Category Archives: Introductions

Week 12 – ROCKET-AF study

Atrial fibrillation (AF) is an incredibly common condition – not a day goes by that I don’t meet a patient with AF. As soon as it is diagnosed doctors and patients have to discuss the issue of anticoagulation, weighing up the risks and benefits for each individual patient due to the increased risk of stroke with AF. At the moment warfarin is the anticoagulant agent used, but it isn’t without its problems.

Warfarin is an effective drug but not a particularly nice drug. Patients face numerous blood tests and dose adjustments, alterations to their diet, the potential of life threatening bleeds and concerns about interactions with other medications. For some patients the potential side effects and effect on their lives leads them to decide to not be anticoagulated.  For years the search has been on for a medication with a similar level of efficacy but reduced interactions and risk of bleeding. Several studies of novel anticoagulants have been published comparing their efficacy to that of warfarin in patients with atrial fibrillation.

The ROCKET-AF study was published in the NEJM in September and was a multi-centre, double blind RCT that compare rivaroxaban (an oral factor Xa inhibitor) with warfarin in over 14,000 patients who were at moderate or high risk of thromboembolic stroke. Patients were divided into two treatment arms:

  • Rivaroxaban group – received a fixed once daily dose of 20mg once daily with normal renal function or 15mg if the creatinine clearance was 30-49ml/min
  • Dose adjusted warfarin aiming for an INR of 2.0 – 3.0

Patients in each group also had a placebo tablet in order to maintain blinding to their treatment arm.

The primary efficacy end point was for stroke (ischaemic or haemorrhagic) and systemic embolism with the principal safety end point being major and nonmajor clinically relevant bleeding events.

Rivaroxaban was found to be non-inferior to warfarin in the prevention of stroke or systemic embolism (1.7% per year comparied to 2.2% in the warfarin group – hazard ratio in the rivaroxaban group was 0.79, p<0.001 for non-inferiority – this is the per-protocol analysis).

For the primary safety endpoint major and clinically relevant nonmajor bleeding occurred in 1475 patients in the rivaroxaban group and 1449 patients in the warfarin group (14.9% and 14.5% per year respectively).

The bottom line:

In conclusion, in this trial comparing a once-daily, fixed dose of rivaroxaban with adjusted-dose warfarin in patients with nonvalvular atrial fibrillation who were at moderate-to-high risk for stroke, rivaroxaban was noninferior to warfarin in the prevention of subsequent stroke or systemic embolism. There were no significant differences in rates of major and clinically relevant nonmajor bleeding between the two study groups, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group.

This week’s journal club focuses on the ROCKET-AF study but also the wider question – is this the beginning of the end of warfarin as the agent of choice for anticoagulation?

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The discussion points will be posted tomorrow and the discussion will start at 19.30 BST (half an hour earlier than normal).

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Week 11 – Introduction: Role of Media Reports in Suicide

This study by Niederkrotenthaler at al., published in the British Journal of Psychiatry, examines the role media content on suicide has in suicidal behaviour in the public, both increase and decrease in suicide rates, and the effect of different types of article.

The current evidence suggests that the media does play a role, with an increase in suicides reported following reports in the media, showing a dose-response relationship between the quantity of reporting and subsequent suicides. Furthermore, the increase in suicide rate is greatest in areas where a higher proportion of the population is exposed to such media reports. This copy-cat behaviour is referred to as the Werther effect, and while not as large as other psychosocial risk factors, does play a role in an individual’s likelihood of taking their own life.

The study looked at 497 suicide reports in the Austrian media in the first half of 2005, and looked for associations between specific characteristics of reports, and subsequent short-term changes in suicide rates. (In addition to the Werther effect, the team refer to any post-reporting reduction in suicide rates as the “Papageno” effect, in reference to Mozart’s The Magic Flute.)

