Richard Lehman’s journal review—23 February 2015

richard_lehmanNEJM 19 Feb 2015 Vol 372
703 In our syphilis lecture at medical school we were told that immigrants coming to the United States of America in bygone days were quarantined on Staten Island and had to undergo testing for Treponema pallidum using the Wassermann Reaction. An unlucky few would test positive not because they had venereal syphilis but because they had yaws, an infectious disease caused by Treponema pallidum subspecies pertenue. I don’t think I have given yaws another thought in the intervening 42 years, but I now learn that it is still very much around in 12 countries in Africa, Asia, and the western Pacific region. It is transmitted by direct skin-to-skin, nonsexual contact and causes a chronic, relapsing disease that is characterized by highly contagious primary and secondary cutaneous lesions and by noncontagious tertiary destructive lesions of the bones. It mostly affects children: hence this trial of single-dose azithromycin in children under the age of 15 on a Papua New Guinean island on which yaws was endemic. Its prevalence dropped steeply and there was no sign of emerging macrolide resistance in the little treponemes.

711 Like all mammals, humans have their own special brood of papillomaviruses which usually just doze about on the skin surface, maybe causing the odd wart now and again. But a few of them have become specialized at travelling by means of sexual intercourse and at causing oncogenic changes, especially in women. At present we use a quadrivalent HPV vaccine to cover the main culprits, but better protection is afforded by a new 9-valent vaccine, according to this industry funded trial. This is bound to be followed by a marketing campaign: Merck my words. (N.B. Merck spends $7.5B on R&D and $9.5B a year on marketing, which is quite a virtuous balance compared with some other companies).

735 Of course the biggest win for a pharmaceutical company is to take an old cheap drug with a known safety profile and sell it in a new formulation for a new indication. Pierre Fabre Dermatologie—a French manufacturer of skin products, in case you wondered—spotted its chance when paediatricians started using propranolol to speed the resolution of infantile haemangiomas. Bring on Hemangiol, a nice formulation of propranolol for the paediatric market. And here is the trial showing that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile haemangioma, funded by Pierre Fabre Dermatologie. I’m afraid my limited internet access prevents me from finding out how the price of Hemangiol compares with generic propranolol.

JAMA 17 Feb 2015 Vol 313

663 I once sat through a presentation by a Dutch medical entrepreneur in which we were shown the continuous monitoring environment of the future, in which every object around us would tell us about our physiology on a second-by-second basis. Either he had a very dry sense of humour, or he actually wanted this to happen. I think he was wearing some stupid kind of watch which monitors his heart rate, BP, and perhaps arterial oxygen saturation. He looks forward to the day when his lavatory will tell him all sorts of things about his urine and stools. Bring it on. John Ioannidis writes about this burgeoning world of “stealth research” in biomedicine, which is fed on hype, and completely bypasses the truth-seeking, time-consuming processes of real science. As they sow, so let them reap. May they know the exact content of their stools. I prefer my watch just to tell me the time, and to keep a good book handy in the lavatory.

677 Why does community-acquired pneumonia still kill people? I used to see it all the time and hardly sent anyone to hospital: but now and again a person would go downhill rapidly. In the days when post-mortem was routine, many people who died from septic shock following pneumonia were found to have infarcted adrenal glands. Why the adrenals? I am wallowing in my own ignorance here, but I do find it interesting that this Spanish ICU study found that giving intravenous methylprednisolone to people with pneumonia and C-reactive protein levels over 150 led to better survival rates than in a placebo (i.e. non-steroid) group. I must emphasize that these were very sick, hospitalized patients and not your everyday chest infection cases in general practice: don’t try this one at home.

687 Whatever helps people to stop inhaling the combustion products of tobacco is good. Of the non-nicotine aids, varenicline has become the most popular, though it’s probably no better than cheap old-fashioned cytisine. In the NHS, there is whole weird structure of smoking cessation theology that GPs are supposed to follow in order to spare the NHS the costs of long-term treatment. I’m not even sure the rules would allow you to carry out the successful strategy of this trial: “Among cigarette smokers not willing or able to quit within the next month but willing to reduce cigarette consumption and make a quit attempt at 3 months, use of varenicline for 24 weeks compared with placebo significantly increased smoking cessation rates at the end of treatment, and also at 1 year. Varenicline offers a treatment option for smokers whose needs are not addressed by clinical guidelines recommending abrupt smoking cessation.”

707 I like it when large observational datasets confirm that what happened in randomized controlled trials actually happens in the hurly-burly of real life practice. The Swedish web system for enhancement and development of evidence based care in heart disease evaluated according to recommended therapies (SWEDEHEART—love it—I shall seek out a swede that is shaped like a heart) registry holds records from 40 616 consecutive patients with NSTEMI who received fondaparinux or low molecular weight heparin between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010. And just as in the OASIS-5 trial, “fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.

JAMA Intern Med Feb 2015
OL A small trial finds that “mindfulness” helps sleep quality in the over-55s more than a traditional routine of “sleep hygiene.” Like all forms of meditation, it is supposed to make you a better person too. Some day soon, in the interests of the lovely one I live and sleep with, I must find out what it is.

