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.
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On Integrated Care

Integrated care is a big issue promoted in the NHS and throughout the world. This push to integrate care includes low- and middle-income countries (LMICs). This is so, despite the demonstrated and often spectacular success of vertical programmes to tackle diseases, such as HIV and malnutrition, in LMICs.[1] Yet, there are compelling reasons to integrate care:

  1. A greater proportion of people now survive to suffer multiple chronic diseases affecting multiple organ systems.
  2. Solipsistic focus on specific (vertical) programmes can lead to neglect and poor quality of the generality of care.
  3. Vertical programmes imply that the diagnosis has been made, yet health services need to cater for people with undiagnosed symptoms.

But what about empirical evidence for integrated programmes? One set of programmes commonly integrated are HIV programmes and programmes targeting maternal and neonatal health. A review by the Cochrane HIV/AIDS group,[2] commissioned by USAID, tackled this particular issue back in 2011 – a time when HIV care was still a critical issue. The results were generally positive. For example, pregnancy rates declined when HIV and family planning services were integrated, and recovery rates from malnutrition improved in studies that examined this outcome. The review also identified factors associated with more or less successful migration from vertical to integrated programmes. Better results can be achieved by upfront investment in the integration process itself, focusing on staff education, preparation of appropriate case-notes and community engagement. In my opinion these are generic success factors for any programme of change.

Integrated care is a pervasive theme in NIHR CLAHRC West Midlands. We have recently completed an authoritative overview of 80 systematic reviews on this topic.[3] [4] Our work has stressed the importance of human resources in effecting service change, most particularly the importance of committed middle managers with high emotional intelligence,[5] and the role of ‘expectancy’, by which we mean that targets or incentives should only be used when the people at whom the target is aimed believe that they know how to achieve the target.[6] Our sister centre, the NIHR Global Health Unit on Improving Health in Slums, is also examining optimal health service configurations in slum areas of Africa and Asia,[7] where we will be studying integrated services using tools developed in CLAHRC WM.

— Richard Lilford, CLAHRC WM Director

References:

  1. Lilford RJ. A Heretical Suggestion! NIHR CLAHRC West Midlands News Blog. 9 February 2018.
  2. Kennedy G, Kennedy C, Lindegren ML, Brickley D. Systematic review of integration of maternal, neonatal and child health and nutrition, family planning and HIV. Report No. 11-01-303-02. Washington, D.C.: Global Health Technical Assistance Project; 2011.
  3. Damery S, Flanagan S, Combes G. Does integrated care reduce hospital activity for patients with chronic diseases? An umbrella review of systematic reviews. BMJ Open. 2016; 6: e011952.
  4. Lilford RJ. Future Trends in NHS. NIHR CLAHRC West Midlands News Blog. 25 November 2016.
  5. Burgess N & Currie G. The Knowledge Brokering Role of the Hybrid Middle Level Manager: the Case of Healthcare. Br J Manage. 2013; 24(s1): s132-42.
  6. Lilford RJ. Financial Incentives for Providers of Health Care: The Baggage Handler and the Intensive Care Physician. NIHR CLAHRC West Midlands News Blog. 25 July 2014.
  7. Lilford RJ. Measuring the Quality of Health Care in Low-Income Settings. NIHR CLAHRC West Midlands News Blog. 18 August 2017.

What are the Effects of Body-Worn Cameras on Police and Citizen Behaviour?

There is evidence that people’s behaviour is altered by being watched.[1] After all this is the basis of the original Hawthorne effect. Likewise, people’s propensity to give to charity is increased if they know they are being observed.[2] So, what about body-worn cameras on police officers? Do they result in more temperate behaviour on the part of the police themselves, and/or the citizens with whom they come into contact?

To find out, a randomised trial was conducted in the US.[3] Most police people randomised to wear the body camera did so, while those in the control group did not. Intention to treat principles were followed. Four types of endpoint were used: use of force, civilian complaints, policing activity, and judicial outcomes.

