Richard Lehman’s journal review—25 September 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM  21 Sep 2017  Vol 377

Good work, Roux-en-Y

Last week, an analysis article in The BMJ pointed out that in type 2 diabetes, weight loss of 15kg often produces biochemical remission. However, maintaining this degree of weight loss is very difficult—except following bariatric surgery, which got little mention. In the 12-year follow up study reported here, Roux-en-Y gastric bypass surgery in very obese people produced a mean weight loss of 45 kg. Three-quarters of patients who were classed as diabetic were no longer so at 2 years, though by 12 years the figure had dropped to 51%. The 12-year incidence of type 2 diabetes was 3% in the surgery group, as compared with 26% in the non-surgery group. Results of surgery in the diabetic population were much better if patients were not taking insulin, supporting the idea that it needs to be done before beta-cell failure is too far advanced.

Genetics and pre-term birth

For those of you who enjoy seeing full-on genomic science in action, this paper on Genetic Associations with Gestational Duration and Spontaneous Preterm Birth is a splendid example. The actual findings aren’t there to be committed to memory, even by most of those in the field: “In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth.” This study took its discovery population from people of European descent in the USA, using money from the March of Dimes fund set up by FD Roosevelt nearly 80 years ago. The replication cohort was from Nordic databases. Gradually we’re building up a picture of which genes might control what in these populations. A great example of international sharing of data in medicine.

Post-marketing studies & the short-sighted watchdog

The US Food and Drug Administration is the world’s best-known watchdog, but thanks to political meddling it is missing most of its teeth. It has lost half of its long-distance vision too. Steven Woloshin and Lisa Schwartz show that the rot set in long before Trump, although they manage a swipe at him in their last paragraph, since he ardently wants things to get worse. The FDA is basically a permissive organisation, especially in its fast-track approval system. Since 2007 it has had the power to mandate phase 4 (post-marketing) studies after allowing companies to try their products out on the public. But 46% of such studies on products licensed in 2009-10 still haven’t been completed in 2017.

JAMA 19 Sep 2017  Vol 318

Cef & met for CS?

In 2014, 24.8% of women who gave birth in the United States were obese (body mass index >29.9). That equates with over 300,000 caesarean sections being performed on obese women every year over there. Here is a trial comparing two days of cefalexin and metronidazole given to such women, compared with placebo. The postpartum antibiotics reduced the wound infection rate from 15% to 6%; but metronidazole is relatively contra-indicated during breastfeeding, so this choice of antibiotics may not be ideal.

JAMA Intern Med Sep 2017 

No added cancer risk from “biologicals” in RA

It takes a long time for the true cancer risk of any drug to be known, but a nationwide cohort study from Sweden is reassuring so far about the medium-term cancer risk associated with newer drugs for rheumatoid arthritis. Scanning the population register from 2006 to 2015, investigators found that the risk of malignant neoplasms did not differ among RA patients treated with a first anti-TNF drug, a second anti-TNF drug, tocilizumab, abatacept, rituximab, or conventional disease-modifying antirheumatic drugs. There may be an increased risk of squamous cell skin cancer with abatacept, but this needs more follow-up.

Low-normal thyroid function for a longer life

Low normal T4? Highish TSH (thyrotropin)? Rejoice: you may live an extra three years, according to the Rotterdam Study, which measured these at the age of 50. Participants with low-normal thyroid function went on to live up to 3.5 years longer overall and up to 3.1 years longer without CVD than participants with high-normal thyroid function.

Ann Intern Med 19 Sep 2017  Vol 167

Better rapid tests for flu

Systematic reviews of diagnostic tests are an acquired taste. Like badly-cooked cuttlefish, they can be chewy, fishy, insipid, and indigestible all at the same time. But here is perfectly grilled example, concluding: “Novel DIAs and rapid NAATs had markedly higher sensitivities for influenza A and B in both children and adults than did traditional RIDTs, with equally high specificities.” It’s rare to see such a crisp conclusion to a diagnostic meta-analysis, which led me to try and find out what this actually means. Here is a short glossary:

  • traditional RIDTs: rapid influenza detection tests which detect viral antigens by immunoassay within 30 minutes, but with low sensitivity,
  • novel DTAs: digital immunoassays,
  • rapid nucleic acid amplification tests.

Just add lemon juice and a little chilli oil, and enjoy.

The Lancet 23 Sep 2017  Vol 390

Continuous glucose monitoring for type 1 diabetic pregnancies

In this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days’ gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy.” So: one trial (as in the title and opening sentence) or two? Definitely two, but we can ignore the one for mothers planning pregnancy, as it showed no benefit from continuous glucose monitoring (CGM) over usual capillary sampling. And if you’re in the habit of skim-reading, note that the pregnant participants did NOT have “gestational diabetes” (whatever that means) but established type 1 diabetes. In this group, CGM showed definite and large benefit in reducing large-for-dates deliveries, neonatal intensive care admissions and neonatal hypoglycaemia. On the other hand, about half the mums experienced soreness at the monitoring site.

How often should you give blood?

Here’s a pragmatic British trial which concludes that “Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors’ quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency.” My take-home on this is that if you have a valuable blood type, you should try donating every 8 weeks if you’re a man, or every 12 weeks if you’re a woman. Otherwise stick to the usual intervals.