OL If you revisit John Yudkin’s Ten Commandments, you will see that the last of them reads “Honour thy elderly patient, for although this is where the greatest levels of risk reside, so do the greatest hazards of many treatments.” Here is a study to prove it. A total of 1127 women and men older than 80 years living in nursing homes in France and Italy were recruited, examined, and monitored for 2 years. Among these, people receiving two or more blood pressure lowering drugs and running systolic BPs of 130 and below were 80% more likely to die during the period of the study. Do not dishonour thy elderly patients by poisoning them with pointless and hazardous medication. And remember that people in nursing homes are at greatest risk, because they are constantly fed with medicines that they might otherwise forget to take, or have the good sense to stop taking.

Ann Intern Med 17 Feb 2015 Vol 162
241 Fusobacterium necrophorum—the death-bearing spindle-shaped rod. What a magnificent name for a microbe. I first heard of it when a colleague became very ill following a sore throat and spent some weeks in hospital. I think she had Lemierre’s syndrome, though the diagnosis was never considered. That is a rare condition where the anaerobic fusobacteria track down and cause havoc to the airway and the lungs. But in fact these germs are commoner in the upper airway than streptococci. In students at the University of Alabama, Birmingham, Fusobacterium necrophorum was detected in 20.5% of patients with sore throat and 9.4% of asymptomatic students. Group A β-hemolytic streptococcus was detected in 10.3% of patients and 1.1% of asymptomatic students. Group C/G β-hemolytic streptococcus was detected in 9.0% of patients and 3.9% of asymptomatic students. Mycoplasma pneumoniae was detected in 1.9% of patients and 0 asymptomatic students.

Lancet 21 Feb 2015 Vol 385
OL When mammographic screening for the early detection of breast cancer was introduced in the UK, its benefits were deliberately talked up to maximize uptake. I won’t rehearse the whole sorry tale because it is so well known to those of us who deplore the harms of screening, which in this case almost certainly outweigh any benefit. An Australian trial compared the effect on “informed choice” of an information package that included information about the harms of overdiagnosis with one that did not. When conceptual knowledge alone was considered, 203 (50%) of 409 women in the intervention group made an informed choice compared with 79 (19%) of 408 in the control group. But an excellent editorial—sadly behind a paywall—points out that conceptual knowledge is far from enough. “Many women will probably trust that an invitation from health authorities strongly indicates that the intervention is worthwhile. This assumption is emphasised by widespread use of prebooked appointments (versus opt-in alternatives), which short-circuit the decision process by indicating a seemingly correct and expected choice. Furthermore, the harms of screening receive little attention in media coverage whereas advantages are typically portrayed through case studies of women and celebrities who claim to have benefited from screening, although the value is effectively impossible to measure for any particular individual.”

BMJ 21 Feb 2015 Vol 350
Time, understanding, human contact, kindness. When I realized that I could offer less and less of these to my patients, I longed to give up general practice. In the years before I left, we were ordered to apply a “depression screening tool” to every patient with a “chronic condition” and then do something about it. The local waiting time for psychological treatment was in excess of 6 months. I could remember a time when I scarcely ever referred anyone for psychological treatment: I would set aside a long session with them and see them afterwards as often as it took. The impossibility of doing this in modern primary care has spawned all sorts of strange solutions, divorced from the complex reality of individual lives lived through years of endurance and decline. In the Manchester COINCIDE trial they tried an intervention that used psychological wellbeing practitioners who had five days of training and saw people for a total of about 4-5 hours in total. The patients were those with diabetes and/or heart disease of mean age 58.5 who scored high on a depression scale. Despite this “brief, low-intensity” (actually protracted, high-intensity) input plus a support team and a workbook for patients, the trial failed to achieve the prespecified level of improvement in depressive symptoms compared with usual care. But The BMJ allows the authors to paint it as a positive result. Ah me, is this the future of primary care?

How about actually listening to patients? I think Rosamund Snow has got off to a brilliant start with her “What your patient is thinking” series. The first article remains the top hit on The BMJ website, and this week’s contribution comes from my Cochrane UK colleague Sarah Chapman, whose weekly blogs on our Evidently website should not be missed. In this article she braces herself to have a cervical smear, knowing she won’t hear a quarter of what the practice nurse is saying to her. Although she has worn a hearing aid for decades, it came as a beautiful shock to her when someone finally asked her “How can I help you hear?”

Plant of the Week: Citrus x aurantium

This used to be the marmalade making season in England. Seville oranges, with their thick pectin-rich peel and bitter flesh, used to be sold by the stone, then peeled and boiled with sugar in an annual ritual which I seem to remember involved putting a lot of old jam-jars in the oven and the copious use of muslin cloth.

There are 40,000 orange trees in Seville and they are a lovely thing to see, almost every one happily decorated with fruit in the middle of February. With the decline of British marmalade making, most of them end up being pulped for compost. When we revisit Seville—an adorable city—we will try and make sure it is at a time of year when the trees are in flower: their scent must be indescribably wonderful.

It is not altogether clear how these oranges came to dominate Seville. I am inclined to credit the Arabs, whose peaceful tolerant rule for centuries in Andalusia was one of the very few instances of sustained beneficence in history. Citrus fruits are widely distributed around the Middle and Far East, and molecular biology has revealed that all modern cultivated Citrus may be derived from as few as three or four ancestral species. Only three domesticated citrus fruits, the citron, pomelo and mandarin are not hybrids. The Seville orange is a hybrid between Citrus maxima (pomelo) which comes from South East Asia and Citrus reticulata (mandarin) which comes from even further east. I guess it is just possible that Muslim traders might have got that far to bring them back before the awful centuries of Christian rule that so thoroughly blighted Spain.