Tag Archives: Peter Chilton

Reducing the Global Burden of Diagnostic Errors

A recent issue of the BMJ Quality and Safety carried an interesting review on the global burden of diagnostic errors in primary care.[1] The review looked at the most common symptoms and conditions affected by such errors; summarised the current interventions; and suggested what could be done next to reduce the global burden of diagnostic errors. The authors found that:

  • Typically there are multiple ‘root causes’ for errors, including both cognitive errors, such as failing to synthesise evidence, and system flaws, such as communication issues.
  • The most common categories of harmful diagnostic errors are infections, cardiovascular disease, cancer, and diseases in children.
  • Very few interventions to reduce errors have been tested empirically.
  • In order to reduce errors successfully there is likely to be a need for multiple interventions.

They go on to propose eight themes for interventions to measure and reduce diagnostic error:

  1. Improving diagnostic reasoning.
  2. Encouraging government policies that support primary care.
  3. Improving information technology.
  4. Involving patients.
  5. Improving access to diagnostic tests.
  6. Developing methods to identify and learn from diagnostic errors.
  7. Optimising diagnostic strategies in primary care.
  8. Providing systematic feedback to clinicians about their diagnoses.

The authors call on the World Health Organization to bring together concerned bodies to address the many challenges that are common across all countries and the opportunities that can be taken to reduce diagnostic error. CLAHRC WM collaborators are working on a more detailed classification system for the theoretical basis for diagnostic error.

— Peter Chilton, Research Fellow

Reference:

  1. Singh H, Schiff GD, Graber ML, Onakpoya I, Thompson MJ. The global burden of diagnostic errors in primary care. BMJ Qual Saf. 2017; 26: 484-94.

Mindfulness for Low Back Pain

Lower back pain is fast becoming a major public health problem. Perhaps because of our increasingly sedentary life style it affects around 75% of the population at some point during their lives. However, there is no optimum clinical treatment. In light of this, many people turn to complementary therapies. A recent systematic review by Anheyer and colleagues [1] looked at the effectiveness of such a therapy, mindfulness-based interventions. Mindfulness-based stress reduction programmes (MBSR), and mindfulness-based cognitive therapy (MBCT) (see main article) usually involve activities such as meditation, yoga, and focusing attention on different parts of the body. The authors identified seven RCTs involving 864 patients, and found that MBSR was associated with statistically significant short-term improvements in pain, compared to standard care, though these weren’t sustained in the long term, and could not be deemed clinically meaningful. However, there were no significant differences when compared to active comparators, such as health education programmes. These were only a limited number of RCTs and there is still a need for long-term RCTs that compare MBSR against active treatments.

— Peter Chilton, Research Fellow

Reference:

  1. Anheyer D, Haller H, Barth J, et al. Mindfulness-based stress reduction for treating low back pain. A systematic review and meta-analysis. Ann Intern Med. 2017; 166: 799-807.

And Today We Have the Naming of Parts*

Management research, health services research, operations research, quality and safety research, implementation research – a crowded landscape of words describing concepts that are, at best, not entirely distinct, and at worst synonyms. Some definitions are given in Table 1. Perhaps the easiest one to deal with is ‘operations research’, which has a rather narrow meaning and is used to describe mathematical modelling techniques to derive optimal solutions to complex problems typically dealing with the flow of objects (people) over time. So it is a subset of the broader genre covered by this collection of terms. Quality and safety research puts the cart before the horse by defining the intended objective of an intervention, rather than where in the system the intervention impacts. Since interventions at a system level may have many downstream effects, it seems illogical and indeed potentially harmful, to define research by its objective, an argument made in greater detail elsewhere.[1]

Health Services Research (HSR) can be defined as management research applied to health, and is an acceptable portmanteau term for the construct we seek to define. For those who think the term HSR leaves out the development and evaluation of interventions at service level, the term Health Services and Delivery Research (HS&DR) has been devised. We think this is a fine term to describe management research as applied to the health services, and are pleased that the NIHR has embraced the term, and now has two major funding schemes ­– the HTA programme dealing with clinical research, and the HS&DR dealing with management research. In general, interventions and their related research programmes can be neatly represented as shown in the framework below, represented in a modified Donabedian chain:

078 DCB - Figure 1

So what about implementation research then? Wikipedia defines implementation research as “the scientific study of barriers to and methods of promoting the systematic application of research findings in practice, including in public policy.” However, a recent paper in BMJ states that “considerable confusion persists about its terminology and scope.”[2] Surprised? In what respect does implementation research differ from HS&DR?

