Category Archives: Director’s Choice – From the Journals

Lead Exposure and DALYs

It is well known that exposure to lead can cause a number of health problems, such as cognitive impairment, cardiovascular problems, low birth weight, etc. Exposure is also associated with a decreased life expectancy and economic output. While many countries have banned the use of lead in products such as petrol and paints, leading to significant declines in the levels of lead recorded in a person’s blood (termed blood lead levels – BLLs) there are still numerous other sources of exposure. In India, for example, studies found elevated BLLs in the population more than ten years after leaded petrol was phased out; sources include from lead smelting sites, some ayurvedic medicines, cosmetics, contaminated food, and contaminated tube wells, rivers and soil. In order to assess the extent of elevated BLLs in India, Ericson and colleagues conducted a meta-analysis of 31 studies totalling 67 samples.[1] Overall, they found a mean BLL of 6.86 μg/dL (95% CI: 4.38-9.35) in children, and 7.52 μg/dL (95% CI: 5.28-9.76) in adults (who did not work with lead). As a reference, the CDC deem a BLL of 5 μg/dL as requiring prompt medical investigation, “based on the 97.5% of BLL distribution among children… in the United States”.[2] From these figures the authors estimated that such high levels of exposure resulted in a DALY loss of 4.9 million (95% CI 3.9-5.6) in 2012. Further, data from other studies suggest that a BLL of 0.1-1.0 μg/dl contributes to loss of a single IQ point, meaning the levels of lead seen in these children would result in an average loss of four IQ points (95% CI 2.5-4.7).

The authors fear that a significant amount of the lead exposure stems from used lead batteries used in motor vehicles, which are often processed informally, and thus call for better regulations and larger studies.

Peter Chilton, Research Fellow

References:

  1. Ericson B, Dowling R, Dey S, et al. A meta-analysis of blood lead levels in India and the attributable burden of disease. Environ Int. 2018; 121(1): 461-70.
  2. Centers for Disease Control and Prevention. CDC Response to Advisory Committee on Childhood Lead Poisoning Prevention Recommendations in “Low Level Lead Exposure Harms Children: A Renewed Call of Primary Prevention”. 2012.
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Health Effects of Armed Conflict: A Truly Fascinating Study

The phenomenon that more people die from the indirect effects of warfare than are killed directly is widely recognised. Wagner and colleagues studied the effect of armed conflict on child mortality in Africa.[1] They used a geospatial approach, linking georeferenced data on armed conflict to georeferenced data from the Demographic and Health Surveys. Their study covered two decades (1995-2015) and 35 African countries. The outcome variable was child survival to the age of one year. Overall, there was nearly an eight-percent increased risk of child death during a year of conflict. However, many of the conflicts were small, and the increased risk of death before the age of one year was over 25% for armed conflicts with more than 1,000 direct fatalities. The cumulative effect over eight years was up to four times higher than the contemporaneous increase, and the effect is greatly increased for long-lasting conflicts. There were significantly stronger effects in rural than in urban areas. The authors also examined child growth and found an increased risk of stunting in relation to conflict.

Sadly, there was no shortage of armed conflicts in the 35 African countries studied – 15,441 armed conflicts were recorded in the Uppsala Conflict Data Program over the two decades. The results reported here represent a massive burden of disease on a scale with malnutrition.

Avoiding conflict is a tricky subject, which lies outside the health domain, and which is discussed in Paul Collier’s book ‘The Bottom Billion’.[2] Conflict is also very strongly associated with national poverty, and generally the avoidance of conflict is, arguably, the biggest threat confronting humankind, as we will discuss in the future.

— Richard Lilford, CLAHRC WM Director

References:

  1. Wagner Z, Heft-Neal S, Bhutta ZA, Black RE, Burke M, Bendavid E. Armed conflict and child mortality in Africa: a geospatial analysis. Lancet. 2018; 392: 857-65.
  2. Collier P. The Bottom Billion: Why the Poorest Countries are Failing and What Can Be Done About It. Oxford: Oxford University Press; 2007.

Monumental Study of Service Interventions to Drive Up the Quality of Care in Low- and Middle- Income Countries

Rowe and colleagues conducted a systematic review covering over half a century of studies of different methods to improve clinician practices.[1] By Jupiter, they scanned over 200,000 citations, selecting 337 studies of 18 improvement methods. Time series studies and studies with contemporaneous controls were included. Effects were measured in percentage point differences in clinical practices – for example the proportion of patients receiving unnecessary treatments.

