Impacts of Post-Hospitalization Accessible Health Technology and Caregiver Support on 90-Day Acute Care Use and Self-Care Assistance: A Randomized Clinical Trial.

Hospitalized patients often are readmitted soon after discharge, with many hospitalizations being potentially preventable. The authors evaluated a mobile health intervention designed to improve post-hospitalization support for older adults with common chronic conditions. All participants enrolled with an informal caregiver or "CarePartner" (CP). Intervention patients received automated assessment and behavior change calls. CPs received automated, structured feedback following each assessment. Clinicians received alerts about serious problems identified during patient calls. Controls had a 65% greater risk of hospitalization within 90 days post discharge than intervention patients (P = .041). For every 6.8 enrollees, the intervention prevented 1 rehospitalization or emergency department encounter. The intervention improved physical functioning at 90 days (P = .012). The intervention also improved medication adherence and indicators of the quality of communication with CPs (all P < .01). Automated telephone patient monitoring and self-care advice with feedback to primary care teams and CPs reduces readmission rates over 90 days.

Effects of Accessible Health Technology and Caregiver Support Posthospitalization on 30-Day Readmission Risk: A Randomized Trial.

INTRODUCTION: Patients with chronic illness often require ongoing support postdischarge. This study evaluated a simple-to-use, mobile health-based program designed to improve postdischarge follow-up via (1) tailored communication to patients using automated calls, (2) structured feedback to informal caregivers, and (3) automated alerts to clinicians about urgent problems. METHODS: A total of 283 patients with common medical diagnoses, including chronic obstructive pulmonary disease, coronary artery disease, pneumonia, and diabetes, were recruited from a university hospital, a community hospital, and a US Department of Veterans Affairs hospital. All patients identified an informal caregiver or "care partner" (CP) to participate in their postdischarge support. Patient-CP dyads were randomized to the intervention or usual care. Intervention patients received weekly automated assessment and behavior change calls. CPs received structured e-mail feedback. Outpatient clinicians received fax alerts about serious problems. Primary outcomes were 30-day readmission rate and the combined outcome of readmission/emergency department (ED) use. Information about postdischarge outpatient visits, rehospitalizations, and ED encounters was obtained from medical records. RESULTS: Overall, 11.4% of intervention patients and 17.9% of controls were rehospitalized within 30 days postdischarge (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.31-1.11; p = 0.102). Compared to intervention patients with other illnesses, those with pulmonary diagnoses generated the most clinical alerts (p = 0.004). Pulmonary patients in the intervention group showed significantly reduced 30-day risk of rehospitalization relative to controls (HR: 0.31; 95% CI: 0.11-0.87; p = 0.026). CONCLUSION: The CP intervention did not improve 30-day readmission rates overall, although post hoc analyses suggested that it may be promising among patients with pulmonary diagnoses.

Improving Post-Hospitalization Transition Outcomes through Accessible Health Information Technology and Caregiver Support: Protocol for a Randomized Controlled Trial.

OBJECTIVE: The goal of this trial is to evaluate a novel intervention designed to improve post-hospitalization support for older adults with chronic conditions via: (a) direct tailored communication to patients using regular automated calls post discharge, (b) support for informal caregivers outside of the patient's household via structured automated feedback about the patient's status plus advice about how caregivers can help, and (c) support for care management including a web-based disease management tool and alerts about potential problems. METHODS: 846 older adults with common chronic conditions are being identified upon hospital admission. Patients are asked to identify a "CarePartner" (CP) living outside their household, i.e., an adult child or other social network member willing to play an active role in their post-discharge transition support. Patient-CP pairs are randomized to the intervention or usual care. Intervention patients receive automated assessment and behavior change calls, and their CPs receives structured feedback and advice via email and automated calls following each assessment. Clinical teams have access to assessment results via the web and receive automated reports about urgent health problems. Patients complete surveys at baseline, 30 days, and 90 days post discharge; utilization data is obtained from hospital records. CPs, other caregivers, and clinicians are interviewed to evaluate intervention effects on processes of self-care support, caregiver stress and communication, and the intervention's potential for broader implementation. The primary outcome is 30-day readmission rates; other outcomes measured at 30 days and 90 days include functional status, self-care behaviors, and mortality risk. CONCLUSION: This trial uses accessible health technologies and coordinated communication among informal caregivers and clinicians to fill the growing gap between what discharged patients need and available resources. A unique feature of the intervention is the provision of transition support not only for patients but also for their informal caregivers.

Molecular basis of Diamond-Blackfan anemia: structure and function analysis of RPS19.