Let’s start with the basics:

  1. HS&DR studies interventions at the service level. So does implementation research.
  2. HS&DR aims to improve outcome of care (effectiveness / safety / access / efficiency / satisfaction / acceptability / equity). So does implementation research.
  3. HS&DR seeks to improve outcomes / efficiency by making sure that optimum care is implemented. So does implementation research.
  4. HS&DR is concerned with implementation of knowledge; first knowledge about what clinical care should be delivered in a given situation, and second about how to intervene at the service level. So does implementation research.

This latter concept, concerning the two types of knowledge (clinical and service delivery) that are implemented in HS&DR is a critical one. It seems poorly understood and causes many researchers in the field to ‘fall over their own feet’. The concept is represented here:

078 DCB - Figure 2HS&DR / implementation research resides in the South East quadrant.

Despite all of this, some people insist on keeping the distinction between HS&DR and Implementation Research alive – as in the recent Standards for Reporting Implementation studies (StaRI) Statement.[3] The thing being implemented here may be a clinical intervention, in which case the above figure applies. Or it may be a service delivery intervention. Then they say that once it is proven, it must be implemented, and this implementation can be studied – in effect they are arguing here for a third ring:

078 DCB - Figure 3

This last, extreme South East, loop is redundant because:

  1. Research methods do not turn on whether the research is HS&DR or so-called Implementation Research (as the authors acknowledge). So we could end up in the odd situation of the HS&DR being a before and after study, and the Implementation Research being a cluster RCT! The so-called Implementation Research is better thought of as more HS&DR – seldom is one study sufficient.
  2. The HS&DR itself requires the tenets of Implementation Science to be in place – following the MRC framework, for example – and identifying barriers and facilitators. There is always implementation in any trial of evaluative research, so all HS&DR is Implementation Research – some is early and some is late.
  3. Replication is a central tenet of science and enables context to be explored. For example, “mother and child groups” is an intervention that was shown to be effective in Nepal. It has now been ‘implemented’ in six further sites under cluster RCT evaluation. Four of the seven studies yielded positive results, and three null results. Comparing and contrasting has yielded a plausible theory, so we have a good idea for whom the intervention works and why.[4] All seven studies are implementations, not just the latter six!

So, logical analysis does not yield any clear distinction between Implementation Research on the one hand and HS&DR on the other. The terms might denote some subtle shift of emphasis, but as a communication tool in a crowded lexicon, we think that Implementation Research is a term liable to sow confusion, rather than generate clarity.

Table 1

Term Definitions Sources
Management research “…concentrates on the nature and consequences of managerial actions, often taking a critical edge, and covers any kind of organization, both public and private.” Easterby-Smith M, Thorpe R, Jackson P. Management Research. London: Sage, 2012.
Health Services Research (HSR) “…examines how people get access to health care, how much care costs, and what happens to patients as a result of this care.” Agency for Healthcare Research and Quality. What is AHRQ? [Online]. 2002.
HS&DR “…aims to produce rigorous and relevant evidence on the quality, access and organisation of health services, including costs and outcomes.” INVOLVE. National Institute for Health Research Health Services and Delivery Research (HS&DR) programme. [Online]. 2017.
Operations research “…applying advanced analytical methods to help make better decisions.” Warwick Business School. What is Operational Research? [Online]. 2017.
Patient safety research “…coordinated efforts to prevent harm, caused by the process of health care itself, from occurring to patients.” World Health Organization. Patient Safety. [Online]. 2017.
Comparative Effectiveness research “…designed to inform health-care decisions by providing evidence on the effectiveness, benefits, and harms of different treatment options.” Agency for Healthcare Research and Quality. What is Comparative Effectiveness Research. [Online]. 2017.
Implementation research “…the scientific inquiry into questions concerning implementation—the act of carrying an intention into effect, which in health research can be policies, programmes, or individual practices (collectively called interventions).” Peters DH, Adam T, Alonge O, Agyepong IA, Tran N. Implementation research: what it is and how to do it. BMJ. 2013; 347: f6753.

