Health workers' perspectives of a mobile health tool to improve diagnosis and management of paediatric acute respiratory illnesses in Uganda: a qualitative study.

OBJECTIVES: Mobile health tools have potential to improve the diagnosis and management of acute lower respiratory illnesses (ALRI), a leading cause of paediatric mortality worldwide. The objectives were to evaluate health workers' perceptions of acceptability, usability and feasibility of Acute Lower Respiratory Illness Treatment and Evaluation (ALRITE), a novel mobile health tool to help frontline health workers diagnose, treat and provide education about ALRI in children <5 years. DESIGN: A qualitative study including semistructured interviews with health facility administrators and focus groups with primary care health workers. SETTING: Two federally funded Ugandan primary care health facilities, one peri-urban and one rural. PARTICIPANTS: We enrolled 3 health administrators and 28 health workers (clinical officers and nurses). INTERVENTION: The ALRITE smartphone application was developed to help frontline health workers adhere to ALRI guidelines and differentiate wheezing illnesses from pneumonia in children under 5 years of age. ALRITE contains a simple decision tree, a partially automated respiratory rate counter, educational videos and an adapted respiratory assessment score to determine bronchodilator responsiveness. We performed a demonstration of ALRITE for participants at the beginning of interviews and focus groups. No participant had used ALRITE prior. RESULTS: Themes impacting the potential implementation of ALRITE were organised using individual-level, clinic-level and health-system level determinants. Individual-level determinants were acceptability and perceived benefit, usability, provider needs and provider-patient relationship. Clinic-level determinants were limited resources and integration within the health centre. Systems-level determinants included medication shortages and stakeholder engagement. CONCLUSIONS: Incorporation of these themes will ready ALRITE for field testing. Early engagement of end users provides insights critical to the development of tailored mHealth decision support tools.

Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aß42:Aß40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model.

TREM2 is an Alzheimer's disease (AD) risk gene expressed in microglia. To study the role of Trem2 in a mouse model of ß-amyloidosis, we compared PS2APP transgenic mice versus PS2APP mice lacking Trem2 (PS2APP;Trem2ko) at ages ranging from 4 to 22 months. Microgliosis was impaired in PS2APP;Trem2ko mice, with Trem2-deficient microglia showing compromised expression of proliferation/Wnt-related genes and marked accumulation of ApoE. Plaque abundance was elevated in PS2APP;Trem2ko females at 6-7 months; but by 12 or 19-22 months of age, it was notably diminished in female and male PS2APP;Trem2ko mice, respectively. Across all ages, plaque morphology was more diffuse in PS2APP;Trem2ko brains, and the Aß42:Aß40 ratio was elevated. The amount of soluble, fibrillar Aß oligomers also increased in PS2APP;Trem2ko hippocampi. Associated with these changes, axonal dystrophy was exacerbated from 6 to 7 months onward in PS2APP;Trem2ko mice, notwithstanding the reduced plaque load at later ages. PS2APP;Trem2ko mice also exhibited more dendritic spine loss around plaque and more neurofilament light chain in CSF. Thus, aggravated neuritic dystrophy is a more consistent outcome of Trem2 deficiency than amyloid plaque load, suggesting that the microglial packing of Aß into dense plaque is an important neuroprotective activity.SIGNIFICANCE STATEMENT Genetic studies indicate that TREM2 gene mutations confer increased Alzheimer's disease (AD) risk. We studied the effects of Trem2 deletion in the PS2APP mouse AD model, in which overproduction of Aß peptide leads to amyloid plaque formation and associated neuritic dystrophy. Interestingly, neuritic dystrophies were intensified in the brains of Trem2-deficient mice, despite these mice displaying reduced plaque accumulation at later ages (12-22 months). Microglial clustering around plaques was impaired, plaques were more diffuse, and the Aß42:Aß40 ratio and amount of soluble, fibrillar Aß oligomers were elevated in Trem2-deficient brains. These results suggest that the Trem2-dependent compaction of Aß into dense plaques is a protective microglial activity, limiting the exposure of neurons to toxic Aß species.