Does missing trust lead to overuse or underuse of health care services?

Research about mistrust in health care often relies on the narrative that lacking trust causes underuse of health care services. This narrative seemed to hold up in the COVID-19 pandemic era, when mistrust in systems and providers led to widely recognized vaccine hesitancy and reluctance to seek care. In this review, we suggest that the "mistrust leads to underuse" narrative is important but incomplete, as mistrust in health care may also cause patients to overuse health care services. We searched the literature for studies, meta-analyses, and interviews that assessed the effect of patient trust on health care utilization. Although overuse literature is sparse, surveys and physician interviews indicate that patients who do not trust their clinicians may seek multiple opinions on the same diagnosis and utilize more costly interventions that are not recommended. Physicians also report being more likely to utilize extraneous tests and medications when patients do not trust them. Hence, problems of trust may lead to both underuse and overuse of health care services. We postulate several factors that may influence whether a mistrustful patient underuses or overuses health care resources, including personal characteristics, environmental characteristics, and levels of analysis, and we encourage more investigation about mistrust and health care overutilization.

Artemisinin-Based Drugs Target the Plasmodium falciparum Heme Detoxification Pathway.

Artemisinin (ART)-based antimalarial drugs are believed to exert lethal effects on malarial parasites by alkylating a variety of intracellular molecular targets. Recent work with live parasites has shown that one of the alkylated targets is free heme within the parasite digestive vacuole, which is liberated upon hemoglobin catabolism by the intraerythrocytic parasite, and that reduced levels of heme alkylation occur in artemisinin-resistant parasites. One implication of heme alkylation is that these drugs may inhibit parasite detoxification of free heme via inhibition of heme-to-hemozoin crystallization; however, previous reports that have investigated this hypothesis present conflicting data. By controlling reducing conditions and, hence, the availability of ferrous versus ferric forms of free heme, we modify a previously reported hemozoin inhibition assay to quantify the ability of ART-based drugs to target the heme detoxification pathway under reduced versus oxidizing conditions. Contrary to some previous reports, we find that artemisinins are potent inhibitors of hemozoin crystallization, with effective half-maximal concentrations approximately an order of magnitude lower than those for most quinoline-based antimalarial drugs. We also examine hemozoin and in vitro parasite growth inhibition for drug pairs found in the most commonly used ART-based combination therapies (ACTs). All ACTs examined inhibit hemozoin crystallization in an additive fashion, and all but one inhibit parasite growth in an additive fashion.