Richard Lehman’s weekly journal review—5 May 2015

richard_lehmanNEJM 30 April 2015 Vol 372
1684 “Virtual Visits—Confronting the Challenges of Telemedicine” is a Perspective piece which starts full of optimism about the potential of telemedicine and then switches tack half way through. “For providers, using telemedicine may be more efficient than seeing patients in brick-and-mortar offices, since it reduces the time and space needed to run a medical practice. For patients, telemedicine can reduce travel expenses and the opportunity costs associated with obtaining care, such as missed hours or days of work.” Actually, that sounds unlikely on first principles. Could telemedicine really save on time and office space? Won’t the great majority of medicine always have to be a direct human interaction? What proportion of illnesses actually lend themselves to remote consultations and how many ill people would rather use a device than see a doctor face to face? Sure enough, when trials have been done—even in convenient chronic conditions with e-savvy populations—they have failed to show any improvements in outcomes and have usually increased service use and costs. Telemedicine may seem like the shiny future, but in reality it is a return to the Middle Ages. Those who could afford a physician would get examined by his clerk, who would take the history, measure the pulse, examine the urine, and report to his gowned master. The physician himself was far too important to actually touch a patient.

1710 Motherhood is not a medical condition, but it becomes one if the mother opts to have a caesarean section. Some would argue that every mother should have that option, while others would argue that we are doing too many and that “we” should be cutting back on operative deliveries. This latter kind of rhetoric pervades a trial carried out in Quebec in which “the intervention involved audits of indications for caesarean delivery, provision of feedback to health professionals, and implementation of best practices.” Note the absence of mothers. “The primary outcome was the caesarean delivery rate in the 1-year postintervention period.” OK, so this trial is a before and after study with a control cluster of Quebec maternity units which did not carry out this kind of audit. And there was scarcely any real difference in outcomes, though because of the enormous numbers (a total of 184 982 participants) there were some borderline statistically significant results in favour of the intervention, entirely among low risk pregnancies.

1722 “The Diabetes Control and Complications Trial (DCCT) showed a beneficial effect of 6.5 years of intensive glycaemic control on retinopathy in patients with type 1 diabetes.” Absolutely. This follow-up study asked the participants annually if they had eye surgery after the end of the trial, and it shows the continuing benefit of that period of tight control, although the absolute reduction in surgery was fairly modest: 8.9% of the tight control group vs 13.4% in the conventional care group over a median of 23 years.

1734 How well up are you on the inflammatory muscle diseases? Can you tell your polymyositis from your inclusion body myositis? This review article will soon get you up to speed. It has a couple of nice illustrations, but those of us who remember the NEJMs of a decade ago will miss those wonderfully complex, whole page diagrams with glistening globes of pale green, pink, and blue moving between strangely shaped organelles and arrows marked with unheard of enzymes. You would feel edified by simply looking at them.

JAMA 28 April 2015 Vol 313
1613 JAMA‘s trip into the future this week is a Viewpoint called Induced Pluripotent Stem Cells. These came on the scene nine years ago and were going to usher in a new era of personalised restorative medicine. As of now, there are 300 NIH registry approved human embryonic stem cell lines, “which represent less than 0.00001% of the world’s 7 billion people and thus do not capture the great majority of human genetic diversity.” I knew nothing at all about the subject before reading this article and I feel I know slightly less now. “Even if iPSC derivation was radically efficient, subsequent regenerative therapies and disease modelling will continue to be limited to only those cell types for which differentiation-from-pluripotency protocols exist.” Meaning that you will probably be dead before your personalised repair kit is ready. Sorry.

1627 About 30 years ago, one of my patients returned from the US with a filter in his inferior vena cava, having had a very expensive pulmonary embolus in the land of the free. This procedure has never caught on in the NHS, and a good thing too. But it persists across the Atlantic, despite many trials proving its lack of effect. The latest shows that “Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months.”

