screening Committee to recommend it. That opinion is totally the opposite to virtually every parent, patient, experience professional and CF clinic Director who have day-to-day contact with cystic fibrosis patients. This is a quite ridiculous situation where so-called “evidence based medicine” is severely hindering progress. The need for neonatal CF screening is so obvious to any experienced person. However, with increasing involvement of Rosie, our Chief Executive and an article for the scientific editor next Sunday Observer we hope to make better progress.

–  The revised guidelines for clinical care. These are virtually finished. The final meeting is tomorrow. Completion of these guidelines will allow accreditation of clinics to be started. It is essential that the care of all CF patients is at the highest possible standard, which is certainly not the case at present.  This must remain one of our main priorities until the more specific therapies such as gene replacement become available. I’ve definitely anxieties about the standards of shared care in some areas of the UK.

– The UK CF Database. After leisurely start progress is now impressive. It is encouraging that recently Great Ormond Street has agreed to come on board submitting their patient data. The use of a database is a major factor in raising clinical standards – to record, measure and compare with the national average and with what others are achieving. We have agreed to cooperate with European CF database. It is important we (at the CF Trust) continue to fund the UK CF database in Dundee as this type of data collection would always be too detailed for the NHS.  We are already seeing some interesting results from the UK database – for example 25% of CF UK patients are receiving more enzymes than the upper limit recommended by the Committee on Safety of Medicines. The new data protection regulations are proving a problem but I’m sure are not insurmountable.

–  The Control of Infection Group’s Pseudomonas aeruginosa Guidelines is completed.  These recommendations confirm a radical approach to reduce the risk of acquiring P aeruginosa. I know they will not be acceptable to all but the group is quite unanimous in recommending complete segregation according to the patient’s Pseudomonas status both in and outside the hospital.

– The Nutrition Group’s report is at last completed and will be presented to the clinic directors later this month,

– Clinical Trials.  The CF Trust is currently funding two major multicentre trials. The first is the TOPIC trial of once versus thrice daily intravenous tobramycin organised by Alan Smyth in Nottingham. The second is the CALICO trial on the value of of oral nutritional supplements organised by Vanessa Poustie and Ros Smith in Liverpool. We have also had an application relating to the use of inhaled corticosteroids. All these trials deal with important clinical issues.

–  Future trials. The use of regular three monthly courses of IV antibiotics for those chronically infected with P.aeruginosa, the Danish method, versus treatment only when an exacerbation of the chest infection occurs. This is a major question which requires a clear answer.

– Multicentre trials. Are very expensive and difficult to organise. The people involved with the TOPIC trial (once versus three times daily IV tobramycin) have learned a great deal, particularly concerning the problems of recruiting patients; indeed, they may require a further year’s funding to achieve the required number of patients.  At the recent Clinical Trials Advisory Group we considered whether the information learned from it could be used in forming a UK Clinical Trials Network (CTN) similar to the one recently started in the United States. The main advantage of a CTN is that if a new treatment to requires testing the machinery is in place without “reinventing the wheel” every time a new clinical trial is organised. As a majority of UK patients are now registered on the UK database the location of patients would be suitable for a particular trial would be known.

2000 Christmas Day in Nottingham with the Haines family

 

                                  Members  of the CF Trust Clinical Standards  Committee