Publications

BACKGROUND

Digital adherence technologies have been widely promoted as a means to improve tuberculosis medication adherence. However, uptake of these technologies has been suboptimal by both patients and health workers. Not surprisingly, studies have not demonstrated significant improvement in treatment outcomes.

OBJECTIVE

This study aimed to optimize a well-known digital adherence technology, 99DOTS, for end user needs in Uganda. We describe the findings of the ideation phase of the human-centered design methodology to adapt 99DOTS according to a set of design principles identified in the previous inspiration phase.

METHODS

99DOTS is a low-cost digital adherence technology wherein tuberculosis medication blister packs are encased within an envelope that reveals toll-free numbers that patients can call to report dosing. We identified 2 key areas for design and testing: (1) the envelope, including the form factor, content, and depiction of the order of pill taking; and (2) the patient call-in experience. We conducted 5 brainstorming sessions with all relevant stakeholders to generate a suite of potential prototype concepts. Senior investigators identified concepts to further develop based on feasibility and consistency with the predetermined design principles. Prototypes were revised with feedback from the entire team. The envelope and call-in experience prototypes were tested and iteratively revised through focus groups with health workers (n=52) and interviews with patients (n=7). We collected and analyzed qualitative feedback to inform each subsequent iteration.

RESULTS

The 5 brainstorming sessions produced 127 unique ideas that we clustered into 6 themes: rewards, customization, education, logistics, wording and imagery, and treatment countdown. We developed 16 envelope prototypes, 12 icons, and 28 audio messages for prototype testing. In the final design, we altered the pill packaging envelope by adding a front flap to conceal the pills and reduce potential stigma associated with tuberculosis. The flap was adorned with either a blank calendar or map of Uganda. The inside cover contained a personalized message from a local health worker including contact information, pictorial pill-taking instructions, and a choice of stickers to tailor education to the patient and phase of treatment. Pill-taking order was indicated with colors, chevron arrows, and small mobile phone icons. Last, the call-in experience when patients report dosing was changed to a rotating series of audio messages centered on the themes of prevention, encouragement, and reassurance that tuberculosis is curable.

CONCLUSIONS

We demonstrated the use of human-centered design as a promising tool to drive the adaptation of digital adherence technologies to better address the needs and motivations of end users. The next phase of research, known as the implementation phase in the human-centered design methodology, will investigate whether the adapted 99DOTS platform results in higher levels of engagement from patients and health workers, and ultimately improves tuberculosis treatment outcomes.

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, can neutralize the virus. It is, however, unknown which features of the serological response may affect clinical outcomes of COVID-19 patients. We analyzed 983 longitudinal plasma samples from 79 hospitalized COVID-19 patients and 175 SARS-CoV-2-infected outpatients and asymptomatic individuals. Within this cohort, 25 patients died of their illness. Higher ratios of IgG antibodies targeting S1 or RBD domains of spike compared to nucleocapsid antigen were seen in outpatients who had mild illness versus severely ill patients. Plasma antibody increases correlated with decreases in viral RNAemia, but antibody responses in acute illness were insufficient to predict inpatient outcomes. Pseudovirus neutralization assays and a scalable ELISA measuring antibodies blocking RBD-ACE2 interaction were well correlated with patient IgG titers to RBD. Outpatient and asymptomatic individuals' SARS-CoV-2 antibodies, including IgG, progressively decreased during observation up to five months post-infection.