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Abstract Objectives This study aimed to characterize the demographic and clinical features of patients with renal cell carcinoma (RCC) post‐surgery for localized or locally advanced disease in a national Danish cohort, with a specific focus on describing recurrence patterns in a subgroup aligned with the adjuvant KEYNOTE‐564 trial classification. Methods This was a retrospective analysis of the Danish Renal Cancer (DaRenCa) database. Eligible subjects were individuals with an RCC diagnosis between January 2014 and December 2017 who subsequently underwent radical or partial nephrectomy. Variables of interest were demographic and clinical characteristics, rates and sites of recurrence. Recurrence rates were also assessed in a subpopulation stratified using the risk classifications of the KEYNOTE‐564 trial. Results A total of 2164 RCC patients were identified. Most patients (84.8%) had non‐metastatic RCC (stage M0). A recurrence was observed in 250 of the M0 patients (13.6%). Patients with a recurrence were older, male, had a higher tumour stage, had undergone radical nephrectomy and had a higher Leibovich score. The majority (74.8%) of M0 patients had recurrence at distant metastatic sites. A total of 392 patients were stratified by the KEYNOTE‐564 risk classification: 335 intermediate‐high risk, 17 high risk and 40 M1 NED (metastatic with no evidence of disease). Recurrence was observed in 37.0%, 88.2% and 27.5% of these risk groups, respectively. Conclusions This study elucidates the rates and determinants of post‐surgical RCC recurrence in Denmark, underscoring the potential of adjuvant immunotherapy in refining therapeutic strategies, identifying suitable beneficiaries and minimizing overtreatment risks in RCC care.

Abstract This phase Ib study compared the effects of AZD9977, a selective mineralocorticoid receptor modulator with predicted low hyperkalemia risk, with spironolactone on serum potassium (sK+) in patients with heart failure (HF) with preserved or mildly reduced ejection fraction (EF; ≥40%), and renal impairment. Patients with HF with EF greater than or equal to 40% and estimated glomerular filtration rate of 40–70 ml/min/1.73 m2 were randomized to once‐daily AZD9977 100 mg or spironolactone 25 mg for 14 days, up‐titrated to AZD9977 200 mg or spironolactone 50 mg for another 14 days. The primary end point was relative change (%) in sK+ for AZD9977 versus spironolactone (baseline to day 28). Serum/urinary electrolytes, fractional excretion (FE) of Na+/K+, plasma aldosterone, cortisol, and renin, and safety were also assessed. Sixty‐eight patients were randomized (AZD9977, n = 33; spironolactone, n = 35). Mean (SD) age was 73.0 (8.5) years, 51.5% men. Mean sK+ change from baseline to day 28 was 5.7% (AZD9977) and 4.2% (spironolactone), and 1.5% and 4.2% at day 14. Relative change (95% confidence interval) in sK+ with AZD9977 versus spironolactone was −0.3% (−5.3% to 4.4%; day 28), and 3.4% (−0.8% to 7.5%; day 14). Median increase from baseline in plasma aldosterone at day 28 was 89.8 pmol/L for AZD9977 and 67.4 pmol/L for spironolactone. Median FE of K+ was 12.9% (AZD9977) and 10.1% (spironolactone). AZD9977 was well‐tolerated. No discontinuations due to hyperkalemia occurred with either treatment. Evidence of target engagement for AZD9977 with a favorable safety profile, supports further evaluation of AZD9977 in patients with HF and renal impairment.

Abstract Aim To describe the state of health of Quebec nursing staff during the pandemic according to their exposure to COVID‐19, work‐related characteristics and sociodemographic factors (gender, generational age group). State of health was captured essentially by assessing psychological distress, depression symptoms and fatigue. Design and methods A large‐scale cross‐sectional study was conducted with 1,708 nurses and licenced practical nurses in Quebec (87% women, mean age of 41 ± 11 years). The survey included several questionnaires and validated health‐related scales (psychological distress, depression symptoms and fatigue). The STROBE guidelines were followed in reporting the study's findings. Results Results showed that the prevalence of psychological distress and depression symptoms was moderate to severe. Women, generation Xers and Yers, nurses who cared for COVID‐19 patients and those with a colleague who was infected with COVID‐19 at work scored higher for fatigue, psychological distress and depression.

