The Impact of Delirium on Recovery in Geriatric Rehabilitation after Acute Infection.

OBJECTIVES: Delirium is common during acute infection in older patients and is associated with functional decline. Geriatric rehabilitation (GR) can help older patients to return to their premorbid functional level. It is unknown whether delirium affects GR outcomes in patients with acute infection. We evaluated whether delirium affects trajectories of activities of daily living (ADL) and quality of life (QoL) recovery in GR after COVID-19 infection. DESIGN: This study was part of the EU-COGER study, a multicenter cohort study conducted between October 2020 and October 2021. SETTING AND PARTICIPANTS: Participants were recruited after COVID-19 infection from 59 GR centers in 10 European countries. METHODS: Data were collected at GR admission, discharge, and at the 6-week and 6-month follow-ups. Trajectories of ADL [using the Barthel index (BI)] and QoL [using the EuroQol-5 Dimensions-5 Level (EQ-5D-5L)] recovery were examined using linear mixed models. RESULTS: Of the 723 patients included (mean age 75.5 ± 9.9 years; 52.4% male), 28.9% had delirium before or during GR admission. Participants with delirium recovered in ADL at approximately the same rate as those without (linear slope effect = -0.13, SE 0.16, P = .427) up to an estimated BI score of 16.1 at 6 months. Similarly, participants with delirium recovered in QoL at approximately the same rate as those without (linear slope effect = -0.017, SE 0.015, P = .248), up to an estimated EQ-5D-5L score of 0.8 at 6 months. CONCLUSIONS AND IMPLICATIONS: Presence of delirium during the acute phase of infection or subsequent GR did not influence the recovery trajectory of ADL functioning and QoL.

Tetrahydrobiopterin and the regulation of hypoxic pulmonary vasoconstriction.

Tetrahydrobiopterin (BH(4)) is an essential cofactor for nitric oxide synthases (NOS). This study investigated the effect of increasing BH(4) levels on hypoxia-induced pulmonary vasoconstriction (HPV). Sprague Dawley rats and hph-1 (BH(4) deficient) mice were given BH(4) before and during HPV in an isolated perfused lung preparation. BH(4) inhibited HPV in a concentration-dependent manner and increased NO metabolites in the perfusate. Bradykinin-induced reductions in HPV were blunted in hph-1 mice and pre-administration of BH(4) restored the response. The effect of BH(4) was attenuated by l-NAME (NOS inhibitor), PTIO (NO scavenger), and catalase (H(2)O(2) catalyser) administered prior to HPV but enhanced by MnTMPyP (superoxide dismutase mimetic). The effect of BH(4) on HPV was partially recapitulated by NH(4), a stereoisomer that shares antioxidant properties with BH(4) but is not a NOS cofactor. The bioavailability of BH(4) is an important determinant of the pulmonary vascular response to hypoxia. Its effects are mediated via nitric oxide, hydrogen peroxide and its antioxidant properties, and are attenuated by oxidant stress. Pharmacological administration of BH(4) may have therapeutic potential in pulmonary hypertension.