Patient Related Outcomes After Receiving a Person Centred Nurse Led Follow Up Programme Among Patients Undergoing Revascularisation for Intermittent Claudication: A Secondary Analysis of a Randomised Clinical Trial.

OBJECTIVE: The aim was to evaluate the effect of a person centred nurse led follow up programme on health related quality of life (HRQoL), health literacy, and general self efficacy compared with standard care for patients undergoing revascularisation for intermittent claudication (IC), and to describe factors associated with HRQoL one year after revascularisation. METHODS: This was a secondary analysis of a randomised controlled trial. Patients with IC scheduled for revascularisation at two vascular surgery centres in Sweden between 2016 and 2018 were randomised to intervention or control. During the first year after surgery, the intervention group received a person centred follow up programme with three visits and two telephone calls with a vascular nurse, while the control group received standard follow up with two visits to a vascular surgeon or vascular nurse. Outcomes were HRQoL measured by VascuQol-6, health literacy, and general self efficacy measured by validated questionnaires. RESULTS: Overall, 214 patients were included in the trial; this secondary analysis comprised 183 patients who completed the questionnaires. One year after revascularisation, HRQoL had improved with a mean increase in VascuQol-6 of 7.0 scale steps (95% CI 5.9 - 8.0) for the intervention and 6.0 scale steps (95% CI 4.9 - 7.0) for the control group; the difference between the groups was not significant (p = .18). In an adjusted regression analysis, the intervention was associated with higher VascuQoL-6 (2.0 scale steps, 95% CI 0.08 - 3.93). There was no significant difference between the groups regarding health literacy or general self efficacy. The prevalence of insufficient health literacy among all participants was 38.7% (46/119) at baseline and 43.2% (51/118) at one year. CONCLUSION: In this study, a person centred, nurse led follow up programme had no significant impact on HRQoL, health literacy, or general self efficacy among patients undergoing revascularisation for IC. The prevalence of insufficient health literacy was high and should be addressed by healthcare givers and researchers.

The SAGA HAT module is tethered by its SWIRM domain and modulates activity of the SAGA DUB module.

The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is a transcriptional co-activator that both acetylates and deubiquitinates histones. The histone acetyltransferase (HAT) subunit, Gcn5, is part of a subcomplex of SAGA called the HAT module. A minimal HAT module complex containing Gcn5 bound to Ada2 and Ada3 is required for full Gcn5 activity on nucleosomes. Deletion studies have suggested that the Ada2 SWIRM domain plays a role in tethering the HAT module to the remainder of SAGA. While recent cryo-EM studies have resolved the structure of the core of the SAGA complex, the HAT module subunits and molecular details of its interactions with the SAGA core could not be resolved. Here we show that the SWIRM domain is required for incorporation of the HAT module into the yeast SAGA complex, but not the ADA complex, a distinct six-protein acetyltransferase complex that includes the SAGA HAT module proteins. In the isolated Gcn5/Ada2/Ada3 HAT module, deletion of the SWIRM domain modestly increased activity but had negligible effect on nucleosome binding. Loss of the HAT module due to deletion of the SWIRM domain decreases the H2B deubiquitinating activity of SAGA, indicating a role for the HAT module in regulating SAGA DUB module activity. A model of the HAT module created with Alphafold Multimer provides insights into the structural basis for our biochemical data, as well as prior deletion studies.

Evaluation of an adaptive, multimodal intervention to reduce postoperative infections following cesarean delivery in Ethiopia: study protocol of the CLEAN-CS cluster-randomized stepped wedge interventional trial.