Before reading on, do you want to guess the result?

102 DCiii - Police Body-Worn Cameras

Well, the results were null. In fact, the direction of effect is (non-significantly) towards more complaints, more instances of use of force, and more people prosecuted. The proportion of people arrested who were then found guilty was almost identical across groups.

This was a large study and could have detected moderate effects. The study was carried out in one particular district, so the results might be context-specific. It could be argued that the control group changed its behaviour as a result of contamination, but this is unlikely as no change was found over time. Use of force was self-reported, and so this might have affected the results. Quite a few locations have community cameras for surveillance and this might have reduced the marginal effect of a body-worn camera. If so, this is yet another example of the rising tide phenomenon described by CLAHRC WM.[4]

— Richard Lilford, CLAHRC WM Director

References:

  1. King D, Vlaev I, Everett-Thomas R, Fitzpatrick M, Darzi A, Birnbach DJ. “Priming” Hand Hygiene Compliance in Clinical Environments. Health Psychol. 2016; 35(1): 96-101.
  2. Ekström M. Do Watching Eyes Affect Charitable Giving? Evidence from a field experiment. Exp Econ. 2012; 15(3): 530-46.
  3. Yokum D, Ravishankar A, Coppock A. Evaluating the Effects of Police Body-Worn Cameras: A Randomized Controlled Trial. Washington, D.C.: The Lac @ DC; 2017.
  4. 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.

Another Spectacular Study Based on Demographic and Health Surveys

Under five mortality has dropped sharply around the world in the last few decades.[1] For example, in sub-Saharan Africa mortality for children aged 1-5 dropped from 42.7 per thousand in 2002-08 to 22.0 per thousand in 2009-14. The situation in twins was recently investigated using data from 90 Demographic and Health surveys across no less than 30 countries.[2] The decline in mortality was much less steep among twins than among singleton live births.

Twins are very vulnerable and have benefited less than singletons from the reduction in child mortality. Clearly, this group of vulnerable people needs special attention.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. UNICEF. Under-Five Mortality. 2018.
  2. Monden CWS, Smits J. Mortality among twins and singletons in sub-Saharan Africa between 1995 and 2014: a pooled analysis of data from 90 Demographic and Health Surveys in 30 countries. Lancet Glob Health. 2017; 5: e673-9.

UK Takes Over From the US as the Home of Trials of Educational Interventions

It is truly wonderful that trials are now so widely used to make causal inferences in education – long the preserve of theory over empirical evidence. I was delighted to see that England has now become, proportionally, the largest education laboratory in the world.[1] This rapid increase in high-quality empirical research in English schools builds on a £135m grant to establish the Education Endowment Foundation. This organisation has commissioned around a tenth of all RCTs ever carried out in education.[2] Already the results are influencing practice – £26m has been allocated to fund breakfast clubs, for example. Many ‘fads’ have been disproven, for example tailoring education according to individual learning styles, streaming pupils by ability,[3] or repeating a year of school.[4] Building on Hattie’s monumental work previously cited in your News Blog,[5] the Education Endowment Foundation has summarised the findings from 13,000 educational trials from around the world. Two-thirds of English teachers have turned to this evidence for guidance. This is a huge success for the values of the Enlightenment and an indication that we are moving to be, in Donald Campbell’s words, “an experimenting society.”

— Richard Lilford, CLAHRC WM Director

References:

  1. The Economist. England has become one of the world’s biggest education laboratories. The Economist. Mar 31, 2018.
  2. Education Endowment Foundation. The EEF at 5. 2016.
  3. Lilford RJ. Evidence-Based Education (or How Wrong the CLAHRC WM Director Was). NIHR CLAHRC West Midlands News Blog. 10 March 2017.
  4. Lilford RJ. Keeping a Child Back at School. NIHR CLAHRC West Midlands News Blog. 10 March 2017.
  5. Hattie J. Visible Learning: A Synthesis of Over 800 Meta-Analyses Relating to Achievement. Oxon, UK: Routledge, 2009.