In this particular study only comparisons of intervention versus control were used. Head-to-head comparisons of different interventions are to be reported separately.

Thirteen different intervention strategies were identified and these include topics such as high-intensity training, supervision, and group problem solving.  All studies were classified on a risk of bias scale; only a small proportion of studies were at low risk of bias.

Training alone had moderate effects on clinical behaviour in the range of 10 to 16 percentage points, but training combined with supervision had somewhat larger effects at about 18 percentage points. The effect of training was generally smaller at less than three percentage points for community health workers. As you might expect, wide differences in methodology and context make comparisons difficult.

This is a large and complex study which bears careful reading. Here are some take home messages from close colleagues:

  • Just like Oxman and colleagues demonstrated with physicians, there are no magic bullets.
  • How much research effort is sub-optimal given the lack of improvement in study quality over time?
  • A deep-dive into the studies to look at the role of context would say “it matters” – the question is how can we use the results to design more effective interventions in the future?

— Celia Taylor

  • Studies of strategies to improve health worker performance and quality in actual practice show there is usually a performance / quality gap even after implementing an intervention.
  • Effect sizes varied widely for most strategies and demonstrates difficulty of how effective a strategy might be in different contexts.
  • Training or supervision alone has small effects so good to combine with group problem solving as these combined have larger effect sizes.

— Jo Sartori

  • Effect sizes varied widely and there was a large risk of bias, so more rigorous studies are needed (panel 3). However, I also thought that the finding that “strategies that included community support plus training, with or without other components, tended to have larger effect sizes”, was interesting.
  • Finally, the ‘group problem solving’ strategy, that I have not heard about before, is something that I’d like to look into more as the authors think this component may benefit other strategies, while alone it brings about moderate effects.

— Maartje Klatter

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Rowe AK, Rowe SY, Peters DH, et al. Effectiveness of strategies to improve health-care provider practices in low-income and middle-income countries: a systematic review. Lancet Glob Health. 2018.

Childhood Diarrhoeal Diseases – Update of the Famous Wolf Review

Yes, the famous Wolf meta-analysis [1] of the impact of drinking water, sanitation and hand-washing (WASH) interventions on childhood diarrhoeal disease has been updated.[2] It is a monumental study and the clever authors had to wrestle to the ground the following issues:

  1. Multiple comparisons across different WASH interventions (14 for studies of drinking water alone).
  2. Different designs – before and after, time series, RCTs, etc.
  3. Problem of reactivity of the outcome measure.
  4. Multiple sources of potential variation, such as urban vs. rural; different levels of coverage and use achieved.

The results enable me to update the model we have already published in the Lancet.[3] Updating the model on drinking water intervention intensity vs. effect we get:

112 DCi - Diarrhoea Figure

Improved sanitation reduces diarrhoea by about 25%, and hygiene interventions by a similar amount (bit the latter are often ephemeral). Logically one would expect the effectiveness of hygiene interventions to reduce in proportion to the effectiveness of water and sanitation interventions. The coverage and uptake varies across studies, so it would be nice to make the above model three dimensional to include the effect of coverage and ‘herd effects’ that might be expected. The authors found that average effect sizes across sanitary interventions were much greater (45%) when coverage exceeded 75% than when it did not (24%), and, as this was part of a meta-regression, I guess they controlled for intervention type.

The authors make a sensitivity adjustment for ‘reactivity’, meaning that people are less likely to report diarrhoea on a survey if they discern that an intervention has been put in place. The fact that diarrhoea rates behave as expected suggests that they are certainly better than meaningless.[4] The meta-regression showed no difference in effect sizes for water intervention across urban and rural areas.

— Richard Lilford, CLAHRC WM Director

References:

  1. Wolf J, Prüss-Ustün A, Cumming O, et al. Systematic review: Assessing the impact of drinking water and sanitation on diarrhoeal disease in low‐and middle‐income settings: systematic review and meta‐regression. Trop Med Int Health. 2014; 19(8): 928-42.
  2. Wolf J, Hunter PR, Freeman MC, et al. Impact of drinking water, sanitation and handwashing with soap on childhood diarrhoeal disease: updated meta-analysis and meta-regression. Trop Med Int Health. 2018; 23(5): 508-25.
  3. Lilford RJ, Oyebode O, Satterthwaite D, et al. Improving the health and welfare of people who live in slums. Lancet. 2017; 389: 559-70.
  4. Lilford RJ. Important New Data on WASH and Nutritional Interventions from Kenya and Bangladesh. NIHR CLAHRC West Midlands News Blog. 18 May 2018.

