Transport to Hospital Times and Survival: The Case of Snake Bite

High-income countries have well developed ambulance services. However, investment in acquiring and maintaining effective systems of transport for sick and injured patients does not seem to have been a priority for many low- and middle-income countries (LMICs).  In some settings, for example post conflict states, lack of ambulance services is understandable; what is the point of transferring people to non-functioning or non-existent hospitals? But most LMICs do have a network of hospitals providing emergency care. The point must be reached where the opportunity costs of further improvements in fixed facilities is less than those of providing transport to reach the facilities in the first place.

There are many types of transport: motorised ambulance, motorbike ambulance, bicycle ambulance, and private vehicles. These different types of transport operate with or without trained clinical staff to accompany the patient. Moreover, there are many different types of clinical scenario where rapid transport may be required, from a very sick child to major trauma. There are also many different settings, rural vs. urban for example. The cost-effectiveness of different forms of transport will vary considerably between these different types of vehicle, different staff configurations, different clinical scenarios, and different geographical settings. Thus, the cost-effectiveness of a given type of transport, staffed in a given way and dealing with a particular clinical scenario, may have different effects and costs in different geographic and social contexts.

However, there is one unifying variable that underpins all cost-effectiveness calculations: this is the function that relates marginal changes in transport times in reaching a facility to the contingent marginal changes in outcome. In many circumstances death is the primary outcome of interest. Then, given an estimate of the relationship between time delay and survival, a local decision-maker can populate a cost-effectiveness model with context specific data. In this way it is possible to calibrate the anticipated benefit of a proposed transport system through its effect on reducing time to treatment.

In a forthcoming paper we will develop the model that relates transfer time to survival, taking into account costs, baseline survival rates, and whether or not treatment is administered in association with transport. To illustrate the model we will populate it with data for one particular scenario: snake bite. We use snake bite as the example, not only for its (considerable) intrinsic interest, but also because the best data we can find for transport time vs. survival rates, relates to snake bite. Our purpose is to illustrate the methodology so that it can be applied more generally. The case for ambulance services, of any particular type and in any setting, turns on its use across all emergency conditions. The investment case certainly could not be made on the basis of just one condition, least of all an uncommon scenario such as snake bite. Nevertheless, the model we propose could be used across a range of common scenarios to build up a case for a particular type of transport in a particular context.

— Richard Lilford, CLAHRC WM Director

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Misquotations

Misquotations, and quotations taken out of context, are as common in science as they are elsewhere. Many years ago I wrote a paper addressing the question of a general trial effect.[1] That is to say, whether a trial results in better outcomes, net of the effectiveness of the trial interventions, compared to no trial. The paper was widely cited, but mainly on the erroneous grounds that it demonstrated the putative trial effect. In fact, our careful analysis is more consistent with no such general trial effect. I was always pleased to be cited but displeased to be misquoted!

A similar phenomenon arises in the lively topic of the economic and employment effects of increasing automation. An extremely widely quoted article, with over 4000 citations, is alleged to have argued that automation would displace 47% of American jobs in less than two decades.[2] In fact, the authors wrote that this is “as an upper bound”. Moreover they were careful to point out that lost jobs will likely be replaced. This conclusion that automation does not destroy jobs is consistent with the evidence from economic history. Previous waves of automation increased prosperity and provided more jobs, at least in the medium-term. However, in the short-term automation pushes down wages. Engels was the first person to notice the delayed effect of automation and prosperity.[3]

— Richard Lilford, CLAHRC WM Director

References:

  1. Edwards SJ, Lilford RJ, Braunholtz DA, Jackson JC, Hewison J, Thornton J. Ethical issues in the design and conduct of randomised controlled trials. Health Technol Assess. 1998; 2(15): 1-132.
  2. Frey CB, Osborne M. The Future of Employment: How Susceptible Are Jobs to Computerisation? Oxford: Oxford University paper; 2013.
  3. Engels F. The Condition of the Working Class in England in 1844. New York; 1887. Available at: http://www.gutenberg.org/files/17306/17306-h/17306-h.htm

 

Another Very Interesting Paper on Molecular Analysis of Stool in Childhood Diarrhoea

We have previously summarised the results of a study using molecular analysis to examine samples from children with and without diarrhoea. Among many interesting findings, this showed that Shigella is one of the most common bacterial causes of childhood diarrhoea.[1][2] A further study by the same investigator team tested stool samples from 1,715 children from eight countries for presence of 29 entertopathogens.[3] This was a reanalysis of a previously published dataset (MAL-ED) using quantitative PCR methods in order to refine the aetiology estimates by increasing the pathogens tested for.

