Tag Archives: Peter Chilton

Reducing Risk of Postpartum Haemorrhage in LMICs

­Worldwide around 127,000 women die each year due to postpartum haemorrhage (the loss of 500ml of blood within the first 24 hours after giving birth), making it the most common cause of maternal death.[1] It is especially prevalent in low- or middle-income countries (LMICs). The standard treatment is administration of oxytocin – however, the drug needs to be kept at 20-25°C, which can be difficult in some countries where refrigeration isn’t reliable in either the hospital or whilst being transported. Thus, there is a need for an alternative option. Widmer and colleagues conducted a double-blind RCT of nearly 30,000 women across ten countries comparing postpartum administration of oxytocin with carbetocin, a heat-stable oxytocin analogue that can be stored at room temperature.[2] Both groups of women showed similar frequencies of blood loss – 14.4% of those given oxytocin lost >500ml of blood, compared to 14.5% given carbetocin (relative risk 1.01, 95% CI 0.95-1.06); while, respectively, 1.45% and 1.51% lost >1000ml of blood (relative risk 1.04, 95% CI 0.87-1.25). There were also no significant differences in necessary interventions or adverse events.

Carbetocin could even perform better than oxytocin in LMICs as the oxytocin was stored in optimum conditions, which may not accurately reflect real-life settings. It will be interesting to track the implementation to uptake of this new finding – any takers?

— Peter Chilton, Research Fellow

References:

  1. World Health Organization. Making Pregnancy Safer. Issue 4. Geneva, CHE: World Health Organization; 2007.
  2. Widmer M, Piaggio G, Nguyen TMH, et al. Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth. New Engl J Med. 2018.
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Using Polio to Treat Cancer

Up until the mid-1950s polio was epidemic across many countries with an estimated 500,000 people paralysed or killed each year. Two vaccines were developed (one by Jonas Salk launched in 1957, the other by Albert Sabin in 1962), which lead to a dramatic decline in cases, and eventually eradication in many high-income countries. Following this the World Health Organization, UNICEF and the Rotary Foundation began an eradication campaign in 1988, and as a result there were only 22 reported polio cases worldwide in 2017. However, recent research has suggested that polio may be able to help patients with grade IV malignant gliomas.[1] Such patients have low survival rates – less than 20 months following diagnosis, and less than 12 months for recurrent gliomas. Current therapies are ineffective, inconsistent in improving survival and have many toxic effects. The trial was conducted using PVSRIPO, a modified live attenuated poliovirus type 1 vaccine. This is able to recognise CD155, a poliovirus receptor that is widely expressed in tumour cells. In total 61 patients were given a dose of PVSRIPO and followed up. Although 19% of patients had moderate-severe (grade 3 or higher) adverse events attributed to PVSRIPO, the overall survival of patients reached a plateau of 21% (95% CI 11-33) at 24 months, which was sustained at 36 months. This was higher than the rate among historical controls.

References:

  1. Desjardins A, Gromeier M, Herndon JE, et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus. New Engl J Med. 2018.

More on Body-Worn Cameras for the Police

In our previous News Blog we talked about a study that looked at the effect body cameras had on the behaviour of police officers.[1] The study found there was no significant differences seen for those who did and did not wear a body camera, and there was no improvement in behaviours. However, as we pointed out the results may have been context-specific as the study was conducted in only one district. Now, News Blog reader Peter Lilford has directed us to a similar study based in the UK and the USA.[2] This study, by researchers at Cambridge University, looked at over 4,000 shifts across seven sites where police officers were randomised to either wear a camera or not. All officers taking part wore a camera at some point over the year-long study. They found that by the end of the study period complaints against police officers had fallen by 93% (p<0.001). However, there was no significant difference in the number of complaints received by those wearing or not wearing a camera. The authors believe that this could be due to ‘contiguous accountability’ from repeated surveillance that even affected departments not taking part in the study. Another factor that the authors believe to be important is that police officers issued a warning at the beginning of any encounter that there was a camera present, perhaps serving to influence the resulting behaviours.