I won’t go into great detail here about the different characteristics of reports that were used, since these can all be found in the methods section of the paper. Briefly, however, they assessed the content of the articles, the extent of the reporting, and the article’s prominence, and coded these semi-quantitatively by noting the absence or presence of a number of attributes. The characteristics of the article’s content (such as “describing the suicide method in the headline”) were generated using guidelines for media reporting of suicide produced by the WHO and a number of other national agencies.

The authors found that suicide rates increased with quantity of reporting, though prominence of the articles was not associated with more suicides. Where the reported method of suicide was jumping, this correlated with an increase in suicide rates (r=0.15, P=0.001), but there was no significant relationship for other methods (NB: suicides by jumping are more likely to be reported by the print media than any other method). Furthermore, dichotomous thinking in the report, reference to multiple suicides and/or a suicide ‘epidemic’, and reporting on myths that surround suicide, were all associated with an increase in suicides in the population. Articles which discussed increasing societal problems as a cause of suicide were also more likely to result in increased suicide rates.

The only characteristic to be associated with reduced suicide rates was that of articles focusing on suicidal ideation (e.g. an aborted suicide; considering suicide but not going through with it). Yet articles which focused on suicide research, reported on expert opinion, or gave contact details for support services (e.g. Samaritans) seemed to cause an increase in suicides, although the authors found that these attributes were likely to be found in media reports that contained unfavourable, sensationalist comments.

The idea that certain types of reporting raise suicide rates does not seem surprising to me. The concept of triggering is well known, and as I understand it, is a bit like the straw that broke the camels back. People who are vulnerable, show suicidal ideation and suicidal urges, may read an article about suicide and be strongly influenced by it. In some instances, it may trigger an individual to attempt suicide. Another example of this is self-help forums on the internet that discuss either suicide or self-harm (by which I mean self-destructive behaviours without suicidal intent). These are full of posts with “**trigger**” in the title, to alert users to potentially upsetting, or “triggering”, content. (Just Google “suicide triggering” to see what I mean.)

But why does reporting instances of suicidal ideation reduce suicide rates? The authors suggest that such articles highlight the reported outcome as “going on living”. I would add that such articles perhaps point out to individuals with suicidal ideation that they are not alone, and that the subsequent reduction in feelings of isolation may play a role. Articles that raise awareness of mental illness can also be beneficial, as discussed in the middle paragraphs of this article (yes, I like cricket and I am biased!).

The key limitations of the study that I could identify (and most of which the authors also identlfied) are as follows:

  • Only print media was analysed. Although a large proportion of the population is exposed to the print media, this research fails to take into account influences from e.g. film / television and the Internet.
  • Limited geographic area.
  • I’m not an expert on stats, but some of their methods seem very complicated to me. Can anyone who knows a bit more explain whether the methods used are solid and reliable or not? There do seem to be a fair few attempts at validation, and the authors report “high intersubjective analytic consensus”.
  • No causality, only correlation, and consequently large potential for confounding factors.
  • Study only looked at 6 months of print media, while suicide rates are known to differ seasonally.
The role of the media in all things medical is important, but this example of suicide rates is, I feel, particularly worthy of discussion, since the outcomes are so evident and tragic. I look forward to this week’s #TwitJC on Sunday evening (8pm UK time; 7pm GMT) and hope it will be both interesting and thought provoking.

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Other links:

Samaritans UK guidelines on reporting suicide.
Media Wise link to an extensive selection of articles and reports on suicide reporting.
This Wired blog looks at copycat suicides, and how the increased prevalence of a new method put first responders at risk.
Press Complaints Commission – Editors’ Code of Practice (See section 5.ii) for mention of suicide)
Mind guidelines on reporting on mental health and suicide.

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Finally, if you, or someone you know, is feeling suicidal, do talk to someone; either someone you know and trust, your GP, or Samaritans on 08457 909090. (Although strictly speaking, based on what I’ve just written, I probably shouldn’t have included that sentence.)

EDIT: Added link to PCC Code of Practice and Mind guidelines.

