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Abstract Practical lab skills are rarely directly assessed. To improve constructive alignment between the described learning outcomes of practical skills and assessment, we developed and tested a certification procedure for microscopy skills. The procedure was embedded into the ordinary learning activity, so no additional time was needed. Three slightly different protocols were developed within the framework of sociocultural learning theory and built like a skill ladder, including direct peer assessment and elements of gamified learning. The protocols varied slightly in the way students were prepared for the certification, the number of steps/levels of achievement, and the consequences of failing. We tested the protocols at three different academic institutions and within 11 courses of varying sizes and academic levels in biology or geology. Feedbacks were collected through online surveys (n = 207) or orally after sessions. One protocol provided instruction videos as preparation material. Instruction videos provided increased understanding of the task, but tactile training was most important for learning. Regardless of institution, type of preparation, and level of former experience, the certification procedure made students clearly more engaged in the exercise. The majority reported that the certification procedure increased their motivation to learn, increased their perceived learning outcome, and was appropriate for assessing practical skills. Students with no or little experience in microscopy before the exercise were more positive about the certification procedure compared to skilled students, and the level of engagement and preparation was higher when there were some consequences of failing. Most students felt comfortable being certified by peers, but some students expressed concern about peers making mistakes. The presented certification procedure can easily be adapted to assess other practical skills and, with some adjustments, be an efficient method for assessment‐as‐learning, merging formative‐ and summative assessment.

Background: Guidance and policy on personalised (or person-centred) care of older people living in care homes advocates that all residents must have their preferences considered, and that all care provided must be reasonably adjusted to meet the person's specific needs. Despite this, research that considers what matters to residents in terms of the care they receive is limited., Objectives: Our review aims to explore care home residents' lived experiences of personalised care and understand what really matters to them., Methods: Six electronic databases (CINHAL, Medline (Ovid), Embase, PubMed, Web of Science & PsychInfo) and Google Scholar (grey literature) were searched to identify qualitative studies relating to personalised care in care home settings, which also included resident (voices) quotes. The literature review and synthesis are reported using eMERGe guidance., Results: Fifteen studies met the inclusion criteria for our meta-ethnography. Four conceptual categories (the challenge of fitting into institutional care, the passing of time, holding onto a sense of self and a desire to feel at home) and two key concepts (creating a culture of purposeful living and caring and forming and maintaining meaningful & empowering relationships) were identified. Finally, a conceptual framework of understanding represents what personally matters to residents in terms of their care., Conclusion: Our meta-ethnography, guided by residents' lived experiences of personalised care, offers a new perspective of what personally matters to residents in terms of the care they receive. The conceptual framework of understanding highlights the importance of moving from an institutional position of doing for residents to a person-centred position of doing with residents., Implications for Practice: Our findings highlight the importance of understanding the differences between personalised and person-centred care for policy and practice. Further considerations are required on how this might be applied through nurse and care home professionals' education and work practices., (© 2023 The Authors. International Journal of Older People Nursing published by John Wiley & Sons Ltd.)

Objective: The development of precision therapeutics for systemic sclerosis (SSc) has been hindered by the lack of models that accurately mimic the disease in vitro. This study was undertaken to design and test a self-assembled skin equivalent (saSE) system that recapitulates the cross-talk between macrophages and fibroblasts in cutaneous fibrosis., Methods: SSc-derived dermal fibroblasts (SScDFs) and normal dermal fibroblasts (NDFs) were cultured with CD14+ monocytes from SSc patients or healthy controls to allow de novo stroma formation. Monocyte donor-matched plasma was introduced at week 3 prior to seeding keratinocytes to produce saSE with a stratified epithelium. Tissue was characterized by immunohistochemical staining, atomic force microscopy, enzyme-linked immunosorbent assay, and quantitative reverse transcriptase-polymerase chain reaction., Results: Stroma synthesized de novo from NDFs and SScDFs supported a fully stratified epithelium to form saSE. A thicker and stiffer dermis was generated by saSE with SScDFs, and more interleukin-6 and transforming growth factor β (TGFβ) was secreted by saSE with SScDFs compared to saSE with NDFs, regardless of the inclusion of monocytes. Tissue with SSc monocytes and plasma had amplified dermal thickness and stiffness relative to control tissue. Viable CD163+ macrophages were found within the stroma of saSE 5 weeks after seeding. Additionally, SSc saSE contained greater numbers of CD163+ and CD206+ macrophages compared to control saSE. TGFβ blockade inhibited stromal stiffness to a greater extent in SSc saSE compared to control saSE., Conclusion: These data suggest reciprocal activation between macrophages and fibroblasts that increases tissue thickness and stiffness, which is dependent in part on TGFβ activation. The saSE system may serve as a platform for preclinical therapeutic testing and for molecular characterization of SSc skin pathology through recapitulation of the interactions between macrophages and fibroblasts., (© 2022 American College of Rheumatology.)