BACKGROUND: We previously developed and pilot tested Clean Cut, a program to prevent postoperative infections by improving compliance with the WHO Surgical Safety Checklist (SSC) and strengthening adherence to infection control practices. This protocol describes the CheckList Expansion for Antisepsis and iNfection Control in Cesarean Section (CLEAN-CS) trial evaluating our program's ability to reduce infections following CS and other obstetric and gynecological operations in Ethiopia. METHODS/DESIGN: CLEAN-CS is a cluster-randomized stepped wedge interventional trial with five clusters (two hospitals per cluster). It aims to assess the impact of Clean Cut on six critical perioperative infection prevention standards including antiseptic practices, antibiotic administration, and routine SCC use. The trial involves baseline data collection followed by Clean Cut training and implementation in each cluster in randomized order. The intervention consists of (1) modifying and implementing the SSC to fit local practices, (2) process mapping each standard, (3) coupling data and processes with site-specific action plans for improvement, and (4) targeted training focused on process gaps. The primary outcome is 30-day CS infection rates; secondary outcomes include other patient-level complications and compliance with standards. Assuming baseline SSI incidence of 12%, an effect size of 25% absolute reduction, and the ability to recruit 80-90 patients per cluster per month, we require a sample of 8100 patients for significance. We will report our study according to CONSORT. DISCUSSION: A cluster-randomized stepped wedge design is well-suited for evaluating this type of surgical safety program. The targeted standards are not in doubt, yet compliance is frequently difficult. Solutions are available and may be recognized by individuals, but teams dedicated to improvement are often lacking. Clean Cut was successfully piloted but requires a more rigorous methodological assessment. We seek to understand the qualities, characteristics, and resources needed to implement the program, the magnitude of effect on processes and outcomes, and to what degree it can enhance compliance with care standards. Challenges include a fraught social and political environment, pandemic travel restrictions, and a limited budget. TRIAL REGISTRATION: ClinicalTrials.gov NCT04812522 (registered on March 23, 2021); Pan-African Clinical Trials Registry PACTR202108717887402 (registered on August 24, 2021).

Effects of a person-centred, nurse-led follow-up programme on adherence to prescribed medication among patients surgically treated for intermittent claudication: randomized clinical trial.

BACKGROUND: Management of intermittent claudication should include secondary prevention to reduce the risk of cardiocerebrovascular disease. Patient adherence to secondary prevention is a challenge. The aim of this study was to investigate whether a person-centred, nurse-led follow-up programme could improve adherence to medication compared with standard care. METHODS: A non-blinded RCT was conducted at two vascular surgery centres in Sweden. Patients with intermittent claudication and scheduled for revascularization were randomized to the intervention or control (standard care) follow-up programme. The primary outcome, adherence to prescribed secondary preventive medication, was based on registry data on dispensed medication and self-reported intake of medication. Secondary outcomes were risk factors for cardiocerebrovascular disease according to the Framingham risk score. RESULTS: Some 214 patients were randomized and analysed on an intention-to-treat basis. The mean proportion of days covered (PDC) at 1 year for lipid-modifying agents was 79 per cent in the intervention and 82 per cent in the control group, whereas it was 92 versus 91 per cent for antiplatelet and/or anticoagulant agents. The groups did not differ in mean PDC (lipid-modifying P = 0.464; antiplatelets and/or anticoagulants P = 0.700) or in change in adherence over time. Self-reported adherence to prescribed medication was higher than registry-based adherence regardless of allocation or medication group (minimum P < 0.001, maximum P = 0.034). There was no difference in median Framingham risk score at 1 year between the groups. CONCLUSION: Compared with the standard follow-up programme, a person-centred, nurse-led follow-up programme did not improve adherence to secondary preventive medication. Adherence was overestimated when self-reported compared with registry-reported.

Increasing patients' awareness of their own health: Experiences of participating in follow-up programs after surgical treatment for intermittent claudication.

INTRODUCTION: Claudication is the most usual symptom of peripheral artery disease, it is described as painful contractions in the leg when walking and alleviated upon resting. People with claudication have an added risk of cardiocerebrovascular events, amputation, and death. Adherence to medical treatment and changes in lifestyles can lower this risk, but this secondary prevention therapy requires engagement, participation, and adherence from the patient. OBJECTIVE: To explore patients' experiences of participating in a 1-year multicentre clinical trial with two follow-up programs evaluating a nurse-led, patient-centered health-promoting programme after surgical treatment for claudication, the FASTIC study. METHODS: A descriptive design with qualitative semi-structured interviews was used among participants in the FASTIC study. The study was conducted at two centres for vascular surgery in the city of Stockholm, Sweden. In all, 17 patients (nine men and eight women) who had completed the FASTIC study participated. Data was analysed using qualitative content analysis with an inductive approach. RESULTS: Two main categories were identified, 'Patient-Professional collaboration' and 'Experience of one´s health', which were associated with four subcategories: facing opportunities and obstacles, cooperating based on the illness experience, increasing awareness of one's own health, and maintaining a healthy lifestyle. CONCLUSIONS: Patients' participation in follow-up programs after surgical treatment for claudication is highly valuable for an increased awareness of one's own health. A person-centered care with patient-professional collaboration is experienced as important for maintaining a health-promoting lifestyle.

