Richard Lehman’s journal review—5 January 2015

richard_lehmanJAMA 24-31 December 2014 Vol 312
2659 The effects of extreme heat on older adults: what a great topic for this cold gloomy time of the year. “Heat wave periods (are) defined as two or more consecutive days with temperatures exceeding the 99th percentile of county-specific daily temperatures,” and in this US study they were matched to non–heat wave periods by county and week. This study went right down from the top of Maine to the bottom of Texas, which may account for its rather weak conclusion: “Among older adults, periods of extreme heat were associated with increased risk of hospitalization for fluid and electrolyte disorders, renal failure, urinary tract infection, septicemia, and heat stroke. However, the absolute risk increase was small and of uncertain clinical importance.”

2668 Back in the mists of time, when I was a long haired medical student with sideburns, there was a drug for type 2 diabetes called phenformin. We were taught not to use it for fear of lactic acidosis, which could be fatal, but to use the newer biguanide metformin instead. By the time I did any actual prescribing for type 2 diabetes, phenformin had disappeared, but some of its ill repute had rubbed off on metformin, which (incredibly) was not licensed for use in America until 1994. Observationally, metformin is the least bad drug to give to people with T2DM, with more favourable cardiovascular outcomes than its rivals and a rate of lactic acidosis indistinguishable from the base rate in diabetes. But its use in people with renal impairment is still hedged with cautions. This excellent review of the evidence suggests that in people with an eGFR above 30, metformin is the first choice drug for T2DM provided that regular monitoring is in place.

Arch Intern Med January 2015 Vol 175
OL One of the most positive developments in 2014 was the formation of an overdiagnosis group among UK general practitioners and their global friends, thanks to the tireless efforts of Margaret McCartney and Julian Treadwell. We must pool efforts to reverse the top-down, experts know best, do as you’re told model of primary care, which is poisoning patient centred medicine in Britain, and which has led to a deep crisis within general practice. This has to be based on better sharing of information with the people we serve. Screening is a classic example. People need to realise that detection is not prevention, and that what is detected as “pre-cancer” would most often never become cancer. Tammy Hoffmann and Chris Del Mar here provide a great resource in the form of a systematic review of Patients’ Expectations of the Benefits and Harms of Treatments, Screening, and Tests. “The majority of participants overestimated intervention benefit and underestimated harm. Clinicians should discuss accurate and balanced information about intervention benefits and harms with patients, providing the opportunity to develop realistic expectations and make informed decisions.” Give us the time and the tools, dear NHS, and we will finish the job. We might even save money, although this is the least of our concerns.

OL There used to be a joke doing the rounds in my junior doctor days about the local teaching hospital cardiologist: “What is the difference between a consultant cardiologist and God?”—pause for deep thought—”God is everywhere but Dr X is never here.” Cardiologists do indeed seem to have more conferences than other mortals. And a rather detailed study of the absent cardiologist effect suggests that this may be a good thing: “High-risk patients with heart failure and cardiac arrest hospitalized in teaching hospitals had lower 30-day mortality when admitted during dates of national cardiology meetings. High-risk patients with AMI admitted to teaching hospitals during meetings were less likely to receive PCI, without any mortality effect.”

OL A Research Letter gives the conclusions of a survey of cardiovascular trials published in December 2012. Doug Altman and colleagues find that fewer than 50% had been registered according to the definition of the International Committee of Medical Journal Editors. The studies that had been registered were larger and more likely to show strong methodological characteristics, but were less likely to report significant positive findings.

OL In my last review I mentioned the old laburnum extract called cytisine as a potentially cheap and useful drug to help smoking cessation. Its expensive derivative varenicline is widely used, but sometimes doesn’t seem to work at standard dosage. Here is a blinded dose escalation study to see if more would work better for those who were having trouble quitting. But: “Increasing varenicline dose in smokers with low response to the drug had no significant effect on tobacco withdrawal symptoms or smoking cessation.” Useful knowledge.

Lancet 3 January 2015 Vol 385
36 “Extensive stage” small cell lung cancer (ES-SCLC) is fatal, with a two year survival of 5%, unchanged for decades. Often it responds to chemotherapy for a few months, and this trial selected such patients and randomised them to receive either thoracic radiotherapy (30 Gy in ten fractions) or no thoracic radiotherapy. All underwent prophylactic cranial irradiation. This was aimed at prolonging life and reducing symptoms, not at curing, since by definition the disease had already spread beyond the thorax. In the first year, it made little difference to survival (33% v 28%), but by the end of the second year, survival was significantly higher in the irradiated group: 13% v 3%. The number needed to treat for one more person alive at two years was 10.9. But, as the editorial points out, decision making needs to be done at an individual level. Several high level people have spoken to me about decision making in cancer multi-disciplinary teams, and they are all concerned that the patient has little or no say while “group-think” will always favour the most aggressive option. This urgently needs to be studied—and changed.