We have ‘audited’ David Peters’ and colleagues BMJ article and found that every attribute they claim for Implementation Research applies equally well to HS&DR, as you can see in Table 2. However, this does not mean that we should abandon ‘Implementation Science’ – a set of ideas useful in designing an intervention. For example, stakeholders of all sorts should be involved in the design; barriers and facilitators should be identified; and so on. By analogy, I think Safety Research is a back-to-front term, but I applaud the tools and insights that ‘safety science’ provides.

Table 2

Term
“…attempts to solve a wide range of implementation problems”
“…is the scientific inquiry into questions concerning implementation – the act of carrying an intention into effect, which in health research can be policies, programmes, or individual practices (…interventions).”
“…can consider any aspect of implementation, including the factors affecting implementation, the processes of implementation, and the results of implementation.”
“The intent is to understand what, why, and how interventions work in ‘real world’ settings and to test approaches to improve them.”
“…seeks to understand and work within real world conditions, rather than trying to control for these conditions or to remove their influence as causal effects.”
“…is especially concerned with the users of the research and not purely the production of knowledge.”
“…uses [implementation outcome variables] to assess how well implementation has occurred or to provide insights about how this contributes to one’s health status or other important health outcomes.
…needs to consider “factors that influence policy implementation (clarity of objectives, causal theory, implementing personnel, support of interest groups, and managerial authority and resources).”
“…takes a pragmatic approach, placing the research question (or implementation problem) as the starting point to inquiry; this then dictates the research methods and assumptions to be used.”
“…questions can cover a wide variety of topics and are frequently organised around theories of change or the type of research objective.”
“A wide range of qualitative and quantitative research methods can be used…”
“…is usefully defined as scientific inquiry into questions concerning implementation—the act of fulfilling or carrying out an intention.”

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

References:

  1. Lilford RJ, Chilton PJ, Hemming K, Girling AJ, Taylor CA, Barach P. Evaluating policy and service interventions: framework to guide selection and interpretation of study end points. BMJ. 2010; 341: c4413.
  2. Peters DH, Adam T, Alonge O, Agyepong IA, Tran N. Implementation research: what it is and how to do it. BMJ. 2013; 347: f6753.
  3. Pinnock H, Barwick M, Carpenter CR, et al. Standards for Reporting Implementation Studies (StaRI) Statement. BMJ. 2017; 356: i6795.
  4. Prost A, Colbourn T, Seward N, et al. Women’s groups practising participatory learning and action to improve maternal and newborn health in low-resource settings: a systematic review and meta-analysis. Lancet. 2013; 381: 1736-46.

*Naming of Parts by Henry Reed, which Ray Watson alerted us to:

Today we have naming of parts. Yesterday,

We had daily cleaning. And tomorrow morning,

We shall have what to do after firing. But to-day,

Today we have naming of parts. Japonica

Glistens like coral in all of the neighbouring gardens,

And today we have naming of parts.

Walking after Paraplegia

For those with paraplegia following spinal cord injury (SCI), a wheelchair is their primary means of mobility. However, this can often lead to medical co-morbidities that contribute significantly to SCI-related medical care costs. According to surveys these patients highly prioritise restoration of walking as a way to improve their quality of life.

A recent paper by King et al. looked at the feasibility of using a brain-computer interface to give paraplegic patients the chance to walk again.[1] The procedure involved linking an electroencephalogram-based system to a functional electrical stimulation system on leg muscles, which can then be controlled by thought. The study used a physically active 26 year-old male who underwent virtual reality training in order to reactivate the areas of the brain responsible for gait, and reconditioning of leg muscles using electro-stimulation. Over 19 weeks the patient was able to successfully complete 30 over-ground walking tests with no adverse events.

The authors concluded that these results provide proof-of-concept for using direct brain control to restore basic walking. Although the current system is likely to be too cumbersome for full-scale adoption, it may represent a precursor to a future, fully implantable system.

— Peter Chilton, Research Fellow

Reference:

  1. King CE, Wang PT, McCrimmon CM, Chou CCY, Do AH, Nenadic Z. The feasibility of a brain-computer interface functional electrical stimulation system for the restoration of overground walking after paraplegia. J Neuroeng Rehab. 2015; 12: 80.

 

 

An Apple a Day…

The old adage, “an apple a day keeps the doctor away” has been put to the test by Davis et al. in a recently published cross-sectional study.[1] The authors studied over 8,000 US adults, comparing those who ate “an apple a day” (based on a dietary recall questionnaire), with those who did not, on the primary outcome of “keeping the doctor away” – no more than one self-reported visit to a physician in the previous year.