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Week 10 – Introduction: Early Palliative Care in Patients with Metastatic NSCLC

I should first admit a small conflict of interest in writing this post: mummy Silvey is a lung cancer nurse specialist and I am very passionate about the care of lung cancer patients as a result. Lung cancer is the most common cancer in the world. According to Cancer Research UK, 1.61 million new cases are diagnosed worldwide each year. Lung cancer has a poor prognosis – patients with non-small cell lung cancer have approximately a 50% 2 year survival rate if the cancer hasn’t metastatised; for patients where the cancer has spread, this falls to 10%. These figures are devastating.

My mum has been a lung cancer nurse specialist for over 10 years now and has previously sat on the NICE guideline committee for lung cancer. When she started her post a senior community nurse told her the importance of referring patients early to the community palliative care team. Most lung cancers are not curable and therefore she felt that the involvement of specialists in palliative care early was vital. Furthermore, she felt these patients needed early pallaitve care input for good symptom control and that this had helped the patients she had looked after. This evidence is ancedotal, but it was her experience. However, there is now evidence to support her views: evidence now exists that shows early palliative care, at time of diagnosis, is both appropriate and beneficial for patients with non-small-cell lung cancer.

The paper #TwitJC will look at this week is “Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer“ by Temel et al., published in the New England Journal of Medicine last year. It is a randomised trial in which 151 newly diagnosed metastatic non-small cell lung cancer patients were ransomised to received either early pallative care in conjunction with standard oncologic care, or to standard oncologic care alone. This trial measured quality of life and mood at baseline and at 12 weeks using the Functional Assessment of Cancer Therapy – Lung and the Hospital Anxiety and Depression Scale, respectively. The primary outcome of the trial was the change in quality of life at 12 weeks.

The results demonstrate that of the 107 patients who completed the assessments, patients assigned to the early palliative care showed a better quality of life than those assigned to standard care (mean score on FACT-L 98 vs 91; P=0.03). Patients in the early palliative care group also had fewer depressive symptoms (using HADS 33% vs 54%; P=0.05).

However, the surprising result was that even though fewer patients in the early palliative care group received aggressive end of life care, the median survival was actually significantly longer in this patient group (11.6 months vs 8.9 months; P=0.02).

The conclusion:

Among patients with metastatic non–small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival.

A list of discussion points will be posted shortly and I look forward to another interesting discussion of a very interesting paper. I would recommend reading the NEJM editorial about this piece of research – it is an insightful read.

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A plea: Lung cancer awareness month is in November. This never gets a high profile but I just want to make people aware of it and remind everyone how important it is to raise the profile of lung cancer. The less of a stigma we have about it and the more we talk about the symptoms of lung cancer hopefully more people will start to come forward earlier with symptoms. Remember that 1 in 9 people who develop lung cancer have NEVER smoked in their lives and many others gave it up years ago. The Roy Castle Foundation is a fantastic organisation helping to raise the profile of lung cancer and is a charity I am proud to support.

Also I would like to dedicate this week’s journal club to my mum – I am constantly in awe of the amazing job she does for her patients everyday and I couldn’t be more proud of her.

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Week 9 – Introduction: Prevention of HIV-1 Infection with Early Antiretroviral Therapy

HIV by numbers (2009 WHO Data):

  • 33.3 million people with HIV
  • 2.6 million new infections with HIV in 2009
  • 1.8 million deaths in 2009

The sheer scale of the burden of HIV is beyond the scope of mere numbers alone but the numbers are staggering. I spent my elective inTanzania and saw first hand the devastating impact HIV has had. Every day the clinic by our house was filled with people coming to be tested, and treated, for HIV. I will never forget the stories that I heard from people affected by this awful virus. I have also witnessed first hand how antiretroviral treatment can transform lives and protect children from mother-to-child transmission of the virus. But transmission of this virus still occurs every second of every day and there have been a huge numbers of studies looking at how to prevent transmission.