Diamond-Blackfan anemia (DBA) is a rare congenital disease linked to mutations in the ribosomal protein genes rps19, rps24 and rps17. It belongs to the emerging class of ribosomal disorders. To understand the impact of DBA mutations on RPS19 function, we have solved the crystal structure of RPS19 from Pyrococcus abyssi. The protein forms a five alpha-helix bundle organized around a central amphipathic alpha-helix, which corresponds to the DBA mutation hot spot. From the structure, we classify DBA mutations relative to their respective impact on protein folding (class I) or on surface properties (class II). Class II mutations cluster into two conserved basic patches. In vivo analysis in yeast demonstrates an essential role for class II residues in the incorporation into pre-40S ribosomal particles. This data indicate that missense mutations in DBA primarily affect the capacity of the protein to be incorporated into pre-ribosomes, thus blocking maturation of the pre-40S particles.

Assembly of C1 and the MBL- and ficolin-MASP complexes: structural insights.

The classical pathway C1 complex, and the MBL-MASP and ficolin-MASP complexes involved in activation of the lectin pathway have several features in common. Both types of complexes are assembled from two subunits: an oligomeric recognition protein (C1q, MBL, L-, H- or M-ficolin), and a protease component, which is either a tetramer (C1s-C1r-C1r-C1s) or a dimer ((MASP)(2)). Recent functional and 3-D structural investigations have revealed that C1r/C1s and the MASPs associate through a common mechanism involving their N-terminal CUB1-EGF region. In contrast, the C1s-C1r-C1r-C1s tetramer and the (MASP)(2) dimers appear to have evolved distinct strategies to associate with their partner proteins. The purpose of this article is to review these recent advances.

The X-ray structure of human mannan-binding lectin-associated protein 19 (MAp19) and its interaction site with mannan-binding lectin and L-ficolin.

MAp19 is an alternative splicing product of the MASP-2 gene comprising the N-terminal CUB1-epidermal growth factor (EGF) segment of MASP-2, plus four additional residues at its C-terminal end. Like full-length MASP-2, it forms Ca(2+)-dependent complexes with mannan-binding lectin (MBL) and L-ficolin. The x-ray structure of human MAp19 was solved to a resolution of 2.5 A. It shows a head to tail homodimer held together by interactions between the CUB1 module of one monomer and the EGF module of its counterpart. A Ca(2+) ion bound to each EGF module stabilizes the dimer interfaces. A second Ca(2+) ion is bound to the distal end of each CUB1 module, through six ligands contributed by Glu(52), Asp(60), Asp(105), Ser(107), Asn(108), and a water molecule. Compared with its counterpart in human C1s, the N-terminal end of the MAp19 CUB1 module contains a 7-residue extension that forms additional inter-monomer contacts. To identify the residues involved in the interaction of MAp19 with MBL and L-ficolin, point mutants were generated and their binding ability was determined using surface plasmon resonance spectroscopy. Six mutations at Tyr(59), Asp(60), Glu(83), Asp(105), Tyr(106), and Glu(109) either strongly decreased or abolished interaction with both MBL and L-ficolin. These mutations map a common binding site for these proteins located at the distal end of each CUB1 module and stabilized by the Ca(2+) ion.

X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement.

C1, the complex that triggers the classical pathway of complement, is assembled from two modular proteases C1r and C1s and a recognition protein C1q. The N-terminal CUB1-EGF segments of C1r and C1s are key elements of the C1 architecture, because they mediate both Ca2+-dependent C1r-C1s association and interaction with C1q. The crystal structure of the interaction domain of C1s has been solved and refined to 1.5 A resolution. The structure reveals a head-to-tail homodimer involving interactions between the CUB1 module of one monomer and the epidermal growth factor (EGF) module of its counterpart. A Ca2+ ion is bound to each EGF module and stabilizes both the intra- and inter-monomer interfaces. Unexpectedly, a second Ca2+ ion is bound to the distal end of each CUB1 module, through six ligands contributed by Glu45, Asp53, Asp98, and two water molecules. These acidic residues and Tyr17 are conserved in approximately two-thirds of the CUB repertoire and define a novel, Ca2+-binding CUB module subset. The C1s structure was used to build a model of the C1r-C1s CUB1-EGF heterodimer, which in C1 connects C1r to C1s and mediates interaction with C1q. A structural model of the C1q/C1r/C1s interface is proposed, where the rod-like collagen triple helix of C1q is accommodated into a groove along the transversal axis of the C1r-C1s heterodimer.