Tuesday, 25 October 2016

#PoliticalSpeak: NHS in crisis

NHS in crisis will innovation be sufficient to change the way we manage MS?  #PoliticalSpeak #MSBlog

The editorial in this week's BMJ (below) says it all. Our attempts to try and improve productivity within Barts-MS may be simply a sticking plaster. It is clear the NHS needs more money. I suspect innovation won't be enough, but is that a reason not to try? 

Our proposal to set-up a Barts-MS Expert Patient Course may be an act of folly. During the course we propose teaching you everything you need to know about MS, the management of MS and how to monitor and manage your own disease. You will then provide you with the tools to get on with it. The system we propose setting-up will allow you to contact us if you run into problems and/or need help, for example with a specialist referral. We will hopefully allow you to self-refer for essential services, for example continence advise and therapy. We also will identify expert patients with MS who can help us run the teaching course and our service on a voluntary basis. If you haven't responded already we would appreciate it if you could complete the survey below. We need the data to make the case to our managers and to Barts Health for crowd funding. 

Andy Cowper. Feature NHS Performance: A view to a plan? BMJ 2016;355:i5583

For almost all the wrong reasons, NHS performance is scarcely out of national news headlines. The State of Care report just published by the Care Quality Commission (CQC) outlines a system having to deal with a record 23 million emergency department attendances and six million hospital admissions in 2015-16.

The CQC chief executive, David Behan, identifies falling and failing social care provision and pressures in primary care as key contributors to problems with NHS performance. “[They] are now beginning to impact both on the people who rely on these services and on the performance of secondary care. The evidence suggests we may be approaching a tipping point,” he said.

The cause is obvious. Despite a 33% rise people aged 85 and over the past decade, the proportion receiving care funded by local authorities has fallen. A National Audit Office review found that local authority income, including council tax, fell by 25.2% in real terms from 2010-11 to 2015-16.

This hits on the same day that NHS England’s latest figures for August 2016 reveal that overall referral-to-treatment performance deteriorated. The total waiting list rose to 3 691 739, and the proportion of people referred for elective care being treated within 18 weeks fell further below target to 90.9% (this is not including providers who, for various reasons, are not reporting their waiting times).

There were 1 931 981 emergency department attendances in August 2016 (3.6% more than in August 2015). Attendances over the past 12 months are 4.2% higher than in the preceding 12 months. The number of days of delayed care rose to 188 000—the highest since monthly data were first collected.

Financial arguments

Yet August 2016 wasn’t all bad news. The financial and performance regulator, NHS Improvement, announced that overall, the NHS provider sector had hit its financial target in the first quarter of the 2016-17 financial year, reversing a three year trend of missing it.

The Treasury is understood to be pressuring NHS leaders to achieve quarterly financial balance at almost any cost and has no appetite to revisit the 2015 comprehensive spending review financial settlement.

The government repeatedly trumpets its £10bn extra for the NHS, saying it only asked for £8bn. This isn’t really true: as financial expert Sally Gainsbury of the Nuffield Trust think tank points out, the “extra” £2bn was allocated before the comprehensive spending review in 2014, to mop up deficits.

In addition, the House of Commons health select committee calculates that the actual increase will be just £4.5bn from 2015-6 to 2020-21.

And Gainsbury adds that once healthcare specific inflation is taken into account, that figure dwindles to £0.8bn.

Pressure on the NHS and social care seems unrelenting. The latest QualityWatch report from the Nuffield Trust and the Health Foundation highlights how what was once considered “winter pressure” is now almost year round. Winter is the new normal.

A sustainable future

It can be hard to remember that when NHS system leaders collaborated to publish the Five Year Forward View two years ago, there was general buy-in to its vision of a more networked system, away from being a heavily acute focused series of organisational silos.

One problem was the lack of a means of delivering the Forward View’s desired change in providers.

One answer emerged in the 44 geographically based sustainability and transformation plans (STPs), announced last December and currently being negotiated and finalised. These bodies, crucially, have £2.1bn of STP funding in 2016-17, which can be withheld from providers and STP “footprints” who do not deliver financial balance.

So STPs are the change delivery vehicle? Politicians may hope so. At Prime Minister’s questions on 12 October, six of the 29 questions were asked on health and NHS issues. The latest parliamentary health questions heard numerous concerns about provider issues and STP processes and results, including from Conservative MPs.

