The Extraordinary Prof Coomarasamy Scores a Hat-trick!

To publish three papers in the New England Journal of Medicine in as many months is something out of the ordinary. Yet this is precisely what Prof Coomarasamy and his colleagues achieved between March and May of this year.[1-3]

The first paper was a randomised trial of prophylactic antibiotics when a woman has an evacuation of the uterus for miscarriage.[1] Over 3,400 people were enrolled across Pakistan, Uganda, Tanzania and Malawi. About one woman in 20 developed some type of pelvic infection, but there was no difference according to treatment group. However, the point estimate was in favour of antibiotics, with a one percentage point difference. Since it is known that prophylactic antibiotics are effective across surgery in general,[4] this failure to find evidence of effectiveness should not be taken as evidence of no effectiveness. The suspicion that the treatment might have been effective is increased by the finding that antibiotics were associated with a significantly lower rate of infection, based on the strict CDC definition. Accordingly, the Bayesian CLAHRC WM Director recommends antibiotics in this situation.

The second trial compared the use of thyroxine versus placebo to reduce the risk of miscarriage in people who have thyroid antibodies, but who are euthyroid.[2] Despite the poor rationale for the treatment to work in those who have normal thyroid levels, some previous studies had shown this treatment to be effective. This, rather than a sound theory, was the rationale for the trial. Not surprisingly, the treatment was ineffective (okay, not effective) in nearly 1,000 woman randomised.

The last trial also evaluated hormonal substitution: in this case progesterone for people with a threatened miscarriage.[3] A drop in progesterone levels is theoretically more likely to be the result, rather than the cause, of miscarriage. However, yet again, previous trials had suggested that progesterone therapy can avert miscarriage. And again, the result was null on nearly 4,200 women recruited at 48 hospitals in the UK.

Congratulations to Prof Coomarasamy and his team on these three important studies.

— Richard Lilford, CLAHRC WM Director

References:

1. Lissauer D, Wilson A, Hewitt CA, et al. A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery. N Engl J Med. 2019; 380: 1012-21.
2. Dhillon-Smith RK, Middleton LJ, Sunner KK, et al. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. N Engl J Med. 2019; 380: 1316-25.
3. Coomarasamy A, Devall AJ, Cheed V, et al. A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. N Engl J Med. 2019; 380: 1815-24.
4. Bowater RJ, Stirling SA, Lilford RJ. Is antibiotic prophylaxis in surgery a generally effective intervention? Testing a generic hypothesis over a set of meta-analyses. Ann Surg. 2009; 249(4): 551-6.

The Mortality Gradient

A young man was admitted to a hospital in North KwaZulu-Natal (a province of South Africa) with a stab wound in the upper left quadrant of the abdomen and a falling blood pressure. Only a skeleton staff was on duty, thanks to a public sector strike taking place at the time. Further, only one member of the team was medically qualified, and she was assisted by two medical students on their elective periods. The doctor anaesthetised and intubated the patient, scrubbed, and then started to open the abdomen. A number of things then happened in rapid succession: the blood was found to have turned a blue colour, the oximetry alarm sounded, and the heart stopped. The doctor opened the chest to give internal cardiac compression but to no avail. On opening the chest the problem was identified. Firstly, the knife had penetrated the diaphragm to enter the left lung; a frequent finding with stab wounds to the upper left abdomen. Secondly, the left main bronchus (windpipe) had been intubated. The result was that only the left lung had been ventilated and air had been forced under pressure into the cavity around the lung. This air, forced into the plural space under pressure, had compressed the chest contents, causing the patient’s oxygen levels to plummet.

Mortality rates from surgery for a given condition are roughly twice as high in low- and middle-income countries (LMICs) as in high-income countries. Why is this?

A very large number of recent studies [1-4] have replicated Aneel Bhangu’s classic study in the British Journal of Surgery,[5] confirming the mortality gradient. That the gradient exists is not in real doubt but its causes are. Possible, non exclusive, causes are:

1. The patient arrives in worse condition in LMICs than in high-income countries because they are in worse shape generally, and/or there were large delays in reaching the health care system.
2. Care is worse before surgery, including longer delays within the health care system, and/or post operative care was suboptimal.
3. Intraoperative care was worse, either in terms of anaesthesia (as in the above example – intubation of the left bronchus is a classic error requiring special vigilance in cases where there is a risk that the integrity of the lung has been compromised), and/or surgery itself.

