Patient Assessment Chronic Illness Care (PACIC) and its associations with quality of life among Swiss patients with systemic sclerosis: a mixed methods study.

BACKGROUND: The Chronic Care Model (CCM) is a longstanding and widely adopted model guiding chronic illness management. Little is known about how CCM elements are implemented in rare disease care or how patients' care experiences relate to health-related quality of life (HRQoL). We engaged patients living with systemic sclerosis (SSc) to assess current care according to the CCM from the patient perspective and their HRQoL. METHODS: We employed an explanatory sequential mixed methods design. First, we conducted a cross-sectional quantitative survey (n = 101) using the Patient Assessment of Chronic Illness Care (PACIC) and Systemic Sclerosis Quality of Life (SScQoL) questionnaires. Next, we used data from individual patient interviews (n = 4) and one patient focus group (n = 4) to further explore care experiences of people living with SSc with a focus on the PACIC dimensions. RESULTS: The mean overall PACIC score was 3.0/5.0 (95% CI 2.8-3.2, n = 100), indicating care was 'never' to 'generally not' aligned with the CCM. Lowest PACIC subscale scores related to 'goal setting/tailoring' (mean = 2.5, 95% CI 2.2-2.7) and 'problem solving/contextual counselling' (mean = 2.9, 95% CI 2.7-3.2). No significant correlations were identified between the mean PACIC and SScQoL scores. Interviews revealed patients frequently encounter major shortcomings in care including 'experiencing organized care with limited participation', 'not knowing which strategies are effective or harmful' and 'feeling left alone with disease and psychosocial consequences'. Patients often responded to challenges by 'dealing with the illness in tailored measure', 'taking over complex coordination of care' and 'relying on an accessible and trustworthy team'. CONCLUSIONS: The low PACIC mean overall score is comparable to findings in patients with common chronic diseases. Key elements of the CCM have yet to be systematically implemented in Swiss SSc management. Identified gaps in care related to lack of shared decision-making, goal-setting and individual counselling-aspects that are essential for supporting patient self-management skills. Furthermore, there appears to be a lack of complex care coordination tailored to individual patient needs.

Patient and healthcare professional eHealth literacy and needs for systemic sclerosis support: a mixed methods study.

OBJECTIVES: We engaged patients with systemic sclerosis (SSc) and healthcare professionals to assess electronic health (eHealth) literacy and needs relating to web-based support using internet-based information and communication technologies (ICT). METHODS: We employed an explanatory sequential mixed methods design. First, we conducted a cross-sectional survey in patients (n=101) and professionals (n=47). Next, we conducted three focus groups with patients, family members and professionals (n=17). RESULTS: Of patients, 89.1% used ICT at least weekly for private communication. Patients reported relatively high comprehension of eHealth information ([Formula: see text] =6.7, 95% CI: 6.2 to 7.3, range 1-10), yet were less confident evaluating information reliability ([Formula: see text] =5.8, 95% CI: 5.1 to 6.4) and finding eHealth apps ([Formula: see text] =4.8, 95% CI: 4.2 to 5.4). Patients and professionals reported little experience with web-based self-management support. Focus groups revealed 'considering non-ICT-accessible groups' and 'fitting patients' and professionals' technology' as crucial for acceptability. In relation to understanding/appraising eHealth, participants highlighted that general SSc information is not tailored to individual's disease course. Recommendations included 'providing timely, understandable and safe information' and 'empowering end-users in ICT and health decision-making skills'. Professionals expressed concerns about lacking resources. Patients were concerned about data security and person-centredness. Key eHealth drivers included 'addressing end-user perceptions' and 'putting people at the centre of technology'. CONCLUSIONS: Patients and professionals need education/training to support uptake of eHealth resources. Key elements include guiding patients to timely/reliable information and using eHealth to optimise patient-provider communication. Design that is responsive to end-users' needs and considers individuals with limited eHealth literacy and/or ICT access appears to be critical for acceptability.