Previous cohort studies have shown that antiretroviral treatment reduces the rate of transmission of HIV. In the August edition of the New England Journal of Medicine Cohen et al published the results of a multicontinent, randomised controlled trial to evaluate the effect of combination antiretroviral therapy on the prevention of HIV-1 transmission to uninfected partners.

A total of 1763 discordant couples were enrolled in this trial, the HIV-1 infected partner had a CD4 count between 350 and 550 cells per cubic millimetre. HIV-1 infected partners were then randomised into the two arms of the study:

  1. Early antiretroviral therapy – therapy commenced at enrolment
  2. Delayed antiretroviral therapy – therapy commenced when the CD4 count dropped below 250 cells per cubic millimetre or a HIV-1 related event occurred

The main question: would antiretroviral treatment of the HIV-1 positive partner reduce the rate of transmission to the non-infected partner as previously suggested by cohort studies?

The headline figure – there were 39 HIV-1 transmission events and 28 of those were genetically linked (i.e. the transmission was from the infected partner). Of these 28 infections only one occurred in the early therapy group, a 96% reduction in the rate of transmission, a staggering result. Of the 27 infections in the delayed-treatment group all occurred when the infected partner was not receiving antiretroviral therapy.

 A second question was asked: would immediate therapy slow disease progression in the HIV-1 infected partner when compared to the delayed therapy? Again the study showed a positive result – a total of 105 participants had at least one clinical end point (see the paper for details). 40 of these were in the early-therapy group and 65 in the delayed therapy group – a reduction of nearly 40% in those treated immediately.

The conclusion:

In this trial, we found that early antiretroviral therapy had a clinical benefit for both HIV-1–infected persons and their uninfected sexual partners. These results support the use of antiretroviral treatment as a part of a public health strategy to reduce the spread of HIV-1 infection.

 A list of discussion points for tomorrow’s journal club will be posted in the morning and I look forward to another interesting discussion of a fascinating paper.

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For anyone interested in HIV I can highly recommend the wonderful book by Elizabeth Pisani – The Wisdom of Whores. There aren’t many books I would describe as a must-read but this is one.

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Week 8 – Introduction: FEAST

A huge number of studies are published in journals everyday. Most are read with interest by people involved in the area in which they are published but few every reach the attention of the world’s media. The FEAST study is an exception to this; it attracted a huge amount of attention, the headline from the BBC news story – “Africa trial questions shock treatment for children” was typical of coverage of this trial.

The use of fluid boluses for shock is an international standard, the American College of Critical Care Medicine recommend the use of 60mls per kg of fluid for a child with a fever who has shock. However, in resource-poor countries these boluses are simply not available.

FEAST – Fluid Expansion as Supportive Therapy – was published in June 2011 in the New England Journal of Medicine with the aim of evaluating the effect of fluid boluses and early fluid resuscitation for shock in febrile children in Sub-Saharan Africa. This was a randomised controlled trial carried out in 6 hospitals inKenya,Tanzania and Uganda. The trial assessed the effects of giving a fluid bolus to children with a febrile illness and impaired perfusion (i.e. children with hypovolaemic shock). Children were randomised into two groups:

  • Stratum A – children without severe hypotension – randomised to receive either a saline bolus (20mls per kg), an albumin bolus (20mls per kg) or no bolus (control group)
  • Stratum B – children with severe hypotension – randomised to receive saline bolus (40mls per kg) or albumin bolus (40mls per kg)

The protocol was changed in June 2010 and initial boluses were increased to 40ml per kg in stratum A and 60mls per kg in stratum B. Children from the age of 60 days to 12 years were included and the exclusion criteria were children with severe malnutrition, diarrhoea, burns, surgery and trauma. All children received appropriate treatment for their condition as well as being involved in the trial.

The primary endpoint was mortality at 48 hours after randomisation.

The study was stopped in January 2011 after the independent data and safety monitoring committee reviewed the 5th interim analysis from the study and recommended stopping owing to safety concerns in both fluid bolus groups.