A fashion has broken out to compare death rates for given conditions across high- and low-income countries, and then ascribe observed differences in outcome to differences in healthcare provision, expressed in terms of lives (or even DALYs) lost. Such an approach can work well at the specific level when two conditions are met:

1. A specific condition is examined and this condition has a poor natural history, but an extremely good prognosis given appropriate medical care. Perinatal haemorrhage and eclampsia are good examples.
2. The way in which healthcare can remedy the situation is well defined. Treatment of ruptured spleen or meningitis are good examples.

Absent conditions fulfilling the above criteria, comparisons between high- and low-income countries should motivate serious investigation for causes. Until the cause of the difference is determined, advocacy based only on differences between high- and low-income countries is without intellectual or moral value. Decisions should be based on the best use of restricted resources and simply pointing out north-south differences in outcomes adds no value to determining priorities within LMICs. It is wasteful to advocate resource allocation under scarcity until the payback among different competing causes has been examined. The correct use of measuring differences in outcome over countries should not be to advocate for resources for action. These differences in outcome should motivate a sober search for these causes, and then for cost-effective short- and long-term solutions.

To that end I am leading a cross NIHR initiative into one particular candidate area – access to hospital when care is sought. I also lead the access theme for the NIHR Global Health Research Unit on Global Surgery. One of our tasks is to model the cost-effectiveness of various solutions to overcome the second barrier to access identified above. Our work is hampered by poor data (poor because it is hard to collect) on effects of delay on outcome. Strangely enough, snakebites is the one area where rather good data exist, so we are starting our work in this, otherwise rather narrow, topic. We also plan to study survival rates in UK by measuring distances from local hospitals in conditions such as leaking aortic aneurysms and heart attack.

In the meantime Dr Bruce Biccard of Cape Town, who leads the hospital care work stream in Global Surgery, is turning his attention from differences in outcome to the causes and remedies.

— Richard Lilford, CLAHRC WM Director

References:

1. Abbott TEF, Fowler AJ, Dobbs TD, Harrison EM, Gillies MA, Pearse RM. Frequency of surgical treatment and related hospital procedures in the UK: a national ecological study using hospital episode statistics. Br J Anaesthesia. 2017; 119(2): 249-57.
2. Anderson GA, Ilcisin L, Abesiga L, et al. Surgical volume and postoperative mortality rate at a referral hospital in Western Uganda: Measuring the Lancet Commission on Global Surgery indicators in low-resource settings. Surgery. 2017; 161(6): 1710-9.
3. GlobalSurg Collaborative. Management and Outcomes Following Surgery for Gastrointestinal Typhoid: An International, Prospective, Multicentre Cohort Study. World J Surg. 2018; 42(10): 3179-88.
4. Biccard BM, Madiba TE, Kluyts H-L. Perioperative patient outcomes in the African Surgical Outcomes Study: a 7-day prospective observational cohort study. Lancet. 2018; 391: 1589-98.
5. GlobalSurg Collaborative. Mortality of emergency abdominal surgery in high-, middle- and low-income countries. Br J Surg. 2016; 103(8): 971-88.

When Randomisation is not Enough: Masking for Efficacy Trials of Skin Disease, Ulcers and Wound Infections

In a previous News Blog [1] we discussed endpoint measurement for trials of wound infection, where the observers were not ‘blinded’ (not masked to the intervention group). Such an approach is simply not adequate, even if the observers use ‘strict criteria’.[1] This is because of subjectivity in the interpretation of the criteria and, more especially, because of reactivity. Reactivity means that observers are influenced, albeit sub-consciously, by knowledge of the group to which patients have been assigned (treatment or not). Such reactivity is an important source of bias in science.[2]

We are proposing a trial of a promising treatment for recurrent leprosy ulcers that we would like to carry out in the Leprosy Mission Hospital in Kathmandu, Nepal. We plan to conduct an efficacy trial of a regenerative medicine (RM) technique where a paste is made from the buffy coat layer of the patient’s own blood. This is applied to the ulcer surface at the time of dressing change. The only difference in treatment will be whether or not the RM technique is applied when the regular change of wet dressing is scheduled. We will measure, amongst other things, the rate of healing on the ulcers and time to complete healing and discharge from hospital.