Response to a sexual risk reduction intervention provided in combination with hepatitis C treatment by HIV/HCV co-infected men who have sex with men: a reflexive thematic analysis.

BACKGROUND: Hepatitis C virus reinfections in HIV-positive men-who-have-sex-with-men (MSM) challenge the effectiveness of antiviral treatment. To fight this problem, an adapted sexual risk reduction intervention was implemented within a hepatitis C treatment trial. Following this, the current study had two aims and describes 1) how the program was received by participants; and 2) their responses to the program regarding sexual risk taking. Based on the participants' input, we hoped to judge the intervention's potential for scale-up. METHODS: Seventeen participants who received the sexual risk reduction intervention in addition to hepatitis C treatment were recruited for semi-structured interviews six to 12 months post-intervention. We evaluated the responses via reflexive thematic analysis and applied the concept of sense-making. RESULTS: Giving hepatitis C a place and living without it again illustrates how participants received the program and how their experiences were altered by the impact of sense-making. Based on their responses, we allocated participants to three groups: 1. Avoid risks: get rid of hepatitis C for life. For these men, hepatitis C remained a life-threatening disease: they actively modified their risk behavior and felt supported by the intervention in maintaining their behavioral changes. 2. Minimize risks: live as long as possible without hepatitis C. In contrast to group 1, these men saw hepatitis C as a manageable disease. The intervention facilitated reflection on risks and how to develop behavioral changes that suited them individually. 3. Accept risks; live with the risk of hepatitis C. These men perceived behavioral changes as much more difficult than "easy" medical treatment. They expected to either undergo repeated rounds of treatment or stay HCV re-infected. CONCLUSION: These results illustrate the diversity of men's responses and their decisions regarding sexual risk behavior after participating in a combination of antiviral treatment and a sexual risk reduction intervention. Two major aspects were identified: 1) Teachable moments, particularly at the time of diagnosis/treatment, could offer an opportunity to develop openness for behavioral change; 2) adapting sexual risk reduction interventions to sense-making patterns could help to improve its effectiveness. Support for reducing infection risk and raising awareness of preventative measures are additional benefits. TRIAL REGISTRATION: Clinical Trial Number: NCT02785666 , 30.05.2016.

A Strategic Core Role Perspective on Team Coordination: Benefits of Centralized Leadership for Managing Task Complexity in the Operating Room.

OBJECTIVE: We examine whether surgical teams can handle changes in task requirements better when their formal leader and strategic core role holder-that is, the main surgeon-is central to team coordination. BACKGROUND: Evidence regarding the benefits of shared leadership for managing complex tasks is divided. We tested whether a strategic core role holder's centrality in team coordination helps teams to handle different types of task complexity. METHOD: We observed coordination as specific leadership behavior in 30 surgical teams during real-life operations. To assess the strategic core role holder's coordination centrality, we conducted social network analyses. Task complexity (i.e., surgical difficulty and unexpected events) and surgical goal attainment were rated in a questionnaire. RESULTS: In the critical operation phase, surgical difficulty impaired goal attainment when the strategic core role holder's coordination centrality was low, while this effect was nonsignificant when his/her coordination centrality was high. Unexpected events had a negative effect on surgical goal attainment. However, coordination centrality of the strategic core role holder could not help manage unexpected events. CONCLUSION: The results indicate that shared leadership is not beneficial when teams face surgical difficulty during the critical operation phase. In this situation, team coordination should rather be centralized around the strategic core role holder. Contrarily, when unexpected events occur, centralizing team coordination around a single leader does not seem to be beneficial for goal attainment. APPLICATION: Leaders and team members should be aware of the importance of distributing leadership differently when it comes to managing different types of task complexity.

Implementation of a multiprofessional, multicomponent delirium management guideline in two intensive care units, and its effect on patient outcomes and nurse workload: a pre-post design retrospective cohort study.

