Tag Archives: Director’s Choice – From the Journals

Low-Tech Solution to a Devastating Infection

What do you do when you finish your bottle of shampoo? Throw it straight in the recycling bin? Turn it into a child’s space rocket? Well, Dr Mohamad Chisti became inspired to invent a treatment for pneumonia.

Globally more than 920,000 children died from pneumonia in 2015, accounting for around 16% of all deaths in under-fives.[1] However, this rate is far higher in low-income countries, such as Bangladesh where the figure is 28%.[2] This is partially due to the greater amount of malnourishment – pneumonia results in inflammation of the alveoli in the lungs, resulting in breathlessness and difficulty breathing – malnourished children do not have the energy required to breath in enough oxygen. The standard treatment listed in World Health Organization guidelines is to deliver ‘low-flow’ oxygen through a face mask or tubes near the nostrils, but this still requires a lot of effort to breathe. Whilst visiting Australia Dr Chisti was shown a bubble-CPAP ventilator for premature babies. This type of ventilator passes exhaled breath through water, which forms bubbles that push fresh air into the lungs and thus makes breathing easier. However, the device is prohibitively expensive for many hospitals in low-income countries. When Dr Chisti spotted a discarded shampoo bottle he realised it could be possible to recreate such a ventilator at a fraction of the cost.[3] Results of a trial to assess the efficacy of bubble-CPAP for children with pneumonia were published in the Lancet in 2015, with positive results,[4] and since then the mortality rate at Dhaka Hospital where the device is used routinely has significantly decreased, as have associated costs.[5] Further trials are starting to be carried out in other hospitals.

— Peter Chilton, Research Fellow

References:

  1. UNICEF. Pneumonia. 2018.
  2. International Centre for Diarrhoeal Disease Research, Bangladesh. Pneumonia and other respiratory diseases. 2018.
  3. Duke T. CPAP: a guide for clinicians in developing countries. Paediatr Int Child Health. 2013; 34(1): 3-11.
  4. Chisti MJ, Salam MA, Smith JH, et al. Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial. Lancet. 2015; 386: 1057-65.
  5. The Economist. How a shampoo bottle is saving young lives. The Economist. 6 September 2018.
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Electronic Health Records and Mortality Rate

In a number of our previous blogs we have looked at the impact of electronic health records,[1-3] and now we add another.[4] In a paper recently published in Health Affairs the authors found that adoption of electronic health records was associated with an improvement in thirty-day mortality rates. Although the mortality rates increased when hospitals initially introduced the system (0.11 percentage points per function [such as radiology reports, laboratory reports, radiology images, medication prescribing, etc.] that was adopted), this improved over time (presumably as staff become more familiar, and were able to integrate the system into their work), and eventually mortality rates had decreased by 0.09% per year, per function adopted. Adding new functions during the study period saw further improvements with a decrease of 0.21% per year, per function. These improvements were greatest in smaller hospitals and those that were not teaching hospitals – perhaps because such hospitals have more opportunity for improvement as they are less likely to have engaged other initiatives; or they may have lacked resources to implement other improvement initiatives.

— Peter Chilton, Research Fellow

References:

  1. Lilford RJ. Going Digital – The Electronic Patient Record. NIHR CLAHRC West Midlands News Blog. 6 May 2016.
  2. Lilford RJ. Electronic Health Record System and Adverse Outcomes. NIHR CLAHRC West Midlands News Blog. 28 October 2016.
  3. Lilford RJ. If You Have Time for Only One Article. NIHR CLAHRC West Midlands News Blog. 24 August 2018.
  4. Lin SC, Jha AK, Adler-Milstein J. Electronic Health Records Associated With Lower Hospital Mortality After Systems Ha­ve Time To Mature. Health Aff. 2018;37(7).

An Aspirin A Day to Keep the Doctor Away?

Many healthy elderly people take a daily dose of aspirin as a preventive measure, often in order to lower their risk of cardiovascular illness. But is this practice beneficial? A series of three analyses in the New England Journal of Medicine suggests not.[1-3] The ASPREE study looked at more than 19,000 healthy elderly individuals, randomly assigning half to receive a daily aspirin, and half to receive a placebo, and followed them for a median of 4.7 years. There was no significant difference between the groups with regards to disability-free survival (p=0.79),[1] or risk of cardiovascular disease,[2] but there was a higher rate of major haemorrhage seen in those taking aspirin (hazard ratio 1.38, 95% CI 1.18-1.62).[1] Further, the authors found that the risk of any-cause mortality was 12.7 (per 1,000 person-years) in those taking aspirin, compared to 11.1 in those taking placebo – a hazard ratio of 1.14 (95% CI 1.01-1.29).[3] The main cause of the excess mortality was cancer-related death: 3.1% of those taking aspirin vs. 2.3% of those taking placebo (hazard ratio 1.31, 95% CI, 1.10-1.56).

