Richard Lehman’s journal review—3 March 2014

richard_lehmanNEJM  27 Feb 2014  Vol 370
799    I’ve reached the age when people look back and sigh and cluck about the way the world has changed since they were children. In the 1950s, the world was actually a pretty nasty place, and at any moment the hydrogen bomb might bring it to an end. People with three copies of chromosome 21 were known as “mongols” and they were generally put in “homes” where they typically died before the age of 40. As medical students in the early 1970s, we had to be told to refer carefully to “Down’s syndrome” rather than mongolism. Amniocentesis in the second trimester was the only means of prenatal diagnosis. Since then, the means to detect and abort trisomic pregnancies have gradually improved, with chorionic villus sampling and nuchal thickness scanning, and various blood tests. I learn from this paper that they include first-trimester serum markers such as pregnancy-associated plasma protein A (PAPP-A) and free beta subunit or total human chorionic gonadotropin (hCG), and second-trimester serum markers such as maternal serum alpha-fetoprotein (MSAFP), hCG, unconjugated estriol, and inhibin. But at the same time, the lives of people with Down’s syndrome have become longer and happier, as they receive proper care and integration into society. So: to abort or not to abort? That is the question, and morally I think it has become more difficult. Technically, though, it has become a lot easier, with the coming of massively parallel sequencing of cell-free DNA (cfDNA testing) in maternal plasma. This US study shows that it is much less likely to throw up false positives for trisomy in low-risk pregnancies than conventional testing. But I don’t envy the parents who are faced with a positive result.

809   If grown-ups in the 1950s and 60s had not been so intent on building hydrogen bombs and having a space race, malaria could have been eliminated from the world. As it is, it is still the first diagnosis that health professionals think of when faced with a febrile child in many parts of the world, and in many cases treatment for malaria is still given blindly. But, say the authors of this Swiss study, “The advent of point-of-care rapid diagnostic tests for malaria presents healthcare providers with a new and daunting challenge: the need to determine the causes of febrile illness and the appropriate course of action when treating children who test negative for malaria.” They used a battery of tests to show that in febrile children in two community settings in Tanzania, 70.5% of the children had viral disease, 22.0% had bacterial disease, and 10.9% had parasitic disease. So in these kids, antimalarials would have a NNT of about 9 and antibiotics a NNT of 4-5. Small wonder that they are given out freely, if they are available. Testing will have to be very cheap and quick if it is to change this.

818   The late 1950s in China are remembered as a time of horror. Mao’s Great Leap Forward in agriculture resulted in mass starvation: recent estimates seem to agree on a figure of about 40 million deaths. A few days ago, I discovered the fact that in the last seven years over 2,000 Chinese babies and children have died from enterovirus 71 hand, foot, and mouth disease. Not a statistic that would have kept Mao awake at night. Modern China may not be perfect, but it is a mark of massive progress that people there are sufficiently concerned about a rare cause of childhood mortality to develop vaccines against enterovirus 71. There seem to be two of them, and they are both effective and safe, according to two phase 3 trials in children living in the “hand, foot, and mouth belt” of modern China.

JAMA 26 Feb 2014  Vol 311
806   The good news: the prevalence of obesity in the USA did not increase between 2011 and 2012. The bad news: the prevalence of obesity in the USA did not fall between 2011 and 2012. More than one-third of adults and 17% of youth in the United States are obese, and the prevalence of American obesity has not changed since 2002. America society is stably obesogenic.

815   American health costs are unsustainably high, and most Americans with multiple long-term conditions lack a single point of call for their healthcare. So the concept of “medical home” became widely touted as a way to coordinate care better and avoid unnecessary hospital admissions. Nice idea, shame about the results: “A multipayer medical home pilot … was associated with limited improvements in quality and was not associated with reductions in utilization of hospital, emergency department, or ambulatory care services or total costs over 3 years.

826   There is something magical in the mumps-measles-rubella vaccine. It seems that wherever it is given, it reduces infections generally for at least a year, leading to substantial falls in children’s mortality in places where childhood infections often kill. A study from Denmark seems to show the same phenomenon, though the analysis is very hard to follow. It shows that “In a cohort of Danish children, receipt of live MMR vs inactivated DTaP-IPV-Hib as the most recent vaccine was associated with a lower rate of hospital admissions for any infections.” The weirdest thing in this study, as in some others, is that the protective effect of MMR vaccine against other infections seems to be cancelled out if you have another vaccine afterwards.

Lancet  1 March 2014  Vol 383
785   Big epidemiology is often enigmatic. The innumerable authors of this paper looked at 22 European cohort studies and “assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2•5 μm (PM2•5), less than 10 μm (PM10), and between 10 μm and 2•5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models.” So back off, simple reader, if you are not up to speed with land use regression models. Studies of this kind are there to be believed, not understood. And they find that long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. Ah yes, you mutter, cardiovascular disease and all that. But no: strangely enough they find no significant association between particulate air pollution and CVD in Europe, as opposed to most other places in the world. Can that really be true? “Well, if you don’t believe it, you can go through the data yourself,” I can hear the authors respond.