The study identified 753 adults who ate at least one apple a day, and, compared to non-apple eaters, they had higher levels of education, were less likely to smoke, and were more likely to be from a racial or ethnic minority (P<0.001). However, after adjusting for socio-demographic and health-related characteristics, there was no statistically significant difference in physician visits (OR 1.19, 0.93-1.53, P=0.15); though they did appear to use fewer prescription medicines (OR 1.27, 1.00-1.63). So maybe we should start using “an apple a day keeps the pharmacist away”?

— Peter Chilton, Research Fellow

Reference:

  1. Davis MA, Bynum JPW, Sirovich BE. Association Between Apple Consumption and Physician Visits Appealing the Conventional Wisdom That an Apple a Day Keeps the Doctor Away. JAMA Intern Med. 2015. [ePub].

So it is not true what they say – traditional healers are not as widely used after all

We have all heard it said that most of the African population makes heavy use of traditional healers alongside allopathic care. According to the WHO, “up to 80% of the population [of African member states] uses traditional medicine for primary health care.”[1] However, this idea has been challenged by Kate Wilkinson, who traced the roots of the claim.[2] She found that it has been copied from document to document from its origins in a 30 year old book available in the University of Witswatersrand library. The statement in the book is not referenced, so does the trail end there? Wilkinson turned to the South African General Household Survey, 2011,[3] and found that traditional healers were the least favoured healthcare provider, comprising first choice for only 0.1% of South Africans. Even allowing for respondent bias, this is not impressive! The South African DHS survey (n=8,115) found that only 2.6% of people reported receiving care from a traditional healer and 3.1% from a faith healer, versus 20.0% reporting contact with a public sector health faculty, and 15.2% reporting such contact with a private provider.[4] Likewise a 2008 survey of households in South Africa (n=4,762) found that only 1.2% of respondents reported using traditional healers,[5] with much lower utilisation rates than public sector clinics or hospitals. Reported use of traditional healers was higher among those of a lower socio-economic status (p<0.01), who were unemployed (p<0.01), lived in rural areas, were aged between 25-49 years and reported low health status (p<0.01), although these associations are not consistent across different countries.[6] [7]

In many traditional African belief systems mental health problems are perceived as being due to ancestors or bewitchment, and traditional healers are viewed as having more expertise in these areas.[8] Maybe consultation rates are higher in mental health? A 2011 cross-sectional survey of 2,514 adult Qatari/Arab expatriates residing in the State of Qatar found that nearly 40% of respondents believed that possession by evil spirits could be a reason for mental illness, and ~50% thought it could be a punishment from God (for comparison, ~80% believed it could be caused by brain disease; ~75% by stress; ~75% by genetic inheritance).[9] The study also found that approximately 40% believed that traditional healers could treat mental illness. Other reasons for preferring to see traditional healers included the psychosocial support afforded, their availability/accessibility, the flexibility in payment (including paying after treatment, in kind, in instalments, or payment being waivered).[10] [11] A 2003 study in Tanzania found that the prevalence of mental disorders among patients of traditional healer centres was approximately twice that of patients attending primary health care clinics.[6] Meanwhile a study in Eastern Uganda found that over 80% of patients diagnosed with psychosis used both biomedical and traditional healing systems, with those combining both seemingly having a better outcome.[12] A study by Sorsdahl et al.[8] looked at care for mental health disorders in South Africa using a national survey of 3,651 adults – only 9% of the respondents reported using traditional healers (and 11% reported consulting a religious/spiritualist advisor), the use of traditional healers was predicted by older age, black race, unemployment, lower education, and having an anxiety or substance-use disorder. A number of small studies have also been conducted in sub-Saharan African countries, which showed that 41-61% of individuals with mental illness were reported to have consulted a traditional healer.[13] [14]

It seems that use of traditional healers is declining in Africa – certainly in South Africa – but that they may have a larger role in mental health. This is a point we propose to investigate under CLAHRC International using the SAGE database.