The headline finding – 48 hour mortality:

  • 10.6% in the albumin bolus group
  • 10.5% in the saline bolus group
  • 7.3% in the control group

The relative risk for any bolus vs control was remarkable – 1.44 (P=0.003). The results were found to be consistent across the trial sites and across the subgroups even in respect to the underlying conditions (malaria, coma, sepsis, acidosis and severe anaemia).

The authors of the paper concluded:

The results of this study challenge the importance of fluid resuscitation as a lifesaving intervention in resource limited setting for children with shock who do not have hypotension and raise questions regarding fluid-resuscitation guidelines in other settings as well

This week I emailed Professor Kathryn Maitland for her thoughts ahead of our discussion and I thank her for taking the time to email me back. Her response:

The major take home message is that we were all surprised by the result. There was no ‘signal’ from the SAE’s and the clinicians involved in the trial — said they all saw children ‘improve’ on boluses and believed that boluses were good. This is why trials are important.

Overall, mortality was lower than they had previously experienced– which was probably due to training of all staff involved in paediatric care.

Professor Maitland also highlights the FEAST study trial video which in her words “takes you to the bedside and puts the trial into context”.

* * *

Tomorrow I will be posting the discussion points for Sunday evening’s journal club meeting and I look forward to critiquing this fascinating paper.

Thank you to @welsh_gas_doctor for his help with this summary.

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Week 7 – Introduction: Benefits of PCI in Stable Coronary Heart Disease

Percutaneous Coronary Intervention (PCI) is a surgery in which obstruction in a stenotic coronary artery is cleared either by balloon angioplasty or stenting. It is a very common procedure, with a 2006 American Heart Association report estimating 1.2 million procedures in 2003 in the US.

PCI is not generally effective in reducing numbers of myocardial infarctions (MI) or mortality in patients with chronic stable angina, but rather only improves quality of life. (This is according to a number of randomised trials and meta-analyses, most notably the highly-publicised COURAGE trial.) Conversely, PCI can be effective in reducing morbidity and mortality in unstable angina.

This study looked at 153 patients who were undergoing diagnostic cardiac catheterisation, but who had also signed consent form for PCI to be performed if it was deemed to be necessary by the interventional cardiologist. They were asked about demographic characteristics, history of angina, whether they felt they were adequately informed about the procedure, and what their expectations of its benefits were.

The study also looked at physicians’ responses to a similar survey. Ten interventional cardiologists and 17 referring cardiologists were asked about their beliefs on the benefits of PCI, and expected outcomes for various hypothetical patients. With interventional cardiologists, the authors also asked about beliefs for study patients undergoing surgery. From my perspective, the numbers here are strikingly small, though since this is a single-centre survey, this probably placed limits on the number of cardiologists who could be asked. It does, however, mean that some of the n numbers in the results section are very small.

The key finding of the paper is that, among patients, 88% believed PCI would reduce their risk of MI, and 82% believed it would reduce their risk of fatal MI; however, among physicians, only 17% believed PCI would reduce the risk of MI and 15% believed it would reduce fatal MI. Furthermore, there was little agreement between individual patients’ and their cardiologists’ responses.

Despite this disparity, most patients reported their doctor spending at least 5 minutes explaining the procedure to them, and over half received some written information on the matter. Furthermore, 96% believed they knew why they might undergo PCI, and more than half felt they had been actively involved in decision making. With patients on whom PCI was carried out, physicians were more likely than patients to believe that the patient had been involved in decision making (78% v 94%). Also of note: patients felt they were at greater risk of MI than their cardiologists did (according to a 5 point Likert scale). Perhaps bizarrely, patients who thought they knew why there were getting PCI were more likely to hold the inaccurate belief that PCI prevented MI though this did not reach significance (Odds ratio = 5.3, CI 0.82-34.53).