43 “A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim one year analysis of clinical and procedural secondary outcomes from a randomised controlled trial.” How the world has longed for this trial! How deeply readers will regret that it is behind a paywall. Abbott Vascular funded the study and “was involved in study design, data collection, data analysis, data interpretation, and writing of this report.” They tell us that it was a draw: “The everolimus-eluting bioresorbable scaffold showed similar one year composite secondary clinical outcomes to the everolimus-eluting metallic stent.” But actually: “There were 17 (5%) major cardiac adverse events in the bioresorbable scaffold group compared with five (3%) events in the metallic stent group, with the most common adverse events being myocardial infarction (15 cases [4%] vs two cases [1%], respectively) and clinically indicated target-lesion revascularisation (four cases [1%] vs three cases [2%], respectively).” So, just four times as many MIs in the first year then. If I were a stentist, I wouldn’t go near these biodegradable things for a long time yet. And by the way, to be at all meaningful, those last percentages should have been 1.2% vs 1.8%.

The BMJ 3 January 2015 Vol 350
There are several things that go up in line with blood glucose, without respecting any threshold, and they include retinopathy, cardiovascular disease generally, and pancreatic cancer. So does that mean that pancreatic cancer is not “bad luck,” but yet another reason to blame people for their “unhealthy lifestyles”—to borrow terms from this week’s deeply unhelpful debate? For any individual, cancer is always “bad luck.” Even if you smoke 60 cigarettes a day, the chances are that you will not get lung cancer: you are just vastly more likely to than a non-smoker. For a lucid exploration of these issues, do read George Davey Smith’s masterly John Snow Lecture of 2011.  This paper shows that the contribution of blood sugar to the total burden of pancreatic cancer is actually quite hard to define, although the authors argue at length that “prediabetes” and “diabetes” must be preventable factors in the global increase in this malignancy, even after adjustment for obesity and smoking. I don’t know. Just one more reason to be active and not to get fat until retirement, I suppose. Though the most active person I’ve ever met got pancreatic cancer.

The Dutch are a practical nation, especially famous for controlling leakages in their water system. They randomized 287 women with symptomatic mild vaginal prolapse to pelvic floor exercises or watchful waiting. Using the validated Pelvic Floor Distress Inventory-20, they were unable to detect a difference between the groups at three months, but 57% of the intervention group reported an overall improvement in symptoms compared with 13% of controls.

Since I started making notes on the main medical journals in 1998, the number and quality of surgical trials has gone up impressively. But things could be a deal better. The study here looks at trials of surgical interventions that were registered five years ago. “One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks.” The accompanying editorial by John Ioannidis is called, “Clinical trials: what a waste.” You will not find a more succinct or damning summary of the subject: everybody needs to read this.

Three and a half years ago, I was astounded when Harlan Krumholz told me of his agreement with Medtronic to open up a sequence of trials on one of their products to independent inspection by two independent groups of analysts. In those days, data sharing was absolutely anathema to the whole of the medical-industrial complex. But the Yale Open Data Access programme went ahead, GlaxoSmithKline broke ranks in industry, Ben Goldacre’s Bad Pharma appeared, AllTrials gathered signatures by the ten thousand, and the European Medicines Agency said it would open up all files submitted to it by industry. Here is a fitting celebration of some of those who took part. I wish there had been room for a few more. While all this was happening, I kept thinking, “The dam is cracking” and then “The dam has burst!” But alas, data do not flow like water: they are a massy solid. One of the reasons that industry is now reconciled to data sharing may be that individual subject re-analysis is a time consuming and costly minority sport, involving great effort on the part of the analysts. There is little funding and there are few experts. There is no crowd out there clamouring to find out the real effects of the drugs we use on a daily basis in clinical practice. But there should be.

Fungus of the Week: Lepista saeva

We took our Christmas Day walk on a hill somewhere in North Wales. Note the wartime vagueness of this description: a fungus hunter never reveals his locations. It was an unkempt meadow occasionally visited by the odd horse or bullock. Here I was delighted to find a clump of field blewits. Unfortunately, my delight was but weakly shared by my fellow walkers, and I had little time to look for more. And when I had thoroughly dried them out, they politely declined my offer to cook them for the guests who were sharing lunch the next day.

This proved to be a mistake, because these guests had grown up in Nottinghamshire, in the days when these fungi were sometimes offered in street markets as “blue buttons” and their superb culinary attributes were well recognised. I once had an old patient who grew up 40 miles further north in Rotherham where 70 years ago they were known and sold as “bluestalks.” Some fungus guides call them blue legs. So I think you can guess their colour. The stems and gills are always tinged with blue, but the caps are typically brownish.

The field blewits are bigger and better than their relatives the wood blewits, purply-brown fungations that can often be found in abundance among leaf mould. But since meadows unaffected by constant cultivation and fungicide spraying are a rarity in modern Britain, so in consequence are field blewits. My Christmas joy at finding them was amply fulfilled when I ate them cooked with bacon and a little shallot, with a dash of cream and a sprinkling of parsley. All mushrooms are good done this way, but these were superb, with a meaty depth of flavour. I shall go back to that field next season, somewhere in North Wales.