Newborn babies feature in Richard’s blog this week, as he finds out how extremely premature babies fare with modern neonatal care, and how a baby’s weight in its first three months can affect its weight in the future. Tuberculosis and chronic obstructive pulmonary disease are among the other things that Richard tells us about, as well, of course, as recommending a plant of the week.
JAMA 3 Jun 2009 Vol 301
Depression is both an inherited trait and a learnt behaviour, and for centuries it was quite prized in the young, as a disincentive to frivolous behaviour and a sign of a religious or philosophical disposition. As Oliver Edwards said to the notoriously depressive Samuel Johnson around 1760, “You are a philosopher, Dr Johnson. I have tried too in my time to be a philosopher; but, I don’t know how, cheerfulness was always breaking in.” The adolescent children of depressive parents are at high risk of developing depression, and this interesting study sought to discover if that can be prevented by teaching cheerfulness – i.e. cognitive therapy. The comparator was our false friend “usual care”, but at least the investigators here apologize for that in their commentary section. What they find is that CB works well in preventing depression in these vulnerable youths unless a parent has active depressive illness, in which case it avails little.
Extremely premature birth is defined as birth before 27 weeks’ gestation. This Swedish study shows how these tiny babies fare with modern intensive neonatal care. Survival at 22 weeks is almost 10%, rising to 85% at 26 weeks.
Babies who get fat in the first three months of life are more likely to become fat, insulin resistant young adults with bad lipid profiles. So it would seem (with wide confidence intervals) from this Dutch cohort of 217 healthy participants now aged 18 to 24 years. It may be that this is a risk factor which is modifiable by giving babies less food than they demand, but it would be a tough study to carry out and we would need to wait about 60 years for some hard outcomes. So my advice to mothers and health visitors would be: don’t weigh babies without good reason, and feed them when they are hungry.
NEJM 4 Jun 2009 Vol 360
The arrival of a new antimicrobial drug is always an occasion for celebration, especially when it is one that was found by good old-fashioned chance and experiment rather than the sort of high tech molecular targeting which none of us could do in our garden shed. The diarylquinolone TMC207 was found to be active – very active indeed, in fact – against Mycobacterium tuberculosis after experiments performed on M smegmatis. So all you need are some agar plates, an incubator, and a supply of whatever it is that gives this mycobacterium its name. If this agent lives up to its early promise, it could be a valuable addition to the weaponry against multidrug-resistant tuberculosis.
In the later nineteenth century, lean writers like Chekhov and Robert Louis Stevenson coughed up blood politely into their handkerchiefs as they travelled across Europe in railway carriages seeking a cure for their tuberculosis. As the same time, the United States of America received millions of the poor and dispossessed of Europe, many of whom had active TB. Quarantine stations began to be set up, the most famous of which was Ellis Island, where immigrants could be kept isolated for months. The word quarantine, by the way, derives from the Italian word for forty, the number of days that the seventeenth century Venetian authorities decreed a ship that might be carrying plague should wait anchored in the Lagoon. Nowadays America is a lot harder to get into, but immigrants and refugees – especially the latter – still account for more than half of the active TB in the US. The solution vigorously advocated in this paper is overseas screening (and treatment) by designated local doctors before entry to the States. It certainly works, but there are no data about what happened to the refugees while they were forced to postpone their flight to freedom.
Chronic obstructive pulmonary disease is, well, chronic, obstructive (partly, anyway), and pulmonary. You tell people to stop smoking, immunize them against influenza and pneumococcus, and give them mucolytics, bronchodilators and antibiotics as required. It’s the fourth commonest cause of death in industrialized nations and might get to number 3 if current tobacco promotion policies prevail. It’s hard to say anything else useful about COPD, but this article on its immunology at least says things that are interesting. It goes in detail through all the damaging things that build up in smokers’ phlegm and also speculates on why many smokers nonetheless manage to avoid getting COPD – it may all depend on T-cell regulation.
Lancet 6 Jun 2009 Vol 373
Gradually, if all goes well, we are going to reach a situation in which most cervical cancer is prevented by polyvalent human papillomavirus vaccination and women only need be screened twice in a lifetime. We are by no means there yet, and this trial of a quadrivalent HPV vaccine shows some of the difficulties. The per-protocol success rate in women aged 24-45 was 90%, but taking a more real-life intention-to-treat analysis, this falls to 31% for preventing persistent new infection within 26 months. And this study tells us nothing about the duration of immunity. For a good analysis of where we stand at the moment, read the accompanying editorial on p.1921.