— Peter Chilton, Research Fellow

References:

  1. Lilford RJ. What are the Effects of Body-Worn Cameras on Police and Citizen Behaviour? NIHR CLAHRC West Midlands News Blog. 1 June 2018.
  2. Ariel B, Sutherland A, Henstock D, et al. Contiguous Accountability: Global Multisite Randomized Controlled Trial on the Effect of Police Body-Worn Cameras on Citizens’ Complaints Against the Police. Crim Just Behav. 2016.

Time to Tweet

A number of studies have suggested various effects that the circadian rhythm has on our lives, from mood [1] to our immune system.[2] It is also likely to impact our day-to-day lives, as such a team at the University of Bristol looked into how it could affect our thoughts and emotions.[3] The authors analysed a sample of over 800m Tweets from UK users posted throughout the day over a four-year period by comparing the words used to linguistic lists that had been designed to infer various psychological states of a person. They found that two independent peak times were able to explain 85% of the variance in word usage seen. The first is a peak at 5-6am that is correlated with analytical thinking, motivational thinking, and personal concerns, and is negatively correlated with negative language and social concerns. The second is a peak at 3-4am, correlated with existential concerns, and negatively correlated with positive emotions. These time peaks are also associated with major changes in neural activity and hormonal levels.

The language we use changes drastically throughout the day, a reflection of changes in our main concerns, and cognitive and emotional processes.

— Peter Chilton, Research Fellow

References:

  1. McClung CA. Circadian genes, rhythms and the biology of mood disorders. Pharmacol Therap. 2007; 114(2): 222-32.
  2. Lange T, Dimitrov S, Born J. Effects of sleep and circadian rhythm on the human immune system. Ann N Y Acad Sci. 2010; 1193:48-59.
  3. Dzogang F, Lightman S, Cristianini N. Diurnal variations of psychometric indicators in Twitter content. PLOS One. 2018.

Recording University Lectures

In this News Blog we have often discussed various interventions aimed at improving the education of students.[1][2] Here is another one. Increasingly universities are encouraging (or mandating) that staff record their lectures so that they can be put online. Not only is this thought to help students who are unable to attend, but it also allows students to repeat sections they may have missed/misheard, etc. However, the pre-recorded nature means that students are not as easily able to get clarifications or take part in discussions, and could miss out by not attending the ‘live’ lecture. Further, knowing that the lecture is available anytime, may mean that students delay watching indefinitely – ‘I’ll watch it tomorrow’, etc.

A before-and-after study by Edwards and Clinton looked at the impact making recorded lectures available had on second year undergraduate students.[3] They found that introducing lecture recording was associated with a significant decrease in lecture attendance, while attendance mediated a negative relationship between the availability of recorded lectures and students’ attainment. When lecture attendance was factored in, there was no significant relationship between watching recorded lectures and attainment. On balance, the study showed that the effects of introducing lecture recording were negative. Based on this, it could be worth reconsidering the move to relying on recorded lectures.

— Peter Chilton, Research Fellow

References:

  1. Lilford RJ. Another Interesting Trial of an Educational Intervention – This Time Concerning Access. 21 July 2017. NIHR CLAHRC West Midlands News Blog.
  2. Lilford RJ. Evidence-Based Education. 24 February 2017. NIHR CLAHRC West Midlands News Blog.
  3. Edwards MR & Clinton ME. A study exploring the impact of lecture capture availability and lecture capture usage on student attendance and attainment. High Educ. 2018.

