Richard Lehman’s journal review—29 February 2016

richard_lehmanNEJM 25 Feb 2016 Vol 374

Aspirin with your cabbage?

728   Most people who undergo coronary artery surgery take aspirin. Nobody knew whether they should carry on or stop when they had their CABG. Now we have the results of a big multinational trial: “Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo.” But I’m puzzled to note that the patients were only “eligible for the trial if they had not been taking aspirin regularly before the trial or had stopped taking aspirin at least four days before CABG surgery.” So why is the article title “Stopping vs. Continuing Aspirin before Coronary Artery Surgery“? I checked with the authors and was told that the trial was designed this way to allay fears that aspirin continued right up to surgery might pose a bleeding risk. Most of the patients were indeed on long-term aspirin which was stopped just for the four days before surgery. I think I understand this, but it still makes the title a poor match for what actually happened in the trial.

Less chemo for ovarian cancer

738   When my mother was recovering from her debulking surgery for ovarian cancer, I stepped aside to discuss the next steps with the registrar in charge. “The boss probably wants her in a trial, but I’ll suggest we just put her on some very gentle chemo,” he said to my great relief. Her next (and last) ten months were far from pleasant, but at least she did not have to go through neutropenia, neuropathy and the other common miseries of chemotherapy with paclitaxel and carboplatin. Nowadays most people with ovarian cancer get bevacizumab, which does genuinely lengthen survival, and paclitaxel and carboplatin still form part of the routine. What happens if you give the paclitaxel more intensively, every week instead of every three weeks? “Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer.

Carotid choices

OL   “In the Carotid Revascularization Endarterectomy versus Stenting Trial, we found no significant difference between the stenting group and the endarterectomy group with respect to the primary composite end point of stroke, myocardial infarction, or death during the periprocedural period or any subsequent ipsilateral stroke during four years of follow-up. We now extend the results to 10 years.” And they find exactly the same thing. There seems absolutely nothing to choose between these options. So does that present an ideal opportunity for shared decision making? I don’t think so. If there is absolutely nothing to choose between two things, how do you make a choice? Toss a coin? Leave it to NICE? Trust your doctor?

JAMA 23 Feb 2016 Vol 315

Statins fail to prevent AKI

OL   Another week, another JAMA, and once again I’m finding it hard to pull out anything for the generalist reader, because this week it’s all about critical care and exciting things like septic shock and acute respiratory distress syndrome that bread-and-butter doctors like me leave to clever sexy people dressed in pale blue pyjamas with short sleeves. There is some passing interest, I guess, in a trial of high-dose atorvastatin to prevent acute kidney injury following cardiac surgery. It made no difference.

No, leave my appendix in please

811   Of much greater interest to most of us is a paper pulled out of JAMA Surgery from December 2015 and commented on under the heading “Shared Decision Making in Uncomplicated Appendicitis: It Is Time to Include Nonoperative Management.” The original paper was a cohort study of 65 patients/families who chose appendicectomy (median age, 12 years) and 37 patients/families who chose nonoperative management (median age, 11 years). A quarter of the non-operative group went on to need operative treatment within a year, but that means that the rest did not, so reducing costs and treatment burden overall. The investigators concluded that “When chosen by the family, nonoperative management is an effective treatment strategy for children with uncomplicated acute appendicitis, incurring less morbidity and lower costs than surgery.” The commentator goes on to state: “Because clinicians will soon be obligated by law to provide information about all potential forms of treatment about appendicitis, surgeons would be well served to take a leadership role in proactively developing decision aids to inform patients about the benefits and risks for both nonoperative antibiotic treatment and surgical treatment of appendicitis. Decision aids would include information on the known and accepted risks and benefits of operative intervention vs antibiotic therapy alone.” Absolutely.

JAMA Intern Med Feb 2016

Teachable diabetes

OL   I don’t usually comment on the excellent “Teachable Moment” articles in JAMA IM, but I declare an interest in this one on Intensive Glycemic Control in Type 2 Diabetes Mellitus—A Balancing Act of Latent Benefit and Avoidable Harm. I met one of the authors five years ago and I’m delighted that she is pursuing an interest in patient-centred care for T2DM. This is not easy. Patients as well as doctors would love to make it so, by simply concentrating on getting glucose levels within a certain range, as if that is going to deliver big benefits and no harms. It was an alluring and widely accepted narrative, but unfortunately it is wrong. Here’s a very simple case to illustrate that. Read it and teach with it.

Buzzed into quitting

OL Smoking university students throughout Sweden were offered the choice to participate in a randomised trial which provided them with 157 text messages based on components of effective smoking cessation interventions for 12 weeks, or a couple of messages thanking them for being part of the trial. The end-point was self-reported abstinence at eight weeks, and it was reached by 25.9% of the intervention group and 14.2% of the controls. This was a somewhat weak study design but it does show that there are non-pharmacological methods that can usefully reduce smoking, at least in the short term.

Mind your backs

OL   And speaking of non-pharmacological interventions, how about mindfulness? The Mindfulness-Based Stress Reduction programme has apparently featured in over a hundred randomized controlled trials, this latest one being in people aged 65 and over with chronic back pain. In a highly selected population of mean age 74.5, the overall effect of mindfulness training was small and poorly sustained, though a few participants showed marked benefit. Worth a try, then? Possibly. Something to be mindful of.