Previous trials of aspirin have shown a protective effect with regards to cancer-related death,[4] suggesting these results should be interpreted cautiously, and that longer term follow-up could be informative.

It is important to note that these were healthy individuals, with no history of cardiovascular disease, dementia or disability, and who had not been previously prescribed aspirin by their doctor.

— Peter Chilton, Research Fellow

References:

  1. McNeill JJ, Woods RL, Nelson MR, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. New Engl J Med. 2018.
  2. McNeill JJ, Wolfe R, Woods RL, et al. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. New Engl J Med. 2018.
  3. McNeil JJ, Nelson MR, Woods RL, et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. New Engl J Med. 2018.
  4. Rothwell PM, Fowkes FGR, Belch JFF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011; 377: 31-41.

Myopia is Caused Partially by Long Hours of Study

It is well known that short-sightedness, or myopia, is associated with the intensity and duration of education.[1] But is this cause and effect? A Mendelian randomisation study, beloved of the CLAHRC WM Director, finds strong evidence for a causal explanation.[2] Using this form of analysis there is a statistically strong association between genes that predispose  to long duration of education and myopia. The reverse does not apply; genes associated with myopia are not associated with duration of education. Together, these findings argue against reverse causality.

That said, the effect, although statistically highly significant, is not large. Genes associated with longer education explain only 7% of the variance in the incidence of myopia.  However, they do suggest that something associated with education is causal of myopia, and it is probable that the intensity of book work is also important. The incidence of myopia has risen dramatically in recent years, especially in China, where both the intensity and duration of education have increased over the last generation. Myopia can sometimes lead to blindness. These results are therefore very important.

It seems that children should have a balanced life between looking at books and screens, versus playing in the outdoors. In fact, there are probably other, even stronger, arguments for such a lifestyle prescription.

— Richard Lilford, CLAHRC WM Director

References:

  1. Gwiazda J, Deng L, Dias L, et al. Association of Education and Occupation with Myopia in COMET Parents. Optom Vis Sci. 2011; 88(9): 1045-53.
  2. Mountjoy E, Davies NM, Plotnikov D, et al. Education and myopia: assessing the direction of causality by mendelian randomisation. BMJ. 2018; 361: k2022.

Changes in Mealtimes Leading to Eating Less

People have long looked for a method of dieting that is effective and easy to undertake. A recent pilot study in the Journal of Nutritional Sciences may offer a new alternative.[1] For ten weeks participants were required to both delay their usual breakfast time and bring forward their evening meal time by an hour and a half – there were no other restrictions on what food they could consume, or what exercises they needed to do. When compared to a control group they found that the participants in the intervention group reduced their daily energy intake (p=0.019), with an associated reduction in adipose levels (p=0.047). Further, there was also a significant difference in fasting glucose levels, though the authors note that this was mainly due to an increase in control participants compared to baseline. Questionnaire results suggest that the reduction in energy intake may have been due to less time for snacking, and/or still feeling full from the previous meal. Unfortunately the majority of participants found that the restrictions were too severe, impacting on their social and family life, and did not believe they could continue past the end of the study.

Although this was only a very small study of 13 participants it shows a potential opportunity for future research.

— Peter Chilton, Research Fellow

Reference:

  1. Antoni R, Robertson TM, Robertson MD, Johnston JD. A pilot feasibility study exploring the effects of a moderate time-restricted feeding intervention on energy intake, adiposity and metabolic physiology in free-living human subjects. J Nutri Sci. 2018;7:e22.

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.

People Designated as Allergic to Penicillin Have an Increased Incidence of Clostridium Difficile Diarrhoea

This hypothesis was tested out by a group of researchers from Harvard using the THIN Database from England [1]; a nice example of the merits of making the data collected in one country available to researchers in another.

The hypothesis that these investigators are examining is obvious: they want to see whether the substitution of broad spectrum antibiotics for penicillin and its analogues, leads to a detectable increase in Clostridium difficile diarrhoea. This is an important investigation, since only 5% of people labelled as allergic, have any real risk of an immediate reaction to penicillin.