Patients will be randomised so as to avoid selection bias and, as the primary endpoints in this efficacy trial are measured during the hospital sojourn (and patients seldom discharge themselves), we are mainly concerned with outcome bias as far as endpoints regarding ulcer size are concerned.

One obvious way to get around the problem of reactivity is to use a well described method in which truly masked observers, typically based off-site, measure ulcer size using photographs. Measurements are based on a sterile metal ruler positioned at the level of the ulcer to standardise the measurement irrespective of the distance of the camera. The measurement can be done manually or automated by computer (or both). But is that enough? It has been argued that bias can still arise, not at the stage where photographs are analysed, but rather at the earlier stage of photograph acquisition. This argument holds that, again perhaps sub-consciously, those responsible for taking the photograph can affect its appearance. The question of blinding / masking of medical images is a long-standing topic of debate.

The ‘gold standard’ method is to have an independent observer arrive on the scene at the appropriate time to make the observations (and take any photographs). Such a method would be expensive (and logistically challenging over long distances). So, an alternative would be to deploy such an observer for a random sub-set of cases. This method may work but it has certain disadvantages. First, it would be tricky to choreograph as it would disrupt the work flow in settings such as that described above. Second, to act as a method of audit, it would need to be used alongside the existing method (making the method still more ‘unwieldy’). Third, the method of preparing the wound would still lie in the hands of the clinical team, and arguably still be subject to some sort of subconscious ‘manipulation’ (unless the observer also provided the clinical care). Fourth, given that agreement would not be exact between observers, a threshold would have to be agreed regarding the magnitude of difference between the standard method and the monitoring method that would be regarded as problematic. Fifth, it would not be clear how to proceed if such a threshold was crossed. While none of these problems are necessarily insurmountable, they are sufficiently problematic to invite consideration of further methods. What might augment or replace standard third party analysis of photographic material?

Here we draw our inspiration from a trial of surgical technique in the field of ophthalmology/orbital surgery.[3] In this trial, surgical operations were video-taped in both the intervention and control groups. With permission of patients, we are considering such an approach in our proposed trial. The vast majority of ulcers are on the lower extremities, so patients’ faces would not appear in the videos. The videos could be arranged so that staff were not individually identifiable, though they could be redacted if and where necessary. We would like to try to develop a method whereby the photographs were directed in real time by remote video link, but pending the establishment of such a link, we propose that each procedure (dressing change) is video-taped, adhering to certain guidelines (for example, shot in high-definition, moving the camera to give a full view of the limb from all sides, adequate lighting, a measurement instrument is included in the shot, etc.). We propose that measurements are made both in the usual way (from mobile phone photographs), and from ‘stills’ obtained from the video-tapes. Each could be scored by two independent, off-site observers. Furthermore the videos could be used as a method of ‘ethnographic’ analysis of the process to surface any material differences between patients in each trial arm in lighting, preparation of ulcer sites, time spent on various stages of the procedure and photograph acquisition, and so on.

Would this solve the problem? After all, local clinicians would still prepare the ulcer site for re-bandaging and, insofar as they may be able to subconsciously manipulate the situation, this risk has not been vitiated. However, we hypothesise that the video will work a little like a black box on an aeroplane; it cannot stop things happening, but it provides a powerful method to unravel what did happen. The problem we believe we face is not deliberate maleficence, but subtle bias at the most. We think that by using the photographic approach, in accordance with guidelines for such an approach,[4] we already mitigate the risk of outcome measurement bias. We think that by introducing a further level of scrutiny, we reduce the risk of bias still further. Can the particular risk we describe here be reduced to zero? We think not. Replication remains an important safeguard to the scientific endeavour. We now turn our attention to this further safeguard.

Leprosy ulcers are far from the only type of ulcer to which the regenerative medicine solution proposed here is relevant. Diabetic ulcers, in particular, are similar to leprosy ulcers in that loss of neural sensation plays a large part in both. We have argued elsewhere that much can be learned by comparing the results of the same treatment across different disease classes. In due course we hope to collaborate with those who care for other types of skin ulcer so that we can compare and contrast and also to advance methodologically. Together we will seek the optimal method to limit expense and disruption of workflow while minimising outcome bias from reactive measurements.