Quality of Care on Removal of Financial Incentives in General Practices

Minchin, et al. report on the use of interrupted time series analyses of electronic medical records to track the effect of removal of financial incentives on provider behaviour.[1] Incentives were withdrawn for 12 quality of care indicators in 2014, while they were retained for six indicators.

The results showed a sharp and almost immediate fall in adherence to the 12 indicators for which the incentive was withdrawn. There was no such drop in performance for the six indicators that were retained.

Many of the measurements of adherence were based on clinician entry into the electronics records to confirm compliance. For example, to confirm that advice on disease prevention had been given. It is therefore possible that clinicians continued to adhere to the tenets of good practice after withdrawal of the incentive, while simply omitting to record this detail in the electronic notes. However, not all measurements were dependent on active clinical entry – for example, the electronic record is populated automatically with blood test results. There was a fall in adherence to previously incentivised indicators, such as blood tests, where physician entry was bypassed, as well as on those that required physician entry. However, the fall in compliance with practice standards that did not depend on physician entry was not as great as the fall in compliance with indicators that depend on physician entry.

The results reported here are broadly in-line with the literature; removal of financial incentives for clinical care standards is generally followed by a decline in performance.

What does this mean for the use of performance measures? One must assume that they cannot be retained in perpetuity; at some point the world must move on, even if only to implement a further set of performance measures.  But my overarching impression is reconfirmed – the use of incentives, measurements and targets is of limited value. In the last analysis, the only way to bring about a sustained, lasting and self-perpetuating improvement in care, is by winning the hearts and minds of clinicians. It is important to kindle a set of high rectitude values, and it is important to select individuals with the right characteristics, i.e. highly principled people with a deep sense of altruism. This is, I am afraid, an ultra-long-term solution – a person’s attitude starts on mother’s knee and is reinforced or supressed by the totality of life experience. Inspiring teachers at medical school and good role models throughout life are critical. That is one reason that I continue to argue that medical ethics and, so-called, ‘communication skills’ should be taught by doctors and not farmed out to philosophers and psychologists.[2] When I was a clinical professor these valuable colleagues taught me, but I taught the students.

— Richard Lilford, CLAHRC WM Director

References:

  1. Minchin M, Roland M, Richardson J, Rowark S, Guthrie B. Quality of Care in the United Kingdom after Removal of Financial Incentives. N Engl J Med. 2018; 379: 948-57.
  2. Lilford RJ. Doctor-Patient Communication in the NHS. NIHR CLAHRC West Midlands News Blog. 24 March 2017.

Unique Study of the Introduction of Commercial ePrescribing Systems Shows an Overall Reduction in Medication Error

This study [1] shows that the introduction of a commercial computerised decision support system resulted in an important reduction in prescribing errors across three hospitals included in this time series study. The result was highly significant in two of the hospitals, but in the remaining hospital a small increase in errors was seen. The latter finding could be ascribed to an increased rate of errors for just two prescriptions, perhaps because staff relied too heavily on the system to guide them.

The study also showed that only about a third of the decision support capacity was enabled across the hospitals. Moreover, the decision concerning which decision algorithm to enable varied considerably across hospitals.

It can be concluded that commercial systems have the potential to reduce error rates. They can almost eliminate errors where the system will refuse to prescribe a medicine because of the egregious nature of the potential error. Service providers need help in implementing these systems so that they consistently enable the most important decision support capabilities. Lastly, staff should be educated as to which capabilities have been enabled and which have not, so that they do not come to place excessive reliance on the decision support system.

N.B. The CLAHRC WM Director was an applicant on the study reported here, though not an author of this particular paper.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Pontefract SK, Hodson J, Slee A, Shah S, Girling AJ, Williams R, Sheikh A, Coleman JJ. Impact of a commercial order entry system on prescribing errors amenable to computerised decision support in the hospital setting: a prospective pre-post study. BMJ Qual Saf. 2018; 27: 725-36.

A Fascinating Service Improvement Cluster Randomised Trial

Most of you know that, across over 150 randomised trials, the effect of simple audit and feedback is a very modest 5% improvement in compliance with a standard of care. Could this be improved by a more active form of feedback based on daily dashboards, as well as weekly performance review?