Abstract Background and aims For cancer patients, comorbid obstructive sleep apnea (OSA) poses additional risk to their surgical/anaesthetic outcomes, quality of life, and survival. However, OSA screening is not well‐established in oncology settings. We tested two screening tools (STOP‐Bang questionnaire [SBQ] and the at‐home monitoring device, ApneaLink™Air), for predicting polysomnography (PSG) confirmed OSA in post‐treatment cancer patients. Methods Breast (n = 56), endometrial (n = 37) and melanoma patients (n = 50) were recruited from follow‐up clinics at Westmead Hospital (Sydney, Australia). All underwent overnight PSG, 137 completed SBQ, and 99 completed ApneaLink™Air. Positive (PPV) and negative (NPV) predictive values for PSG‐determined moderate‐to‐severe OSA and severe OSA, were calculated using an SBQ threshold ≥3 au and ApneaLink™Air apnoea‐hypopnea index thresholds of ≥10, ≥15 and ≥30 events/h. Results Both SBQ and ApneaLink™Air had high NPVs (92.7% and 85.2%–95.6% respectively) for severe OSA, but NPVs were lower for moderate‐to‐severe OSA (69.1% and 59.1%–75.5%, respectively). PPV for both tools were relatively low (all

Abstract Hypophosphatasia (HPP) is an underrecognized, complex bone mineralization disorder with variable manifestations caused by one or two deleterious variants in the alkaline phosphatase (ALPL) gene. Expanded carrier screening (ECS), inclusive of ALPL, intends to inform reproductive risk but may incidentally reveal an HPP diagnosis with 50% familial risks. We sought to investigate at‐risk individuals and develop a multidisciplinary referral and evaluation protocol for ECS‐identified ALPL heterozygosity. A retrospective database query of ECS results from 8 years to 1 month for heterozygous pathogenic/likely pathogenic ALPL variants was completed. We implemented a clinical protocol for diagnostic testing and imaging, counseling, and interdisciplinary care management for identified patients, and outcomes were documented. Heterozygous ALPL variants were identified in 12/2248 unrelated patients undergoing ECS (0.53%; heterozygote frequency 1/187). Of 10 individuals successfully contacted, all demonstrated symptomatology and/or alkaline phosphatase values consistent with HPP. ECS may reveal incidental health risks, including recognition of missed HPP diagnoses in ALPL heterozygotes. In our cohort, all ECS‐identified ALPL heterozygotes with clinical and/or biochemical data available demonstrated features of HPP. Referral to a genetics professional familiar with HPP is indicated for family history assessment, genetic counseling, cascade testing, and long‐term bone health management.

Abstract Thyroid cancer is the most common endocrine cancer, with papillary thyroid carcinoma (PTC) accounting for the majority of these cases. Cerebellar metastasis is rarely the presenting feature and confers poor prognosis. Genetic mutations in this setting are most commonly TERTp, in contrast to BRAFV600E in the majority of PTC. We report the case of an 82 year‐old male who presented with a symptomatic right cerebellar lesion and underwent surgical resection to demonstrate metastatic PTC. Extensive workup with computed tomography, neck ultrasound and FDG‐PET was suggestive of a left thyroid primary lesion, with FNA confirming PTC. However, total thyroidectomy demonstrated incidental microMTC (medullary thyroid microcarcinoma, defined as tumour