— Richard Lilford, CLAHRC WM Director

References:

1. Lilford RJ. Before and After Study Shows Large Reductions in Surgical Site Infections Across Four African Countries. NIHR CLAHRC West Midlands News Blog. 10 August 2018.
2. Kazdin AE. Unobtrusive measures in behavioral assessment. J Appl Behav Anal. 1979; 12: 713–24.
3. Feldon SE, Scherer RW, Hooper FJ, et al. Surgical quality assurance in the Ischemic Optic Neuropathy Decompression Trial (IONDT). Control Clin Trials. 2003; 24: 294-305.
4. Bowen AC, Burns K, Tong SY, Andrews RM, Liddle R, O’Meara IM, et al. Standardising and assessing digital images for use in clinical trials: a practical, reproducible method that blinds the assessor to treatment allocation. PLoS One. 2014;9(11):e110395.

Trials are Not Always Needed for Evaluation of Surgical Interventions: Does This House Agree?

I supported the above motion at a recent surgical trails meeting in Bristol. What where are my arguments?

I argued that there were four broad categories of intervention where trials were not needed:

1. Where causality is not in dispute

This scenario arises where, but for the intervention, a bad outcome was all but inevitable. Showing that such an outcome can be prevented in only a few cases is sufficient to put the substantive question to bed. Such an intervention is sometimes referred to as a ‘penicillin-type’ of intervention. Surgical examples include heart transplantation and in vitro fertilisation (for people both of whose Fallopian tubes have been removed). From a philosophy of science perspective, causal thinking requires a counterfactual: what would have happened absent the intervention? In most instances a randomised trial provides the best approximation to that counterfactual. However, when the counterfactual is near inevitable death, then a few cases will be sufficient to prove the principle. Of course, this is not the end of the story. Trials of different methods within a generic class will always be needed, along with trials of cases where the indication is less clear cut, and hence where the counterfactual cannot be predicted with a high level of certainty. Nevertheless, the initial introduction of heart transplantation and in vitro fertilisation took place without any randomised trial. Nor was such a trial necessary.

2. Speculative procedures where there is an asymmetry of outcome

This is similar to the above category, but the justification is ethical rather than scientific. I described a 15 year old girl who was born with no vagina but a functioning uterus. She was referred to me with a pyometra, having had an unsuccessful attempt to create a channel where the vagina should have been. The standard treatment in such a dire situation would have been hysterectomy. However, I offered to improvise and try an experimental procedure using tissue expansion methods to stretch the skin at the vaginal opening and then to use this skin to create a functioning channel linking the uterus to the exterior. The patient and her guardian accepted this procedure, in the full knowledge that it was entirely experimental. In the event, I am glad to report that the operation was successful, producing a functional vagina and allowing regular menstruation.[1] The formal theory behind innovative practice in such dire situations comes from expected utility theory.[2] An example is explicated in the figure.

This example relates to a person with very low life expectancy and a high-risk procedure that may either prove fatal or extend their life for a considerable time. In such a situation, the expected value of the risky procedure considerably exceeds doing nothing and is preferable, from the point of view of the patient, to entry in an RCT. In fact, the expected value of the RCT (with a 1:1 randomisation ratio) is (0.5 x 0.25) + (0.5 x 1.0) = 0.625. While favourable in comparison to ‘no intervention’, it is inferior in comparison with the ‘risky intervention’.

3. When the intervention has not been well thought through

Here my example was full frontal lobotomy. Trials and other epidemiological methods can only work out how to reach an objective, not which objective to reach or prioritise. Taking away someone’s personality is nota fair price to pay for mental calmness.

4. When the trial is poor value for money

Trials are often expensive and we have made them more so with extensive procedural rules. Collection of end-points by routine systems is only part of the answer to this question. Hence trials can be a poor use of research resources. Modelling shows that the value of the information trials provide is sometimes exceeded by the opportunity cost.[3-5]

Of course, I am an ardent trialist. But informed consent must be fully informed so that the preferences of the patient can come into play. I conducted an RCT of two methods of entering a patient into an RCT and showed that more and better information reduced willingness to be randomised.[6] Trial entry is justified when equipoise applies, and the ‘expected value’ of the alternative treatment is about the same.[7] The exception is when the new treatment is unlicensed. Then equipoise plus should apply – the expected value of trial entry should exceed or equal that of standard treatment.[8]

— Richard Lilford, CLAHRC WM Director

References:

1. Lilford RJ, Sharpe DT, Thomas DFM. Use of tissue expansion techniques to create skin fplas for vaginoplasty. Case report. Br J Obstet Gynacol. 1988;95: 402-7.
2. Lilford RJ. Trade-off between gestational age and miscarriage risk of prenatal testing: does it vary according to genetic risk? Lancet. 1990; 336: 1303-5.
3. De Bono M, Fawdry RDS, Lilford RJ. Size of trials for evaluation of antenatal tests of fetal wellbeing in high risk pregnancy. J Perinat Med. 1990; 18(2): 77-87.
4. Lilford R, Girling A, Braunholtz D. Cost-Utility Analysis When Not Everyone Wants the Treatment: Modeling Split-Choice Bias.Med Decis Making. 2007; 27(1): 21-6.
5. Girling AJ, Freeman G, Gordon JP, Poole-Wilson P, Scott DA, Lilford RJ. Modeling payback from research into the efficacy of left-ventricular assist devices as destination therapy. Int J Technol Assess Health Care. 2007; 23(2): 269-77.
6. Wragg JA, Robison EJ, Lilford RJ. Information presentation and decisions to enter clinical trials: a hypothetical trial of hormone replacement therapy. Soc Sci Med. 2000; 51(3): 453-62.
7. Lilford J. Ethics of clinical trials from a Bayesian and decision analytic perspective: whose equipoise is it anyway?BMJ. 2003; 326: 980.
8. Robinson EJ, Kerr CE, Stevens AJ, Lilford RJ, Braunholtz DA, Edwards SJ, Beck SR, Roelwy MG. Lay public’s understanding of equipoise and randomisation in randomised controlled trials. Health Technol Assess. 2005; 9(8): 1-192.

The Sexual Politics of the Operating Theatre

When I lead the Patient Safety Research Portfolio on behalf of the Chief Medical Officer, I commissioned an ethnographic study of the operating theatre environment from Steven Harrison of Manchester.[1] The study chronicled a tale of persistent interruption during surgical operations – telephones rang, messages were sent from the wards, people burst in with the latest cricket score, and so on. Harrison speculated that such a string of interruptions would be inimical to patient safety. He was right; we have cited evidence that frequent interruptions are indeed a threat to patient safety.[2] Repeated distraction intrudes on working memory and thereby predisposes to error – a factor long recognised in aviation (see also the following news blog article).

It turns out that more subtle processes are also in play – gender mix has a large effect on a behaviour, at least according to observations of 400 doctors and nurses during 200 surgical operations.[3] The study was carried out by experts on animal behaviour and the findings showed that the doctors and nurses tended to mimic those of animals in the wild. Think of that next time you have a surgical operation!  Conflict between individuals was twice as likely in teams led by men as in teams led by women. Regardless of who led the team, conflict was much less when the team leader was the opposite gender to the rest of the team.

In previous issues of your news blog, we have cited comparisons between male and female doctors.[4] [5] In all cases the female doctors show higher performance. As pointed out in these blogs, these findings are replicated over many complex tasks in the modern economy. I am led to the conclusion  that the evolutionary characteristics of women are more conducive  for high performance in the modern collaborative economy, then those which males acquired in order to hunt animals and repel enemies. But all is not lost for us men. Awareness of our own foibles is the first step to adaptation and more effective functioning in the modern workplace.

— Richard Lilford, CLAHRC WM Director

References:

1. Harrison S. Operating theatres – the threats to patient safety. PSRP Briefing Paper. PS008. 2006.
2. Lilford RJ. Interruptions Lead to Errors. NIHR CLAHRC West Midlands News Blog. 23 March 2018.
3. Jones LK, Jennings BM, Higgins MK, de Waal FBM. Ethological observations of social behavior in the operating room. Proc Nat Acad Sci. 2018.
4. Lilford RJ. Are Female Doctors Better Than Male Doctors? NIHR CLAHRC West Midlands News Blog. 13 January 2017.
5. Lilford RJ. “Why Can’t a Man be More Like a Woman” – Revisited. NIHR CLAHRC West Midlands News Blog. 27 October 2017.

Distraction and Clinical Errors in an Emergency Department

What is not in doubt, is that distraction increases error rates in laboratory studies.[1] However there are very few studies of the effect of distracting clinicians in the real world of clinical practice. Such studies are very difficult to mount since they require real-time observation and a valid measure of clinical performance.