— Richard Lilford, Director CLAHRC WM;

— Peter Chilton, Research Associate;

— Oyinlola Oyebode, Associate Professor in Public Health

References:

  1. World Health Organization. Traditional Medicine. Fact sheet No. 134. 2003.
  2. Wilkinson K. Do 80% of S. Africans regularly consult traditional healers? The claim is false. Africa Check. 2013.
  3. Statistics South Africa. South African General household survey, 2011. Pretoria: Statistics South Africa. 2012.
  4. MRC South Africa. South Africa Demographic and Health Survey, 2003. Part III. Pretoria: MRC South Africa. 2003.
  5. Nxumalo N, Alaba O, Harris B, Chersich M, Goudge J. Utilization of traditional healers in South Africa and costs to patients: Findings from a national household survey. J Pub Health Pol. 2011; 32 (s1): s124-36.
  6. Sorsdahl K, et al. Traditional healers in the treatment of common mental disorders in South Africa. J Nerv Ment Dis. 2009; 197(6): 434-41.
  7. Bener A, Ghuloum S. Gender differences in the knowledge, attitude and practice towards mental health illness in a rapidly developing Arab society. Int J Psych. 2011; 57(5): 480-6.
  8. Ae-Ngibise K, Cooper S, Adiibokah E, Akpalu B, Lund C, Doku V. ‘Whether you like it or not people with mental problems are going to go to them’: A qualitative exploration into the widespread use of traditional and faith healers in the provision of mental health care in Ghana. Int Rev Psychiatr. 2010, 22(6):558-67.
  9. Mbwayo AW, Ndetei DM, Mutiso V, Khasakhala LI. Traditional healers and provision of mental health services in cosmopolitan informal settlements in Nairobi, Kenya. Afr J Psychiatry. 2013;16(2):134-40.
  10. Ngoma M, Prince M, Mann A. Common mental disorders among those attending primary health clinics and traditional healers in urban Tanzania. Br J Psych. 2003; 183: 349–355.
  11. Abbo C. Profiles and outcome of traditional healing practices for severe mental illnesses in two districts of Eastern Uganda. Global Health Action. 2011; 4.
  12. Freeman M, Lee T, Vivian W. Evaluation of mental health services in the Orange Free State. Parktown, South Africa: Department of Community Health, University of the Witwatersrand Medical School. 1994.
  13. Ensink K, Robertson B. Patient and Family Experiences of Psychiatric Services and Indigenous Healers. Transcultural Psych. 1999;36(1):23–43.
  14. Patel V, Simunya E, Gwanzura F. The pathways to primary mental health care in high density suburbs in Harare, Zimbabwe. Soc Psych Psych Epid. 1997; 32: 97–103.

A Mysterious Disease with Unknown Cause

At the recent CAHRD (Centre for Applied Health Research and Delivery) Consultation in Liverpool, the CLAHRC WM Director was reminded of a curious tropical disease, which he would like to share with readers of our blog.

Children being tied to a tree, or chained in their home while their parents work in the nearby fields. Neglect? Or a sad necessity in some parts of Africa where a little known disease has been devastating communities? A growing number of children in late childhood/early adolescence are being afflicted by nodding disease – suffering from, among other things, seizures and cognitive difficulties. Many parents fear that without taking drastic measures they will return to find their child has wandered into the bush, unlikely to ever return, or has accidentally injured herself. Crucially, the medical community have not been able to pinpoint a definite cause, let alone a cure.

Nodding disease has only been diagnosed in three, non-contiguous rural areas of Africa – western and central South Sudan, southern Tanzania and northern Uganda (Figure 1).[1] Estimates suggest 3,000–8,000 cases have already been reported [1] – figures higher than recorded Ebola cases.[2] Although nodding disease has only recently come to the attention of the wider medical community (the Center for Disease Control (CDC) began to study the disease in 2009), it first emerged in the 1960s.[1] [3]

Map of South Sudan, Uganda and Tanzania
Figure 1. Map of South Sudan, Uganda and Tanzania

Its name comes from the characteristic symptom of the disease – an uncontrollable nodding of the head that is a direct result of seizures causing a brief lapse in muscle tone. These seizures are of various severities, and often begin when the child eats or the ambient temperature drops, generally not stopping until the child has finished eating or has warmed up. In latter stages of the disease this can lead to severe malnutrition as children are no longer able to eat. (Curiously it has been reported that no seizures occur when an affected child is given an unfamiliar food, such as chocolate.)[4] Over time the symptoms worsen – from a few times a week, the nodding episodes begin to happen daily, then every few hours, and are followed by increasingly worse bouts of confusion, lethargy and convulsions. Eventually there is permanent and completely stunted growth of the body and the brain, leading to mental retardation.[1] MRI scans of affected children have shown significant brain atrophy and damage to the hippocampus and glial cells.[3]