796   The female pelvic floor is a frequent source of trouble, especially for those who have undergone the indignities of childbirth and are approaching the indignities of old age. The British POPPY trial attempted to assess the effect of pelvic floor exercises for reducing the symptoms of prolapse: women received one-to-one instruction and support from a physiotherapist, and the primary endpoint was participants’ self-report of prolapse symptoms at 12 months. You can argue about the meaning of symptom scores in this context, but perhaps the most impressive objective outcome was a halving in the rate of surgical referral in the intervention group.

807   The acronym of the next trial was MERTH, which would be the reaction if anyone asked me last week to tell them all I know about melioidosis. But for your sake, dear reader, I have looked it up in Wikipedia and read this paper. Melioidosis is an infection that you risk if you happen to mess about with the soil of places like northern Australia or Thailand. The case-fatality rate in the latter country is 43%, showing that Burkholderia pseudomallei, a gram-negative soil bacterium, is a bug that you need to diagnose and kill as quickly as you can. The latter is done initially with parenteral antibiotics such as ceftazidine or meropenem, but this needs to be followed up with at least three months of oral antibiotics. That’s where this trial came in: it aimed to determine whether you need to add minocycline to trimethoprim-sulfamethoxazole in order to prevent long-term relapses of melioidosis. It shows that you can safely omit the minocycline and so get a higher rate of treatment adherence.

OL   A European observational study finds that higher nurse-to-patient ratios, and higher levels of nurse training, are associated with lower rates of hospital mortality. “These associations imply that patients in hospitals in which 60% of nurses had bachelor’s degrees and nurses cared for an average of six patients would have almost 30% lower mortality than patients in hospitals in which only 30% of nurses had bachelor’s degrees and nurses cared for an average of eight patients.” Hmmm. Discuss in your next seminar on evidence-based health policy.

BMJ  1 Mar 2014  Vol 348
Thanks to this research from Ontario, we know that between 2003 and 2010, 49.2% of post-surgical patients aged 66 or older were discharged from hospital with an opioid prescription, and 3.1% continued to receive opioids for more than 90 days after surgery. Compared with other hospitals and other populations, is this good, bad, or average? What were the opioids in question? Et cetera. An odd study to sit without context in the pages of the BMJ.

Even odder is the BMJ‘s choice of a paper showing that US Medicare recipients can obtain opioids from a variety of different medical providers if they so wish. Yup, that’s the way it is over there.

I have no idea whether or not I have localized prostate cancer, and I would like it to remain that way. With or without PSA, diagnosis is a lottery, and so, to some extent, is treatment. The only risk measure to have stood the test of time, once the diagnosis has been made, seems to be the Gleason index. At least that’s the way I read it. It’s a hugely complicated field, and this paper‘s greatest value, for me, lies in its summary of the existing observational evidence relating to the treatment of localized prostate cancer. If cancer-specific survival is your main aim (and I don’t really understand why it should be) then go for radical surgery if you are relatively young and fit. On the other hand, by going that way you run the greatest risk of  impotence and incontinence. That’s not something these investigators measured. Nor did they compare the results of watchful waiting. Their main comparator was radiotherapy, which gives less good results for cancer-specific death, unless it has already metastasized. So are you clear now how you should advise your patient? Me neither.

Plant of the Week: Corylus maxima “Red Zellernus”

This the time of catkins, hanging in pretty dangles of straw yellow from every hazel in the hedgerows and woods of England. My rather ancient copy of the Shorter Oxford English Dictionary tells me that the word catkin derives from the Dutch katteken; which is all very well, but why should Englishmen use the Dutch word for a little cat to describe “a unisexual inflorescence, consisting of rows of apetalous flowers ranged in circles along a slender stalk; the whole forming a cylindrical, downy-looking, usu. pendant spike; an amentum?”

Well, catkins they shall ever be for the children of these dampy islands, bringing memories of school nature walks in the sleety wind, to be followed by pussy willows and frog spawn and the Easter holidays.

Occasionally my eye is caught by trees bearing pink or purple catkins. These are so desirable. The nearest we come to possessing one of our own is a common purple hazel bush which we have moved and maltreated over the years. But at Bluebell Nursery, where Bob Vernon has spent decades introducing the best and rarest trees and shrubs to England, you can buy the showiest of the native hazel varieties for catkin splendour. The one he recommends is called “Red Zellernus,” which will give you a reliable crop of nuts as well. Actually this is just a misspelling derived from rote Zellernuss, the German for red hazelnut.

Bob’s catalogue also illustrates a Turkish hazelnut with longer, pinker catkins, Corylus colurnus “Te Terra Red.” And for the ultimate purple catkin experience, he used to offer Garrya elliptica “Burgundy Wine”, but it proved very hard to propagate and very miffy. After killing it twice, I did not dare to return for a third plant. A pity: a garrya with handsome winter leaves of purple and covered with purple catkins might be quite a sight.