Richard Lehman’s journal review—28 April 2014

richard_lehmanNEJM  24 Apr 2014  Vol 370
1583   The New England Journal has put so many good articles online first lately that I’ve left myself with thin pickings this week. This big French study of blood pressure targets in septic shock has been on the website for some weeks, and I didn’t comment on it sooner because I have only ever treated a single patient for septic shock in my working life. At the time I was a house officer on a urology ward. Despite my best efforts over a day and a night, he survived. Physiological emergencies cause a flow of adrenaline: there is an urge to do everything possible. A mean blood pressure of 65mm Hg doesn’t seem enough to keep anyone’s kidneys working, so this trial used adrenaline (epinephrine) or noradrenaline to push it up to a target of 80 or 85 in the intervention group. But these patients did no better than those whose BPs stayed at 65 or 70.

JAMA  23/30 Apr 2014  Vol 311
1622   Reading this week’s JAMA makes me think we need better outcomes research in stroke medicine. Two papers in this neurology-themed issue are devoted to systems changes aimed at reducing event-to-needle times for stroke; i.e. shortening the time between the actual event and the moment when tissue plasminogen activator reaches the cerebral circulation.  One moment the leather-clad young RAF pilots are lounging in the sunshine drinking tea and smoking their pipes: the next  moment the siren sounds and they are racing to their Spitfires to shoot down bandits. Never did so many owe so much to so few. But is this really true of crash teams for stroke? In this PHANTOM-S trial, ambulances in Berlin were set up with their own CT scanners, at a cost of a million euros each, and manned by teams trained to give tPA. Berliners giving a history suggesting Schlaganfall would rapidly hear the siren of an approaching Ambulanz; they would be whisked into the scanner; images would be relayed to waiting radiologists; and if there was clot, the tPA would go in before the vehicle reached the hospital door. This happened some weeks and not others. In the active weeks, alarm-to-treatment time was reduced by 25 minutes. Although the trial went on for 18 months and covered a catchment of 1.3 million people, it could not demonstrate any improvement in mortality. Never did so few owe so little to so many?

1632   Meanwhile in the USA Gregg Fonarow and colleagues were trying out a new in-hospital protocol for reducing door-to-needle time in ischaemic stroke. All Get With The Guidelines (GWTG)—Stroke hospitals were encouraged to participate and each hospital received a detailed tool kit, including the 10 key strategies, protocols, stroke screening tools, order sets, algorithms, time trackers, patient education materials, and other tools. This massive effort across more than a thousand hospitals resulted in a reduction of median door-to-needle time from 77 to 67 minutes, and was associated with a before-and-after reduction in all-cause in-hospital mortality from 9.93% to 8.25%, and a rise of 5% in the number of patients discharged to their own homes. Note that we cannot know how much of this was due to any part of this complex intervention.

1652   A randomized trial comparing intravenous lorazepam with intravenous diazepam for paediatric status epilepticus reminds me of another once-in-a-career experience I had with a nine year-old boy back in the heroic days of general practice. After some minutes of fighting on the floor carpet, I managed to get diazepam into a vein. Nowadays I believe there are buccal and intranasal benzodiazepines to allow the more dignified termination of fits. But this was an in-hospital study, so IV was the standard: and there was no difference between the two agents.

1661   About a year ago, I was alarmed to read a population screening study in Shanghai showing that 6% of the population had unruptured arteriovenous malformations in their brains. My advice at the time was not to go near a brain vessel scanner unless you had very good reason to. This Scottish study proves me correct. “Among patients aged 16 years or older diagnosed as having unruptured bAVM, use of conservative management compared with intervention was associated with better clinical outcomes for up to 12 years. Longer follow-up is required to understand whether this association persists.” In other words, you are much better off not knowing about it.

JAMA  Intern Med  April 2014  Vol 174
OL   With all bad forms of screening, there is a “gratitude paradox” which Lisa Schwarz and Steve Woloshin have described very well. You get the fright of your life; it turns out to be a false alarm; but you are grateful nonetheless, saying “just think, it could have been a cancer, so I’m really lucky.” This study of women’s attitudes following false-positive mammograms provides a classic example: ” False-positive mammograms were associated with increased short-term anxiety but not long-term anxiety, and there was no measurable health utility decrement. False-positive mammograms increased women’s intention to undergo future breast cancer screening and did not increase their stated willingness to travel to avoid a false-positive result.”

OL   Since taking a statin, I have got fatter. I am part of a trend, according to an analysis of data from the National Health and Nutrition Examination Survey, 1999 through 2010 (N.B. I’m keeping the American “through” here because it is a useful construction). “Caloric and fat intake have increased among statin users over time, which was not true for nonusers. The increase in BMI was faster for statin users than for nonusers.” So far, so incontestable: this was a thoroughly conducted survey. But now for the speculation: “Efforts aimed at dietary control among statin users may be becoming less intensive. The importance of dietary composition may need to be reemphasized for statin users.” We’ve no idea whether this is actually true of this population, let alone individuals within it. It certainly isn’t true for me. I’ve always just eaten what I enjoy: I just need more exercise.

