DAS181 treatment of severe lower respiratory tract parainfluenza virus infection in immunocompromised patients: A phase 2 randomized, placebo-controlled study

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. RESULTS: A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). CONCLUSIONS: The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877

Services used by perinatal substance-users with child welfare involvement: a descriptive study

Abstract Background Substance use during pregnancy often leads to involvement in the child welfare system, resulting in multiple social service systems and service providers working with families to achieve successful child welfare outcomes. The Vulnerable Infants Program of Rhode Island (VIP-RI) is a care coordination program developed to work with perinatal substance-users to optimize opportunities for reunification and promote permanency for substance-exposed infants. This paper describes services used by VIP-RI participants and child welfare outcomes. Methods Data collected during the first four years of VIP-RI were used to identify characteristics of program participants, services received, and child welfare outcomes: closed child welfare cases, reunification with biological mothers and identified infant permanent placements. Descriptive Results Medical and financial services were associated with positive child welfare outcomes. Medical services included family planning, pre- and post-natal care and HIV test counseling. Financial services included assistance with obtaining entitlement benefits and receiving tangible support such as food and clothing. Conclusions Findings from this study suggest services that address basic family needs were related to positive child welfare outcomes. The provision of basic services, such as health care and financial assistance through entitlement benefits and tangible donations, may help to establish a foundation so mothers can concentrate on recovery and parenting skills. Identification of services for perinatal substance users that are associated with more successful child welfare outcomes has implications for the child welfare system, treatment providers, courts and families.</p