{"id":26650,"date":"2013-05-28T11:19:50","date_gmt":"2013-05-28T10:19:50","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=26650"},"modified":"2013-05-28T11:23:13","modified_gmt":"2013-05-28T10:23:13","slug":"richard-lehmans-journal-review-28-may-2013","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2013\/05\/28\/richard-lehmans-journal-review-28-may-2013\/","title":{"rendered":"Richard Lehman&#8217;s journal review\u201428 May 2013"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" alt=\"Richard Lehman\" src=\"http:\/\/www.bmj.com\/site\/blog\/icons\/richard_lehman.jpg\" width=\"160\" height=\"108\" align=\"left\" \/><strong>JAMA\u00a0 22 May 2013\u00a0 Vol 309<\/strong><br \/>\n2105\u00a0\u00a0 Viewpoints carry with them an offer of agreement or disagreement, and everything I write in these columns is based on that. I hope you sometimes click on the links, and I often wish you would disagree with me more. I hope the same goes for the authors of this <a href=\"http:\/\/jama.jamanetwork.com\/article.aspx?articleid=1690707\">Viewpoint piece<\/a> about Medication Nonadherence: a Diagnosable and Treatable Medical Condition, but they sound almost angrily in earnest. \u201cTo further improve the diagnostic accuracy of the problem, attention should be paid to the underlying behavior(s) at hand. There are at least six representative medication nonadherence phenotypes, highlighting the differences in underlying behaviors and barriers that exist at the patient level&#8230;\u201d \u201cEach medication nonadherence phenotype requires different diagnostic tools and treatments\u2026\u201d The mechanistic jargon proceeds relentlessly: find out the adherential fault your patient suffers from, and take correctional action. Personally I think most \u201cnonadherence\u201d is due to a failure to gain the patient\u2019s trust and understanding in the first place: perhaps we\u2019d do better by examining some \u201chealth professional non-communication phenotypes\u201d and correcting them with education about shared decision making.<br \/>\n<!--more--><\/p>\n<p>2139\u00a0\u00a0 Oh boy, what exactly does it take to get a Preliminary Report into JAMA? <a href=\"http:\/\/jama.jamanetwork.com\/article.aspx?articleid=1690699\">On the showing of this one<\/a>\u2014you can read it in full\u2014it\u2019s a six week intervention for something that can\u2019t really be defined or measured without stress testing. The intervention is escitalopram (the entaniomer of citalopram) and the \u201cdisease\u201d is mental stress induced myocardial ischaemia. The outcome measure was not symptomatic\u2014because the patients\u2019 symptoms were already controlled with \u00df-blockers\u2014but ischaemic change on an exercise test performed after a mentally stressful activity performed without \u00df-blockade. Those on escitalopram showed a bit less of this. I just don\u2019t get it. It\u2019s not even as if it was a drug company trial to market escitalopram. I don\u2019t know what it was for.<\/p>\n<p>2111\u00a0\u00a0 Oxygen therapy for very premature babies has been investigated for over 50 years, and I thought we knew as much as we were ever likely to about it. <a href=\"http:\/\/jama.jamanetwork.com\/article.aspx?articleid=1684963\">But here comes another trial<\/a> aimed at determining the best target arterial oxygen saturation in very preterm infants\u2014and it shows no difference in outcomes whether you aim for sats of 85-89% or 91-95%.<\/p>\n<p><strong>NEJM\u00a0 23 May 2013\u00a0 Vol 368<\/strong><br \/>\n1963\u00a0\u00a0 Outcomes in cystic fibrosis continue to improve year on year, and a gene based cure is no longer an impossible mirage; but in the meantime, kids with CF continue to develop lung damage at varying rates from the age of 10 weeks onwards. <a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1301725\">An Australian study<\/a> finds that the rate of development of bronchiectasis is closely associated with the neutrophil elastase activity measured in bronchoalveolar lavage fluid sampled at 3 months. It\u2019s not a nice test to have to perform on little babies, but I guess if it helps to guide future therapy, it\u2019s worth it.<\/p>\n<p>1971\u00a0\u00a0 \u201cThe Sturge\u2013Weber syndrome and port-wine stains are caused by a somatic activating mutation in GNAQ. <a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1213507\">This finding confirms a long-standing hypothesis<\/a>.