We explore the views of managers' knowledge needs and use to optimise care practices and enhance the life experience for older people living, and staff working, in long-term care homes (with and without nursing). This paper contributes to previous research by offering insights into the knowledge types drawn upon and used by managers to inform efforts to better support gaining and mobilising knowledge. Using a pragmatic qualitative approach, we undertook 19 semi-structured interviews with managers and leaders in 15 care homes in the South West of England, varying in geographical location, size and type of ownership. We did a thematic analysis of the data using Framework Analysis. Our interpretations were informed by the existing literature on knowledge types. We identified three themes from our analysis as to managers' knowledge needs and use when implementing changes. First, views about training and formal reports or "explicit knowledge" consisting of the two sub-themes "gaining explicit knowledge" and "research knowledge". Second, perspectives relating to practical experience or "tacit knowledge" and judging the use of knowledge in particular cases or "phronesis". Third, the role of emotion in managers' knowledge needs and use. We found that having knowledge was positively valued by managers and leaders for improving care practices and enhancing the lives of people residing in care homes. Tacit knowledge and phronesis were particularly highly valued and we note challenges with the perceived applicability, relevance and use of research evidence. We identify that emotions are an important component within knowledge use and a need to further understand how to support the emotional wellbeing of managers so they can support care staff and residents. Greater consideration is needed as to how to optimise gaining and mobilising all knowledge types - "know-what," "know-how," "know-when" and "know-feel" - to benefit people living, and staff working, in care homes., (© 2020 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Aims: Concomitant cardiac amyloidosis (CA) in severe aortic stenosis (AS) is difficult to recognize, since both conditions are associated with concentric left ventricular thickening. We aimed to assess type, frequency, screening parameters, and prognostic implications of CA in AS., Methods and Results: A total of 191 consecutive AS patients (81.2 ± 7.4 years; 50.3% female) scheduled for transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Overall, 81.7% underwent complete assessment including echocardiography with strain analysis, electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), 99m Tc-DPD scintigraphy, serum and urine free light chain measurement, and myocardial biopsy in immunoglobulin light chain (AL)-CA. Voltage/mass ratio (VMR; Sokolow-Lyon index on ECG/left ventricular mass index) and stroke volume index (SVi) were tested as screening parameters. Receiver operating characteristic curve, binary logistic regression, and Kaplan-Meier curve analyses were performed. CA was found in 8.4% of patients (n = 16); 15 had transthyretin (TTR)-CA and one AL-CA. While global longitudinal strain by echo did not reliably differentiate AS from CA-AS [area under the curve (AUC) 0.643], VMR as well as SVi showed good discriminative power (AUC 0.770 and 0.773, respectively), which was comparable to extracellular volume by CMR (AUC 0.756). Also, VMR and SVi were independently associated with CA by multivariate logistic regression analysis (P = 0.016 and P = 0.027, respectively). CA did not significantly affect survival 15.3 ± 7.9 months after TAVR (P = 0.972)., Conclusion: Both TTR- and AL-CA can accompany severe AS. Parameters solely based on ECG and echocardiography allow for the identification of the majority of CA-AS. In the present cohort, CA did not significantly worsen prognosis 15.3 months after TAVR., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

As progressive organ shortage in cardiac transplantation demands extension of donor criteria, effort is needed to optimize graft survival. Reactive oxygen and nitrogen species, generated during organ procurement, transplantation, and reperfusion, contribute to acute and late graft dysfunction. The combined application of diverse substances acting via different molecular pathways appears to be a reasonable approach to face the complex mechanism of ischemia reperfusion injury. Thus, an antioxidant solution containing α -ketoglutaric acid, 5-hydroxymethylfurfural, N -acetyl-L-methionine, and N -acetyl-selenium-L-methionine was combined with endogenous angiotensin-(1-7). Its capacity of myocardial protection was investigated in isolated Langendorff-perfused rat hearts subjected to warm and cold ischemia. The physiological cardiac parameters were assessed throughout the experiments. Effects were evaluated via determination of the oxidative stress parameters malondialdehyde and carbonyl proteins as well as immunohistochemical and ultrastructural tissue analyses. It was shown that a combination of 20% ( v / v ) antioxidant solution and 220 pM angiotensin-(1-7) led to the best results with a preservation of heart tissue against oxidative stress and morphological alteration. Additionally, immediate cardiac recovery (after warm ischemia) and normal physiological performance (after cold ischemia) were recorded. Overall, the results of this study indicate substantial cardioprotection of the novel combination with promising prospective for future clinical use., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Michaela Andrä et al.)