Vaccinating Against Mosquitoes

Getting bit by a mosquito could potentially lead to a wide variety of infections – dengue, yellow fever, Zika, malaria, etc. The usual method to try to prevent the spread of these diseases is vaccination, but this is hindered in most of these diseases due to the various sub-types and strain variations. But what if there was another way? That is what Jessica Manning and colleagues are looking into – developing a vaccine against mosquito saliva.[1] When a mosquito bites a person, it first injects its saliva into the blood stream before drinking blood, which triggers the person’s innate immune response. This immune response can then inadvertently help spread any pathogens through the lymphatic system. However, the authors hypothesise that by vaccinating a person against the saliva itself then the body will have a different, targeted immune response, which can hopefully destroy the pathogens before they spread and cause infection. A proof of principle has already been shown in animals that have been vaccinated against sand fly saliva, which prevents infection by Leishmania.

Although there is still a long way to go, it is an interesting approach that should be closely monitored.

— Peter Chilton, Research Fellow

Reference:

  1. Manning JE, Morens DM, Kamhawi S, Valenzuela JG, Memoli M. Mosquito Saliva: The Hope for a Universal Arbovirus Vaccine? J Infect Dis. 2018; 218 (1): 7-15.

Are You Getting Enough?

Most people are aware of the importance of getting a good night’s sleep, but for many actually achieving this amidst work, household chores, children and needing to binge the latest television series, it is difficult. How dangerous is a lack of sleep though? A recent study [1] looked at data from over 43,000 Swedish people, followed up over 13 years, and found that adults (under the age of 65) who slept for fewer than five hours a night all week have a higher mortality risk compared to those who sleep for six or seven hours (hazard ratio 1.65, 95% confidence intervals 1.22-2.23). However, this could be counteracted by getting longer sleep on the weekend – people who had no more than five hours in the week, but were able to get at least eight hours on the weekend had no increased mortality. On the other end of the scale, the research also found that those people who regularly slept for more than eight hours also had a higher rate of mortality compared to those with six or seven hours (hazard ratio 1.25, 95% CI 1-05-1.50). After the age of 65 there doesn’t appear to be any differences. Of course, it is unknown what the causal relationship is between sleep and mortality, and the authors suggest that underlying health problems could be the cause of both extreme sleep patterns and increased mortality.

— Peter Chilton, Research Fellow

References:

  1. Åkerstedt T, Ghilotti F, Grotta A, Zhao H, Adami HO, Trolle-Lagerros Y, Bellocco R. Sleep duration and mortality – does weekend sleep matter? J Sleep Res. 2018.

Widespread Use of Antibiotics to Reduce Child Mortality

As discussed in our previous News Blog,[1] the rise in antibiotic resistance is a worrying situation, and it is widely recommended to limit the prescription of antibiotics to patients who are confirmed to have a treatable bacterial infection. However, a recent trial in three sub-Saharan African countries did the exact opposite with a mass distribution of azithromycin, a broad-spectrum antibiotic, to children under five with the aim of reducing child mortality.[2] This was a cluster-randomised trial of around 190,000 children in 1,533 communities of Malawi, Niger and Tanzania who were assigned to receive four biannual doses of antibiotic or a placebo. Overall, the mortality rate was 14.6 deaths per 1,000 person-years in areas that received the antibiotic, compared to 16.5 deaths in communities that received the placebo, while mortality was also 13.5% lower (95% confidence interval, 6.7-19.8) (p<0.001). The effect was greatest in the youngest sub-group of children, those aged between one and five months, with the authors estimating that one in four expected deaths were prevented due to administration of the antibiotic. There were no differences in serious adverse events within a week of administration. If this strategy was to be more widely rolled out, one approach to combat resistance developing would be to limit it to the populations most in need and only for a short time.[3]

— Peter Chilton, Research Fellow

References:

  1. Chilton PJ. Non-Antibiotic Medicines May Increase Antibiotic Resistance. NIHR CLAHRC West Midlands News Blog. 18 May 2018.
  2. Keenan JD, Bailey RL, West SK, Arzika AM, for the MORDOR Study Group. Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. New Engl J Med. 2018; 378: 1583-92.
  3. Maxmen A. Giving at-risk children pre-emptive antibiotics reduces deaths. Nature. 25 April 2018.