NHS Providers (whose name describes its constituency) expressed the sector’s serious doubts to the health select committee last week. Chief executive, Chris Hopson, called many STPs “vastly overambitious,” adding that their authors “are now looking at a set of figures that to be frank just look completely undeliverable. Our members are spending quite a lot of time creating plans that in their view are not deliverable, and usually involve major structural service changes because that’s the only way they can create a balanced plan.”

It bodes ill if the authors of the only game in town don’t believe in their STPs. In a recent interview, Simon Stevens reflected at length on the funding question. His concluding remarks offer politicians a lightly veiled warning of a change that is going to come: “Since we’re now facing a tougher challenge than set out in the Five Year Forward View, there will inevitably be pressures, choices, and controversies as the NHS copes with these constraints. Frontline staff, clinicians, and local NHS leaders need full national backing and support in doing so.”

The political and public reaction to STPs is about to get interesting.

JCV are we in safer times?

Acta Neurol Scand. 2016 Oct 20. doi: 10.1111/ane.12699. [Epub ahead of print]

JCV serology in time: 3 years of follow-up.

Cambron M, Hadhoum N, Duhin E, Lacour A, Chouraki A, Vermersch P.



Although many neurologists are reluctant to use natalizumab in MS (multiple sclerosis) given the increased risk for PML (progressive multifocal leukoencephalopathy), trust was regained with the introduction of JCV antibody titres as a potent disease-modifying therapy. Literature shows that in patients with a negative JCV serology, the risk of PML is virtually non-existent. Unfortunately, seroconversion causes concern amongst many neurologists. Furthermore, when patients seroconvert, it is still unclear what the risk is of passing the important threshold of 1.5.


JCV serology data of 161 patients were analysed, upon treatment with natalizumab at the University Hospital in Lille, France, between May 2012 and November 2014.


Of the 81 patients who tested negative for JCV antibody at baseline, 23 (28.3%) seroconverted but only seven (8.6%) passed the threshold of 1.5. Of the 80 patients testing positive for JCV antibody at baseline, eight had an initial JCV antibody titre of 0.9 or lower of which only one of eight (12.5%) patients passed the threshold of 1.5 in the following 3 years. Eight of 15 (53.3%) patients passed this threshold if the initial serology was higher than 0.9.


JCV-negative patients and JCV-positive patients with antibody levels below or equal to 0.9 both have a low risk of surpassing the 1.5 threshold.

Figure: Google trends for interest in natalizumab from 2004 - current. The peak in 2005 corresponds to suspension of marketing authorization of natalizumab (Tysabri) by the FDA.

The John Cunningham virus causes a serious demyelinating CNS disorder called progressive multifocal leukoencephalopathy (PML). Although, 33-91% of the general population is positive for the virus, only half of PwMS are positive for the antibody (the seroconverted). PML risk is at the heart of natalizumab therapy; public and professional concerns over this have not yet been convincingly allayed. In addition, there is the added concern of seroconversion on therapy; with some researchers (most recently N Schwab's group at ECTRIMS 2016) suggesting that those on natalizumab seroconvert at higher rates than expected by aging.

A lot of sweat has therefore gone into a developing an antibody test (STRATIFY) that can be used to risk stratify PML development in natalizumab users. An index threshold of 1.5 is used by many as the cut-off. In this study, Cambron et al. wanted to investigate the risk of an initially negative antibody test person passing the threshold of 1.5. They found that 28.3% seroconverted with 8.6% passing the threshold of 1.5. They found that the likelihood of seropositivity increased in those receiving a higher number of infusions. But they also then suggest that the ones with an index of =/<0.9 had a lower risk of passing the 1.5 threshold (an oxymoron possibly).

I'm not sure how this allays my fears. The authors conclude: "Patients who have a positive response to natalizumab and a positive JCV index values below 0.9 can be reassured and safely continue their natalizumab treatment, obviously with an accurate clinical and radiological follow-up". And therein lies the problem, a negative baseline test is not fool-proof or protective against PML development (see Abstract P1259 below), and where cases of diagnosed PML are concerned, their defining characteristics are being JCV positive and receiving natalizumab for >2 years (see Abstract P1111 below)!

Maybe, we need to stop worrying our heads over this one; there is only so many ways you can cut a cake.

Abstract: P1259, ECTRIMS 2016
Progressive multifocal leukoencephalopathy in a JCV seronegative patient treated by natalizumab : a new case report
Author(s):N Hadhoum ,V Neuville ,P Vermersch
Background: the prediction of the risk of progressive multifocal leukoencephalopathy (PML) is crucial to guide natalizumab (NTZ) prescription and ensure a higher safety use. The JCV index (a corollary to antibody titer) is a predictive factor of PML.