The ASCC2 CUE domain in the ALKBH3-ASCC DNA repair complex recognizes adjacent ubiquitins in K63-linked polyubiquitin.

Alkylation of DNA and RNA is a potentially toxic lesion that can result in mutations and even cell death. In response to alkylation damage, K63-linked polyubiquitin chains are assembled that localize the Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3-Activating Signal Cointegrator 1 Complex Subunit (ASCC) repair complex to damage sites in the nucleus. The protein ASCC2, a subunit of the ASCC complex, selectively binds K63-linked polyubiquitin chains via its coupling of ubiquitin conjugation to ER degradation (CUE) domain. The basis for polyubiquitin-binding specificity was unclear, because CUE domains in other proteins typically bind a single ubiquitin and do not discriminate among different polyubiquitin linkage types. We report here that the ASCC2 CUE domain selectively binds K63-linked diubiquitin by contacting both the distal and proximal ubiquitin. The ASCC2 CUE domain binds the distal ubiquitin in a manner similar to that reported for other CUE domains bound to a single ubiquitin, whereas the contacts with the proximal ubiquitin are unique to ASCC2. Residues in the N-terminal portion of the ASCC2 α1 helix contribute to the binding interaction with the proximal ubiquitin of K63-linked diubiquitin. Mutation of residues within the N-terminal portion of the ASCC2 α1 helix decreases ASCC2 recruitment in response to DNA alkylation, supporting the functional significance of these interactions during the alkylation damage response. Our study reveals the versatility of CUE domains in ubiquitin recognition.

Follow-up after surgical treatment for intermittent claudication (FASTIC): a study protocol for a multicentre randomised controlled clinical trial.

BACKGROUND: Intermittent claudication (IC) is a classic symptom of peripheral arterial disease, and strongly associated with coronary heart disease and cerebrovascular disease. Treatment of IC and secondary prevention of vascular events include best medical treatment (BMT), changes in lifestyle, most importantly smoking cessation and increased physical exercise, and in appropriate cases surgery. A person-centred and health promotion approach might facilitate breaking barriers to lifestyle changes and increasing adherence to secondary prevention therapy. The FASTIC study aims to evaluate a nurse-led, person-centred, health-promoting follow-up programme compared with standard follow-up by a vascular surgeon after surgical treatment for IC. METHODS: The FASTIC-study is a multicentre randomised controlled clinical trial. Patients will be recruited from two hospitals in Stockholm, Sweden after surgical treatment of IC through open and/or endovascular revascularisation and will be randomly assigned into two groups. The intervention group is offered a nurse-led, person-centred, health-promoting programme, which includes two telephone calls and three visits to a vascular nurse the first year after surgical treatment. The control group is offered standard care, which consists of a visit to a vascular surgeon 4-8 weeks after surgery and a visit to the outpatient clinic 1 year after surgical treatment. The primary outcome is adherence to BMT 1 year after surgical treatment and will be measured using The Swedish Prescribed Drug Registry. Clinical assessments, biomarkers, and questionnaires will be used to evaluate several secondary outcomes, such as predicted 10-year risk of cardiovascular and cerebrovascular events, health-related quality of life, and patients' perceptions of care quality. DISCUSSION: The FASTIC study will provide important information about interventions aimed at improving adherence to medication, which is an unexplored field among patients with IC. The study will also contribute to knowledge on how to implement person-centred care in a clinical context. TRIAL REGISTRATION: ClinicalTrials.govNCT03283358, registration date 06/13/2016.

Predicting Survival of Small Intestine Neuroendocrine Tumors: Experience From a Major Referral Center.