Lancet  26 Apr 2014  Vol 383
1465    The northern Slavonic nations have been drinking vodka for about 1200 years. In the three Russian cities of Barnaul, Byisk, and Tomsk the lure of daily alcoholic oblivion seems to be pretty strong. This in turn leads to permanent oblivion. This is described in a sad study, which took vodka-drinking histories from 200 000 adults in these cities during 1999—2008. Most people there smoke, and vodka-drinking is low amongst non-smokers. Among 57 361 male smokers with no previous disease, the estimated 20-year risks of death at ages 35—54 years were 16% for those who reported consuming less than a bottle of vodka per week at baseline, 20% for those consuming 1—2•9 bottles per week, and 35% for those consuming three or more bottles per week. Lessons: if you live in Barnaul, Byisk, or Tomsk, get out; if you are a smoker, stop; and if you drink three bottles of Russian vodka a week, switch to one bottle of Polish vodka, sipped straight from the freezer: it is so much nicer.

1483   The European Surgery in Ectopic Pregnancy (ESEP) study group can disband: they have done their job. This was to find out if there was any advantage in salpingotomy over salpingectomy for ectopic pregnancy. It seems obvious that surgery that preserves the Fallopian tube (salpingotomy) will give mothers a better chance of successful pregnancy in the future. But that is simply not the case: “in women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy.”

OL   The foundation stone of modern evidence synthesis was Iain Chalmers’ work on neonatal outcomes, but midwifery continues to be rife with mythology. Mothers, not unnaturally, want to hold their new born baby rather than watch somebody else hold it for a minute at the level of their vagina. But there is a widespread belief that delayed clamping of the cord can only be safe if the cord is not lifted above the birth canal. Obstetricians in three Argentinian hospitals put this to the test. They conclude that “position of the newborn baby before cord clamping does not seem to affect volume of placental transfusion. Mothers could safely be allowed to hold their baby on their abdomen or chest.” Then mothers can cry out “Oh, you’re so beautiful!”—though this is something to do with oxytocin and never, in my experience, actually the case.

BMJ  26 Apr 2014  Vol 348
Two studies in the BMJ this week address the thorny issue of whether the overseas entry exams run by the Professional and Linguistic Assessments Board assure the same level of competence as the examinations required of UK graduates. The answer, as you will all know from media coverage, is a resounding no. The authors of the first study attempt a polite British compromise in their conclusion: ” PLAB is a valid assessment of medical knowledge and clinical skills, correlating well with performance at MRCP(UK) and MRCGP. PLAB graduates’ knowledge and skills at MRCP(UK) and MRCGP are over one standard deviation below those of UK graduates.” So it’s a valid assessment, but it lets too many people through, and so is not fit for purpose. I wonder how long it will take us polite Britons to sort out this uncomfortable situation.

A study from Sweden reminds us that men over 60 with a prostate specific antigen level below 1 are most unlikely ever to die of prostate cancer. Men over 60 with a PSA over 2 are less likely to die of prostate cancer if they undergo regular screening. So PSA screening is a good thing? If you particularly fear death from prostate cancer, yes, provided you realize you stand a greater chance of unnecessary treatment than of treatment that will lengthen your life. But the alternative to dying from prostate cancer is not happy immortality, but dying of something which may well be just as nasty. Discuss this with your GP, say the investigators. Thanks.

Another BMJ, another systematic review. I am not complaining: in fact I now even have a small role in the UK Cochrane Collaboration, so part of my job is to encourage people to meta-analyze to their hearts’ content, provided they follow our handbook. This review looks at the effectiveness of screening sigmoidoscopy and screening colonoscopy in the prevention of colorectal cancer occurrence and deaths. Here is a form of screening that even I can support—unlike faecal occult blood screening, I might add. “Compelling and consistent evidence from randomised controlled trials and observational studies suggests that screening sigmoidoscopy and screening colonoscopy prevent most deaths from distal colorectal cancer.” Forget the smears of poo on bits of cardboard—cut straight to the scope.

Plant of the Week: Paeonia mlokosewitchii

Some plants flower gloriously for one day after 100 years, emitting a terrible stench overnight, and then die. So we should not resent the odd plant in our garden that flowers for just a few days each year with great beauty but little scent, and grows steadily over a whole human lifetime. Two that nobody should be without are the little spring-flowering Sanguinaria canadensis, which has just had its few days of dazzling white glory, and the much larger peony species from the Caucasus which bears the mangled name of the Polish botanist Ludwik Młokosewicz.

There is something about the papery lemon-yellow flowers of this plant that makes us go weak at the knees whenever we see it. They have a faint grassy scent. When the sun shines through these petals, it produces a light like nothing else on earth. Plants used to be very hard to come by, but we now have three. One of them was grown from seed, and has flowers in which the pure yellow is contaminated with intrusions of pink. It lacks the magic of the true species but is very attractive in its own right. The flowers of these plants last a few days each—less in a rainy week. But their leaves consist of lobes of soft green which stay attractive until the autumn; and each time you go by, you think of how many flowers you might swoon over the next season.