Richard Lehman’s journal review—20 May 2012

Richard LehmanJAMA 15 May 2013  Vol 309
2016    I got into a bit of a muddle with this paper, but I blame JAMA. Let me test you out: the abstract says “Long-term follow-up of the randomized, masked 2-year Colpopexy and Urinary Reduction Efforts (CARE) trial of women with stress continence who underwent abdominal sacrocolpopexy between 2002 and 2005 for symptomatic POP and also received either concomitant Burch urethropexy or no urethropexy.” Then in the first section of the full text the cohort is described as from a “multicentre, randomized, masked trial in women without stress urinary incontinence (SUI).” Because I’ve never before heard women described as being “with stress continence,” and then randomized to incontinence surgery, my mind supplied the prefix “in.” Did yours? Anyway, let’s get this quite clear: the women in this study had pelvic organ prolapse without stress incontinence and they all got a procedure called abdominal sacrocolpopexy, by which the vaginal vault is fixed to the sacral anterior longitudinal ligament. Half of them also got the procedure called Burch urethropexy to support the urethra and hopefully prevent stress incontinence. They were asleep during the procedures and not told whether or not they had the Burch procedure. Stay with me—we are nearly there. At seven years, a lot of the sacrocolpopexy procedures had come adrift anatomically and the women who had the concomitant Burch procedure had less stress incontinence. So are you now clear about the message of this paper for patients and general clinicians? I can’t say that I am, but it is a nice piece of work and I hope that it will be of interest to urogynaecologists and those in the IDEAL collaboration who study surgical trial methods.

2035   The older Rational Clinical Examination articles include some classics of the medical literature, but alas this new one is not among them. It was doomed from the start: “Do Findings on Routine Examination Identify Patients at Risk for Primary Open-Angle Glaucoma”—now what would your answer be? Send them to a doctor who can examine eyes. Correct. “The best available data support examination by an ophthalmologist as the most accurate way to detect glaucoma.”

NEJM  16 May 2013  Vol 368
This week’s NEJM is dominated by hepatitis C (HCV) and a new drug called sofosbuvir. So—why the fuss about sofosbuvir? I think you really have to be a hepatitis C expert to understand, so let me try and become one for your sakes, since the journal provides a review article designed for that very purpose, and an editorial which I am sure to understand once I have read the review.

Some hours later. Sorry folks, this isn’t really working. The level of technical detail defies any attempt at summarization and things are changing by the week. Deaths from HCV have now overtaken deaths from HIV in the USA, despite the staggering rate of progress in knowledge and therapy. Here are some soundbites: “The speed of development of drugs to treat HCV infection is unprecedented. The publication of clinical data with respect to sofosbuvir comes only 3 years after the publication of the chemical discovery of the compound.” “Only 20 years after the discovery of the hepatitis C virus (HCV), a cure is now likely for most people affected by this chronic infection, which carries a substantial disease burden, not only in the United States but also worldwide.”

Progress in HCV therapy is a perfect showcase for what modern pharma can do when faced with a huge new challenge and market. Although HCV is nearly as elusive a target as HIV, laboratories are providing drugs targeted at new mechanisms almost every month, and bringing them to trial with unprecedented speed. The US Food and Drug Administration (FDA) has helped by reducing its standard for licensing from 24 to 12 weeks of sustained viral suppression. The viral gene gnomes have helped by identifying 6 major HCV genotypes. This is therapeutic science at its swiftest and sexiest: and patients are certainly benefitting.

I can’t really tell you if the fuss about sofosbuvir is warranted: the hope is that it will do away with the need for interferon in many patients. But next week we may get evenbettervir which hits more subtypes, and finally bigbuxovir which sweeps the market and makes billions for its manufacturer. And then what? Lots of head-to-head trials on a bewildering array of combinations; more attention to long-term safety issues; cost-benefit calculations which change every couple of weeks with the pricing of the drugs; and above all, treatment regimens which are inaccessible to the great majority of those who need them worldwide. It would be sad, but I suspect true, if the quote I gave above should really read, “a cure is now likely for most people affected by this chronic infection, provided they have the means to afford it or someone else is paying.”

Lancet  18 May 2013  Vol 381
This week’s Lancet is given over entirely to interventional and observational research and analysis from the resource-poor world. The Lancet’s leadership in this is something the world should be grateful for, even though articles are all hidden behind an Elsevier paywall. I’ll try to give you a flavour of some of them.

Saving Newborn Lives is the name of one of the funders of a big cluster-randomized trial in rural Malawi; it was aimed at doing just that, and succeeded. The interventions were either the formation of women’s groups, or the deployment of peer counsellors, or both, in a 2×2 factorial design. The end-points were maternal mortality, infant mortality, and the uptake of breastfeeding. The biggest mortality differences seemed to come from the women’s groups, but the counsellors did well too.

That’s the same message as emerges from a systematic review of women’s groups practising participatory learning and action, compared with usual care, on birth outcomes in low-resource settings. “With the participation of at least a third of pregnant women and adequate population coverage, women’s groups practising participatory learning and action are a cost-effective strategy to improve maternal and neonatal survival in low-resource settings.”

But beyond this basic stage of disseminating health information, it’s not all good news. The enormous WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS) looks with dismay at the maternal and neonatal outcomes of health facilities in Africa, Asia, Latin America, and the Middle East that dealt with at least 1000 childbirths per year and had the capacity to provide caesarean section. “High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities we studied. If substantial reductions in maternal mortality are to be achieved, universal coverage of life-saving interventions need to be matched with comprehensive emergency care and overall improvements in the quality of maternal health care.”