Case presentation: here we report a case of a 55-year-old female diagnosed with multiple sclerosis in 1996. Because of a continued clinical disease activity despite interferon, she was switched to NTZ. A total of 84 infusions were administered between 2011 and 2016. She never received any prior immunosuppressor and has been tested negative for anti-JCV antibodies: index at 0.22 in 06/2014 and 0.11 in 06/2015 and 10/2015. The annual MRI were strictly stable. During a routine follow-up, the patient complained of a right-sided lower limb paresis. NTZ was immediately stopped. Brain magnetic resonance imaging revealed a sub-cortical white matter lesion, hypoT1, hyperT2 in the left parietal lobe invading the U-fibers in DIR sequence. PML was suspected then confirmed by detection of JCV-DNA in the CSF (2 analyses: 11 then 68 copies/ml). The peripheral CD4+ T-cell count was 1149/mm3, CD8+ at 395/mm3. Note that the JCV index was still negative at the diagnosis and 15 days later. We investigate the lymphopenia and found a probable common variable immune deficiency (CVID) with severe hypogammaglobulinemia (3g/dL), surprisingly asymptomatic until now. A JCV seroconversion was noted at 3 months (index at 3.48).

Discussion: it is well-known that PML risk is influenced by NTZ duration, prior use of immunosuppressors and seropositivity for the JCV. The JCV seronegativity status does not allow to exclude any risk of PML. Indeed, de novo infection with seroconversion is theoretically possible and underestimate rate of infection appears likely (in case of low viremia). One recent publication reports a NTZ-related PML diagnosed 2 weeks after negative anti-JCV antibody assay and 2 others PML due to NTZ were tested negative (prior to diagnostic) among the 541 reported cases. In our case, we can hypothesize that the JCV index were false negative results as the asymptomatic CVID imply a fail in humoral responses.

Conclusion: this case must not undermine the central role of the JCV index in predicting the risk of PML. However, it seems wise to regularly control the blood lymphocyte phenotype and immunoglobulins. CVID is the one of the most common causes of adult immunodeficiency.

Abstract: P1111, ECTRIMS 2015
JCV (John Cunningham virus) index: follow-up of a French cohort
Author(s):S. Mathais ,A. Gayou ,X. Moisset ,J.C. Ouallet ,B. Pereira ,A. Ruet ,F. Taithe ,K.-K. Kounkou ,E. Dumont ,B. Brochet ,P. Clavelou

Objectives: Patients receiving natalizumab (NTZ) are at risk of PML (Progressive Multifocal Leukoencephalopathy) due to JCV reactivation. In order to predict that risk we currently use the JCV index. Recently, cut-off values for the JCV index have been published. The risk of PML seems to be very low under 0.9, low between 0.9 and 1.5 and high above 1.5.

We wanted to better characterize the JCV index and its evolution and check whether the suggested thresholds were applicable to our cohort.

Methods: This study was conducted in two French University Hospitals (Bordeaux and Clermont-Ferrand) until the 31/12/2014. We included 352 patients over 18 years with a relapsing-remitting multiple sclerosis and at least one JCV index. We got 908 samples. Three subjects developed a PML. We evaluated the seropositivity for JCV, the potential modifying factors of JCV index (before and under NTZ), its evolution under NTZ and particularly in case of PML.

Results: 63.2% of NTZ-naïve patients were positive for JCV. At this stage the JCV index is statistically related with the age but independent from sex, disease duration or anterior exposure to immunosuppressive agents. Among the patients finally treated with NTZ 39.7% were positive for JCV at baseline and 55% at the last JCV index. On NTZ only the treatment duration was statistically related to the evolution of the JCV index. 84.5% of subjects remained stable during the follow-up specially if they were initially positive for JCV (45.4%). 6.7% seroconverted and 1.5% seroreverted. Our three cases of PML presented two risk factors (over 2 years of NTZ and seropositivity for JCV). Their indexes were above 1.5 for at least 3 months prior PML.

Conclusions: JCV index seems to remain fairly constant over time and the published threshold for high PML risk (1.5) was confirmed in our cohort.

