Human-centered Design of a Health Recommender System for Orthopaedic Shoulder Treatment.

Background: Rich data on diverse patients and their treatments and outcomes within Electronic Health Record (EHR) systems can be used to generate real world evidence. A health recommender system (HRS) framework can be applied to a decision support system application to generate data summaries for similar patients during the clinical encounter to assist physicians and patients in making evidence-based shared treatment decisions. Objective: A human-centered design (HCD) process was used to develop a HRS for treatment decision support in orthopaedic medicine, the Informatics Consult for Individualized Treatment (I-C-IT). We also evaluate the usability and utility of the system from the physician's perspective, focusing on elements of utility and shared decision-making in orthopaedic medicine. Methods: The HCD process for I-C-IT included 6 steps across three phases of analysis, design, and evaluation. A team of informaticians and comparative effectiveness researchers directly engaged with orthopaedic surgeon subject matter experts in a collaborative I-C-IT prototype design process. Ten orthopaedic surgeons participated in a mixed methods evaluation of the I-C-IT prototype that was produced. Results: The HCD process resulted in a prototype system, I-C-IT, with 14 data visualization elements and a set of design principles crucial for HRS for decision support. The overall standard system usability scale (SUS) score for the I-C-IT Webapp prototype was 88.75 indicating high usability. In addition, utility questions addressing shared decision-making found that 90% of orthopaedic surgeon respondents either strongly agreed or agreed that I-C-IT would help them make data informed decisions with their patients. Conclusion: The HCD process produced an HRS prototype that is capable of supporting orthopaedic surgeons and patients in their information needs during clinical encounters. Future research should focus on refining I-C-IT by incorporating patient feedback in future iterative cycles of system design and evaluation.

Quality of Life for Late Life Patients: Mixed-Methods Evaluation of a Whole-Person Approach for Patients With Chronic Illnesses.

Quality of life (QOL) for patients with serious illness in late life is important for patients and policy makers and has implications for improved care delivery. This mixed-methods evaluation examined the effectiveness of a new whole-person approach to late life care-the LifeCourse-which provides patients with ongoing, across-setting assistance from lay health care workers, supported by a clinical team. We investigated whether participation in LifeCourse improves QOL for intervention patients, compared with usual care controls. QOL was assessed using baseline and 6 months Functional Assessment of Chronic Illness Therapy-Palliative version tool ( n = 181 patients and 126 controls). LifeCourse had a significant positive effect on overall QOL for patients when compared with controls. Interview data revealed that participants adjusted expectations when assessing QOL and actively sought out ways to maintain QOL with meaningful activities and needed services. LifeCourse offers a promising model for improving QOL for late life patients.

Measuring caregiver activation to identify coaching and support needs: Extending MYLOH to advanced chronic illness.

INTRODUCTION: Family and friends of seriously ill patients are key partners in providing support and health care at home, managing relationships with clinicians, and navigating complex health care systems. Becoming a knowledgeable, confident, and effective caregiver is a developmental process we term 'caregiver activation' and could be facilitated by clinicians equipped with suitable tools. Managing Your Loved One's Health (MYLOH) is a new tool to identify gaps in caregivers' knowledge, skills, and access to clinical and personal support. Created in partnership with caregivers and clinicians, MYLOH items reflect the essential dimensions of caregiving and can be used to tailor caregiver coaching to domains of greatest need. In this study, we extend MYLOH's initial focus on dementia care to caregivers of patients with other chronic life-limiting illnesses. METHODS: MYLOH was completed by primary caregivers (n = 190) of people with a range of advanced chronic illnesses enrolled in the LifeCourse study, an innovative, whole-person approach to health management. Item relevance and responses were compared by group across MYLOH items and domains using z-tests for equality of proportions. RESULTS: All MYLOH items were relevant to caregiving for all types of chronic illness; only 13% of caregivers answered "not my responsibility" to any question. MYLOH identified caregiving struggles across patient diagnosis groups with a few, disease-specific 'hotspots'. Overall, 64% of caregivers scored low in activation on at least one healthcare management task, especially getting enough help with caregiving, managing everyday caregiving tasks, understanding/managing medications, and knowing how to respond to rapid changes in care recipients' health status. No difficulty was unique to a specific type of care recipient illness. CONCLUSIONS: MYLOH has potential as a tool for identifying caregiver coaching and support needs in managing a range of serious chronic illnesses. Caregiving difficulties endorsed by over 20% of caregivers should be core components of chronic illness management programs regardless of disease focus, with disease-specific tailoring as required. MYLOH may be useful in evaluating caregiver interventions and health systems' performance in integrating caregivers into the care management of patients with complex life-limiting illness.

Effect of a Whole-Person Model of Care on Patient Experience in Patients With Complex Chronic Illness in Late Life.