This study was based on over 64,000 people with putative penicillin allergy and nearly 200,000 matched comparators. Over a mean of six years of follow up, an approximately 70% increase in risk of C. difficile was observed among patients labelled allergic to penicillin. The authors suggest routine testing for penicillin allergy, but I think this would be logistically hard to achieve, and recommend more careful history taking when making the original diagnosis. Other measures to reduce the incidence of Clostridium difficile diarrhoea, such as more circumspect prescription of fluoroquinolones, should also be pursued.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Blumenthal KG, Lu N, Zhang Y, et al. Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ. 2018; 361: k2400.

Embolisation of the Hypertrophic Prostate: a Good Idea?

The above BMJ article [1] caught my eye because a dear friend of mine suffered a severe side effect following embolisation of his prostate gland. The study was an open label, randomised trial from Switzerland.

The study calls itself a non-inferiority trial. However, with a total of only 103 participants, it is insufficiently powered to exclude serious side effects or, for that matter, to detect worthwhile benefits. In any event there was no difference in symptom scores after 12 weeks, but the point estimate favoured the traditional transurethral resection of the prostate over embolisation. No difference in clinical symptoms was noted statistically, but the point estimate favoured surgery and follow-up was for three months only. There was no real difference in side effects, but dynamic studies showed a greater return towards normal in the surgery group.

In my humble opinion, this trial is completely inadequate to drive a change in practice and I recommend further, much larger, RCTs with longer follow-up.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Abt D, Hechelhammer L, Müllhaupt G, et al. Comparison of prostatic artery embolisation (PAE) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia: randomised, open label, non-inferiority trial. BMJ. 2018; 361: k2338.

An Article about Citizen Science Published in Science

News blog readers are referred to the above thoughtful article,[1] which discusses the rise in citizen science, and the policy response in the USA.

The article covers three crucial areas: intellectual property, research integrity, and protection of the citizen scientist. Potential problems are identified and sensible solutions offered. However, the article is clearly not concerned with clinical or health services research. Here, additional issues of confidentiality and protection of patients and the public come into the frame. This is a topic which has been covered in a recent issue of your News Blog.[2]

— Richard Lilford, CLAHRC WM Director

References:

  1. Guerrini CJ, Majumder MA, Lewellyn MJ, McGuire AL. Citizen Science, Public Policy. Science. 2018; 361(6398): 134-6.
  2. Lilford RJ. Patient and Public Involvement: Direct Involvement of Patient Representatives in Data Collection. NIHR CLAHRC West Midlands News Blog. 4 August 2017.

The Effect Moving Has on Young People

A number of years ago researchers from CLAHRC WM Theme 2, Youth Mental Health, worked on a prospective birth cohort study of ~6,500 children, which found a significant association between how often children moved schools and the incidence of psychotic-like symptoms.[1] Now, a similar study has been conducted with 1.4 million young Swedish people followed up until their 29th birthday.[2] In this study the authors focused on how often and how far participants moved house, and at what age, and any associations with non-affective psychosis. They found that frequent moves were associated with a significant increase in the risk of non-affective psychosis (p<0.001), and that adolescents who moved regularly between the ages of 16-19 had the strongest association with an increased adjusted hazard ratio for psychosis risk of 1.99 (95% CI, 1.30-3.05) when compared to those who did not move. Those who moved in adulthood (older than 20 years) showed little variation in risk, with only those who moved at least four times showing a significantly increased risk. The authors found that moves that resulted in changes in schools and/or friendship groups were most strongly associated with a future risk of psychosis.

For another interesting study that looked at the effect moving to areas of higher income had on mental health, you may like to look at our previous News Blog.[3]

— Peter Chilton, Research Fellow

References:

  1. Singh SP, Winsper C, Wolke D, Bryson A. School Mobility and Prospective Pathways to Psychotic-like Symptoms in Early Adolescence: A Prospective Birth Cohort Study. J Am Acad Child Adolesc Psych. 2014; 53(5): 518-27.
  2. Price C, Dalman C, Zammit S, Kirkbridge JB. Association of Residential Mobility Over the Life Course With Nonaffective Psychosis in 1.4 Million Young People in Sweden. JAMA Psychiatry. 2018.
  3. Lilford RJ. Neighbourhood Effect and Child Development – Long-term Results of a RCT. NIHR CLAHRC West Midlands News Blog. 17 June 2016.