Monday, 24 October 2016

#ClinicSpeak & #OffLabel: rituximab in sweden

The MS off-label vs. licensed-innovator drug wars are about to get nasty. #ClinicSpeak #MSBlog #OffLabel

The study below summarises the off-label experience of using rituximab to treat both relapsing and progressive forms of MS in Sweden. An updated data set was presented at ECTRIMS to gasps from the audience. It is clear that anti-CD20 therapies are very effective DMTs, in both relapsing and progressive MS. These results are no surprise and back-up an enlarging data set on the efficacy of anti-CD20 therapies in MS. 

Rituximab is about to come off-patent and there are several rituximab biosimilars waiting in the wings , with one already available in India. Off-label rituximab may therefore disrupt the MS market, particularly markets that are price sensitive. We tried to get NHS England to let us use rituximab in the NHS and they said no. The reason was that rituximab was not licensed for treating MS. It is clear that the NHS don't mind promoting and supporting the use of off-label drugs provided they are low cost and don't involve specialist commissioning, i.e. payment from central, rather than local, budgets. This is the NHS version of Catch-22! With the NHS on its knees you would expect them to embrace off-label drugs. I suspect they want to avoid any more high profile legal disputes with Pharma. 

As you are aware we have included rituximab on our essential off-label DMT list and we continue to encourage neurologists in resource-poor settings to consider using rituximab in patients with highly-active MS. In wealthier, developed markets, the debate about high-cost innovator drugs is getting very heated. We are fortunate in the NHS to have NICE that assesses the cost-effectiveness of drugs and negotiates a very good deal of the NHS. In other countries, particularly the USA, this does not occur and drug price inflation has become a political issue. The USA is now subsidising international drug development and this position is unsustainable in the long-term.

For people with MS the good news is that the ocrelizumab, a follow-on from rituximab, should be licensed in the major markets within the next 12-24 months. Ocrelizumab has several advantages over rituximab, the main one being that it is less immunogenic than rituximab with a very low anti-drug antibody rate. An interesting question will arise is whether or not these advantages will change prescribing habits in countries such as Sweden and the USA. 

Salzer et al. Rituximab in multiple sclerosis: A retrospective observational study on safety and efficacy. Neurology. 2016 Oct 19. pii: 10.1212/WNL.0000000000003331.

OBJECTIVE:  To investigate the safety and efficacy of rituximab in multiple sclerosis (MS).

METHODS: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded.

RESULTS: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS). At baseline, 26.2% had contrast-enhancing lesions (CELs). Patients were treated with 500 or 1,000 mg rituximab IV every 6-12 months, during a mean 21.8 (SD 14.3) months. During treatment, the annualized relapse rates were 0.044 (RRMS), 0.038 (SPMS), and 0.015 (PPMS), and 4.6% of patients displayed CELs. Median Expanded Disability Status Scale remained unchanged in RRMS (p = 0.42) and increased by 0.5 and 1.0 in SPMS and PPMS, respectively (p = 0.10 and 0.25). Infusion-related AEs occurred during 7.8% of infusions and most were mild. A total of 89 AEs grades ≥2 (of which 76 infections) were recorded in 72 patients. No case of progressive multifocal leukoencephalopathy was detected.

CONCLUSIONS: This is the largest cohort of patients with MS treated with rituximab reported so far. The safety, clinical, and MRI findings in this heterogeneous real-world cohort treated with different doses of rituximab were similar to those reported in previous randomized controlled trials on B-cell depletion therapy in MS.

CoI: multiple

Getting the Right Models

Lassmann H, Bradl M.Multiple sclerosis: experimental models and reality. Acta Neuropathol. 2016 Oct 20. Review.

One of the most frequent statements, provided in different variations in the introduction of experimental studies on multiple sclerosis(MS), is that "Multiple sclerosis is a demyelinating autoimmune disease and experimental autoimmune encephalomyelitis (EAE) is a suitable model to study its pathogenesis". However, so far, no single experimental model covers the entire spectrum of the clinical, pathological, or immunological features of the disease. Many different models are available, which proved to be highly useful for studying different aspects of inflammation, demyelination, remyelination, and neurodegeneration in the central nervous system. However, the relevance of results from such models for MS pathogenesis has to be critically validated. Current EAE models are mainly based on inflammation, induced by auto-reactive CD4+ T-cells, and these models reflect important aspects of MS. However, pathological data and results from clinical trials in MS indicate that CD8+ T-cells and B-lymphocytes may play an important role in propagating inflammation and tissue damage in established MS. Viral models may reflect key features of MS-like inflammatory demyelination, but are difficult to use due to their very complex pathogenesis, involving direct virus-induced and immune-mediated mechanisms. Furthermore, evidence for a role of viruses in MS pathogenesis is indirect and limited, and an MS-specific virus infection has not been identified so far. Toxic models are highly useful to unravel mechanisms of de- and remyelination, but do not reflect other important aspects of MS pathology and pathogenesis. For all these reasons, it is important to select the right experimental model to answer specific questions in MS research.