PURE exercise

The Prospective Urban Rural Epidemiologic (PURE) study looked at 130,000 people spread across high-income countries, where physical activity is mainly recreational, and lower-income countries, where physical activity is mainly non-recreational. Same difference: whether you do it for pleasure or necessity, physical activity is associated with less cardiovascular disease in middle life, and greater longevity.

The BMJ 23 Sep 2017  Vol 358

Sore throats on steroids

Most of us can remember nights when our throats have been so sore that we couldn’t sleep or swallow our own saliva. Usually the next night is better, unless it’s due to glandular fever, in which case a short course of steroids can bring relief. In fact there’s now pretty good evidence that a single dose of corticosteroid can shorten the pain of most sore throats. The MAGICapp team have produced a nice decision tool for clinicians based on the latest systematic review. I really admire their work, but I do have doubts about the wisdom of prescribing even minimal courses of steroids for self-resolving symptoms, however painful. Randomised trials are all but useless for picking up rare but life-threatening adverse effects, and just a few serious infections or deaths would be too high a price for the relief of self-limiting illness.

Resistant hypertension

Resistant hypertension is a term I resist, largely because of the word “hypertension”. I’d suggest PEBP. Persistently elevated blood pressure. But never mind. The point is to understand why it is “resistant” or “persistently elevated” and whether this matters. It is commonest in the over-80s. Although it’s associated with cardiovascular events in that age group and below, we just have to give people a choice. There is no single cause, and piling on more drugs may be futile. But I digress. Here you can track the incidence and prevalence of PEBP/RHT in the UK over the last two decades.

Incidence went up markedly to 2004, and then dropped markedly. Prevalence kept going up until 2007, but that has waned a bit too. For further discussion.

Plant of the Week: Agastache mexicana “Red Fortune”

A couple of years ago we bought a wonderfully aromatic plant from the urbane owner of Kiftsgate House, whose gardens contain the most loving assemblage of plants in England. Its label says it is a short-lived perennial called Agastache “Posie,” but I think he was trying to hide the terrible fact that its full name is “Rosie Posie”.

Whatever it may be called, this is an essential plant in every way, with wispy grey-green foliage which exudes a marvellous scent, and spires of dusky red-pink flowers from July until the first frosts. For the purposes of this review I shall pretend that it is really Agastache mexicana “Red Fortune”, because this looks identical. I just cannot bring myself to praise anything called “Rosie Posie”.

Our plant is now half a metre high and very woody. I fear that I have left it too late to take successful cuttings, and we will probably have to replace it next spring, since “short-lived perennial” is gardeners’ code for “bound to die within three years”. I already have my eye on a very attractive alternative Agastache called “Summer Sunset”. Like rosemary and lavender, these are “postman’s trouser” plants, ideal for giving aromatic joy when spilling over the path that leads to your post-box.

  • George

    It’s fascinating that high TSH and low T4 within the normal range are associated with longer life and freedom from CVD, because they are also associated with elevated cholesterol, mainly LDL-C.
    https://www.ncbi.nlm.nih.gov/pubmed/22730515
    (Unfortunately information on this correlation wasn’t published in the Rotterdam study).
    So maybe we’re closer to understanding why LDL as a predictor of CVD is less reliable that most other measures, and why it seems to be associated with longevity rather than its opposite in some populations. Thyroxine stimulates HMG-CoA reductase, i.e. cholesterol synthesis, as well as increasing LDL receptor uptake, so maybe there’s no advantage to lower LDL via a thyroid mechanism, and negative effects of higher thyroid function on clotting to offset it.
    So perhaps we have a picture where people with higher LDL due to either dairy fat consumption or high-normal TSH tend to have an advantage, or at least no disadvantage, but where people with high LDL due purely to LDL genetic factors, and maybe other factors like a high trans fat diet, don’t. Accounting for varied and inconsistent associations, and high risk of overdiagnosis, based on off-treatment LDL levels alone.
    Maybe.

  • Cat Chatfield

    One addendum to the analysis of the JAMA Intern Med trial for Cef & Met after Caesarean section: Metronidazole is currently considered to be safe to use with breastfeeding. Caution is considered with large (2g) doses but the doses given in this trial were 500mg 8hrly so this does not apply in this case.

    It’s surprising how many drugs which have been considered to be contra-indicated with breastfeeding in the past are now considered safe and it’s important to highlight these in the interests of (possibly) improving our low breastfeeding rates in the UK.

    https://www.sps.nhs.uk/articles/metronidazole-is-it-safe-to-use-with-breastfeeding/
    http://www.bmj.com/content/358/bmj.j3681

  • mark aley

    So, steroid for a sore throat: From the paper–>

    “harm seems unlikely with one steroid dose”… well that’s reassuring, we don’t really know.

    “The treatment is inexpensive and likely to be offered in the context of a consultation that would have taken place anyway”, well yes, but the subsequent consultations after every sore
    throat (and steroid load build up) because you have not educated the patient about self-limitation, self
    management etc, will add a huge toll… Not to mention decimating the primary care work force as even more viral infections enter my room for me to catch… thanks, and I don’t think I will be taking the Dex when they do (Rum toddy’s work for me!)