The use of non-medical referral, community referral or social prescribing interventions has been proposed as a cost-effective alternative to help those with long-term conditions manage their illness and improve health and well-being. However, the evidence base for social prescribing currently lags considerably behind practice. In this paper, we explore what is known about whether different methods of social prescribing referral and supported uptake do (or do not) work. Supported by an Expert Advisory Group, we conducted a realist review in two phases. The first identified evidence specifically relating to social prescribing in order to develop programme theories in the form of 'if-then' statements, articulating how social prescribing models are expected to work. In the second phase, we aimed to clarify these processes and include broader evidence to better explain the proposed mechanisms. The first phase resulted in 109 studies contributing to the synthesis, and the second phase 34. We generated 40 statements relating to organising principles of how the referral takes place (Enrolment), is accepted (Engagement), and completing an activity (Adherence). Six of these statements were prioritised using web-based nominal group technique by our Expert Group. Studies indicate that patients are more likely to enrol if they believe the social prescription will be of benefit, the referral is presented in an acceptable way that matches their needs and expectations, and concerns elicited and addressed appropriately by the referrer. Patients are more likely to engage if the activity is both accessible and transit to the first session supported. Adherence to activity programmes can be impacted through having an activity leader who is skilled and knowledgeable or through changes in the patient's conditions or symptoms. However, the evidence base is not sufficiently developed methodologically for us to make any general inferences about effectiveness of particular models or approaches., (© 2019 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

This multicenter, randomized, double-blind, placebo-controlled study assessed ambrisentan or placebo in patients with inoperable chronic thromboembolic pulmonary hypertension. Futility of enrollment led to early termination. Trends of improvement in favor of ambrisentan versus placebo in the primary and some secondary endpoints were observed; adverse event profiles were similar between groups.

Patient registries are a valuable tool in the research of rare conditions such as pulmonary hypertension (PH). We report comprehensive hemodynamic and survival data of 174 patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), included in the prospective Latvian PH registry over a period of > 9 years. In total, 130 adult PAH patients (75%) and 44 adult CTEPH patients (25%) were enrolled. The median follow-up period was 33 months for PAH and 18 months for CTEPH, P = 0.001. Latvian CTEPH patients had significantly higher plasma levels of B-type natriuretic peptide, higher pulmonary vascular resistance, and lower cardiac index than Latvian PAH patients. Calculated incidence of PAH and CTEPH in Latvia in 2016 was 13.7 and 5.1 cases per million inhabitants, calculated prevalence was 45.7 and 15.7 cases per million inhabitants, respectively. Survival rates at one, three, and five years for PAH patients was 88.0%, 73.3%, and 58.1%, and 83.8%, 59.0%, and 44.2% for CTEPH patients, respectively. We compared our study results with data from European adult PH registries. Latvian PAH patients had the fourth lowest and CTEPH patients the lowest one-year survival rate among European adult PH registries. As most PH registries in Europe are small, yet with equivalent patient inclusion criteria, it would be desirable to combine these registries to produce more reliable and high-quality study results.

Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t 1/2 ), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (C max ) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher C avg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 C max and diarrhea with tIRI C max . Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m 2 (free-base; equivalent to 80 mg/m 2 salt base) Q2W over 100 mg/m 2 Q3W., (© 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Despite decades of clinical use, the pharmacokinetics and the effects of acetylsalicylic acid (ASA) in critically ill patients remain ill-defined. We aimed to investigate the pharmacokinetics and the effects of different ASA formulations during critical illness., Design: A cross-sectional study and a randomized, parallel-group trial were performed. Critically ill patients under chronic oral ASA treatment (100 mg enteric-coated) were screened for high 'on-treatment' platelet reactivity (HTPR) according to arachidonic acid-induced whole-blood aggregometry. Thirty patients with HTPR were randomized to receive 100 mg ASA intravenously, 100 mg enteric-coated ASA bid (bis in die) or 81 mg chewable ASA (n = 10 per group). Serum thromboxane B2 (TXB2) levels, ASA and salicylic acid levels were quantified., Results: Of 66 patients, 85% (95% confidence intervals 74-93%) had HTPR. Compared to baseline infusion of 100 mg, ASA significantly reduced platelet aggregation after 24 h to median 80% (Quartiles: 66-84%). Intake of 81 mg chewable ASA significantly reduced platelet aggregation to 75% (54-86%) after four hours, but increased it to 117% after 24 h (81-163%). Treatment with 100 mg enteric-coated ASA bid decreased platelet aggregation after 24 h to median 56% (52-113%). Baseline TXB2 levels were median 0·35 ng/mL (0·07-0·94). Infusion of ASA or intake of 100 mg ASA bid reduced TXB2 levels to 0·07-0·18 ng/mL after 24 h, respectively. Chewable ASA reduced TXB2 levels only transiently. Pharmacokinetic analysis revealed highly variable absorption patterns of oral ASA formulations., Conclusion: There is a very high prevalence of HTPR in critically ill patients on peroral ASA therapy, caused by an incomplete suppression of TXB2 and/or by impaired absorption of ASA., (© 2017 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Emergency ambulance calls represent one of the routes of emergency hospital admissions from care homes. We aimed to describe the pattern of ambulance call rates from care homes and identify factors predicting those homes calling for an ambulance most frequently. We obtained data from South Western Ambulance Service NHS Foundation Trust on 3138 ambulance calls relating to people aged 65 and over from care homes in the Torbay region between 1 April 2012 and 31 July 2013. We supplemented this with data from the Care Quality Commission (CQC) website on home characteristics and outcomes of CQC inspections. We used descriptive statistics to identify variation in ambulance call rates for residential and nursing homes and fitted negative binomial regression models to determine if call rates were predicted by home type (nursing versus residential), the five standards in the CQC reports, dementia care status or travel time to hospital. One hundred and forty-six homes (119 residential and 27 nursing) were included in the analysis. The number of calls made ranged from 1 to 99. The median number (IQR; range) of calls per resident per year was 0.51 (0.21-0.89; 0.03-2.45). Nursing homes had a lower call rate than residential homes [adjusted rate ratio (ARR) 0.29; 95% CI: 0.22-0.40; P < 0.001]; care homes failing the quality and suitability of management standard had a lower call rate compared to those who passed (ARR 0.67; 95% CI: 0.50-0.90; P = 0.006); and homes specialising in dementia had a higher call rate compared to those not specialising (ARR 1.56; 95% CI: 1.23-1.96; P < 0.001). These findings require replication in other regions to establish their generalisability and further investigation is required to determine the extent to which call rate variability reflects the different needs of resident populations or differences in care home policies and practice., (© 2016 John Wiley & Sons Ltd.)

We conducted an international study to evaluate practices in the diagnosis and management of patients with chronic thromboembolic pulmonary hypertension (CTEPH) globally across different regions. Between August and October 2012, CTEPH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 2-5 most recent patients with CTEPH. Overall, 496 physicians (Europe: 260; United States: 152; Argentina: 52; Japan: 32) completed the questionnaire and provided patient record data for 1,748 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension (PH) center ranged from 38% in France and Italy to 83% in the United States. A large proportion of patients did not undergo ventilation/perfusion scanning (46%-67%) or right heart catheterization (24%-57%) for the diagnosis of CTEPH. Referral rates for pulmonary endarterectomy evaluation ranged from 25% in Japan to 44% in Europe, with higher referral rates in PH centers; the main reasons for lack of referral were that surgery was not considered unless medical treatment was failing and patient refusal. Other variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of combination treatment in the United States than in Europe. Physicians' perceptions of their treatment strategy were generally consistent with patient record data. Results from this study, which includes a global aspect of CTEPH care, demonstrate not only regional differences in CTEPH management but, more importantly, considerable nonadherence to the diagnosis and treatment guidelines for CTEPH, even in PH centers.

We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients' New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%-21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH.

The endocrine action of medroxyprogesterone acetate (MPA) has been claimed to be of a glucocorticoid-like nature. Upon clinical observation, MPA has been shown to improve life quality and overall well-being in patients with advanced breast cancer, renal carcinoma, prostatic carcinoma, and uterine adenocarcinoma. The authors have evaluated MPA endocrine action by the administration of human corticotropin releasing factor (hCRF) in a 90-minute assay in 15 patients with advanced breast cancer or renal cell carcinoma both, before the initiation of oral high-dose MPA treatment (1000 mg MPA) as well as after at least 10 days of therapy. The curves for corticotropin, beta-endorphin, and cortisol responses to hCRF of tumor patients who were tested before the initiation of MPA treatment were parallel to the curves of a healthy control group of probands tested under equal conditions, although at significantly higher respective hormone levels. In patients with malignant disorders assayed after MPA administration, both basal and peak hormone levels were found to be comparable with values obtained in healthy controls. In conclusion, MPA appeared to act at a suprapituitary level since pituitary responsiveness to hCRF was preserved under MPA treatment. Moreover, it appeared that MPA brought the hormonal stress state found in patients with malignant tumors back to normal.