We are at a time of animal bashing as there is not a model that has all elements of MS. That is true, but we have to remember that we can only model what you are told happens and here the pathology has much to answer. 

When I started my MS career it was written over and over again that MS was a disease of the white matter, but you just needed a pair of eyes to see that wasn't the case because you can see grey matter lesions with the naked eye.

Maybe the problem was the pathologists weren't doing the dissection, they maybe had technicians doing the work dissecting the brain, doing the sections and then staining with luxol fast blue, but because them pathologists siad there was no myelin in the grey matter the technicians would destain the sections until there was no stain in the grey matter and lesions missed. It was only when they started staining with antibdies that gey matter lesions were evident.
The imagers had missed this too because their machines could pick up lesions.

Then there is nerve loss issues...it has only become an issue when it was rediscovered in 1997/1998, but there was a long literature and agin using your eyes atrophy can be seen with the naked eye.

The problem is if you looked a group of pathologists in a room we would get the same answer of what are the pathological mechanisms occuring in MS.

What happens when you look weeks and months and years after the event. We know in EAE it looks very different. 

However the authors have a point because the models are driving ideas on potential therapies and there are powerful dogmas driving these choices. If the choices are based on false ideas then they are a based on a pack of cards....waiting to fall.

We are focusing on Th17 as a cause of MS....CD4 depletion has failed, blocking interleukin 17 has failed...(reducing lesion load by 50% is a failure). what's the evidence to support this in MS

What are the CD8 doing what makes them arrive. Surely the target must be in the CNS tissue they are attacking. If it is a virus it must be there...why have the not been found..have they been found as every cell has endogenous retro virus in its genome, in most cases live virus is not made.

Should we be depleting CD8 cells?.....would this be dangerous 
because CD8 cells have regulatory cells in their population

What are B cells doing, presenting antigen to T cells, what type of B cells are important? Depleting B cells can certainly work in MS

What is happening in areas distant from where the pathology is done, etc, etc etc. 

I've seen loads of reviews questioning animal work but essentially nothing questioning the pathology and the clinical work. It is bad for business because it is suggesting the neuros are fallible.

Baker D, Amor S.Experimental autoimmune encephalomyelitis is a good model of multiple sclerosis if used wisely. Mult Scler Relat Disord. 2014;3(5):555-64.

Baker D, Amor S. Mouse models of multiple sclerosis: lost in translation?Curr Pharm Des. 2015;21(18):2440-52

However ,we know this is true because we not finding enough useful treatments and as ProFG has said I think we have thrown away useful treatments. Not the stuff you want to hear, not the stuff that puts the academics in a good light.

I think that response to therapy tells us alot and there has to by clues in interogating this. 

Is it all EBV and an ant-virus response.

Sunday, 23 October 2016

#ClinicSpeak & #PoliticalSpeak: time for a revolution in the way we manage MS

With the NHS on its knees we need to innovate and change the way we manage MS. #ClinicSpeak #PoliticalSpeak #MSBlog

Last week at our Barts-MS Strategy day we heard that a very important, almost essential, business case had been turned down by our senior management team. We were simply asking for a new nursing post to help with our expanding MS service. The reason is that our NHS Trust (Barts Health) is in financial special measures; there are no funds to support any new service developments. This is despite our MS service being very profitable, in fact the most profitable service in our neuroscience cluster. This puts Barts-MS in a very difficult position and we now have to consider how we manage our future commitments to our patients going forward. 

The financial constraints we are working under in the NHS are the worst in living memory and are putting us under considerable strain. Please see the excerpts below from a Guardian article, about Barts Health NHS Trust, that was published earlier this year.

We therefore had a short brain storming session on Thursday and we came to the conclusion that we are going to have to make fundamental changes to how our MS service works. We need to be radical. How do you as someone with MS feel about managing, and monitoring, your own disease and being helped by other people with MS?

We propose setting-up a Barts-MS Expert Patient Course during which we will teach you everything you need to know about MS, the management of MS and how to monitor and manage your own disease. We will then provide you with the tools to get on with it. The system we set-up will allow you to contact us if you run into problems and/or need help, for example with a specialist referral. We will hopefully allow you to self-refer for essential services, for example continence advise and therapy. We also will identify expert patients with MS who can help us run the teaching course and our service on a voluntary basis. It is our ambition to run, and coordinate, the largest self-management MS service in the country.