There is currently no cure, with treatment confined to managing the symptoms. Anticonvulsants, such as sodium valproate,[5] have been administered in an attempt to control the nodding, and although there has been some indication that this has helped, with children regaining some degree of normality – once again being able to talk or walk – the underlying damage remains and the condition continues to worsen.[6]

A number of causes have been looked into, and subsequently ruled out – exposure to wartime chemicals, consumption of meat from monkeys, ingestion of toxic substances (e.g. coated seeds distributed by relief agencies that were meant for planting), or contaminated relief foods.[1] [7]

A potential cause that is still being considered is a possible autoimmune response linked to infection with microfilaria parasites – the age range of sufferers (5-15 years old), is similar to certain parasitic infections and epilepsy syndromes.[1] Originally researchers thought it could be linked to Onchocerca volvulus, a parasitic worm that is carried by black fly. Victims have generally been concentrated near fast-flowing rivers, such as the Yei in South Sudan, which are home to black fly.[7] Further, infection with O. volvulus is prevalent in areas of outbreak, with 93% of sufferers in some areas estimated to harbour the parasite, a figure significantly higher than those without the disease.[8] O. volvulus also causes river blindness (onchocerciasis), which has been tentatively linked to other forms of epilepsy,[9] as well as stunted growth.[10] However, O. volvulus is very common in many areas which have not seen the disease,[1] and a study in Tanzania found no significantly elevated levels of antibodies in the cerebrospinal fluid of patients.[3] Perhaps the cause lies in a closely-related or variant strain of the parasite, or there is an unidentified co-factor that is needed in combination with O. volvulus infection. A second potential cause that is being looked into is linked to malnutrition (many of the affected populations have recently been displaced, or are amongst the poorest in the region)[1] and/or vitamin B6 (pyridoxine) deficiency.[1] A trial administering vitamin B6 to patients has been set up to study this possibility.[11]

Although the local governments are trying to help – the Uganda Ministry of Health allocated $1.4 million of their budget to mount a response, and deployed teams of health workers to affected areas to distribute anticonvulsants [6] – outside donors and non-governmental organisations are needed if there is to be a solution any time soon.

— Peter Chilton, CLAHRC WM Research Associate

References:

  1. Dowell SF, Sejvar JJ, Riek L, et al. Nodding Syndrome. Emerg Infect Dis. 2013; 19(9): 1374-84.
  2. Centers for Disease Control and Prevention. Chronology of Ebola Hemorrhagic Fever Outbreaks. 2014. [Online].
  3. Winkler AS, Friedrich K, König R, et al. The head nodding syndrome – Clinical classification and possible causes. Epilepsia. 2008; 49 (12): 2008-15.
  4. World Health Organization. World Health Organization joins other partners to support Nodding Disease investigations in Southern Sudan. 2011. [Online].
  5. Idro R, Musubire KA, Mutamba BB, et al. Proposed guidelines for the management of nodding syndrome. Afr Health Sci. 2013; 13(2): 219-32.
  6. Kielty M. Nodding Syndrome: A Devastating Medical Mystery in Uganda. National Public Radio. 2013. [Online].
  7. Vogel G. Mystery Disease Haunts Region. Science. 2012; 336(6078): 144-6.
  8. Harding A. ‘Nodding disease’ hits Sudan. BBC News. 2003. [Online].
  9. Kaiser C, Pion SDS, Boussinesq M. Case-control Studies on the Relationship between Onchocerciasis and Epilepsy: Systematic Review and Meta-analysis. PLoS Negl Trop Dis. 2013; 7(3): e2147.
  10. Ovuga E, Kipp W, Mungherera M, Kasoro S. Epilepsy and retarded growth in a hyperendemic focus of onchocerciasis in rural western Uganda. East Afr Med J. 1992; 69(10): 554-6.
  11. Dowell S, Sejvar J, Bunga S, Idro R. Treatment of Nodding Syndrome – A Randomized Blinded Placebo-Controlled Crossover Trial of Oral Pyridoxine and Conventional Anti-Epileptic Therapy, in Northern Uganda — 2012. Clinical Trials Registry. 2012. [Online].