These problems were surmounted in an interesting and important study from Australia.[2] Distraction was observed in real-time by trained observers in the emergency department. Performance was measured by means of prescription error rates, which were adjudicated independently of the study by trained pharmacists. The independent effect of various factors that might interact with distraction were estimated by means of multi-variable analysis. The study showed that, independent of age or seniority, there was a very large increase in clinical prescribing errors when doctors were distracted.

Previous laboratory studies have shown a relationship between so called ‘working memory’ and predisposition to make errors when distracted. So the investigators carried out a psychological test for working memory in the clinical study. They found that, independently of age, the higher the working memory, the lower the effect of distraction.

This study provides convincing evidence that reducing distractions is an important requirement in clinical environments, such as the operating theatre and the emergency department. Of course, there may be a trade-off here; avoiding distractions might place other patients at risk. And it is hard to see how distractions can be totally avoided in a frenetic environment, such as that prevailing in the emergency department.

So, it is important not to act in a reflex way, given these findings, and mandate zero tolerance for distraction. But we should bear down on distraction, as discussed in the previous article.

— Richard Lilford, CLAHRC WM Director

strong>References:

1. Lilford RJ. Interruptions Lead to Errors. NIHR CLAHRC West Midlands News Blog. 23 March 2018.
2. Westbrook JI, Raban MZ, Walter SR, Douglas H. Task errors by emergency physicians are associated with interruptions, multitasking, fatigue and working memory capacity: a prospective, direct observation study. BMJ Qual Saf. 2018; 27: 655-63.

Before and After Study Shows Large Reductions in Surgical Site Infections Across Four African Countries

This important study from the WHO Infection Prevention and Control global unit was based on a multi-component intervention.[1] The intervention consisted of a number of specific measures, including not shaving the skin prior to surgery, antibiotic prophylaxis and proper skin preparation. It also included some generic cultural components, including the promotion of operating theatre discipline.

The incidence of post-operative infections of the surgical site was halved from 8% to about 4% following implementation of the intervention. No contemporaneous national initiative took place in any of the countries concerned, so I think that a general temporal effect, or rising tide,[2] is unlikely. Moreover, process measures improved in line with the clinical outcomes. A cause-effect explanation is thus plausible.

Yet, people will be properly sceptical of this result. Determining a surgical site infection (SSI) is subjective, as has been shown in many empirical studies.[3] Such measurements are likely to be reactive, meaning that there is an interaction between the intervention and the outcomes observed. The way to get around this is to objectify the observations in some way, such as by blinding the observers. Reactivity is a limitation on most studies of SSIs, whether randomised or observational. In my opinion, it is worth spending additional money to avoid this problem, which cannot simply be wished away. Possible methods to get around the problem include: use of observers who move from institution to institution and who do not know where or when interventions were implemented; or use of images scored blindly by independent observers. If this is too expensive, then independent sampling of wards taken at random by a truly blinded observer should be used. In the meantime, given the likely reactivity of the measurement, it is prudent to interpret RCTs of methods to reduce SSIs with caution.

— Richard Lilford, CLAHRC WM Director

References:

1. Allegranzi B, Aiken AM, Kubilay NZ, et al. A multimodal infection control and patient safety intervention to reduce surgical site infections in Africa: a multicentre, before-after, cohort study. Lancet Infect Dis. 2018; 18: 507-15.
2. Chen YF, Hemming K, Stevens AJ, Lilford RJ. Secular trends and evaluation of complex interventions: the rising tide phenomenon. BMJ Qual Saf. 2016; 25: 303-10.
3. Taylor JS, Marten CA, Potts KA, et al. What is the Real Rate of Surgical Site Infection? J Oncol Pract. 2016; 12(10): e878-83.

Which are the Most Cost-Effective Surgical Operations for Low- and Middle-Income Countries?

I recently came across a Lancet review on essential surgery: operations that should be available to even very poor communities.[1] The authors sensibly divide the list into those that should be available in first-level hospitals, and those that should be available in specialist (tertiary) hospitals.

Obstetrical and gynaecological procedure’s rank high in the first list, including caesarean section, surgery for ectopic pregnancy, and tubal ligation. There are a large number of operations related to trauma, including chest drain, complex fracture reduction, laparotomy, amputation, and debridement. Also included for the first-level hospitals are a range of general surgical procedures, such as repair of perforations, appendectomy, hernia repair, and colostomy.