BACKGROUND: Patients with serious chronic illness are at a greater risk of depersonalized, overmedicalized care as they move into later life. Existing intervention research on person-focused care for persons in this transitional period is limited. OBJECTIVE: To test the effects of LifeCourse, a team-based, whole-person intervention emphasizing listening to and knowing patients, on patient experience at 6 months. DESIGN: This is a quasi-experimental study with patients allocated to LifeCourse and comparison groups based on 2 geographic locations. Robust change-score regression models adjusted for baseline differences and confounding. SETTING/PARTICIPANTS: Patients (113 intervention, 99 comparison in analyses) were individuals with heart failure or other serious chronic illness, cancer, or dementia who had visits to hospitals at a large multipractice health system in the United States Midwest. MEASUREMENTS: Primary outcome was 6-month change in patient experience measured via a novel, validated 21-item patient experience tool developed specifically for this intervention. Covariates included demographics, comorbidity score, and primary diagnosis. RESULTS: At 6 months, LifeCourse was associated with a moderate improvement in overall patient experience versus usual care. Individual domain subscales for care team, communication, and patient goals were not individually significant but trended positively in the direction of effect. CONCLUSION: Person-focused, team-based interventions can improve patient experience with care at a stage fraught with overmedicalization and many care needs. Improvement in patient experience in LifeCourse represents the sum effect of small improvements across different domains/aspects of care such as relationships with and work by the care team.

A mixed methods analysis of quality of life among late-life patients diagnosed with chronic illnesses.

BACKGROUND: Quality of life (QOL) is an important consideration for people living with advancing chronic conditions. Palliative care providers speak about how, despite physical decline in late life, many patients report growth and meaning in other domains. This mixed methods study uses QOL survey responses to explore domain trajectories and interview data to explore how patients with advancing chronic conditions experience distinct QOL domains. METHODS: The study sample includes 156 now-deceased participants who completed the FACIT-Pal quarterly, and 40 (10 now-deceased) participants who discussed QOL in an interview. Mean subscale scores were plotted over participants' last 18 months to reveal QOL trajectories. Interview data were analyzed to reveal how participants' experience, actions and cognitive processes influenced QOL scores. RESULTS: Physical and functional subscale ratings show gradual decline. Emotional QOL maintains with a small dip 2-3 months before death, and social QOL ratings improve in participants' final 3 months. Participants create and strengthen relationships that help them better manage health and receive instrumental and emotional support; seek activities in which they can find joy, meaning, and purpose; and support cognitions through which patients accept and communicate about illness, and emphasize positives. CONCLUSION: QOL domains exist in different trajectories. Despite physical and functional decline, participant ratings of emotional QOL maintain and ratings of social QOL improve at end of life. Understanding the processes through which participants countered declining QOL may help providers identify how to best support and promote improved QOL for patients during their final months.

Structural and functional properties of peptides based on the N-terminus of HIV-1 gp41 and the C-terminus of the amyloid-beta protein.

Given their high alanine and glycine levels, plaque formation, alpha-helix to beta-sheet interconversion and fusogenicity, FP (i.e., the N-terminal fusion peptide of HIV-1 gp41; 23 residues) and amyloids were proposed as belonging to the same protein superfamily. Here, we further test whether FP may exhibit 'amyloid-like' characteristics, by contrasting its structural and functional properties with those of Abeta(26-42), a 17-residue peptide from the C-terminus of the amyloid-beta protein responsible for Alzheimer's. FTIR spectroscopy, electron microscopy, light scattering and predicted amyloid structure aggregation (PASTA) indicated that aqueous FP and Abeta(26-42) formed similar networked beta-sheet fibrils, although the FP fibril interactions were weaker. FP and Abeta(26-42) both lysed and aggregated human erythrocytes, with the hemolysis-onsets correlated with the conversion of alpha-helix to beta-sheet for each peptide in liposomes. Congo red (CR), a marker of amyloid plaques in situ, similarly inhibited either FP- or Abeta(26-42)-induced hemolysis, and surface plasmon resonance indicated that this may be due to direct CR-peptide binding. These findings suggest that membrane-bound beta-sheets of FP may contribute to the cytopathicity of HIV in vivo through an amyloid-type mechanism, and support the classification of HIV-1 FP as an 'amyloid homolog' (or 'amylog').

Membrane perturbing actions of HIV type 1 glycoprotein 41 domains are inhibited by helical C-peptides.