Every month, somebody sends me a magazine called “Guidelines”, and once or twice a year (I can’t remember, because I always give it away) I get a fat little Compendium of Guidelines as well. And then there are the NICE guidelines, which form a weighty dust-covered green heap on a consulting room shelf. My computer is loaded with lots more guidelines. The practice generates its own guidelines too. When I am dying, people will treat me according to end-of-life guidelines, and at my funeral they will sing “Guide me, O thou great Jehovah”. Until that day, I will continue to rail against guidelines, which are always a mixture of evidence and “expert opinion” and are out of date before the ink is dry on their innumerable pages and appendices. This preambulatory rant leads us to the study in question (CLOTS trial 1), which examines the RCP and SIGN guideline recommendation that all patients suffering from immobility due to acute stroke should be made to wear thigh length graduated compression stockings. Well, they shouldn’t. These stockings increase the incidence of skin breaks, ulcers, blisters and necrosis and do nothing to reduce deep vein thrombosis after stroke.
An excellent seminar on neurofibromatosis type 2 gives you a chance to know everything about it if you happen to have a patient or family with the condition – it occurs in one in 25 000 live births and is inherited as an autosomal dominant with almost 100% penetrance by the age of 60. It has a genetic locus called NF2. That’s the kind of genetics I can remember. It usually presents with hearing loss in young adulthood due to vestibular schwannoma. The other common manifestations are meningiomas and ependymomas. Enough about NF2: what are the other neurofibromatoses? There’s NF1, formerly called von Recklinghausen’s disease or peripheral neurofibromatosis – that’s the commonest kind, formally separated from NF2 only as recently as 1987. The third kind is still called schwannomatosis.
BMJ 6 Jun 2009 Vol 338
Writing about cancer screening in these columns, I’ve tended to adopt the wearily sceptical tone of a GP who deals the daily burden of anxiety brought on by “abnormal” mammograms, CIN3 of the cervix, high PSAs and so forth, but I was put on my mettle last year when the greatest figure in the field, Martin Vessey FRS, wrote to chide me gently for my blindness to the population benefits of screening. Knowing that MV may be reading this, I shall try to look at this study of flexible sigmoidoscopy for the prevention of colorectal carcinoma from his position as chairman of a national screening committee. What we want, of course, is to reduce the increasing mortality burden of this common cancer in the general population. There may be preventive measures – reducing red meat consumption, perhaps, or banning barbecues, or encouraging the use of NSAIDs, but these are not serious propositions for the moment. The main screening options are testing for occult blood in stool samples (the currently preferred strategy), universal one-time sigmoidoscopy, or universal one-time colonoscopy. At first sight, this Norwegian trial is a flop: “a reduction in incidence of colorectal cancer screening with flexible sigmoidoscopy could not be shown after 7 years’ follow-up.” The accompanying editorial (p.1339) on the other hand hails the trial as “suggesting that the intervention may be effective in reducing mortality from colorectal cancer”. Both ineffective and effective: it all depends on which data you choose to look at. The trial does show a definite large decrease in cancers for those who turned up for the investigation, diluted out if you look at intention-to-treat (I.e. all those invited): so if people could be persuaded to turn up in large numbers to have a tube up their bottoms, this might work. I see a difficult advertising campaign ahead.
“QOF for diabetes: can Practices and Patients both be Winners?” is the title of a short lecture I shall be giving in Birmingham and London next week. Tickets are changing hands for astronomical sums. This analysis of the effect of the introduction QOF on diabetic outcomes could not have come at a better time for me. The presentation is a bit obscure and the printed version omits the key table, but the message is clear: the coming of QOF slowed down the improvement in targets such as HbA1c , blood pressure and cholesterol. “The surprising and important message is that left to themselves, doctors tend to pursue good clinical practice for the benefit of their patients, while if made to jump through hoops for money, they will jump the hoops and leave it at that,” as I shall be telling my audience.
Ann Intern Med 2 Jun 2009 Vol 150
How likely are you, a non-diabetic adult aged between 45 and 64, to cross the magic threshold of fasting blood sugar and become a fully paid-up type 2 diabetic? This study validates a new risk score based on glucose, waist circumference, triglycerides, maternal diabetes, black race, paternal diabetes, LDL-cholesterol, short stature, uric acid, age over 55, hypertension, rapid pulse and non-use of alcohol. It’s pretty good. Get searching your computer, download this paper (it’s free), find those high-risk patients and call them in for exercise and weight reduction before they reach 7 mmol/L fasting glucose.
Or should we be looking to reduce their levels of aldosterone? I’ve been interested in this hormone for many years since it became clear that it plays a key role in heart failure and resistant hypertension. This intriguing review looks at its role in the so-called metabolic syndrome as well, which is a conglomeration of risk factors often associated with the later development of diabetes. Blocking aldosterone can improve pancreatic insulin secretion, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation. It looks as if we might be giving our pre-diabetic and diabetic patients a lot more spironolactone and eplerenone in the future.
Plant of the Week: Parahebe catarractae
Not a shrub, not a perennial, not an alpine: this invaluable little space-filler is often described as a sub-shrub, a mass of wiry stems covered in attractive small evergreen leaves and small fragrant white flowers veined with violet throughout the summer. There are mauve-purple sorts which are best avoided. If you want something entirely trouble-free to cover an edge or tumble over a stone all year round, this is the thing. But it does need sun, and you need to lift it off the ground from time to time to destroy any infant gastropods that it might be providing asylum to.