While the original study found that 32.8% of diarrhoea samples were attributable to an infectious aetiology, this new analysis found 64.9% attributable. Thus, the more rigorous method doubled the proportion of diarrhoea cases that could be attributed to a specific pathogen. Diarrhoea attributable to pathogens during the first year of life was lower (50.5%) than during the second year (82.8%). The study also found that viral diarrhoea was most common (36.4%), then bacterial (25.0%) and parasitic (3.5%). Ten pathogens accounted for 95.7% of attributable diarrhoea. Again, Shigella was shown to be the most common (26.1%), followed by sapovirus (22.8%) and rotavirus (20.7%).

The CLAHRC WM Director has questions:

  1. What causes the unattributable cases, especially in the first year of life?
  2. Did all cases really have diarrhoea? It is a diagnosis that is partly ‘in the eye of the beholder’.[4]
  3. Contrary wise, how can we be sure that the agent detected was causal of the condition?

— Richard Lilford, CLAHRC WM Director
— Peter Chilton, Research Fellow

References:

  1. Liu J, Platts-Mills JA, Juma J, et al. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet. 2016; 388: 1291-301.
  2. Lilford RJ. Did You Ever Want to Know What Bugs Were Actually in Diarrhoea? NIHR CLAHRC West Midlands News Blog. 11 November 2016.
  3. Platts-Mills JA, Liu J, Rogawski ET, et al. Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study. Lancet Glob Health. 2018; 6(12): e1309-18.
  4. Lilford RJ. Childhood Diarrhoeal Diseases – Update of the Famous Wolf Review. NIHR CLAHRC West Midlands News Blog. 19 October 2018.

Use of a Menstrual Cup

There is a rising awareness of ‘Period Poverty[1] where girls and women simply cannot afford a constant supply of menstrual products. While this is a particular concern in low- and middle-income countries (LMICs), it also affects people in high-income countries, such as the UK where 10% of girls have reported being unable to afford menstrual products.[2] With choices limited, a lack of affordable and effective products can result in leakage, chaffing and increase the risk of urogenital infections, as well as lead to social stigma and a negative impact on schooling and employment. Many argue that reusable products would be a more effective alternative to single-use products currently favoured by agencies providing aid in LMICs settings.

A systematic review published in the Lancet Public Health looked at evidence from 43 studies on the effectiveness of using a menstrual cup.[3] Fifteen of these studies were conducted in low- and middle-income countries. Four studies looked at leakage compared to usual products, finding comparable results. Overall, the authors found that the use of menstrual cups were a safe option for managing menstruation, with very few serious adverse events reported. However, as menstrual cups need to be manually removed with clean hands and cleaned thoroughly before being used again, there may be a greater risk in areas with poor facilities.

Although the conclusions are promising, more good quality studies are needed, as only two of the quantitative studies analysed were of moderate-to-high quality. Furthermore, studies regarding cost-effectiveness and environmental effects are also required, though the authors estimated significant savings compared to both sanitary pads and tampons.

In light of this study there is also a need for information regarding menstrual cups to be made more prominent in educational materials, especially as participants reported using a menstrual cup required a period of familiarisation.

— Peter Chilton, Research Fellow

References:

  1. George A. The Shame of Period Poverty is Keeping British Girls Out of School. Let’s Break the Silence. The Guardian. 19 December 2017.
  2. Plan International UK. Research on Period Poverty and Stigma. 20 December 2017.
  3. van Eijk AM, Zulaika G, Lenchner M, et al. Menstrual Cup Use, Leakage, Acceptability, Safety, and Availability: a Systematic Review and Meta-Analysis. Lancet Public Health. 2019.

