Another Paper on Applied Use of Behavioural Science Published in the Journal ‘Science’

We recently reported an article from Science on an educational intervention to improve the quality of clinical care delivered by informal providers in rural settings in India.[1] A further article has now been published in the journal describing how principles derived from behavioural theory were used to influence physician prescribing behaviour.[2] The prescribing practice targeted in the article concerned inappropriate prescribing of narcotics for chronic, non-cancer, pain. The participants, who did not consent to the study, were groups (clusters) of 861 clinicians who had prescribed opiates to someone who then died of an opioid overdose. Since more than one clinician prescribes to a given decedent (person who has died) the clinicians were clustered by the person for whom they had prescribed and who had then died of complications of opioid use. The clusters were randomised into two groups (84 intervention and 86 controls). The intervention group received a letter, supportive in tone, from the ‘medical examiner’ who is a person of authority dealing with unexpected deaths (a type of coroner). The letter described the problem and reiterated official advice.

The headline result was a highly significant decrease of nearly 10% in narcotic prescriptions in a difference-in-difference analysis across the clusters. In addition, a smaller proportion of people were started on narcotics, and a lower proportion on high dose prescriptions were issued, in the intervention group. In your next News Blog we will describe a CLAHRC WM trial based on similar behavioural principles.

— Richard Lilford, CLAHRC WM Director

References:

1. Lilford RJ. A Fascinating Trial of an Educational Intervention to Improve the Quality of Care in Rural India. NIHR CLAHRC West Midlands News Blog. 4 May 2018.
2. Doctor JN, Nguyen A, Lev R, et al. Opioid prescribing decreases after learning of a patient’s fatal overdose. Science. 2018; 361: 588-90.

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.

Not Taking a Full Course of Antibiotics

The Academic edition of the BMJ comes out once a month; readers may have noticed that one or more BMJ articles feature in alternate News Blogs. The most recent issue of the BMJ had less papers that caught my eye than most. There was lots of worthy stuff. For example, age-specific dementia incidence is declining slightly,[1] antidepressants may very slightly increase the risk of autism if taken during pregnancy,[2] specialist palliative care has rather small effects on quality of life,[3] exercise and diet reduce the risk of high blood pressure in women who had high blood pressure in pregnancy.[4] There was also an excellent article on the precision of cluster randomised trials by CLAHRC WM collaborator Karla Hemming.[5] But the article that really caught my eye was a commentary on the importance of completing a full course of antibiotics as prescribed.[6]

Of course, we always love articles that confirm our prior beliefs. I have always thought that insisting that people take a ‘full course’ of antibiotics to reduce resistance is illogical. Prolonging exposure of the bacterial population to the antibiotic is likely to increase the chance for selection to take place. And that is exactly what this study confirms. Apparently the idea that it was important to take the full course of treatment was based on Albert Alexander’s Staphylococcal sepsis, which re-established itself when Howard Florey’s penicillin ran out.[7] However, the wisdom of continuing antibiotics until the infection is quelled somehow became translated into instructions to finish the course even if infection is no longer a threat. Remember, genetic mutations arise spontaneously and are only selected for when the antibiotic is present in the environment. It follows that the shortest course of antibiotics compatible with effective treatment should be used. And, of course, resistance does not just appear among the organisms causing the infection, but among all the organisms carried in the patient’s body, some of which may go on to infect another person. The argument against continuing to take antibiotics once the threat has passed is therefore unequivocal. It may be necessary to continue antibiotic treatment to prevent a relapse, as was the case for the hapless Alexander, and middle ear infections have a tendency to relapse, but we should not insist on taking a full course simply to prevent antibiotic resistance; the opposite is the case.

— Richard Lilford, CLAHRC WM Director

References:

1. Ahmadi-Abhari S, Guzman-Castillo M, Bandosz P, et al. Temporal trend in dementia incidence since 2002 and projections for prevalence in England and Wales to 2040: modelling study. BMJ. 2017; 358: j2856.
2. Rai D, Lee BK, Dalman C, et al. Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ. 2017; 358: j2811.
3. Gaerner J, Siemens W, Meerpohl JJ, et al. Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis. BMJ. 2017; 357: j2925.
4. The International Weight Management in Pregnancy Collaborative Group. Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials. BMJ. 2017; 358: j3119.
5. Hemming K, Eldridge S, Forbes G, Weijer C, Taljaard M. How to design efficient cluster randomised trials. BMJ. 2017; 358: j3064.
6. Llewelyn M, Fitzpatrick JM, Darwin E, et al. The antibiotic course has had its day. BMJ. 2017; 358: j3418.
7. Abraham EP, Chain E, Fletcher CM, et al. Further observations on penicillin. Lancet. 1941; 358: 177-89.

Step Wedge Cluster Design for Service Delivery Interventions Comes to New England Journal of Medicine

Dreischulte and colleagues randomised 34 practices in clusters using a step-wedge design, to evaluate a complex intervention to reduce prescription errors in primary care.[1] The intervention included an educational component and informatics (as in the famous PINCER trial [2]), but also included a financial incentive. There was a marked drop in the types of high-risk prescribing targeted in the intervention. In addition, admissions decreased in the hypothesised direction. Adjustments were made for intra-class correlations at various time points, but what about temporal trends? Is this the first step wedge cluster study in the world’s top medical journal?

— Richard Lilford, CLAHRC WM Director

References:

1. Dreischulte T, Donnan P, Grant A, et al. Safer Prescribing – A Trial of Education, Informatics, and Financial Incentives. New Engl J Med. 2016; 374(11): 1053-64.
2. Hemming K, Chilton PJ, Lilford RJ, Avery A, Sheikh A. Bayesian cohort and cross-sectional analyses of the PINCER trial: a pharmacist-led intervention to reduce medication errors in primary care. PLoS One. 2012; 7(6): e38306.