1645 From 410 CE (AD), Norfolk was a popular destination for tribes settling in Britain, mostly Angles from the far north west of Germany. Ængla-land soon stretched from the land of the Norðfolk down to the lands of the Suðfolk and Kent. The ethnicity of East Anglia has changed remarkably little since the sixth century when Wuffa was its king, which makes it a favourite spot for epidemiologists wanting a truly English sample. Some Angles carry a susceptibility locus for rheumatoid arthritis: the HLA-DRB1 locus. Here’s a study showing that not only does this make them more likely to get RA, but also makes it more likely that it will progress aggressively. The investigators used the Norfolk Arthritis Register as a discovery cohort and the Early Rheumatoid Arthritis Study as an independent replication cohort for studies of radiographic outcome.

1657 On the rare occasions when you read every word of a published clinical trial, don’t you feel virtuous? I don’t grudge you that, because it can be quite hard work. But if I hope to have taught you anything, it’s never to trust in published data alone. So if you are doing a systematic review to find out the sum of knowledge about a particular intervention, you really must try to get full datasets of clinical study reports and individual participant data (IPD). There are far too few workers in this field. I suspect that for every thousand career academics trying to churn out research papers, there is one meta-analyst who is competent to handle IPD. In the UK, Lesley Stewart is our shining light, and here she sets out the PRISMA-IPD statement of best practice.

JAMA Intern Med April 2015 Vol 175
OL I’m just old enough to remember the days when a diagnosis of Hodgkin’s lymphoma was a death sentence. It started becoming curable about 50 years ago, and the first survivor in this Dutch follow-up study was treated in 1965. Treatment for Hodgkin’s usually involves mediastinal radiotherapy and anthracycline chemotherapy, both of which are toxic to the heart. So this study shows that the price of surviving the lymphoma is a markedly increased risk of heart disease. After 35 years or more, patients still had a 4- to 6-fold increased standardised incidence ratio of CHD or heart failure compared with the general population. Within the cohort, the 40 year cumulative incidence of cardiovascular diseases was 50%.

Ann Intern Med 21 April 2015 Vol 162
533 Last year I had several tries at writing a short critique of the National Institute for Health and Care Excellence guideline on statins, but in the end I had such a severe hemiplegic migraine that I decided that I might die in the attempt. Fortunately, others have risen to the challenge, and I hope that continuing debate about this issue will mark a turning point in our conceptualisation of population risk and how to make decisions with individuals. One of the most extraordinary recommendations was to offer all people over the age of 85 a statin because of their 10+% risk of a cardiovascular event. In this paper, an attempt is made to predict the cost effectiveness of statin treatment of all American adults aged 75 to 94 years using Markov modelling. Do access it if you are interested, but to me it just proves how inadequate the data are to support such modelling, even if it was legitimate to apply it . . . But don’t get me started. I can feel a migraine coming on.

Lancet 2 May 2015 Vol 385
1758 I think if I had a favourite drug, it would have to be amoxicillin. It may have saved more lives than any other drug across the world. It works in situations where there is no access to diagnostic testing, as in the two African primary care trials reported here. In the first, the investigators enrolled 2333 infants aged 0–59 days with fast breathing as the only sign of possible serious bacterial infection at the five study sites across Congo, Kenya, and Nigeria. They were randomised to receive either injectable procaine benzylpenicillin–gentamicin once per day or oral amoxicillin treatment twice per day for seven days. The two groups did equally well. It was the same story in another Gates funded trial using different criteria for possible serious bacterial infection. We should treasure amoxicillin, and use it as we do in UK general practice, where its effectiveness has remained constant for decades.

OL But with antibacterials, context is everything. The gram-negative organisms that cause urinary tract infections are extremely good at changing their patterns of resistance, and appropriate prescribing depends on matching these as best one can. The design of this trial comparing ceftolozane-tazobactam with levofloxacin for hospitalised patients with UTI strikes me as all wrong. It was run by the manufacturer, called Cubist Pharmaceuticals, in 209 centres in 25 countries, mostly from Eastern Europe with a scattering from other places around the world. “Treatment with ceftolozane-tazobactam led to better responses than high dose levofloxacin in patients with complicated lower-urinary tract infections or pyelonephritis.” Well, it would, wouldn’t it, if local usage meant that most urinary pathogens were already resistant to fluoroquinolones. If this is Cubist pharmacology, I don’t like it. Give me a nice Rembrandt instead.