Lancet 27 Feb 2016 Vol 387

Anastrozole v tamoxifen

849   Three important papers about hormonal treatment for ductal carcinoma-in-situ of the breast have been on the Lancet website for many weeks and now appear in print. They are models of their kind and together they allow women to make choices about their long-term treatment based on very clear and patient-centred evidence. I’ll try and take you through them but I’ll begin with a caveat. I began writing notes on the main journals for my practice when I’d been a GP for 20 years and noticed nobody else nearby was reading them. Eighteen years on, I’m no longer a working clinician but I find I still have a passion for wondering how medicine could be done better. What you read in these blogs is nothing more or less than me thinking aloud about that.

I find it hard to get my head round ductal carcinoma-in-situ of the breast because everybody does. Take this from the first article: “Originally called early or minimal breast cancer, ductal carcinoma in situ is now classified as stage 0 breast cancer and is regarded by some experts as a precancerous entity. As a result, debate is ongoing as to whether ductal carcinoma in situ should be treated as a malignancy or as a precursor of cancer.” For something we don’t understand the natural history of, DICS is treated with amazing aggression. Perhaps in the fullness of time we may be able to stratify these (mostly mammography-detected) lesions and spare women the full array of partial mastectomy, radiotherapy, chemotherapy (sometimes) and long-term hormonal treatment. In fact we already have DNA markers which can spare many women chemotherapy. The trials here are all about the long-term hormonal treatment: should it be tamoxifen or anastrozole?

The first two reports are from the NSABP B-35 trial, and together they provide exceptionally clear evidence for decision making by women facing the prospect of long-term hormonal drug treatment. “The primary outcome was breast cancer-free interval, defined as time from randomisation to any breast cancer event (local, regional, or distant recurrence, or contralateral breast cancer, invasive disease, or ductal carcinoma in situ), analysed by intention to treat. Compared with tamoxifen, anastrozole treatment provided a significant improvement in breast cancer-free interval, mainly in women younger than 60 years of age.”

857   The second paper goes one better and describes the patient-reported outcomes of the alternative treatments, for example: “Vasomotor symptoms (1·33 vs 1·17; p=0·011), difficulty with bladder control (0·96 vs 0·80; p=0·0002), and gynaecological symptoms (0·29 vs 0·18; p<0·0001) were significantly more severe in the tamoxifen group than in the anastrozole group. Musculoskeletal pain (1·50 vs 1·72; p=0·0006) and vaginal symptoms (0·76 vs 0·86; p=0·035) were significantly worse in the anastrozole group than in the tamoxifen group. Sexual functioning did not differ significantly between the two treatments (43·65 vs 45·29; p=0·56).” There’s even a nice graphic charting them by age. And of course in real life it will be easy for women to switch from one treatment to the other. So here is a shared decision maker’s paradise: excellent quality evidence relating to harms and benefits, ripe for conversion into decision tools.

866   The third paper provides additional evidence from the IBIS-II DCIS trial, showing that in postmenopausal women there were no clear efficacy differences. The adverse effects reported were somewhat different, “with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen.”

BMJ 27 Feb 2016 Vol 352

My blood pressure, your decision?

By contrast with breast DCIS, raised blood pressure is extremely common, in both sexes. Does that mean that it is more important or less important for individuals to make their own choices about long-term treatment, based on good evidence? Answer that for yourself, but the current model is for NICE to decide, doctors to prescribe, and patients to obey. The BMJ hosts two important hypertension papers in its vestigial research section this week, one a systematic review and the other a randomised trial. Together they are the subject of a commentary on BP targets in primary care, which begins conventionally enough:

“Management of high blood pressure is crucial, to forestall end organ damage, disability, and death and to reduce societal costs from cardiovascular disease. Good management is particularly important in general practice, where most patient care occurs.”

Well yes, sort of, though whether societal costs are lowered by people in retirement living longer is always a moot point. And do most GPs have any means of knowing the exact cardiovascular risk and number needed to treat/harm for every patient on BP lowering treatment? I’m glad that the article gets ever more subversive as it goes along, climaxing in the concluding paragraph: “Applying targets achieved from highly selected populations to real world patients in primary care may result in overzealous treatment decisions. Unless doctors and patients share realistic treatment goals that work across all their comorbidities, we risk perpetuating a disease specific perspective on treatment that often results in an unbearable treatment burden for patients and even in harms.”

I’ll just give you the headline messages from the papers themselves. The meta-analysis of BP lowering in diabetes concludes: “Antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.”

The second paper is a report of the PAST-BP (Prevention After Stroke—Blood Pressure) open label randomised controlled trial. It doesn’t report on “hard” outcomes but shows that if you aim for a target systolic BP of 130, you will achieve a 3mm lower BP than if you use a target of 140 in people who have had a stroke or TIA. On the other hand, more of them will give up: 52 out of 266 withdrew from the intensive arm of the study versus 32 out of 263 in the standard arm.

Plant of the Week: Hermodactylus tuberosus

We’ve never had much luck with the little blue winter-flowering irises which can be so pretty in February, but we have had almost too much luck with their close relative from Greece, the Hermodactylus. It has completely taken over a small raised bed, though only a fraction of the bulbs flower in any one year.

I’ve just looked it up in Wikipedia only to find that it has been returned to the genus Iris under its old name of Iris tuberosa. Botanists, honestly. All the while it has retained its English name, the widow iris, due to its exceptionally lugubrious flowers. These form a triple mantle of black framed with green and yellow, fitting for the most bereft of spouses. Moreover they exhale a scent which is almost redolent of the late departed, tinged with just a hint of widowly perfume.