The physician responses to hypothetical scenarios also generated some interesting results, perhaps most significantly:

In the first 2 scenarios, 70% of cardiologists did not identify any bnefit associated with PCI, yet 43% of these indicated that they would proceed to PCI anyway

I can’t help but question why a doctor would go ahead with a procedure from which they could foresee no benefit. In addition, this recent study also showed that for non-acute indications, 12% of PCIs were classified as inappropriate. The majority of these procedures performed in patients with little to no angina or with low-risk ischemia on stress testing.

Patients overestimating the benefits of drugs is not limited to PCI and cardiology, but why is it that patients perceive benefit when there is none? Given that most patients in this study had a discussion with their cardiologist, why were they not better informed about the potential outcomes of PCI? Is it a failure to adequately distinguish between unstable and stable angina? It does follow logically that alleviating the symptoms of cardiovascular disease would alter some underlying mechanisms to reduce the risk of MI, but shouldn’t cardiologists be making it clear to patients that this is not the case? What can doctors do differently to communicate effectively with their patients?

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If you have any other comments on the paper, please do raise them this evening. As usual, a bit before 8 o’clock this evening (UK time, so 7pm GMT) I’ll post the key points for discussion.

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Week 6 – Introduction: Beta-Blockers and COPD

Beta blockers are widely prescribed for a range of conditions and are now widely used in the management of cardiovascular disease. Patients with chronic obstructive pulmonary disease (COPD) often have concurrent co-morbidities including cardiovascular disease. However there has been concerns regarding the prescription  β-blockers in these patients due to worries about the effect it may have on their respiratory function:

  • evidence that the use of  β-blockers in patients with COPD may lead to a reduction in their lung function (by reducing their FEV1 - Forced expiratory volume in one second)
  • β-blockers may increase airway hyperresponsiveness

One of the mainstays of treatment of COPD is the use of beta-agonists and there have been concerns that  β-blockers may lead to inhibition of the bronchodilator response to these drugs.

As such there has been some reluctance to prescribe  β-blockers in these patients. This paper published in the BMJ looked at the use of  β-blockers in patients with COPD to assess the effect on mortality, hospital admissions and exacerbations when used in combination with established therapy for COPD.

This was a retrospective cohort study which identified cases from a disease-specific database in Tayside which is used by GPs and secondary care respiratory physicians. All patients fulfil the GOLD guidelines for diagnosis of COPD and data on these patients was collected by respiratory nurses at yearly visits. The authors then identified patients who had an admission to hospital due to COPD and also gathered data on the prescription of respiratory and cardiovascular drugs and on deaths from the general register.

The main outcome measures were hazard ratios from all cause mortality, emergency oral corticosteriod use (use to treat exacerbations of COPD) and respiratory related hospital admissions. In these patients 88% of the β-blockers used were cardioselective.

The results – this paper showed a 22% reduction in all cause mortality in patients prescribed  β-blockers. There was a reduction in the adjusted hazard ratio for patients prescribed β-blockers with standard treatment for COPD compared to those who weren’t (0.28 vs 0.43). The paper also showed a reduction in oral corticosteriod use and hospital admission. There was no adverse effect on lung function detected at all stages of the stepwise treatment approach to COPD.

The authors of this paper concluded that:

 β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function

A list of discussion points will be posted shortly. Thank you to @amcunningham for suggesting this paper.

Posted in Introductions, Week 6 | 1 Comment

Week 5 – Introduction: Safer Surgery Checklist

A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population – Haynes et al for the WHO Safe Surgery Saves Lives Study Group

The paper chosen for this week’s journal club has had an impact on patient safety worldwide: As an F1 during my colorectal surgery job (on the rare occasions I went to theatre) I saw how this paper has changed practice with the implementation of the WHO safe surgery checklist.

In the surgical setting it has been estimated that almost half of all complications are unavoidable. This is a huge patient safety issue. In 2008, the WHO published guidelines to ensure the safety of surgical patients. From this, the authors of the NEJM paper designed a 19 item checklist with the with the aim of reducing surgical complications and its subsequent morbidity and mortality.