AIM OF THE STUDY: Delirium is a frequent intensive care unit (ICU) complication, affecting 26% to 80% of ICU patients, often with serious consequences. This study aimed to evaluate the effectiveness, costs and benefits of following a standardised multiprofessional, multicomponent delirium guideline on eight outcomes: delirium prevalence and duration, lengths of stay in ICU and hospital, in-hospital mortality, duration of mechanical ventilation, and cost and nursing hours per case. It also aimed to explore the associations of delirium with length of ICU stay, length of hospital stay and duration of mechanical ventilation. METHODS: This retrospective cohort study used a pre-post design. ICU patients in an historical control group (n = 1608) who received standard ICU care were compared with a postintervention group (n = 1684) who received standardised delirium management – delirium risk identification, preventive measures, screening and treatment – with regard to eight outcomes. The delirium management guideline was developed and implemented in 2012 by a group of experts from the study hospital. As appropriate, descriptive statistics and multivariate, multilevel models were used to compare the two groups and to explore the association between delirium occurrence and the selected outcomes. RESULTS: Twelve percent of the 1608 historical controls and 20% of the 1684 postintervention patients were diagnosed with delirium according to the ICD-10 delirium diagnosis codes. Patients being treated for heart disease, and those with septic shock, ARDS, renal insufficiency (acute or chronic), older age and higher numbers of comorbidities were significantly more likely to develop delirium during their stay. Multivariate models comparing the historical controls with the post intervention group indicated significant differences in delirium period prevalence (odds ratio 1.68, 95% confidence interval [CI] 1.38–2.06; p <0.001), length of stay in the ICU (time ratio [TR] 0.94, CI 0.89–1.00; p = 0.048), cost per case (median difference 3.83, CI 0.54–7.11; p = 0.023) and duration of mechanical ventilation (TR 0.84, CI 0.77–0.92; p <0.001). The observed differences in the other four outcomes – in-hospital mortality, delirium duration, length of stay in the hospital, and nursing hours per case – were not significant. Delirium was a significant predictor for prolonged duration of mechanical ventilation and for both ICU and hospital stay. CONCLUSION: Standardised delirium management, specifically delirium screening, supports timely detection of delirium in ICU patients. Increased awareness of delirium after the implementation of standardised multiprofessional, multicomponent management leads to increased therapeutic attention, a prolongation of ICU stay and increased costs, but with no influence on mortality.

Exploring healthcare providers' mental models of the infection prevention "patient zone" - a concept mapping study.

Background: Pathogen transmission plays a major role in the development of healthcare-associated infections. The "patient zone" concept developed as part of the World Health Organization's "Five moments of hand hygiene" aims to distinguish surfaces primarily contaminated by flora of a single patient, i.e. inside the patient zone, from those outside the patient zone containing foreign and potentially harmful microorganisms. Discrepancies in healthcare provider (HCP) internal conceptual representations (i.e. mental models) of the patient zone may lead to missed infection prevention measures that could result in patient harm. We explored HCPs' mental models of the patient zone that shape how they interact with the work environment. Methods: We conducted individual concept mapping interviews supported by a card-sorting technique to examine HCPs' mental models of the patient zone and compared these to IPC expert models. Ten participants (five nurses, five physicians) without IPC specialization and two IPC experts provided definitions of the patient zone and allocated 32 items to "inside" or "outside" the patient zone while verbalizing their thought processes. We calculated similarity as percent agreement among participants and accuracy as percent allocated consistently with expert consensus. A content analysis of interview recordings served to identify mental models underlying the allocation decisions. Results: Our study revealed limited similarity among participants, with seven of 32 items allocated consistently among all participants. Overall, 68% of items were sorted accurately according to expert consensus. Identified mental models were categorized as follows: "Patient contact", the patient zone defined according to objects having patient contact; "Sectors", the patient zone as a defined physical space; "Disinfection", the patient zone deduced based on need to disinfect hands and objects; and "Context-dependency", the patient zone defined depending on the context of an object's use. Conclusions: Our study revealed ambiguity surrounding the patient zone concept as evidenced by low similarity between participants and important discrepancies between participant and expert mental models. Such ambiguity may lead to inconsistent application of the patient zone concept and represents a patient safety risk. Initiatives to improve understanding and application of the patient zone concept should focus on establishing consistent, theoretically founded mental models.