OL That pharma funded trial exemplifies everything I dislike most about The Lancet: I’ll leave it for you to judge whether a high level medical journal should publish studies with this standard of design and reporting. Let’s move to what they do best, which is big surveys of population wide topics. This week’s goody is an open access paper on the future of life expectancy and life expectancy inequalities in England and Wales, using Bayesian spatiotemporal forecasting. Detail! Charts you can understand! Great rainy afternoon skim reading. Men are catching up with women. But it will take some time for the poor to catch up with the rich. All very topical in Election Week. So who will you vote for? The party which will best reduce inequality and improve the NHS, I hope.

The BMJ 2 May 2015 Vol 350
Stents, mabs, and NOACs. They’ve dominated the journals these last 17 years, and I hope you haven’t grown as weary trying to follow them as I have trying to write about them. NOACs are novel oral anticoagulants. Throughout the 2000s, they started pouring from the drug companies. These exciting drugs promised an end to the need for warfarin and blood testing. One week it would be apixaban for atrial fibrillation. The next week it might be dabigatran for VTE. As they proliferated, and one began to multiply all the drugs by all the indications by all the comparisons, it seemed that the line might stretch to th’ crack of doom. One began to lose the will to read, if not to live. This week’s BMJ attempts a reality check in the form of two American papers comparing dabigatran v rivaroxaban v warfarin for all indications in relation to the risk of gastrointestinal bleeding. They are much of a muchness, within wide confidence intervals.

A pragmatic Norwegian trial compares microdecompression with laminectomy in the surgical treatment of central stenosis of the lumbar spine. The results were identical at one year. And at four years, according to a recent American trial, they would have equalled the results of doing nothing.

So how can the incoming government rescue the NHS? The level of public debate has largely been pathetic, but I’m slightly bucked by the analysis essay by Jan Filochowski. It seems to me that he’s saying we just need to get everything working to capacity so as to make rational use of the workforce, equipment, and all fixed costs within the system. The internal market is just a huge expensive stupidity. Not only did it set costs soaring, it also built in conflicts and divisions between primary and secondary care, which dislocate the common endeavour of caring for ill people and are profoundly damaging to patients and those who try to help them.

Blake for Election Week:

In my Exchanges every land
Shall walk; and mine in every land,
Mutual shall build Jerusalem,
Both heart in heart and hand in hand.

(from Jerusalem written and etched 1804-1820: Plate 27, Introduction to Ch2)

  • Alberto E Tozzi

    Telemedicine and skepticism

    Provided that skepticism is almost always a healthy approach to exciting news, I think that we should put telemedicine in the right context.

    I find that telemedicine is an enabler rather than a potentially effective intervention, and as such, it should be evaluated with the right outcome measures. Beyond clinical outcomes (that however are not frequently approached with sound study designs) other
    indicators as quality of life of patients, time saved in completing processes, quality of procedures, workload saved by health professionals (and potentially reinvested), plus direct and indirect costs, should be taken into account. A complete spectrum of these indicators is rarely included in studies evaluating the impact of telemedicine interventions.

    A second important component relies in the primary rationale of telemedicine: improving accessibility to health care. We still live in a world where access to health resources is not equally distributed and where an Internet connection may make a difference.

    But in my opinion, one of the most crucial components is empowering patients and supporting their autonomy in managing their condition. I personally hope that technology and telemedicine will help health systems to shift toward a participatory approach.

    Having said that, I must say that telemedicine is not for every health process or intervention. We should carefully evaluate readiness of persons involved and feasibility of telemedicine
    interventions in each setting before we start.

    Finally, telemedicine should be a powerful tool for implementing EBM guidelines. I cannot forget how frequently EBM recommendations fail because they are not efficiently transmitted to patients.

    I do not think that technology can replace the human touch of doctors, but I am a strong supporter of patient empowerment and process simplification. Indeed, patients involved in telemedicine interventions do feel involved in a closer relationship with their
    doctor compared with usual care.

    Alberto E Tozzi