Nutritional supplements for patients being treated for active visceral leishmaniasis

Estefanía Custodio<sup>a</sup>; Jesús López‐Alcalde<sup>a</sup>; Mercè Herrero; Carmen Bouza; Carolina Jimenez; Stefan Storcksdieck genannt Bonsmann; Theodora Mouratidou; Teresa López‐Cuadrado; Agustin Benito; Jorge Alvar

doi:10.1002/14651858.CD012261.pub2

Suplementos nutricionales para pacientes en tratamiento para la leishmaniasis visceral activa

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References

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References to other published versions of this review

Jump to:

excluded studies
additional references

Custodio E, Herrero M, Bouza C, López‐Alcalde J, Benito A, Alvar J. Nutritional supplements for patients being treated for active visceral leishmaniasis. Cochrane Database of Systematic Reviews 2016, Issue 6. [DOI: 10.1002/14651858.CD012261]

Characteristics of studies

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Aruoma 2006	Participants without VL.
Croft 1985	In vitro study that did not include humans.
Diro 2015	Study did not evaluate the effects of nutritional supplement.
Duke 2011	Study design: not a controlled‐clinical trial.
Maciel 2014	Participants with VL not being treated for VL.
NCT01069198	The control group received placebo rather than an active treatment for VL.
Thakur 2010	Study did not evaluate the effects of nutritional supplement.

Abbreviations: VL: visceral leishmaniasis.

Figure 1

Study flow diagram

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Table 1. Research recommendation

What are the effects of nutritional supplements in patients being treated for active visceral leishmaniasis (VL)? Evidence: we found no eligible studies for this systematic review.
Elements	Proposal	Comments
Population	People being treated for VL	Include all relevant participant groups, such as people with HIV. Large, adequately powered trial. Preferably multi‐centre trial, in order to achieve adequate sample size (Laville 2017). Stratify allocation according to age and basic nutritional status, to enable robust a priori subgroup analyses.
Intervention	Oral nutritional supplement	If only a nutrient is tested, a placebo can be easily used, and a blinded RCT can be conducted (Laville 2017). The study should be planned with few interventions, to allow the effect of the micronutrient to be evaluated. Provide details of all the interventions and co‐interventions undertaken, of their compliance and their acceptability (Hoffmann 2014; MRC 2008). In order to disentangle the effects of the nutrient on the outcome measure, the co‐interventions must be similar in all study groups. Compliance can be checked by counting pills, and possibly by assessing the nutrient concentration or related functions (Laville 2017).
Comparison	Placebo
Outcomes	Relevant outcomes for key stakeholders defined, measured, collected, and reported in an objective, reliable, accurate, and actionable way	To our knowledge, there is no 'core outcome set' (COS)^a developed with a rigorous methodology for RCTs of nutritional supplements. COS for RCTs of nutritional supplements should be developed with the method proposed in the COMET Handbook (Williamson 2017). Blinding of patients, care givers and outcome assessment should be ensured with the use of placebo as a control group. The use of objective outcomes that are less susceptible to bias can also minimize the risk of detection bias (Lin 2012). Relevant harms related to the use of nutrients should be specified beforehand, and should be assessed (Ioannidis 2004).
Study type	RCT	Cluster‐RCTs (RCTs that randomize groups (clusters) rather than individuals) have several advantages compared to individual‐RCTs (López‐Alcalde 2015). For example, they may be less costly and time‐consuming, as they simplify the logistics of implementation (Smith 2008); they control for confounding (Safdar 2008), and minimize treatment contamination^b between intervention and control participants (Hayes 2000); they are better for measuring the overall group effect of an intervention, and for judging effectiveness (Hayes 2000), that is, the extent to which a specific intervention, when used under ordinary circumstances, does what it is intended to do (Cochrane 2017). Moreover, they have broader generalizability. For example, cluster‐RCTs minimize the Hawthorne effect, which is the effect on the people being studied (usually positive or beneficial), of being under study (Porta 2008).
Abbreviations: COS: core outcome set; HIV: human immunodeficiency virus; RCT: randomized controlled trial; VL: visceral leishmaniasis. ^aCore outcome set: agreed standardized set of outcomes that should be measured and reported in all trials for a specific clinical area (Williamson 2012). ^bContamination: in a controlled trial, contamination is the inadvertent application of the intervention being evaluated to people in the control group, or the inadvertent failure to apply the intervention to people assigned to the intervention group (Cochrane 2017).

Table 1. Research recommendation

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Summary of findings for the main comparison. Nutritional supplements versus no nutritional supplements for people who are being treated for active visceral leishmaniasis (VL)

Nutritional supplements versus no nutritional supplements for people who are being treated for active VL
Patient or population: people who are being treated for active VL Setting: any Intervention: nutritional supplements Comparison: no nutritional supplements
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with no nutritional supplements	Risk with nutritional supplements
Primary cure	No trials met the inclusion criteria. Thus, there is no data for this outcome.		‐	(0 RCTs)	‐	‐
Definitive cure	No trials met the inclusion criteria. Thus, there is no data for this outcome.		‐	(0 RCTs)	‐	‐
Treatment completion	No trials met the inclusion criteria. Thus, there is no data for this outcome.		‐	(0 RCTs)	‐	‐
Self‐reported recovery from illness or resolution of symptoms	No trials met the inclusion criteria. Thus, there is no data for this outcome.		‐	(0 RCTs)	‐	‐
Weight gain, increased skinfold thickness, or other measures of lean or total mass, or growth in children	No trials met the inclusion criteria. Thus, there is no data for this outcome.		‐	(0 RCTs)	‐	‐
Adverse outcomes	No trials met the inclusion criteria. Thus, there is no data for this outcome.		‐	(0 RCTs)	‐	‐
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
Abbreviations: CI: confidence interval; VL: visceral leishmaniasis; RCT: randomized controlled trial; RR: risk ratio; OR: odds ratio.

Summary of findings for the main comparison. Nutritional supplements versus no nutritional supplements for people who are being treated for active visceral leishmaniasis (VL)

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References

References to studies excluded from this review

Aruoma 2006 {published data only}

Croft 1985 {published data only}

Diro 2015 {published data only}

Duke 2011 {published data only}

Maciel 2014 {published data only}

NCT01069198 {published data only}

Thakur 2010 {published data only}

Additional references

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Actor 1960

Alvar 2006

Alvar 2008

Alvar 2012

Anstead 2001

Badaró 1986

Boelaert 2014

Brown 2006

Burford 2013

Bush 2017

Campbell 2012

Carrillo 2015

Cerf 1987

Chappuis 2007

Chartres 2016

Cheeran 2010

Cochrane 2017

Collin 2004

Covidence 2017 [Computer program]

Dye 1993

Elmahallawy 2015

Equator Network 2017

FAO/WHO/UNICEF 2001

Ferreira 2018

Food and Nutrition Board 2006

Freitas‐Junior 2012

Garg 2004

Harhay 2011

Hayes 2000

Higgins 2011

Hoffmann 2014

Hotez 2004

Ioannidis 2004

Ioannidis 2016

Jakobsen 2013

Laville 2017

Lefebvre 2011

Liberati 2009

Lin 2012

Luz 2001

López‐Alcalde 2015

Maki 2014

Malafaia 2009

Mittra 2000

MRC 2008

Murray 2005

NVBDCP Programme 2017

Olliaro 2005

Ortiz‐Moncada 2011

Porta 2008

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Safdar 2008

Schulz 2010

Serafim 2010

Smith 2008

Sterne 2014

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van Griensven 2014

Van Weyenbergh 2004

Welch 2017

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