To find out, Patel and colleagues conducted a cluster randomised trial in which one group of hospital-based clinical teams (control teams) received the standard feedback, consisting of twice monthly emails depicting performance on quality metrics.[1] The intervention team also received, in addition, access to daily updated performance dashboards, as well as in-person review of performance data. The authors refer to this enhanced audit and feedback as ‘next-generation audit and feedback’. A total of 40 medical teams participated in the trial. The outcome was a composite of various performance criteria, such as medicine reconciliation and a timely discharge summary. The intervention mimics a method that produced improvements in medicine administration in our CLAHRC West Midlands.[2]

The trail showed a sharp increase in performance in the intervention group compared to the control teams. But that is not all. The investigators introduced a wash-out period – that is to say, they withdrew the intervention but continued to monitor performance. What do you think happened?

The intervention did not stick – the enhanced performance in the intervention group soon reverted to baseline. The improvement in performance was considerably greater than that observed in most quality improvement studies, but it was ephemeral. Other studies have also found that using face-to-face performance review is more effective than more passive feedback methods. I really liked the idea of a wash-out – expect to see this in a CLAHRC near you! And the transient nature of the improvement provides further evidence in support of my conclusion – we should aim for deep change in attitudes, in addition to more surface level approaches to behaviour change.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Patel S, Rajkomar A, Harrison JD, Prasad PA, Valencia V, Ranji SR, Mourad M. Next-generation audit and feedback for inpatient quality improvement using electronic health record data: a cluster randomised controlled trial. BMJ Qual Saf. 2018; 27: 691-9.
  2. Coleman JJ, Hodson J, Brooks HL, Rosser D. Missed medication doses in hospitalised patients: a descriptive account of quality improvement measures and time series analysis. Int J Qual Health Care. 2013; 25(5): 564-72.

Cannabis and Schizophrenia: Which Way Around Does Causality Run?

Does cannabis lead to schizophrenia or does schizophrenia lead to the use of cannabis? That there is a strong, dose-related, association between the use of cannabis and the development of schizophrenia is not in doubt. But association studies cannot prove causality. Furthermore, a dose response can be seen where exposure to the putative causative agent and the true causative agent are correlated.

Genes to the rescue! Power and colleagues looked to see whether genetic polymorphisms that are associated with cannabis use are also associated with schizophrenia in people not exposed to cannabis.[1] They found that genes that pre-disposed to cannabis use also pre-disposed to schizophrenia, independently of whether the person actually used cannabis. The strength of the association between cannabis use predisposing genes and schizophrenia was the same in people who used cannabis, as in those who have never used this substance. Moreover, the risk was the same irrespective of the dose of cannabis consumed. The genetic predisposition to consume cannabis explained less than one-tenth of the variance in cannabis use. Nevertheless, this finding suggests that it is the predisposition to use cannabis, rather than the cannabis itself, that causes the psychiatric symptoms. If corroborated, then this study has important implications for policy.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Power RA, Verwij KJH, Zuhair M, et al. Genetic predisposition to schizophrenia associated with increased use of cannabis. Mol Psychiatr. 2014; 19: 1201-4.

Food Allergies and Childbirth

In a previous News Blog we looked at the practice of swabbing babies delivered via Caesarean section with vaginal fluid in an attempt to reduce the incidence of allergies in the child.[1] Another study has now been reported that could potentially strengthen this argument.[2] This was a nationwide cohort study conducted in Sweden that looked at over 1 million children, their route of delivery and the incidence of food allergies. Overall 2.5% of children were diagnosed with a food allergy, and this was positively associated with those who were delivered via C-section (hazard ratio 1.21, 95% CI 1.18-1.25) – both elective and emergency. Analysis of the data suggests that an extra 5 in 1,000 children delivered via C-section would develop a food allergy (compared to the reference group).

Interestingly there was also a negative association with those who were born prematurely (earlier than 32 weeks) (HR 0.74, 95% CI 0.56-0.98). The authors suggest this may be due to the postnatal care preterm infants receive, or is due to an immature gastrointestinal tract.

— Peter Chilton, Research Fellow

References:

  1. Lilford RJ. Exposure of the Baby to a Rich Mixture of Coliform Organisms from the Birth Canal. NIHR CLAHRC West Midlands News Blog. 22 April 2016.
  2. Mitselou N, Hallberg J, Stephansson O, Almqvist C, Melén E, Ludvigsson JF. Cesarean delivery, preterm birth, and risk of food allergy: Nationwide Swedish cohort study of more than 1 million children. J Allerg Clin Immunol. 2018.

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.