An ultra-high affinity ligand of HIV-1 TAR reveals the RNA structure recognized by P-TEFb.

The HIV-1 trans-activator protein Tat binds the trans-activation response element (TAR) to facilitate recruitment of the super elongation complex (SEC) to enhance transcription of the integrated pro-viral genome. The Tat-TAR interaction is critical for viral replication and the emergence of the virus from the latent state, therefore, inhibiting this interaction has long been pursued to discover new anti-viral or latency reversal agents. However, discovering active compounds that directly target RNA with high affinity and selectivity remains a significant challenge; limiting pre-clinical development. Here, we report the rational design of a macrocyclic peptide mimic of the arginine rich motif of Tat, which binds to TAR with low pM affinity and 100-fold selectivity against closely homologous RNAs. Despite these unprecedented binding properties, the new ligand (JB181) only moderately inhibits Tat-dependent reactivation in cells and recruitment of positive transcription elongation factor (P-TEFb) to TAR. The NMR structure of the JB181-TAR complex revealed that the ligand induces a structure in the TAR loop that closely mimics the P-TEFb/Tat1:57/AFF4/TAR complex. These results strongly suggest that high-affinity ligands which bind the UCU bulge are not likely to inhibit recruitment of the SEC and suggest that targeting of the TAR loop will be an essential feature of effective Tat inhibitors.

A hospital-wide evaluation of delirium prevalence and outcomes in acute care patients - a cohort study.

BACKGROUND: Delirium is a well-known complication in cardiac surgery and intensive care unit (ICU) patients. However, in many other settings its prevalence and clinical consequences are understudied. The aims of this study were: (1) To assess delirium prevalence in a large, diverse cohort of acute care patients classified as either at risk or not at risk for delirium; (2) To compare these two groups according to defined indicators; and (3) To compare delirious with non-delirious patients regarding hospital mortality, ICU and hospital length of stay, nursing hours and cost per case. METHODS: This cohort study was performed in a Swiss university hospital following implementation of a delirium management guideline. After excluding patients aged < 18 years or with a length of stay (LOS) < 1 day, 29'278 patients hospitalized in the study hospital in 2014 were included. Delirium period prevalence was calculated based on a Delirium Observation Scale (DOS) score ≥ 3 and / or Intensive Care Delirium Screening Checklist (ICDSC) scores ≥4. RESULTS: Of 10'906 patients admitted, DOS / ICDSC scores indicated delirium in 28.4%. Delirium was most prevalent (36.2-40.5%) in cardiac surgery, neurosurgery, trauma, radiotherapy and neurology patients. It was also common in geriatrics, internal medicine, visceral surgery, reconstructive plastic surgery and cranio-maxillo-facial surgery patients (prevalence 21.6-28.6%). In the unadjusted and adjusted models, delirious patients had a significantly higher risk of inpatient mortality, stayed significantly longer in the ICU and hospital, needed significantly more nursing hours and generated significantly higher costs per case. For the seven most common ICD-10 diagnoses, each diagnostic group's delirious patients had worse outcomes compared to those with no delirium. CONCLUSIONS: The results indicate a high number of patients at risk for delirium, with high delirium prevalence across all patient groups. Delirious patients showed significantly worse clinical outcomes and generated higher costs. Subgroup analyses highlighted striking variations in delirium period-prevalence across patient groups. Due to the high prevalence of delirium in patients treated in care centers for radiotherapy, visceral surgery, reconstructive plastic surgery, cranio-maxillofacial surgery and oral surgery, it is recommended to expand the current focus of delirium management to these patient groups.