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.

Important New Data on WASH and Nutritional Interventions from Kenya and Bangladesh

Two recent cluster RCTs published in Lancet Global Health have reported on WASH (water quality, sanitation and handwashing) and nutritional interventions.[1] [2] One was conducted in Bangladesh and the other in Kenya; they were both based on recruitment of pregnant woman, who were then grouped in delineated clusters based on geographical proximity. The studies were all entirely rural.

Both studies found that nutritional interventions, either singly or in combination with other wash interventions, improved child growth. The Kenyan study found no benefit for WASH interventions on reported rates of diarrhoea. However, the Bangladesh study did find a reduction of diarrhoea of about 40% in the WASH intervention groups. A follow-on study to the Bangladesh trial at one year of age found an improvement in developmental milestones across all of the intervention groups.[3]

Probably the strongest message to come out here, is that nutritional interventions improve growth in deprived rural populations. This is consistent with most, but not all, previous literature. The discordant effects of WASH interventions on diarrhoea rates across Kenya and Bangladesh is puzzling and no convincing explanation is offered by the authors. I note, however, that the prevalence of diarrhoea was much higher in Kenya than in Bangladesh. Of course, that provides more headroom for improvement In the Kenyan setting, making the discordant results even more perplexing. One possibility, is that reported diarrhoea rates are just a very poor marker for gastrointestinal disease. Worse still, they are ‘reactive’, meaning that if people are aware that they are on the receiving end of an intervention to reduce diarrhoea rates, then they may report less diarrhoea, even if the true prevalence is unchanged.[4] We are investigating this possibility in a study in Mwanza, Tanzania, which we are conducting in collaboration with UN-Habitat. I am not sure how to interpret these results with respect to the theory that chronic gastrointestinal infections aggrevate malnutrition by causing a chronic malabsorptive small bowel enteropathy.

It is interesting to compare these results with the effects of the sanitary revolution in Europe and North America over a century ago.[5] Here again, water and sanitation had modest and inconsistent effects on childhood diarrhoea, but with much more dramatic effects on typhoid and cholera. Taken in the round these recent results reported in Lancet Global Health are consistent with historical data.

— Richard Lilford, CLAHRC WM Director

References:

  1. Luby SP, Rahman M, Arnold BF, et al. Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Bangladesh: a cluster randomised controlled trial. Lancet Glob Health. 2018; 6: e302-15.
  2. Null C, Stewart CP, Pickering AJ, et al. Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Kenya: a cluster-randomised controlled trial. Lancet Glob Health. 2018; 6: e316-29.
  3. Tofail F, Fernald LCH, Das KK, et al. Effects of water quality, sanitation, hand washing, and nutritional interventions on child development in rural Bangladesh (WASH Benefits Bangladesh): a cluster-randomised controlled trial. Lancet Child Adolesc Health. 2018; 2: 255-68.
  4. Clasen T, Boisson S, Routray P, Torondel B, Bell M, Cumming O, et al. Effectiveness of a rural sanitation programme on diarrhoea, soil-transmitted helminth infection, and child malnutrition in Odisha, India: a cluster-randomised trial. Lancet Glob Health. 2014; 2(11): e645-53.
  5. Szreter S. The Population Health Approach in Historical Perspective. Am J Public Health. 2003; 93(3): 421-31.

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.

Effective Collaboration between Academics and Practitioners Facilitates Research Uptake in Practice

New research has been conducted by Eivor Oborn, Professor of Entrepreneurship & Innovation at Warwick Business School and Michael Barrett, Professor of  Information Systems & Innovation Studies at Cambridge Judge Business School, to better understand the contribution of collaboration in bridging the gap between research and its uptake in to practice (Inform Organ. 2018; 28[1]: 44-51).