Specialist procedures that should be available in tertiary hospitals include congenital abnormalities (especially cleft lip and club foot) and eye surgery (cataract extraction or eyelid repair for trachoma).

But how cost-effective are all these procedures? A recent study in PLOS One summarises some of the recent evidence.[2] The most cost-effective surgery is emergency caesarean section and voluntary male circumcision. This is followed in increasing order by: cataract surgery, cleft lip and palate surgery, hernia repair, breast cancer surgery, trauma surgery, colorectal surgery, and non-emergency orthopaedic conditions. I think vesicovaginal fistula should be high on the list.

One notes that most, but not all, of the highly cost-effective surgical conditions relate to acute presentations rather than chronic conditions. This underlines the critical importance of access to first-level hospital care. Such access is crucial, not only for surgical conditions, but also acute medical conditions such as meningitis, malaria and snake bites.

— Richard Lilford, CLAHRC WM Director

References:

1. Mock CN, Donkor P, Gawande A, Jamison DT, Kruk ME, Debas HT, for the DCP3 Essential Surgery Author Group. Essential surgery: key messages from Disease Control Priorities, 3rd edition. Lancet. 2015; 385: 2209-19.
2. Horton S, Gelband H, Jamison D, Levin C, Nugent R, Watkins D. Ranking 93 health interventions for low- and middle-income countries by cost-effectiveness. PLoS ONE. 2017; 12(8): e0182951.

A JAMA Article that Spectacularly Misses the Point

A recent article in JAMA Surgery examined complication rates from bariatric surgery across a large number of hospitals in the US.[1] They found implausibly large differences ranging from 0.6% to 10.3%; a 17-fold difference. There was no real effect of surgical volume on these outcome rates. The authors go on at some length about risk adjustment and sampling variation, thereby spectacularly missing the point. Different observers determined the adverse events in different centres. In general, observers have a very low reliability. Such high Inter-observer variation has been demonstrated for wound infections and anastomotic leak in numerous studies. If you want to compare hospitals, then unless you have a very firm outcome such as death, you must have lots of observers and all the observers must examine different institutions. Those who try to drive up quality and safety need a much more sophisticated understanding of measurement theory.

— Richard Lilford, CLAHRC WM Director

Reference:

1. Ibrahaim AM, Ghaferi AA, Thumma JR, Dimick JB. Variation in Outcomes at Bariatric Surgery Centers of Excellence. JAMA Surg. 2017; 152(7): 629-36.

Keyhole Treatment of Ruptured Abdominal Aneurism

When I was a junior houseman I assisted at three operations to repair ruptured aortic aneurisms and all the patients died on the table – a horrible feeling that made a lasting impression on my young mind. That was a particularly bad run, but ruptured aneurism is a mortal condition, so a recent RCT of keyhole (endovascular) treatment funded by the HTA programme caught my eye.[1] I had a further reason to be interested because around a decade ago I chaired the steering committee for a trial of endovascular repair of un-ruptured aneurisms.[2] This showed that the keyhole approach was superior – higher survival rate, less complications, much less pain. What about ruptured aneurisms then? The recent trial enrolled over 600 people, and nearly half died within 90 days of the operation. However, the proportion of deaths was slightly higher in the open surgery group, and quality of life among the survivors was worse in the open surgery than in the endovascular group.[1] Endovascular repair emerges as the operation of choice. Mean follow-up was for about four years. Thirty centres took part (one in Canada, the rest in the UK), which makes the results pretty generalisable to the UK as a whole, since I guess about a third of hospitals took part. Some of the remainder may not have facilities for endovascular repair, so it will be interesting to observe the patterns of open vs. endovascular repair over the next decade. And congratulations to all who contributed to this iconic study.

— Richard Lilford, CLAHRC WM Director

References:

1. IMPROVE Trial Investigators. Comparative clinical effectiveness and cost effectiveness of endovascular strategy v open repair for ruptured abdominal aortic aneurysm: three year results of the IMPROVE randomised trial. BMJ. 2017; 359: j4859.
2. The United Kingdom EVAR Trial Investigators. Endovascular versus Open Repair of Abdominal Aortic Aneurysm. N Engl J Med. 2010; 362: 1863-71.