{"id":46609,"date":"2020-02-07T18:57:10","date_gmt":"2020-02-07T17:57:10","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=46609"},"modified":"2020-02-07T18:57:10","modified_gmt":"2020-02-07T17:57:10","slug":"alex-nowbars-weekly-journal-review-7-february-2020","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2020\/02\/07\/alex-nowbars-weekly-journal-review-7-february-2020\/","title":{"rendered":"Alex Nowbar\u2019s weekly journal review\u20147 February 2020"},"content":{"rendered":"<p class=\"standfirst\">Alex Nowbar reviews the latest research from the top medical journals.<\/p>\n<p><!--more--><img loading=\"lazy\" decoding=\"async\" class=\"alignleft size-full wp-image-43001\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/alex_nowbar.jpg\" alt=\"\" width=\"160\" height=\"160\" srcset=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/alex_nowbar.jpg 160w, https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/alex_nowbar-150x150.jpg 150w\" sizes=\"auto, (max-width: 160px) 100vw, 160px\" \/><\/p>\n<p><em><b>The Lancet<\/b><\/em><\/p>\n<p><span style=\"text-decoration: underline\"><b>The coronavirus 99<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\">After several cases of pneumonia of unknown aetiology in December 2019, a novel coronavirus was identified and named 2019-nCoV. In their single centre, retrospective study, <a href=\"https:\/\/doi.org\/10.1016\/S0140-6736(20)30211-7\" target=\"_blank\" rel=\"noopener noreferrer\">Chen et al<\/a> analysed data from the first 99 cases admitted to Jinyintan Hospital in Wuhan, China. Of these 99 patients, 82 had a fever at presentation, 81 had a cough, and a third had shortness of breath. Many presented with organ failure, 17 had acute respiratory distress syndrome, and 74 had bilateral pneumonia on imaging. They all received antivirals, and most received antibiotics. By 25 January 2020, 31 had been discharged from hospital while 11 had died. From such a small sample size, few conclusions can be drawn on who is most likely to be affected, but in this study, it was mostly men, particularly those who smoked or had an underlying chronic condition.<\/span><\/p>\n<p><em><b>NEJM<\/b><\/em><\/p>\n<p><span style=\"text-decoration: underline\"><b>Coronavirus\u2014a perfect storm?<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\"><a href=\"https:\/\/www.nejm.org\/doi\/10.1056\/NEJMoa2001316\" target=\"_blank\" rel=\"noopener noreferrer\">Li et al<\/a> analysed the first 425 cases of 2019-nCoV pneumonia in Wuhan, specifically looking at the epidemiology. The key point from this analysis was the source of the new virus\u2014a live animal and seafood market. The mean incubation period was five days. Critically for this epidemic, the virus is easily transmitted from human to human and has a basic reproductive number of 2.2. The basic reproductive number is the number of further cases one case generates on average during the infective period assuming an uninfected population. If this is greater than 1, it is very easy for the virus to spread. So it is no understatement that 2019-nCoV is a global emergency. More work in this area is emerging every day as the situation evolves.<\/span><\/p>\n<p><span style=\"text-decoration: underline\"><b>A small step for acute kidney injury<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\">Unless you are a renal physician, acute kidney injury (AKI) can make you feel impotent. We offer little else other than monitoring. This American <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1911481\" target=\"_blank\" rel=\"noopener noreferrer\">study<\/a> describes a protein with a pivotal role in the pathogenesis of AKI which one day could lead to a giant leap in prevention of this condition. The protein is called soluble urokinase plasminogen activator receptor (suPAR). High suPAR levels before coronary angiography, cardiac surgery and ITU admission were associated with AKI. The sample size tested was modest \u2013 3827 for angiography, but only 250 for cardiac surgery and 692 for those who were critically ill. The link with high suPAR was also confirmed in their mouse model of suPAR overexpression. The animal model also revealed the mechanism of injury might be heightened energetic demand and mitochondrial superoxide generation. The distant hope is that this evidence for the role of suPAR could be used to develop a therapy to prevent and\/or treat AKI.<\/span><\/p>\n<p><span style=\"text-decoration: underline\"><b>The ugly head of cancer screening<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\">The NELSON <a href=\"https:\/\/www.nejm.org\/doi\/10.1056\/NEJMoa1911793\" target=\"_blank\" rel=\"noopener noreferrer\">trial<\/a> randomised 13195 men aged 50-74 years with a significant smoking history to either lung cancer screening with computed tomography (CT) or no screening. An interesting feature of the screening programme used in this study was the way indeterminate results were handled\u2014by assessing growth rate on imaging. The headline finding was lower rates of lung cancer deaths in the screening group. The rate ratio of deaths from lung cancer in the screening group compared with the control group was 0.76. This is impressive at first glance, but is it enough? To determine whether to offer lung cancer screening in the manner trialled, we need to consider whether there is a benefit for overall survival and whether there is overall harm from the downstream testing triggered by CT findings. These data are convincing in their ability to detect lung cancers at an earlier stage, when perhaps they are more amenable to curative surgery, and this did seem to save lives from cancer. It is unclear if this offsets the harms of false positives and subsequent testing since reporting of the harms is lacking.