Much has been written on the role of knowledge exchange to bridge the academic-practitioner divide. The common view Is that academics ‘talk funny’, using specialised language, which often leads to the practical take home messages being missed or ‘lost in translation’. The challenge for academics is to learn how to connect ‘theory or evidence driven’ knowledge with practitioners’ knowledge to ‘give sense’ and enable new insights to form.

The research examines four strategies by which academics may leverage their expertise in collaborative relationships with practitioners to realise, what the authors term: ‘Research Impact and Contributions to Knowledge’ (RICK).

  1. Maintain critical distance
    Academics may adopt a strategy of maintaining critical distance in how they engage in academic-practitioner relations for a variety of reasons, for example, to retain control of the subject of investigation.
  2. Prompt deeper engagementAcademics who are immersed in one domain, become fluent in a new language and gain practical expertise in this second (practical) domain. For example, in the Warwick-led NIHR CLAHRC West Midlands, academics are embedded and work closely with their NHS counterparts. This provides academics with knowledge -sharing and -transfer opportunities, enabling them to better respond to the knowledge requirements of the health service, and in some scenarios, co-design research studies, and catalyse upon opportunities to promote the use of evidence from their research activities.
  3. Develop prescience
    Prescience describes a process of anticipating what we need to know – almost akin to ‘horizon-scanning’. A strategy of prescience would aim to anticipate, conceptualize, and influence significant problems that might arise in domains over time. The WBS-led Enterprise Research Centre employs this strategy and seeks to answer one central question: ‘what drives SME growth?’
  4. Achieve hybrid practices
    Engaged scholarship allows academics to expand their networks and collaboration with other domains and in doing so generate an entirely new field of ‘hybrid’ practices.

The research examines how the utility (such as practical or scientific usefulness) of contributions in academic-practitioner collaboration can be maximised. It calls for established journals to support a new genre of articles that involve engaged scholarship, produced by multidisciplinary teams of academic, practitioners and policymakers.

The research is published in Information & Organization journal, together with a collection of articles on Research Impact and Contributions to Knowledge (RICK) – a framework coined by co-author on the above research, Prof Michael Barrett.

— Nathalie Maillard, WBS Impact Officer

Patient Reported Outcome Measures: A Tool for Individual Patient Management, Not Just for Research

Research and practice are often thought of as totally different types of activity. For instance, research is governed by an extensive set of procedural requirements that do not apply to standard practice. However, many inquiries that would have counted as research in earlier times are now embedded in management and governance practices. Take, for instance, outcomes of treatments and procedures. When the CLAHRC WM Director was a young doctor a study of the outcomes of, say, 50 Wertheim’s hysterectomies would be a typical research undertaking. Now, this may be considered a standard audit and may take place as part of a hospital’s prudent monitoring of its work. CLAHRCs have a long tradition of building data analysis into routine practice.

One active area of practice concerns patient-reported outcome measures (PROMs).  Often thought of as endpoints for research, CLAHRC WM collaborator Melanie Calvert and members of the Centre for Patient Reported Outcomes Research, are working closely with clinicians at University Hospital Birmingham NHS Foundation Trust to capture electronic PROMs which are used for real-time monitoring of patient symptoms and to tailor care to individual patient needs. Prof Calvert notes that these data have the potential to be used for multiple purposes: aggregated data may be used to inform and improve service delivery, whilst individual patient data may be used alongside remote clinical monitoring to guide frequency of outpatient appointments. Attendance at the hospital can be flexible and dictated by patient need and response to therapy.

You can hear more about their work and exciting new developments in PROMs research at the forthcoming PROMS conference, sponsored by CLAHRC WM and hosted by the University of Birmingham on Wednesday 20 June 2018. You can register online by clicking here. Registration is open until 11 June.

— Richard Lilford, CLAHRC WM Director

— Melanie Calvert, Professor of Outcomes Methodology