The surgical safety checklist is a simple intervention, a checklist that is followed at three key points with the whole surgical team present – before the induction of anaesthesia, before skin incision and before the patient leaves the operating theatre. The primary endpoint of the study was the occurrence of any major complication, including death, during a period of postoperative hospitalisation, up to 30 days (complications were defined as outlined in the American College of Surgeons’ National Surgical Quality Improvement Program).

The trial was run at eight sites in a range of healthcare settings worldwide. Before the checklist was implemented at the trial sites, baseline data, including complication rates, were reported for 3,733 patients at all trial sites. The checklist was then implemented, consecutively enrolling patients over the age of 16 years undergoing non-cardiac surgery. During the pre-checklist period the rate of any complication at all sites was 11%. After the implementation of the checklist this fell to 7% (P<0.001). The total in-hospital rate of death fell from 1.5% to 0.8% (P=0.003). The authors of the paper concluded that:

 Applied on a global basis, this checklist program has the potential to prevent large numbers of deaths and disabling complications, although further study is needed to determine the precise mechanism and durability of the effect in specific settings.

According to the WHO over 3000 hospitals worldwide have now implemented the surgical safety checklist, an impressive figure that shows how research can translate into a world-wide change in practice. Tonight night at 8.00pm BST we will be discussing this paper – a list of discussion points will be posted shortly. I look forward to another interesting and lively debate.

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Week 4 – Introduction and Discussion points: Medical schools and Performance in MRCP

Thank you Fi for asking me to write an introduction and suggest some discussion points for tonight’s Twitter journal club. Having a special interest in medical education I was very happy to see this paper by McManus et al. suggested for Week 4 of the journal club.

Discussion point 1: What factors do you think might explain variation in performance in MRCP between medical schools?

What did authors do? They looked at outcomes in MRCP (Member of the Royal College of Physicians) examination for entrants from all medical schools between 2003 and 2005. They found that in the Part 1 and 2 exams, Cambridge, Oxford, and Newcastle graduates did significantly better than average , and the performance of Liverpool, Aberdeen, Dundee and Belfast students was significantly worse. In the PACES section (a clinical examination based on a modified OSCE) Oxford students performed significantly and Liverpool, Dundee and London students significantly worse.
This first part of the analysis is quite easy to understand but the authors then go on to construct a multi-level model to see if they can explain variation between the medical schools.
Since it is known that ethnicity and gender are correlated with MRCP performance, and they had this as individual level data, they adjusted for this.

Discussion point 2: Is it surprising that the average offer to those applying to a medical school may predict performance of graduates in MRCP?
Two complex analyses were performed in this study: a multilevel model, and a structural equation model. Unfortunately the results of the multilevel model are not produced in an easy to understand format, although there is a figure in an additional file which is downloadable.
The authors looked for correlations between medical school performances in MRCP and a plethora of other factors. This information was pulled from other sources such as the Guardian tables, a survey of the cohort of medical students who started university in 1990/1, and the offers which each medical school made to students in the mid-1990s.
They found correlations between:
- Offers made to students (A level or Scottish higher grades)- the higher the offer the better the performance
- The proportion of final year medical students reporting being interested in a career as a physician, and reporting interesting medical teaching, and better performance in MRCP.
- The higher the percentage of graduates taking MRCP, the better the performance.
However when these factors were analysed together, it was only admission grades that seemed significant.
They also looked at correlations with data from the Guardian tables. In a multiple regression, again only admission criteria were found to be significant.
In the multilevel model, the entrance qualifications of graduates were found to explain 62% of variance, which in this type of study is a large amount. 38% of variance remained unexplained but a commenter has suggested that the contribution of entrance qualifications may be under-estimated because of the ‘ceiling effect’- many entrants may have been offered the highest grades of 3 As.