OBJECTIVE: Neuroendocrine tumors (NETs) comprise 41.8% of small intestine malignancies. The NET nomogram is a 15-item prognostic tool that includes relevant factors for guiding management decisions. This is the first external validation of this tool among American patients at a tertiary treatment center. METHODS: Patients who underwent surgical intervention from 2005 to 2017 were screened by retrospective chart review. Nomogram scores were calculated following the methods outlined by Modlin et al (Neuroendocrinology. 2010;92:143-157). Validation assessed the association between nomogram scores and survival using Wilcoxon test and Cox regression. RESULTS: Among the 121 patients selected, the NET nomogram significantly predicted survival as a continuous variable (P < 0.01) and when dichotomized using 83 points to distinguish low-risk versus high-risk groups (P < 0.01). However, the nomogram was not universally applicable as even at our specialty center, variables such as chromogranin A and urinary 5-hydroxyindoleacetic acid are not routinely collected, whereas others, like tumor grade, do not reflect the most recently updated classifications. CONCLUSION: The NET nomogram accurately identified patients at low and high risk of death. However, revision to update prognosticators could improve its usefulness for predicting survival of small intestine NETs.

Structural, Mechanistic, and Antigenic Characterization of the Human Astrovirus Capsid.

UNLABELLED: Human astroviruses (HAstVs) are nonenveloped, positive-sense, single-stranded RNA viruses that are a leading cause of viral gastroenteritis. HAstV particles display T=3 icosahedral symmetry formed by 180 copies of the capsid protein (CP), which undergoes proteolytic maturation to generate infectious HAstV particles. Little is known about the molecular features that govern HAstV particle assembly, maturation, infectivity, and immunogenicity. Here we report the crystal structures of the two main structural domains of the HAstV CP: the core domain at 2.60-Å resolution and the spike domain at 0.95-Å resolution. Fitting of these structures into the previously determined 25-Å-resolution electron cryomicroscopy density maps of HAstV allowed us to characterize the molecular features on the surfaces of immature and mature T=3 HAstV particles. The highly electropositive inner surface of HAstV supports a model in which interaction of the HAstV CP core with viral RNA is a driving force in T=3 HAstV particle formation. Additionally, mapping of conserved residues onto the HAstV CP core and spike domains in the context of the immature and mature HAstV particles revealed dramatic changes to the exposure of conserved residues during virus maturation. Indeed, we show that antibodies raised against mature HAstV have reactivity to both the HAstV CP core and spike domains, revealing for the first time that the CP core domain is antigenic. Together, these data provide new molecular insights into HAstV that have practical applications for the development of vaccines and antiviral therapies. IMPORTANCE: Astroviruses are a leading cause of viral diarrhea in young children, immunocompromised individuals, and the elderly. Despite the prevalence of astroviruses, little is known at the molecular level about how the astrovirus particle assembles and is converted into an infectious, mature virus. In this paper, we describe the high-resolution structures of the two main astrovirus capsid proteins. Fitting these structures into previously determined low-resolution maps of astrovirus allowed us to characterize the molecular surfaces of immature and mature astroviruses. Our studies provide the first evidence that astroviruses undergo viral RNA-dependent assembly. We also provide new insight into the molecular mechanisms that lead to astrovirus maturation and infectivity. Finally, we show that both capsid proteins contribute to the adaptive immune response against astrovirus. Together, these studies will help to guide the development of vaccines and antiviral drugs targeting astrovirus.

Patterns and correlates of sexual initiation, sexual risk behaviors, and condom use among secondary school students in Ethiopia.

This study explored the patterns and socio-demographic correlates of sexual initiation, subsequent risk behaviors, and condom use among secondary school youth across Ethiopia. A total of 1,102 students were selected on convenience basis from five urban schools (in Baher Dar, Dessie, Awassa, Jimma, and Dire Dawa) and surveyed about their sexual and preventive behaviors using an extensive questionnaire. Data were analyzed using bivariate and multivariate statistical procedures. One third (33.3%) of the youth reported to have had sexual intercourse prior to the study. Mean age of sexual initiation was 15.3 (SD = 2.5) years. Two-thirds of the sexual initiations were unprotected and some occur with higher risk groups, including much older (15.5%) or casual/commercial sex partners (9.1%). Multi-partnered sex (52.7%) and sex with casual (30.4%) or commercial (25.3%) partners were the most commonly reported lifetime risk behaviors. Although 56.7% of the youth ever used condoms, only less than half of these used them regularly. On the positive note, 83.4% of the youth expressed intentions to use condoms in the future. Socio-demographic characteristics, particularly gender, location, and age, were significantly correlated with sexual and preventive behaviors. Implications of these findings to health education programs for youth are discussed.