Probiotic Treatment Reduces the Incidence of Severe Sepsis in Neonates in India

Every now and then the CLAHRC WM Director spots an article that was published a few years ago, that he would have summarised had he seen it, and that is still topical. Such an article was an RCT of a probiotic administered in combination with a nutritional supplement. The idea behind the nutritional agent is that it will enable the probiotic bacteria to flourish in the host intestine [1] – the combination of probiotic and nutritional agents is called a ‘synbiotic’. Over four-and-a-half-thousand infants (2 to 4 days old), across 149 villages, were randomised to intervention or control. The trial, reported in Nature, had to be stopped early, so great was the reduction in neonatal sepsis in the intervention group.

Interestingly, the death rates in the Nature study were not different between study arms, but then only ten children died overall. Very interestingly, the incidence of pneumonia was reduced, alongside sepsis, in the intervention group. This study was completed in 2012, but was not published until 2017.

An updated systematic review from 37 RCTs found that probiotics significantly decreased the risk of late-onset sepsis (p=0.0007).[2] This study of nearly 10,000 babies is the largest of any meta-analysis in Neonatology. The results are significant even if studies at high risk of bias are excluded. There was no evidence of small study / publication bias in the funnel plot. Overall, the result remained significant irrespective of which bacterial strains were retained in the meta-analysis.

So, the meta-analysis, now reinforced by the Nature study, really does suggest that probiotics are effective. Lactobacillus and Bifidus are the two most widely used bacterial species, but the Nature study used only Lactobacilli.

— Richard Lilford, CLAHRC WM Director

References:

  1. Panigrahi P, Parida S, Nanda NC, et al. A randomized symbiotic trial to prevent sepsis among infants in rural India. Nature. 2017; 548: 407-12.
  2. Rao SC, Athalye-Jape GK, Deshpande GC, Simmer KN, Patole SK. Probiotic Supplementation and Late-Onset Sepsis in Preterm Infants: A Meta-Analysis. Pediatrics. 2016; 137(3): e20153684.

The Role of Fathers in Child Rearing

A recent article published in the Pediatrics journal summarises evidence on the role of fathers in development of children.[1] The studies are mainly of an observational nature, as one might expect, but the article pays scant attention to the limitations of this sort of evidence. However, despite the methodological naivety of the article, many of the findings are of interest. Furthermore, they are consistent across a large number of studies.

There are strong and consistent correlations between the presence of a father and psychological and functional outcomes for children. Similar findings apply in the adolescent years. Fathers tend to play more with their children than do mothers. Roughhouse play is particularly associated with healthy adaptation in the children. The mental health of fathers is strongly associated with child development. Interestingly, male testosterone levels increase during conception and decrease during child rearing. There are consistent differences between mothers and fathers in the neurological pathways that are activated during child rearing.

The CLAHRC WM Director found these results emotionally appealing, and wonders about the effect of grandparents on child development.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Yogman M, Garfield CF, Committee on Psychosocial Aspects of Child and Family Health. Fathers’ Roles in the Care and Development of Their Children: The Role of Pediatricians. Pediatrics. 2016; 138(1): e20161128.

Interventions Targeted Across a Community vs. Interventions Targeted at Specific Individuals

Behaviour change has often been viewed as an individual issue. Since individuals are the target of a behaviour change intervention, it seems natural to focus the intervention on the individuals whose behaviour one wishes to change. So, if one wishes to improve breastfeeding or encourage hygienic preparation of infant foods, then the target group would naturally be young mothers.

However, these targeted interventions have often produced disappointing results when evaluated rigorously. There are a number of reasons to think that a more general, or community-wide, intervention would be more effective (or augment the effect of the personal approach). Firstly, in terms of evolutionary theory, humans have evolved to work collaboratively in hierarchical groups. Humans could not get very far in the savannah as individuals; so like many animals their success depended on group action. Secondly, the emerging acceptance of the trans-theoretical framework has emphasised multiple barriers, including social barriers. Bandura showed how exquisitely sensitive individuals are to social signals and to the influence of leaders.[1]

As a result of this thinking, interventions are increasingly targeted, not only at the front line, but also the local social structures and hierarchies. For example recent work on infant hygiene and breastfeeding has been focused at the community level, rather than on individual mothers.[2][3] Similarly, interventions to improve services recognise the importance off including, not only front line staff, but other levels in the hierarchy.[4][5]

— Richard Lilford, CLAHRC WM Director

References:

    1. Bandura A. Social Learning Theory. Englewood Cliffs, NJ: Prentice Hall, 1977.
    2. Lilford RJ. Cluster Trial of Home Visits for Newborn Children in Sub-Saharan Africa. NIHR CLAHRC West Midlands News Blog. 6 May 2016.
    3. Kirkwood BR, Manu A, ten Asbroek AHA, et al. Effect of the Newhints home-visits intervention on neonatal mortality rate and care practices in Ghana: a cluster randomised controlled trialLancet. 2013; 381(9884): 2184-92.
    4. Lilford RJ. Reports of a Hospital-Wide Improvement Programme. NIHR CLAHRC West Midlands News Blog. 21 June 2019.
    5. Chatfield SC, Volpicelli FM, Adler NM, et al. Bending the cost curve: quasi-experimental analysis of a value transformation program at an academic medical centerBMJ Qual Saf. 2019; 28: 449–58.

 

Rotavirus Vaccine

Gastroenteritis as a result of rotavirus infection is a major cause of morbidity and mortality among children under 5 years old, with around 215,000 deaths in 2013.[1] Thankfully there is now a vaccine available, and hospital admissions and deaths have been shown to have declined significantly since its introduction. However, not all countries have incorporated the rotavirus vaccine into their national immunisation programmes. A recent paper in Lancet Global Health used data from the WHO-coordinated Global Rotavirus Surveillance Network to look at the impact the vaccine has had worldwide, as it had not previously been analysed using primary data.[2]

More than 400,000 children from 82 countries were admitted to hospital with acute gastroenteritis over the study period, with around one-third being tested positive for rotavirus. The impact analysis of the study looked at a subset of ~300,000 children and found that there was a decline of 39.6% (95% CI 35.4-43.8) in admissions in countries that had introduced the vaccine into their immunisation programme, compared to the years before, resulting in rotavirus being detected in around 23% of admissions. Meanwhile, in countries that did not include the vaccine there was no significant change in rotavirus detected over time, remaining stable at around 38% of admissions. Further, in countries that had introduced the vaccine, the age distribution of children that tested positive for rotavirus gastroenteritis was skewed towards older children, perhaps as a result of the improved protection.

References:

  1. Tate JE, Burton AH, Boschi-Pinto C, Parashar UD; World Health Organization-Coordinated Global Rotavirus Surveillance Network. Global, regional, and national estimates of rotavirus mortality in children <5 years of age, 2000–2013. Clin Infect Dis. 2016; 62: S96-S105.
  2. Aliabadi N, Antoni S, Mwenda JM, et al. Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008–16: findings from the Global Rotavirus Surveillance Network. Lancet Glob Health. 2019; 7(7): e893-903.

The Famous Million Deaths Study in India: Kidney Failure

As people urbanise, one may expect increasing incidence of diabetes and high blood pressure. High blood pressure and diabetes damage the kidneys. So this study,[1] based on the above iconic population dataset, investigated kidney deaths over a decade. Indeed, the investigators found a substantial increase in deaths from kidney failure. The increase was greater in urban areas than in rural areas. These spatial and temporal differences parallel the increasing prevalence of the underlying disorders. The study is based on verbal autopsies, and so the death rates of 2.1% and 2.9% at the beginning and end of the study period may not be literally correct. But the relative risk increase of over 40% is likely valid, as it is based on consistent methodology.

Once your kidneys pack up you need either dialysis or transplant. These are expensive – the per capita GDP (international $ at PPP) of India is about $7,000. The CLAHRC WM Director has assisted at kidney transplant operations and can confirm that it is a very easy operation that could be Taylorised [2] and performed by supervised technicians. But the logistics of a living donor exchange programme make it more expensive. Kidney transplants are widespread in high-income countries and rare in low-income countries. Access to transplants in middle-income countries is extremely variable.[3] In the USA the mean kidney transplant cost is over $82,000.[4] The Peninsula Technology Assessment Group have developed a good economic model. Someone should work out the relationship between per capital GDP and cost-effectiveness of a kidney transplant programme. Health economic evaluations in a global context should be deployed as a way of determining the stages in an economy’s development at which various treatments exceed their opportunity cost. We are working on such a project with respect to provision of motorised, motorbike or other forms of transport for acutely sick people as part of the NIHR Global Health Research Unit on Global Surgery.