To kick-start this we will need some priming money to design, produce materials, run the course and pilot the self-management component of the service. We envisage the need to create an online self-management web app that will incur costs (design and tech input). As we won't be able to get any funding from our Trust for this new service, we propose running a crowd-funding campaign. To kick-start it we will need something in the order of £6,000-£10,000. Do you think a Barts-MS Self-Management Service is a good idea and do you think we should be raising money for the community to set it up? Desperate times requires outside the box thinking; we need to revolutionise the way we manage MS, and finding that we have been painted into a corner means we have to try something new and radical.

Denis Campbell. The Guardian London hospital trust heading for biggest overspend in NHS history. Sunday 7 February 2016  and Last modified on Tuesday 10 May 2016.


.... The biggest hospital trust in the country is set to run up a £134.9m deficit this year – by far the largest ever overspend in the history of the NHS.
..... Barts Health NHS Trust, which runs four hospitals in east London, employs 15,000 people and serves an area containing 2.5 million people, is on course to have failed to balance its books by that margin when the NHS financial year ends on 31 March. Its overspend is 69% bigger than the trust’s £79.6m overspend – also a record at the time – in 2014-15.

..... “These forecast deficits provide further evidence of the escalating financial crisis in the NHS, as well as the longstanding challenges facing London’s health system. In the case of Barts, these pressures have been exacerbated by the costs of a major PFI development,” said Prof Chris Ham, chief executive of the independent health thinktank, the King’s Fund.

..... Barts’s deficit may end up even bigger than £134.9m. At its board meeting last week, Chrisha Alagaratnam, the trust’s interim chief financial officer, disclosed that the deficit had already reached £115.6m by the end of November, “which represented a £24.4m adverse position against the financial plan”. That overshoot was due to it having made too few savings, received less income than expected and been fined for missing key NHS targets.

..... The sheer size of the deficits run up in the capital suggested that the £1.8bn of extra funding the NHS in England has been given for next year, which the health secretary, Jeremy Hunt, has earmarked to wipe out collective overspend by trusts may prove inadequate, added Ham. “The extra funding provided by the government is being used mainly to get the NHS back into financial balance but even this must be in doubt given the scale of the deficits now being reported. 2016/17 will be a make-or-break year for the NHS,” he said.

.... Alwen Williams, Barts’s chief executive, said that although its deficit was England’s biggest, the trust’s huge size and income meant it was no worse in relative terms than those of other trusts. Barts’s income is about £1.4bn a year, so its overspend represents about 10% of its budget.

..... “Since we are the biggest NHS trust in the country, it is not surprising we are forecasting the largest deficit, although as a proportion of turnover it is comparable to other acute trusts in England,” she said.

..... Nevertheless we are taking concerted steps to improve our financial position by improving the productivity of our four hospitals, working with commissioners to ensure that any money that might have been levied in fines and penalties is reinvested in the trust, and recruiting to permanent posts rather than using expensive agency staff.”

..... Reports presented at Barts’s board meeting last week showed that, of the £68m a month it spends on its workforce’s wages, £7m goes on agency staff. The trust has calculated about £30m of the £80m-a-year cost of agency staff is taken up by the premiums the staffing agencies charge.

..... Barts last year was fined £56m by local NHS organisations for failing to treat A&E patients within four hours and those waiting for planned care within 18 weeks. It is thought to be paying out even more in fines this year as pressure on NHS services has led to most trusts missing key targets.

.... In all, 18 of London’s 37 NHS Trusts are due to record a collective deficit of £582.3m, Burt disclosed. Senior NHS sources said that the fact that so many trusts cannot balance their books shows the NHS is receiving too little money to cope with rising demand, despite its budget having been ringfenced and growing in real terms.

..... GPs fear that hospitals will continue receiving so much extra cash to tackle their financial problems that their practices will not get the extra money – £2bn a year by 2020 – that Hunt has promised.

..... “The alarming size and scale of the deficits facing London’s hospital trusts means that any of the oft quoted extra money for GPs is unlikely to reach local practices or help improve access for patients. Instead, we will see commissioning bodies diverting funds from primary care to keep the lights on in the capital’s hospitals,” said Dr Michelle Drage, chief executive of Londonwide LMCs (local medical committees).