Patient evaluation of Klick, a technology-enabled, nurse-delivered HIV outpatient pathway.

OBJECTIVES: Klick is a clinic-specific, digitally supported outpatient pathway of care for people living with HIV (PLWH). It involves a smartphone application (app) for PLWH to self-manage their care, navigate access to the clinic and communicate with their healthcare provider. We present a patient evaluation of Klick. METHODS: Patients use Klick to book/reschedule appointments, view laboratory results, request medication, access remote nurse-delivered consultations and communicate with clinicians. In October 2022, Klick was evaluated by PLWH through a questionnaire and interviews. RESULTS: Between August 2020 and April 2024, 5859 patients had registered to use Klick; during April 2024 alone, 2509 (43%) used Klick. In October 2022, 1661 PLWH were invited to complete surveys, of whom 362 (22%) responded. These respondents were 95% (340/358) male and 84% (298/354) white, and 63% (227/359) were in the age range 41-60 years. Respondents felt Klick was easy to use (average score 4.3/5), and 92% thought having a clinic-specific app was important/very important. Respondents valued the following app features as important/very important - online booking (93%); viewable results (94%); prescription requests (90%) - and rated their experience of using them highly - 91% for e-booking and 91% for viewable results. A total of 93% said they would recommend Klick to friends and 82% rated Klick as above average/excellent. CONCLUSIONS: PLWH reported high levels of satisfaction using a clinic-specific mHealth app to manage their HIV care and demonstrated sustained active use. Klick was rated easy to use, as helping to meet healthcare needs and as providing a superior experience for some aspects of care. Other HIV clinics or services managing chronic conditions could benefit from the adoption of personalized digital solutions to enhance patient care.

Beta-amyloid fragment 25-35 causes mitochondrial dysfunction in primary cortical neurons.

Beta-amyloid deposition and compromised energy metabolism both occur in vulnerable brain regions in Alzheimer's disease. It is not known whether beta-amyloid is the cause of impairment of energy metabolism, nor whether impaired energy metabolism is specific to neurons. Our results, using primary neuronal cultures, show that 24-h incubation with A beta(25-35) caused a generalized decrease in the specific activity of mitochondrial enzymes per milligram of cellular protein, induced mitochondrial swelling, and decreased total mitochondrial number. Incubation with A beta(25-35) decreased ATP concentration to 58% of control in neurons and 71% of control in astrocytes. Levels of reduced glutathione were also lowered by A beta(25-35) in both neurons (from 5.1 to 2.9 nmol/mg protein) and astrocytes (from 25.2 to 14.9 nmol/mg protein). We conclude that 24-h treatment with extracellular A beta(25-35) causes mitochondrial dysfunction in both astrocytes and neurons, the latter being more seriously affected. In astrocytes mitochondrial impairment was confined to complex I inhibition, whereas in neurons a generalized loss of mitochondria was seen.

Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities.

Disrupted energy metabolism, in particular reduced activity of cytochrome oxidase (EC 1.9.3.1), alpha-ketoglutarate dehydrogenase (EC 1.2.4.2) and pyruvate dehydrogenase (EC 1.2.4.1) have been reported in post-mortem Alzheimer's disease brain. beta-Amyloid is strongly implicated in Alzheimer's pathology and can be formed intracellularly in neurones. We have investigated the possibility that beta-amyloid itself disrupts mitochondrial function. Isolated rat brain mitochondria have been incubated with the beta-amyloid alone or together with nitric oxide, which is known to be elevated in Alzheimer's brain. Mitochondrial respiration, electron transport chain complex activities, alpha-ketoglutarate dehydrogenase activity and pyruvate dehydrogenase activity have been measured. Beta-amyloid caused a significant reduction in state 3 and state 4 mitochondrial respiration that was further diminished by the addition of nitric oxide. Cytochrome oxidase, alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase activities were inhibited by beta-amyloid. The K(m) of cytochrome oxidase for reduced cytochrome c was raised by beta-amyloid. We conclude that beta-amyloid can directly disrupt mitochondrial function, inhibits key enzymes and may contribute to the deficiency of energy metabolism seen in Alzheimer's disease.