A Peptidomimetic Antibiotic Targets Outer Membrane Proteins and Disrupts Selectively the Outer Membrane in Escherichia coli.

Increasing antibacterial resistance presents a major challenge in antibiotic discovery. One attractive target in Gram-negative bacteria is the unique asymmetric outer membrane (OM), which acts as a permeability barrier that protects the cell from external stresses, such as the presence of antibiotics. We describe a novel ß-hairpin macrocyclic peptide JB-95 with potent antimicrobial activity against Escherichia coli. This peptide exhibits no cellular lytic activity, but electron microscopy and fluorescence studies reveal an ability to selectively disrupt the OM but not the inner membrane of E. coli. The selective targeting of the OM probably occurs through interactions of JB-95 with selected ß-barrel OM proteins, including BamA and LptD as shown by photolabeling experiments. Membrane proteomic studies reveal rapid depletion of many ß-barrel OM proteins from JB-95-treated E. coli, consistent with induction of a membrane stress response and/or direct inhibition of the Bam folding machine. The results suggest that lethal disruption of the OM by JB-95 occurs through a novel mechanism of action at key interaction sites within clusters of ß-barrel proteins in the OM. These findings open new avenues for developing antibiotics that specifically target ß-barrel proteins and the integrity of the Gram-negative OM.

Compliance with guidelines and predictors of mortality in hemodialysis. Learning from Serbia patients.

OBJECTIVES: The aims of the study were to determine the percentage of patients on regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and find out factors associated with the risk of time to death and the association between guidelines adherence and patient outcome. METHODS: A cohort of 2153 patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia were followed from January 2010 to December 2012. The percentage of patients failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin (>110g/L), serum phosphorus (1.1-1.8mmol/L), calcium (2.1-2.4mmol/L) and iPTH (150-300pg/mL) was determined. Cox proportional hazards analysis was used to select variables significantly associated with the risk of time to death. RESULTS: The patients were on regular HD for 5.3±5.3 years, dialyzed 11.8±1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s-phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had 11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of patients. Using Cox model (adjustment for patient age, gender, duration of HD treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic nephropathy were selected as significant independent predictors of time to death. When targets of five examined parameters were included in Cox model, target for KtV, hemoglobin and iPTH were found to be significant independent predictors of time to death. CONCLUSION: Substantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.

Adaptive coordination in surgical teams: an interview study.

BACKGROUND: Effective teamwork has been recognised as a major contributor to safe patient care in surgery. Previous research has highlighted the importance of adaptive coordination for effective performance in acute care settings. Expanding this line of research this study explores the coordination behaviours and adaptive coordination strategies employed by surgical teams and identifies relevant situational characteristics influencing those coordination processes. METHOD: We conducted a qualitative content analysis of semi-structured interviews with 33 surgical team members (nurses and physicians) from different specialties and hospitals. RESULTS: We identified coordination behaviours (i.e. task management, information management, teaching and leadership) and adaptive coordination strategies triggered by varying requirements due to non-routine events, intraoperative complications and differing level of experience among operating room staff. Interviewees highlighted the importance of effectively managing challenging moments and the supporting effect of positive climate on teamwork. CONCLUSIONS: This study complements previous research on the non-technical skills underpinning safe performance in surgical teams. It highlights the central role of coordination and points out the ways in which situational variability requires the team to behave adaptively.

How DNA polymerase X preferentially accommodates incoming dATP opposite 8-oxoguanine on the template.