— Richard Lilford, CLAHRC WM Director

References:

  1. Dare AJ, Fu SH, Patra J, Rodriguez PS, Thakur JS, Jha P, for the Million Death Study Collaborators. Renal failure deaths and their risk factors in India 2001-13: nationally representative estimates from the Million Death Study. Lancet Glob Health. 2017; 5: e89-95.
  2. Lilford RJ. Bariatric Surgery – Improve Five Year Outcomes. NIHR CLAHRC West Midlands News Blog. 23 June 2017.
  3. Garcia GG, Harden P, Chapman J; World Kidney Day Sterring Committee 2012. The Global Role of Kidney Transplantation. Nephron Clin Pract 2012; 120(2): c101-6.
  4. Evans RW & Kitzman DJ. An Economic Analysis of Kidney Transplantation. Surg Clin North Am. 1998; 78(1): 149-74.

Providing Healthcare to People in Urban Settlements in Poor Countries: a Story of Two Options

There can be a little doubt that primary preventive care should be delivered close to people’s homes. How else can we ensure that children are vaccinated, detect early signs of malnutrition, and provide better water and sanitation? But reactive care, when the system reacts to a patient’s expressed need, is also very important. The historical foundations of medical care rest entirely on meeting this need.

Emerging findings from our work in urban settlements (soon to be published) shows that local people consult healthcare providers frequently. They attend pharmacies, local independent providers, local clinics funded by NGOs or local government, and they also travel further afield to attend public or private hospital outpatient departments. Only rarely do they attend traditional healers for “health care” needs.

While people in urban settlements, just like those in high-income countries, often turn to pharmacies, they also make heavy use of clinical services other than pharmacies. When accessing such clinical services, a person will have a choice between seeing a clinician in the local environment or traveling to a nearby hospital. Clearly, the local provider is more convenient. However, it would appear that many people are prepared to put up with the inconvenience of traveling to a local hospital. Presumably they are making a trade-off between perceived quality and convenience.

There are reasons to believe that there are indeed real differences in quality between the various providers of clinical services. We are currently conducting a review of the literature on the quality of ambulant care in low-income countries. It is quite clear from this work that the quality of care delivered to patients in close proximity to their homes is dismal in low- and middle-income countries. There is little evidence on care quality in public hospitals. However, emerging findings from a study we have conducted suggest that care is much better in public hospitals than among informal providers. If this is confirmed, then we will know that there is a genuine trade-off between quality of care provided by public hospitals and the convenience of accessing providers nearer to home.

While both provision within communities and in public hospitals will be available for the foreseeable future, policy can determine which comes to predominate over the next few decades. Do we wish to encourage highly accessible local provision? Or are we prepared to go for a more centralised model? The World Health Organization strongly favour primary care development, but is vague on where this should be delivered, and stops short of favouring a dispersed model.

More research is certainly required, both into patient choice and the relative quality differences that different types of provider deliver.[1] However, we do need to consider the implications of different findings that might emerge. We might find that outpatient provision in public institutions, and perhaps also well run private hospitals, is much superior to more distributed provision by independent providers in low-income countries. We might also find that people are prepared to travel in order to access a better quality of service. In that case, it might be better to concentrate on improving outpatient provision in larger institutions and slant policy away from local independent providers, or, in addition, regulation and strengthening the demand side may be required.

In theory, there may be good arguments for a hub and spoke model, where well-organised and government institutions have hard-to-reach clinics. However, logistics and finance restrain the choice of policy. For example, the perhaps appealing option of a central hospital hub operating spoke clinics in local communities might be practically impossible. So our next task is to work out the logistics of various patterns. The status quo is lots of independent providers, a small number of local clinics, and a hospital at some distance (Figure 1). We need to understand the logistics and indicative costs of moving to an even more strongly centralised, or a hub and spoke model (Figures 2 and 3).

128 DCB - Providing Healthcare Figure 1128 DCB - Providing Healthcare Figure 2128 DCB - Providing Healthcare Figure 3

Whatever happens, policy should be driven by research results to better understand the quality of provision, the trade-offs that local people wish to make, and the logistical and financial implications of different service configurations.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Lilford RJ. Public versus Private Providers: Simple Solutions are Simplistic! NIHR CLAHRC West Midlands News Blog. 10 August 2018.