\u201d Ah, good.<\/p>\n<p>1980\u00a0\u00a0 I make high demands of any screening procedure: a reduction in all cause-mortality is my gold standard. That is a statistical tall order, but at least there should be a robust reduction in younger deaths, and hence in life years gained. By such standards, low-dose CT lung scans for heavy smokers (depending on definition) do seem to cut the mustard. <a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1209120\">The latest figures come from 53,439 participants randomised to plain X ray or CT<\/a>, and suggest \u201c that a reduction in mortality from lung cancer is achievable at US screening centers that have staff experienced in chest CT.\u201d Nicely cautious wording.<\/p>\n<p>1992\u00a0\u00a0 \u201cDigenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family.\u201d OK: you have 3 patients; that\u2019s a good start. And the conclusion: \u201cThe syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. <a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1215993\">These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction<\/a> and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease.\u201d Well, an unheard-of disease in a consanguineous family, anyway. More funding please?<\/p>\n<p>2004\u00a0\u00a0 The \u201cblocked pipes\u201d metaphor for coronary heart disease is so embedded in our thinking that it\u2019s quite a challenge to persuade people\u2014even doctors\u2014to realise that the most dangerous places in the coronary arteries are usually not the places which look narrowest on angiograms. On the contrary, the most likely places for acute ulceration and clot formation are the soft fatty uncalcified lesions that may not even cause much apparent stenosis. If only we had better methods for identifying them. You can read all about this\u2014and much else\u2014<a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMra1216063\">in a really helpful single-author update on mechanisms of acute coronary syndromes,<\/a> which is well worth seeking out if you are not a subscriber.<\/p>\n<p><strong>Lancet\u00a0 25 May 2013\u00a0 Vol 381<\/strong><br \/>\n1817\u00a0 You don\u2019t have to be an oncologist to have heard of CHOP chemotherapy, though you do if you are going to treat newly diagnosed diffuse large B-cell non-Hodgkin lymphoma. This isn\u2019t a particularly rare malignancy, accounting for a third of non-Hodgkin lymphoma, and <a href=\"http:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736%2813%2960313-X\/abstract\">this admirable trial<\/a> managed to collect 1080 newly diagnosed patients and follow them up for 2 years after randomisation to either R-CHOP (rituximab plus CHOP) every 14 days or every 21 days. Never mind the detail: the fact is that the lighter regimen proved as good as the heavier, which has to be good news.<\/p>\n<p>1827\u00a0 For reasons I won\u2019t try to explain, I have become keenly interested in the meta-analysis of individual patient data. Not that I would dream of trying it at home, which would be like trying to build a large hadron collider in the back garden. This is complex, grown-up stuff, and <a href=\"http:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736%2813%2960140-3\/abstract\">this one meta-analysis involved 15 centres spread across the USA, Italy, Australia and the UK<\/a>. They analysed data for 83 399 women with 306 617 women-years of follow-up to determine the long-term effect of selective oestrogen receptor modulators (SERMs) on the incidence of breast cancer in high-risk women. The drugs used were tamoxifen, raloxifene, arzoxifene, and lasofoxifene, compared with placebo in all but one trial. The nine trials they examined are quite heterogeneous but a clear message emerges: \u201cFor all SERMs, incidence of invasive oestrogen (ER)-positive breast cancer was reduced both during treatment and for at least 5 years after completion.\u201d There was an increase in thromboembolic events but a 34% protection from vertebral fracture. But despite all this painstaking work, the devil remains in the detail when making treatment long-term decisions for individual women.