Evaluating the Impact of a Pediatric Inpatient Social Care Program in a Community Hospital.

OBJECTIVES: To evaluate the impact of implementing a stakeholder-informed social risk screening and social service referral system in a community hospital setting. METHODS: We implemented a stakeholder-informed social care program at a community hospital in April 2022. The evaluation included patients aged 0 to 17 years admitted to the pediatric unit between April 2021 and March 2022 (1 year preimplementation) and between April 2022 and March 2023 (1 year postimplementation). For a random subset of 232 preimplementation and 218 postimplementation patients, we performed manual data extraction, documenting program process measures and preliminary effectiveness outcomes. We used χ square and Wilcoxon rank tests to compare outcomes between the preimplementation and postimplementation groups. Multivariable logistic regression was used to assess the preliminary effectiveness of the social care program in identifying social risks. RESULTS: Screening rates were higher in the postimplementation group for nearly all social domains. Compared with preimplementation, the postimplementation group had higher rates of social risks identified (17.4% vs 7.8% [P < .01]: adjusted odds ratio 2.9 [95% confidence interval 1.5-5.5]) on multivariate testing. Social work consults were completed more frequently and earlier for the postimplementation group (13.8.% vs 5.6% [P < .01]) and median (19 hours vs 25 hours [P = .03]), respectively. Rates of communication of social risks in discharge summaries were higher in the postimplementation group (46.8% vs 8.2% [P < .001]). CONCLUSIONS: The implementation of a stakeholder-informed social care program within a community hospital setting led to the increased identification of social risks and social work consultations and improved timeliness of social work consultations and written communication of social risks in discharge summaries for primary care providers.

Hydrophobic sliding: a possible mechanism for drug resistance in human immunodeficiency virus type 1 protease.

Hydrophobic residues outside the active site of HIV-1 protease frequently mutate in patients undergoing protease inhibitor therapy; however, the mechanism by which these mutations confer drug resistance is not understood. From analysis of molecular dynamics simulations, 19 core hydrophobic residues appear to facilitate the conformational changes that occur in HIV-1 protease. The hydrophobic core residues slide by each other, exchanging one hydrophobic van der Waal contact for another, with little energy penalty, while maintaining many structurally important hydrogen bonds. Such hydrophobic sliding may represent a general mechanism by which proteins undergo conformational changes. Mutation of these residues in HIV-1 protease would alter the packing of the hydrophobic core, affecting the conformational flexibility of the protease. Therefore these residues impact the dynamic balance between processing substrates and binding inhibitors, and thus contribute to drug resistance.

Cooperative effects of drug-resistance mutations in the flap region of HIV-1 protease.

Understanding the interdependence of multiple mutations in conferring drug resistance is crucial to the development of novel and robust inhibitors. As HIV-1 protease continues to adapt and evade inhibitors while still maintaining the ability to specifically recognize and efficiently cleave its substrates, the problem of drug resistance has become more complicated. Under the selective pressure of therapy, correlated mutations accumulate throughout the enzyme to compromise inhibitor binding, but characterizing their energetic interdependency is not straightforward. A particular drug resistant variant (L10I/G48V/I54V/V82A) displays extreme entropy-enthalpy compensation relative to wild-type enzyme but a similar variant (L10I/G48V/I54A/V82A) does not. Individual mutations of sites in the flaps (residues 48 and 54) of the enzyme reveal that the thermodynamic effects are not additive. Rather, the thermodynamic profile of the variants is interdependent on the cooperative effects exerted by a particular combination of mutations simultaneously present.