To study the membrane actions of various domains of HIV-1 glycoprotein 41,000 (gp41), synthetic peptides were prepared corresponding to the N-terminal fusion region (FP; gp41 residues 519-541), the nearby N-leucine zipper domain (N-peptides; DP-107; gp41 residues 560-597), the C-leucine zipper domain (C-peptides; DP-178; gp41 residues 645-680), and the viral envelope adjacent domain that partially overlaps DP-178 (Pre-TM; gp41 residues 671-690). With erythrocytes, FP, DP-107, and Pre-TM induced hemolysis and cell aggregation; the order for hemolytic activity was Pre-TM > FP > DP-107, but each was equally effective in aggregating cells at the highest peptide concentrations tested. DP-178 produced neither hemolysis nor aggregation, but efficiently reduced FP-, DP-107-, and Pre-TM-induced membrane actions. Fourier transform infrared spectroscopy indicated that the membrane perturbations of Pre-TM, as well as the ability of DP-178 to block membrane activities of other gp41 domains, are dependent on Pre-TM and DP-178 each maintaining helical conformations and tryptophans at residues 673, 677, and 679. These results suggest that the corresponding N-terminal fusion, N-leucine zipper, and viral membrane-adjacent regions of HIV-1 gp41 may similarly promote key membrane perturbations underlying the merging of the viral envelope with the cell surface. Further, the antiviral mechanism of exogenous DP-178 (clinically approved enfuvirtide) may be partially explained by its coordinate inhibition of the fusogenic actions of the FP, DP-107, and Pre-TM regions of gp41.

Conformational mapping of the N-terminal peptide of HIV-1 gp41 in lipid detergent and aqueous environments using 13C-enhanced Fourier transform infrared spectroscopy.

The N-terminal domain of HIV-1 glycoprotein 41,000 (gp41) participates in viral fusion processes. Here, we use physical and computational methodologies to examine the secondary structure of a peptide based on the N terminus (FP; residues 1-23) in aqueous and detergent environments. (12)C-Fourier transform infrared (FTIR) spectroscopy indicated greater alpha-helix for FP in lipid-detergent sodium dodecyl sulfate (SDS) and aqueous phosphate-buffered saline (PBS) than in only PBS. (12)C-FTIR spectra also showed disordered FP conformations in these two environments, along with substantial beta-structure for FP alone in PBS. In experiments that map conformations to specific residues, isotope-enhanced FTIR spectroscopy was performed using FP peptides labeled with (13)C-carbonyl. (13)C-FTIR results on FP in SDS at low peptide loading indicated alpha-helix (residues 5 to 16) and disordered conformations (residues 1-4). Because earlier (13)C-FTIR analysis of FP in lipid bilayers demonstrated alpha-helix for residues 1-16 at low peptide loading, the FP structure in SDS micelles only approximates that found for FP with membranes. Molecular dynamics simulations of FP in an explicit SDS micelle indicate that the fraying of the first three to four residues may be due to the FP helix moving to one end of the micelle. In PBS alone, however, electron microscopy of FP showed large fibrils, while (13)C-FTIR spectra demonstrated antiparallel beta-sheet for FP (residues 1-12), analogous to that reported for amyloid peptides. Because FP and amyloid peptides each exhibit plaque formation, alpha-helix to beta-sheet interconversion, and membrane fusion activity, amyloid and N-terminal gp41 peptides may belong to the same superfamily of proteins.

Conformational mapping of the N-terminal peptide of HIV-1 gp41 in membrane environments using (13)C-enhanced Fourier transform infrared spectroscopy.

The N-terminal domain of HIV-1 glycoprotein 41000 (FP; residues 1--23; AVGIGALFLGFLGAAGSTMGARSCONH(2)) participates in fusion processes underlying virus--cell infection. Here, we use physical techniques to study the secondary conformation of synthetic FP in aqueous, structure-promoting, lipid and biomembrane environments. Circular dichroism and conventional, (12)C-Fourier transform infrared (FTIR) spectroscopy indicated the following alpha-helical levels for FP in 1-palmitoyl-2-oleoylphosphatidylglycerol (POPG) liposomes-hexafluoroisopropanol (HFIP)>trifluoroethanol (TFE)>phosphate-buffered saline (PBS). (12)C-FTIR spectra also showed disordered FP structures in these environments, along with substantial beta-structures for FP in TFE or PBS. In further experiments designed to map secondary conformations to specific residues, isotope-enhanced FTIR spectroscopy was performed using a suite of FP peptides labeled with (13)C-carbonyl at multiple sites. Combining these (13)C-enhanced FTIR results with molecular simulations indicated the following model for FP in HFIP: alpha-helix (residues 3-16) and random and beta-structures (residues 1-2 and residues 17-23). Additional (13)C-FTIR analysis indicated a similar conformation for FP in POPG at low peptide loading, except that the alpha-helix extends over residues 1-16. At low peptide loading in either human erythrocyte ghosts or lipid extracts from ghosts, (13)C-FTIR spectroscopy showed alpha-helical conformations for the central core of FP (residues 5-15); on the other hand, at high peptide loading in ghosts or lipid extracts, the central core of FP assumed an antiparallel beta-structure. FP at low loading in ghosts probably inserts deeply as an alpha-helix into the hydrophobic membrane bilayer, while at higher loading FP primarily associates with ghosts as an aqueous-accessible, beta-sheet. In future studies, (13)C-FTIR spectroscopy may yield residue-specific conformations for other membrane-bound proteins or peptides, which have been difficult to analyze with more standard methodologies.