<\/span><\/p>\n<p><span style=\"text-decoration: underline\"><b>Pneumothorax and much-needed randomisation<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\"><a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1910775\" target=\"_blank\" rel=\"noopener noreferrer\">Brown et al<\/a> randomised 316 patients with moderate to large primary pneumothorax to either interventional or conservative management. We have essentially just been assuming intervention is the only form of management even though we would rather avoid them. Chest drains are painful and carry significant risks. The primary endpoint was complete radiographic resolution at 8 weeks. The study boldly concluded that conservative treatment was noninferior to interventional management. Before patients are denied interventional management, we must bear in mind two features of this study. First, patients were aged 14 to 50 and had unilateral pneumothorax. Second the study was unblinded and this could have biased patient and clinician behaviour thus influencing the outcome. The authors even state \u201cTreating clinicians were more likely than the independent radiologists who were unaware of the trial-group assignments to report full radiographic resolution in the group receiving interventional management, which biased the primary-outcome findings in favour of interventional treatment.\u201d I appreciate that placebo-controlling an intervention is very challenging but one has to randomise to test its efficacy.<\/span><\/p>\n<p><em><b>Annals of Internal Medicine<\/b><\/em><\/p>\n<p><span style=\"text-decoration: underline\"><b>Heart failure discharge services<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\"><a href=\"https:\/\/doi.org\/10.7326\/M19-1980\" target=\"_blank\" rel=\"noopener noreferrer\">Blum et al<\/a> performed a rigorous cost-effectiveness analysis of three types of post-discharge heart failure transitional care\u2014disease management clinics, nurse home visits, and nurse case management. These data were from observational studies as well as randomised controlled trials, so this places significant limitations on the findings. And the services assessed were diverse and varied in content and delivery. Nevertheless, compared with standard care, all types of transitional care were more effective than standard care and cost more than standard care. Nurse home visits were the most cost-effective. <\/span><span style=\"font-weight: 400\">Readmission following a hospital stay for heart failure is a significant challenge for healthcare services and patients and this study gives credence to the idea that transitional care for heart failure should be part of standard care, an idea which in the UK is already well established.<\/span><\/p>\n<p><em><b>JAMA<\/b><\/em><\/p>\n<p><span style=\"text-decoration: underline\"><b>Dropping isolated diastolic hypertension<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\">I am always ready to delete a clinical label from the medical armamentarium. Isolated diastolic hypertension (IDH) is a great one to be able to drop because it had created a market for antihypertensive therapy that could well have done people more harm than good in terms of anxiety and pill burden. Using various observational studies set in the community, <a href=\"http:\/\/doi.org\/10.1001\/jama.2019.21402\" target=\"_blank\" rel=\"noopener noreferrer\">McEvoy et al<\/a> assessed cardiovascular outcomes in thousands of people with isolated diastolic hypertension as defined by two guidelines (<\/span><span style=\"font-weight: 400\">\u2265<\/span><span style=\"font-weight: 400\">80\u2009mm\u2009Hg and \u226590\u2009mm\u2009Hg) compared with normotensive participants. The lower threshold was included in the most recent US guideline with little to no evidence. Using the lower threshold, the prevalence of IDH was 6.5%\u2014that\u2019s a lot of people to potentially medicate. By the higher threshold, the prevalence was only 1.3%. The result of this study was that IDH was not associated with increased risk of cardiovascular outcomes. This doesn\u2019t mean that diastolic hypertension isn\u2019t prognostically important though. These results only apply to raised diastolic blood pressure when the systolic blood pressure is in normal range.<\/span><\/p>\n<p><em><b>JAMA Internal Medicine<\/b><\/em><\/p>\n<p><span style=\"text-decoration: underline\"><b>Cardiac test clash<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\">The common scenario of discordant test results poses the question of which test to \u201cbelieve\u201d. <a href=\"http:\/\/doi.org\/10.1001\/jamainternmed.2019.6958\" target=\"_blank\" rel=\"noopener noreferrer\">Daubert et al<\/a> studied over 15,000 patients who had had both ECG and exercise stress echo from a single centre in the US. They were interested in the rate of major adverse cardiac events in those with positive ECG and negative stress echo compared to those with both positive ECG and positive stress echo. Negative stress echo is considered to be associated with a better prognosis so it is important to understand the significance of the positive exercise test with a negative stress echo. People with submaximal exercise tests were excluded from the analysis. The cardiac event rate in positive ECG and negative stress echo group was 14.6%, 8.5% if both tests negative and 37.4% if both tests positive. This clear stratification of risk indicates a prognostic role for abnormal exercise ECG. It also calls into question the idea that regional wall motion abnormalities abnormalities occur before ST segment changes or angina.<\/span><\/p>\n<p><span style=\"text-decoration: underline\"><b>Risk stratification after acute kidney injury<\/b><\/span><\/p>\n<p><span style=\"font-weight: 400\">As we simply watch the renal numbers wobble up and down in despair, <a href=\"http:\/\/doi.org\/10.1001\/jamainternmed.2019.6390\" target=\"_blank\" rel=\"noopener noreferrer\">Hsu et al<\/a> have been busy assessing the association of post-AKI proteinuria (specifically the urine albumin to creatinine ratio) with increased risk of future loss of renal function. The ASSESS-AKI Study is a prospective matched cohort study set in 4 US centres with 5 years of follow-up. Proteinuria after AKI was found to be useful for stratifying risk of kidney disease progression. The authors conclude that proteinuria measurements after AKI should become more widespread but they acknowledge limitations of their study such as small numbers of severe AKI and lack of a validation cohort. More precise prediction of future kidney disease may not enable us to prevent it but at the very least it is useful for monitoring and planning.<\/span><\/p>\n<p><i><span style=\"font-weight: 400\"><strong>Alex Nowbar<\/strong> is a clinical research fellow at Imperial College London<\/span><\/i><\/p>\n<p><em><strong>Competing interests:<\/strong> None declared<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Alex Nowbar reviews the latest research from the top medical journals. 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