Electronic Decision-Support Improves Diarrhoeal Disease Guideline Adherence ((mHealth Diarrhoeal Management, mHDM, Trial): A Cluster Randomized Controlled Trial

Background: Acute diarrhoeal disease management often requires rehydration alone without antibiotics. However, antibiotics are frequently used inappropriately and this is an important driver of antimicrobial resistance. The mHDM trial was conducted to determine if electronic decision-support improves rehydration and antibiotic guideline adherence in resource-limited settings. Methods: A cluster randomized controlled trial was conducted at ten district hospitals in Bangladesh. Inclusion criteria were patients two-months of age or older with uncomplicated acute diarrhoea. Admission orders were observed without intervention followed by randomization to electronic ('Rehydration Calculator') or paper formatted World Health Organization guidelines. Generalized linear mixed-effect models, accounting for hospital clustering, served as the analytical framework. Findings: Of 6,577 screened patients, 4,975 were enrolled. There was no statistical difference between electronic and paper decision-support for IV fluids ordered (interaction p=0.31). Among severely dehydrated patients, volumes were 29.2% higher (0.014 L/kg) for electronic compared to paper decision-support (0.062 L/kg, 95%CI 0.051-0.076 vs 0.048 L/kg, 95%CI 0.039-0.058; interaction p=0.01). Inappropriate antibiotics decreased with electronic decision-support, including a 28.5% decrease for electronic (97.2%, 95%CI 90.3-99.3 to 68.7%, 95%CI 40.9-87.4) compared to a 23.8% increase for paper (43.1%, 95%CI 19.8-70.0 to 66.9%, 95%CI 39.8-86.1) among children under 5 years (interaction p<0.001). Class-switching from non-indicated (ciprofloxacin, metronidazole; interaction p values <0.001) to indicated (azithromycin; interaction p<0.001) antibiotics occurred for both decision-support methods. Interpretation: Electronic decision-support, and paper to a lesser extent, improved guideline adherence with a prominent reduction of inappropriate antibiotic orders. The accessibility of the electronic medium offers scalability to improve guideline adherence for acute diarrhoeal disease management and combat antibiotic resistance globally. Trial Registration: This trial was registered at clinicaltrials.gov (NCT03154229). Funding Statement: This work was supported by the National Institutes of Health [DP5OD019893; R21TW010182] to EJN. Internal support was provided by the University of Florida and Stanford University. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Research ethics boards at the IEDCR (IEDCR/IRB/2017/10), icddr,b (ERC and RRC PR-17036) and University of Florida (IRB201601762) approved this study. A Data and Safety Monitoring Board (DSMB) was assembled at the icddr,b. The protocol received independent evaluation by three international experts. The US Department of Health and Human Services human experimentation guidelines were followed during this research.