Non-Antibiotic Medicines May Increase Antibiotic Resistance

Alexander Fleming predicted the emergence of antibiotic resistance, and he was soon proved right. The increase in antibiotic resistant bacteria has been at least partially due to the over prescribing of antibiotics by GPs, healthcare centres, etc.[1] Steps have been taken in­­ recent years to combat this,[2] though a recent database study by Smieszek, et al. estimated that between 8.8%-23.1% of antibiotic prescriptions in English primary care were inappropriate,[3] and the situation is much worse in low- and middle-income countries.[4] Now, a study published in Nature by staff from the European Molecular Biology Laboratory has found potential risk from prescribing non-antibiotics.[5]

Previous research has found that medication that targets human cells, as opposed to microbes (for example, anti-diabetics, proton pump inhibitors, non-steroidal anti-inflammatory drugs) may alter the composition of the gut flora. In order to determine the extent of such effects the authors tested over 1,000 drugs against 40 human gut bacterial strains. They found that 24% of those with human targets inhibited the growth of at least one of the strains (and 5% affected at least ten strains). While this could offer new avenues for future drug-therapy research and personalised medicine, the authors also found strong correlation between resistance to antibiotics and to drugs that target human cells, likely due to common mechanisms conferring resistance. This means there is a potential risk of non-antibiotics promoting antibiotic resistance in some bacteria – a concern with the large amount of non-antibiotics taken on a regular basis by a large number of people.

— Peter Chilton, Research Fellow

References:

  1. Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, Laxminarayan R. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014; 14(8): 742-50.
  2. Hoffman SJ, Outterson K, Røttingen J-A, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ. 2015; 93(2): 66.
  3. Smieszek T, Pouwels KB, Dolk FCK, et al. Potential for reducing inappropriate antibiotic prescribing in English primary care. J Antimicrobial Chemo. 2018; 73(s2): ii36-43.
  4. Das J, Chowdhury A, Hussam R, Banerjee AV. The impact of training informal health care providers in India: A randomized controlled trial. Science. 2016; 354: aaf7384.
  5. Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018; 555: 623-8.

Prescribing Homeopathic Medicine

While there is no experimental evidence that homeopathy works,[1] and NHS England recommend that it no longer be prescribed,[2] it continues to be prescribed by a number of healthcare professionals and is still licensed by the MHRA.[3] Many have argued that even if it doesn’t work there is no harm in using it as long as conventional medicine and/or treatments are also used, and that might even benefit some patients through the placebo effect. However, a recent paper lead by Ben Goldacre reveals a different story.[4]

The authors looked at all 7,618 primary care practices in England over a six month period and found that 8.5% prescribed homeopathy. Those practices that were in the lowest scoring quartile for general prescribing quality (as assessed through cost-effectiveness, efficacy and safety of prescribed medicines) were 2.1 times (95% confidence interval: 1.6-2.8) more likely to prescribe homeopathy when compared to those practices in the highest quartile. Further, practices that spent the most on medicines that were of ‘low value’ were 2.6 times as likely (95% CI 1.9-3.6) to prescribe homeopathy. There was no significant association between homeopathy prescription and patient outcomes or patient recommendation.

Although these associations are unlikely to be directly causal, the authors argue that it is likely to reflect underlying features of the practice, such as respect for best practice guidelines. The CLAHRC WM Director is an unreformed upholder of The Enlightenment and holds no truck with homeopathy.

 — Peter Chilton, Research Fellow

References:

  1. National Health and Medical Research Council. NHMRC Statement on Homeopathy and NHMRC Information Paper – Evidence on the effectiveness of homeopathy for treating health conditions. 2015.
  2. NHS England. Items which should not routinely be prescribed in primary care: Guidance for CCGs. 2017.
  3. Medicines and Healthcare products Regulatory Agency. Register a homeopathic medicine or remedy. 19 October 2017.
  4. Walker AJ, Croker R, Bacon S, et al. Is use of homeopathy associated with poor prescribing in English primary care? A cross-sectional study. J Roy Soc Med. 2018.