The modified base 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxoG) is a common DNA adduct produced by the oxidation of DNA by reactive oxygen species. Kinetic data reveal that DNA polymerase X (pol X) from the African swine fever virus incorporates adenine (dATP) opposite to oxoG with higher efficiency than the non-damaged G:C basepair. To help interpret the kinetic data, we perform molecular dynamics simulations of pol X/DNA complexes, in which the template base opposite to the incoming dNTP (dCTP, dATP, dGTP) is oxoG. Our results suggest that pol X accommodates the oxoGsyn:A mispair by sampling closed active conformations that mirror those observed in traditional Watson-Crick complexes. Moreover, for both the oxoGsyn:A and oxoG:C ternary complexes, conformational sampling of the polymerase follows previously described large subdomain movements, local residue motions, and active site reorganization. Interestingly, the oxoGsyn:A system exhibits superior active site geometry in comparison to the oxoG:C system. Simulations for the other mismatch basepair complexes reveal large protein subdomain movement for all systems, except for oxoG:G, which samples conformations close to the open state. In addition, active site geometry and basepairing of the template base with the incoming nucleotide, reveal distortions and misalignments that range from moderate (i.e., oxoG:Asyn) to extreme (i.e., oxoGanti/syn:G). These results agree with the available kinetic data for pol X and provide structural insights regarding the mechanism by which this polymerase can accommodate incoming nucleotides opposite oxoG. Our simulations also support the notion that α-helix E is involved both in DNA binding and active site stabilization. Our proposed mechanism by which pol X can preferentially accommodate dATP opposite template oxoG further underscores the role that enzyme dynamics and conformational sampling operate in polymerase fidelity and function.

[Comparative study of the efficacy of different regimens of intermittent subcutaneous dosing of erythropoietin beta in treatment of renal anemia in chronic dialysis patients].

INTRODUCTION: The use of erythropoietin (EPO) in the treatment of renal anemia is justified by more than 15 years of experience. Clinical trials have shown that subcutaneous erythropoietin beta (Recormon - F. Hoffmann-La Roche) therapy once weekly, or even once every two weeks has proven successful. The aim of this study was to evaluate the efficacy of different regimes of Recormon therapy in maintaining stable levels of hemoglobin (Hb) and hematocrit (HCT) in hemodialysis patients. MATERIAL AND METHODS: An open, comparative, multicenter study was divided into three arms of patients and lasted for 24 weeks. 98 patients with stable Hb level (>100 g/l), were treated with a stable dose of Recormon, and had a ferritin level > 200 microg/l and transferrin saturation >20%. During the first 8 weeks all were on the usual 2-3 times weekly epo dosage. 8 weeks later, 70 patients received epo once weekly, while 28 patients (group 1) maintained the same regimen for the entire study period. After another 8 weeks, 21 of those 70 patients receiving epo once weekly, received it once every two weeks (group 3), while 49 patients continued once weekly regimen to the end of the trial (group 2). The primary efficacy parameter was the percentage of patients maintaining their target Hb and HCT levels (>100 g/l and >30% for HB and HCT respectively). RESULTS: 86 patients (87.75%) completed the study (25 from group 1, 42 from group 2 and 19 from group 3). One patient was excluded because he was transplated during the study, one due to uncontrolled hypertension, while 10 patients, all from the same center, were excluded due to protocol violation (4-week gap in epo therapy due to problems with epo supply). Efficacy analysis included per-protocol population (86 patients). Hb levels remained stable (>100 g/l) in all three groups. Although there were statistically significant differences in Hb levels between visits (p=0,026), there were no statistically significant differences between groups throughout the study (p=0,439). HCT levels remained stable (>30%) in all three groups throughout the study, without statistically significant differences between visits (p=0,053) and between groups (p=0,155). The average epo doses were not statistically significantly different between visits (p=0,676) or between groups (p=0,512). The main tolerability parameters: sitting systolic (SSBP) and diastolic (SDBP) blood pressures were monitored at all visits. Statistical analysis showed that there were no differences in SSBP or SDBP between visits or groups of patients throughout the study. CONCLUSION: All three dosing regimens of subcutaneous epo beta were statistically equivalent in maintaining target Hb and HCT levels. Once weekly or once every two weeks administration of epo beta does not lead to dose increase, and provides greater opportunities to individualize treatment for every single patient and may lead to better compliance.