Control of population growth is still the human race’s most important priority, in my opinion. That means universal access to contraception, and the next survey seeks to find out how far that is being achieved. The two authors have done a heroic job going through the national survey data available for 2003, 2008, and 2012. The irony is that the number of childbearing women is increasing rapidly and matching the increase in provision of contraception.

BMJ  18 May 2013  Vol 346
Let the Patient Revolution Begin: a great editorial by some great people. The only possible ray of hope amongst the destruction of the NHS in general, and primary care in particular, is that patients will say “Enough is enough. We own this service and you must listen to us and make it work for us.” And the same could even apply in the USA, one day. I spent my whole professional career trying to provide continuity of care and trying to promote a vision of locally available services based on close linkages with specialist providers. But despite all the rhetoric, every political and managerial development has moved the NHS further from that goal. In a piece ostensibly about multimorbidity, Martin Roland joins the chorus which blames GPs for fragmenting the care of patients: as if we had much choice in the matter. But what little choice we do have, we must use. Our efforts will be entirely futile unless we really create a partnership with the people we serve, and shape our efforts according to their needs and not the convenience of managers and providers.

Two injections of 3ml of autologous blood around the mid-portion of the Achilles tendon: what’s that meant to do? It’s meant to help the resolution of mid-portion tendinopathy: and it seems that this sort of procedure has caught on in many circles (see editorial). This Australian trial confirms that it is a bloody silly idea.

Are you a man? Are you in your early sixties? Don’t have any prostate symptoms? Well, my friend, let me tell you something: the chances are that before very long, your stream won’t be so good and you’ll be getting up at night like me. Just let me do a rectal examination. There, you see, your prostate feels quite big. So don’t wait for symptoms to happen: take dutasteride now! Proven to REDUCE the onset of prostate symptoms over four years in men with benign enlargement. Oh, and you can put your trousers back on now.

You’ll be tired by now of me banging on about the need for long term proof of safety and a reduction in patient important adverse events before awarding a licence for sugar lowering drugs in type 2 diabetes. Sitagliptin is one of a group of drugs (DPP 4 inhibitors) which is coming under close scrutiny for possible harms to the pancreas; following short-term trials, it was licensed in 2006 under the brand name of Januvia. Here is a survey of a large US provider database looking at outcomes over 2.5 years. They detect no increase in acute pancreatitis and a neutral effect on all cause hospital admission and mortality. But that is not the end of the matter, as the editorial explains. It’s a well-conducted study, but in a drug that may be taken for decades, insufficient to allay all concerns.

JAMA Intern Med  13 May 2013  Vol 173
People who are given corticosteroids often have conditions that increase the risk of venous thromboembolism (VTE), so how can you tell if the corticosteroids themselves cause VTE, or whether it’s all confounding by indication, to use the EBM jargon? It’s something the authors of this Denmark-wide case-control study have considered carefully. Filling in a prescription for steroids in Denmark is associated with a doubling in the risk of VTE. Confronting the confounding issue, they respond, “we consider a biological mechanism likely because the association followed a clear temporal gradient, persisted after adjustment for indicators of severity of underlying disease, and existed also for noninflammatory conditions.”

If you use a non-benzodiazepine hypnotic (a “Z-drug”) for nursing home patients, you will increase their chance of a hip fracture. “New users and residents having mild to moderate cognitive impairment or requiring limited assistance with transfers may be most vulnerable to the use of these drugs.” Sometimes life is exactly as you expect.

Lock ‘em up and stop them having any cigs: that’ll cure them. But in fact the fascist method of smoking cessation is almost uniformly unsuccessful. Prisoners released from American jails where they were forced to give up smoking are back smoking regularly at 3 months in 98% of cases, male and female. Those offered the WISE intervention, described in this study, sustained a quit rate of 12% at 3 months. It’s a sad, mad world.

Plant of the Week: Pawlonia fargesii

After praising the amazing Chinese plant finds of the French missionaries Père Delavay and Père David, I must now complete the story with Père Paul Guillaume Farges. Although he was sent to China at much the same time as his illustrious confrères, it took him over 20 years to get posted to Chongquing where a priest could fulfil his true vocation to collect plants as well as to feed the faint and hungry heathen with the riches of the word. Unfortunately for Farges, by that time the best Chinese plants had been spoken for by others; so his efforts (amounting to 4000 plants) are remembered by relatively few well known species, though he has a whole genus of bamboos named after him.

The pawlonia is a show stopping tree in full flower, with huge upright panicles of scented lilac-blue foxglove blooms. Its northern limit in England seems to be in the middle of Oxfordshire. A lovely example has flowered for decades in Oxford Botanic Garden, whereas two examples (one mine) grew tall and flowered for a few years just 25 miles to the north, and then gave up in disgust at the lack of sun and the damp of our summers and winters. Mine was labelled fargesii but looked exactly the same as the species tomentosa: and in fact the two are now considered to be essentially the same plant. Poor Père Farges gets third prize again: now no longer his own species, but just a variety.

  • Jane

    Dear Richard, sounds crazy as you describe but CARE trial only seems strange because its all about occult (hidden) stress incontinence- the kind that surgical of correction of prolapse often reveals