Discussion point 3: Are the authors correct to conclude that this analysis suggests that a national exit exam should be introduced?
What do the results of this study mean? To place the study in context it is perhaps useful to start with the last words of the authors in the paper. They believe that this analysis supports the case for the “introduction of a national licensing examination” in the UK.
We don’t have a national exit exam in the UK. Instead the General Medical Council (GMC) regulates medical education through individual medical schools. Quality assurance of medical education and the final exams which must be passed to gain provisional entry to the medical register rests with the GMC and external examiners.
This analysis shows that different medical schools admit students with different school qualifications, and that the higher the entrance requirements, the greater the success may subsequently be in MRCP. McManus et al refer to a study which shows this is also true of performance in MRCGP exams, but I cannot find that publication.

Discussion point 4: How should we judge the performance of medical schools? Is performance of graduates in post-graduate examinations important?
When this study was published it contributed to discussion about whether a national exit exam should be introduced. Ian Noble, a Sheffield medical student, writing in the BMJ, suggested that medical schools should be judged on whether the graduates they produced performed as competent foundation doctors, not on how well graduates performed in subsequent examinations. Since it is rare for graduates to be pulled up for poor clinical performance this suggests that we have no problem for a national exit exam to solve.

Discussion point 5: How helpful is it to read reviewer’s comments on a paper? Is this something that all journals should aim for?
This paper is published in BMC Medicine which also posts the comments of the peer-reviewers. One of the reviewers suggested that this paper should not be published as although it involved a commendable analysis of multiple datasets it did not “help me to understand the problems in medical education better, nor does it help me to improve medical education or to advance medical education as a science”. The authors’ response to this criticism is also published. The reviewers and the main author also had a dispute over another analysis published in BMC Medicine on gender and ethnicity and success in MRCP. But that discussion was pre-submission so is private correspondence between those involved.

Conflict of Interest: I’m a Belfast graduate!

Posted in Discussion Outlines, Introductions, Week 4 | 2 Comments

Week 3 – Introduction: CRASH-2

For the past two weeks Twitter journal club has looked at two fairly old but still very relevant papers. The paper chosen for this week is at the cutting edge of research and recently won the award for Research Paper of the Year at the 2011 BMJ Awards. This award recognises a paper that the judges believe will have an impact on doctors and patients over the next 5 to 10 years.

The results of CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) were published in The Lancet in June 2010. This was a randomised placebo controlled trial which recruited 20,211 trauma patients with, or at risk of significant haemorrhage in 274 hospitals in 40 countries. Patients were randomised into two arms of the study – either to receive placebo or the drug tranexamic acid. Tranexamic acid is an antifibrinolytic, this drug works by blocking sites on an enzyme that causes blood clot breakdown. The trial was designed to assess whether early administration of this treatment (within eight hours) would have an impact on patient deaths due to bleeding.

The headline finding – all-cause mortality was significantly reduced with tranexamic acid (14.5% in the treatment group vs 16.0% in the placebo group – relative risk 0·91, 95% CI 0·85—0·97; p=0·0035). Risk of death due to bleeding was also significantly reduced (4·9% in the treatment group vs 574 5·7% in placebo group ; relative risk 0·85, 95% CI 0·76—0·96; p=0·0077).

The number needed to treat in this trial – 67, an impressive result (from all-cause mortality figures). The findings of this large scale study have the potential to have a huge impact on the management of trauma patients – the authors of the study have called for this drug to be available to doctors treating trauma patients worldwide and that it should be considered for the WHO’s List of Essential Medicines. As the CRASH 2 team said at the BMJ awards:

“Our research showed that giving tranexamic acid to bleeding trauma patients is both effective and cost effective. These findings are of global importance because every year, over 2 million people die from traumatic haemorrhage”

A very simple intervention with a relatively inexpensive drug that could have a global impact on the mortality of trauma victims worldwide – this is why we have chosen to discuss CRASH-2 in this week’s journal club.

I will be posting a list of discussion points in advance of the journal club on Sunday at 8pm BST. I am very excited to have the opportunity to critique this paper and look forward to another interesting and informative discussion.

Posted in Introductions, Week 3 | 1 Comment