<\/p>\n<p>1835\u00a0\u00a0 And now for one of those really weird <a href=\"http:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736%2812%2962166-7\/abstract\">phase 1 trials that the <em>Lancet<\/em> <\/a>frequently features. These things really baffle me, because if you look at the Lancet\u2019s spin-off journals, you\u2019ll find plenty of stuff worth reading by most generalists. Whereas this is a report of an experimental treatment used on nine Australians with nodular basal cell carcinoma of the skin. They all got various doses of Dz13 injected into their tumours, and none of them suffered any harm. \u201cDz13 is a deoxyribozyme that targets JUN messenger RNA and has inhibited the growth of a range of tumours in mice.\u201d There was some reduction in the size of five of the tumours. Since practically every white Australian over the age of 50 has at least one BCC, I wouldn\u2019t advise anyone to wait until this treatment becomes more widely available. You\u2019re better off trying kangaroo spit on the night of a full moon, or whatever else local tradition suggests. Then see a proper doctor and have the thing frozen or cut out.<\/p>\n<p><strong>BMJ\u00a0 25 May 2013\u00a0 Vol 346<\/strong><br \/>\nThis is the most shocking and shaming medical paper I\u2019ve read for a long time: <a href=\"http:\/\/www.bmj.com\/content\/346\/bmj.f2539\">a survey of the gap in life expectancy for preventable physical illness in psychiatric patients<\/a>. It comes from Western Australia, which presumably enjoys the same standards of psychiatric care as the rest of the rich world. \u201cWhen using active prevalence of disorder (contact with services in previous five years), the life expectancy gap increased from 13.5 to 15.9 years for males and from 10.4 to 12.0 years for females between 1985 and 2005. Additionally, 77.7% of excess deaths were attributed to physical health conditions, including cardiovascular disease (29.9%) and cancer (13.5%). Suicide was the cause of 13.9% of excess deaths.\u201d This is a scandal which needs urgent further investigation: are we becoming indifferent to physical illness and early death in the mentally ill? And are the newer drugs like olanzapine and quetiapine that we hand out so liberally actually contributing to an epidemic of cardiovascular disease in these patients?<\/p>\n<p><a href=\"http:\/\/www.bmj.com\/content\/346\/bmj.f2350\">Another depressing paper follows<\/a>, though this is more for health service researchers and outcomes nerds. As a would be fledgling nerd of this feather, I had a touching faith that in the UK, the prevalence and incidence of major conditions like myocardial infarction could be determined accurately from a single database: unlike the USA, where there is a confusion of multiple agencies and registries. But the actual UK situation revealed in this paper is dreadful: look at the video abstract comparing data from the Clinical Practice Research Datalink (primary care data), Hospital Episode Statistics (hospital admissions), the disease registry MINAP (Myocardial Ischaemia National Audit Project), and the Office for National Statistics mortality register (cause specific mortality data). Minimal overlap! \u201cEach data source missed a substantial proportion (25-50%) of myocardial infarction events. Failure to use linked electronic health records from primary care, hospital care, disease registry, and death certificates may lead to biased estimates of the incidence and outcome of myocardial infarction.\u201d Phew! And I thought this was going to be easy. Maybe I should get digging that hadron collider in the garden after all.<\/p>\n<p><a href=\"http:\/\/www.bmj.com\/content\/346\/bmj.f2450\">A Dutch study investigating pneumonia in primary care uses chest radiography as the diagnostic gold standard<\/a>. On that basis, absence of runny nose and presence of breathlessness, crackles and diminished breath sounds on auscultation, tachycardia, and fever give an area under the ROC curve of 70%. If you add in a CRP&gt;30, that improves to 77%. If you add in procalcitonin, nothing changes. But what does this actually mean? That you are going to withhold antibiotics until you can be more certain the patient has radiologically visible pneumonia? Or until she has a CRP in the target range? This study contributes to a literature which swings this way and that, but for me it has no lessons for clinical practice.<\/p>\n<p>A few months ago, I commented on a perspective piece by Harlan Krumholz in the <em>NEJM<\/em> where he proposed the concept of a \u201cpost-hospital syndrome\u201d of debility leading to repeated admission. This rings true in my own experience as a GP, and it is a concept taken up and expanded by hospital consultant Hugh McIntyre in a Personal View with the title \u201c<a href=\"http:\/\/www.bmj.com\/content\/346\/bmj.f3242\">Admission to hospital could be considered a disease.<\/a>\u201d Everyone dealing with sick people needs to read this article and consider how it matches their own experience. Why do we send people to hospital? Is it because we expect the clever doctors to make some big improvement in their treatment, e.g. for heart failure? Do we expect patients to come out less frail, or more? How can we create a system which is more humane and less futile? Moving care into the community is not the answer, <a href=\"http:\/\/www.bmj.com\/content\/346\/bmj.f3186\">as an excellent editorial<\/a> points out: we need a different structure of local hospital care.<\/p>\n<p><strong>Ann Intern Med\u00a0 21 May 2013\u00a0 Vol 158<\/strong><br \/>\n709\u00a0\u00a0 Prostate cancer in elderly men is generally something they die with rather than die from, as we have all been taught for decades. <a href=\"http:\/\/annals.org\/article.aspx?articleid=1688109\">A survey of 3183 American men with non-metastatic prostate cancer fleshes out this concept usefully<\/a>. Overall it is certainly true, and the more comorbidity you suffer from, the higher is your chance that you will die from that rather than from prostate cancer: but for men with higher Gleason scores, and low morbidity scores, there may still be a place for aggressive early\u00a0 treatment.<\/p>\n<p>727\u00a0\u00a0 If you have stable coronary artery disease, your choices lie between optimal medical therapy, percutaneous coronary intervention (which generally means drug-eluting stents these days) or coronary artery bypass surgery. As a certain number of cardiologists read these reviews, I will avoid entering this minefield and simply give you the <a href=\"http:\/\/annals.org\/article.aspx?articleid=1679804\">conclusions of this study<\/a> of 105 156 propensity score\u2013matched Medicare patients aged 66 and over who were followed up between 1992 and 2008. \u201cPatients with diabetes, heart failure, peripheral arterial disease, or tobacco use had the largest predicted differences in survival after CABG, whereas those with none of these factors had slightly better survival after PCI.\u201d<\/p>\n<p><strong>Plant of the Week: <a href=\"http:\/\/www.bbc.co.uk\/gardening\/plants\/plant_finder\/plant_pages\/929.shtml\"><em>Trollius<\/em> x \u201cCheddar\u201d<\/a><\/strong><\/p>\n<p>Soft pale yellow is always a delight in the garden, and just now the finest examples are provided by two plants:<em> Paeonia mlokosewiczii<\/em> and this lovely Trollius, a non-invasive buttercup with double flowers held high. It needs moisture and prefers part shade, and unfortunately differs from the common buttercup in that, when grown in such damp places, its leaves seem quite attractive to slugs and snails. Guard it carefully, with chemicals if you must, or with beer traps, or with punitive gastropod-hunting expeditions by torchlight.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>JAMA\u00a0 22 May 2013\u00a0 Vol 309 2105\u00a0\u00a0 Viewpoints carry with them an offer of agreement or disagreement, and everything I write in these columns is based on that. I hope [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2013\/05\/28\/richard-lehmans-journal-review-28-may-2013\/\">More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":38363,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[111],"tags":[],"class_list":["post-26650","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-richard-lehmans-weekly-review-of-medical-journals"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Richard Lehman&#039;s journal review\u201428 May 2013 - The BMJ<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.bmj.com\/bmj\/2013\/05\/28\/richard-lehmans-journal-review-28-may-2013\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Richard Lehman&#039;s journal review\u201428 May 2013 - The BMJ\" \/>\n<meta property=\"og:description\" content=\"JAMA\u00a0 22 May 2013\u00a0 Vol 309 2105\u00a0\u00a0 Viewpoints carry with them an offer of agreement or disagreement, and everything I write in these columns is based on that. 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