Abstract Background To produce graduates with strong knowledge and skills in the application of evidence into healthcare practice, it is imperative that all undergraduate health and social care students are taught, in an efficient manner, the processes involved in applying evidence into practice. The two main concepts that are linked to the application of evidence into practice are “evidence‐based practice” and “evidence‐informed practice.” Globally, evidence‐based practice is regarded as the gold standard for the provision of safe and effective healthcare. Despite the extensive awareness of evidence‐based practice, healthcare practitioners continue to encounter difficulties in its implementation. This has generated an ongoing international debate as to whether evidence‐based practice should be replaced with evidence‐informed practice, and which of the two concepts better facilitate the effective and consistent application of evidence into healthcare practice. Objectives The primary objective of this systematic review was to evaluate and synthesize literature on the effectiveness of evidence‐informed practice versus evidence‐based practice educational interventions for improving knowledge, attitudes, understanding, and behavior of undergraduate health and social care students toward the application of evidence into practice. Specifically, we planned to answer the following research questions: (1) Is there a difference (i.e., difference in content, outcome) between evidence‐informed practice and evidence‐based practice educational interventions? (2) Does participating in evidence‐informed practice educational interventions relative to evidence‐based practice educational interventions facilitate the application of evidence into practice (as measured by, e.g., self‐reports on effective application of evidence into practice)? (3) Do both evidence‐informed practice and evidence‐based practice educational interventions targeted at undergraduate health and social care students influence patient outcomes (as measured by, e.g., reduced morbidity and mortality, absence of nosocomial infections)? (4) What factors affect the impact of evidence‐informed practice and evidence‐based practice educational interventions (as measured by, e.g., course content, mode of delivery, multifaceted interventions, standalone intervention)? Search Methods We utilized a number of search strategies to identify published and unpublished studies: (1) Electronic databases: we searched Academic Search Complete, Academic search premier, AMED, Australian education index, British education index, Campbell systematic reviews, Canada bibliographic database (CBCA Education), CINAHL, Cochrane Library, Database of Abstracts of Reviews on Effectiveness, Dissertation Abstracts International, Education Abstracts, Education complete, Education full text: Wilson, ERIC, Evidence‐based program database, JBI database of systematic reviews, Medline, PsycInfo, Pubmed, SciELO (Scientific Electronic Library Online), and Scopus; (2) A web search using search engines such as Google and Google scholar; (3) Grey literature search: we searched OpenGrey (System for Information on Grey Literature in Europe), System for information on Grey Literature, the Society for Research on Educational Effectiveness, and Virginia Henderson Global Nursing e‐Repository; (4) Hand searching of journal articles; and (5) Tracking bibliographies of previously retrieved studies. The searches were conducted in June 2019. Selection Criteria We planned to include both quantitative (including randomized controlled trials, non‐randomized controlled trials, quasi‐experimental, before and after studies, prospective and retrospective cohort studies) and qualitative primary studies (including, case series, individual case reports, and descriptive cross‐sectional studies, focus groups, and interviews, ethnography, phenomenology, and grounded theory), that evaluate and compare the effectiveness of any formal evidence‐informed practice educational intervention to evidence‐based practice educational intervention. The primary outcomes were evidence‐informed practice and evidence‐based practice knowledge, attitudes, understanding, and behavior. We planned to include, as participants, undergraduate pre‐registration health and social care students from any geographical area. Data Collection and Analysis Two authors independently screened the search results to assess articles for their eligibility for inclusion. The screening involved an initial screening of the title and abstracts, and subsequently, the full‐text of selected articles. Discrepancies were resolved through discussion or consultation with a third author. We found no article eligible for inclusion in this review. Main Results No studies were found which were eligible for inclusion in this review. We evaluated and excluded 46 full‐text articles. This is because none of the 46 studies had evaluated and compared the effectiveness of evidence‐informed practice educational interventions with evidence‐based practice educational interventions. Out of the 46 articles, 45 had evaluated solely, the effectiveness of evidence‐based practice educational interventions and 1 article was on evidence‐informed practice educational intervention. Hence, these articles were excluded as they did not meet the inclusion criteria. Authors' Conclusions There is an urgent need for primary studies evaluating the relative effectiveness of evidence‐informed practice and evidence‐based practice educational interventions targeted at improving undergraduate healthcare students' competencies regarding the application of evidence into practice. Such studies should be informed by current literature on the concepts (i.e., evidence‐informed practice and evidence‐based practice) to identify the differences, similarities, as well as appropriate content of the educational interventions. In this way, the actual effect of each of the concepts could be determined and their effectiveness compared.

Abstract Background Achondroplasia, caused by a pathogenic variant in the fibroblast growth factor receptor 3 gene (FGFR3), leads to significant multisystem complications across the lifespan that may affect the health‐related quality of life (HRQoL) of individuals and families living with the condition. Methods The objective of this qualitative study was to describe the HRQoL of children and adolescents with achondroplasia and their caregivers. Thirty‐four caregivers and 12 adolescents from the United States and Spain participated in one of eight focus groups or completed an individual interview, which was audio‐recorded and transcribed. Thematic analysis of qualitative data was performed to identify commonly occurring themes pertaining to HRQoL. Results Caregivers and adolescents described challenges with physical functioning and medical complications due to achondroplasia. Key challenges included difficulties performing activities of daily living, issues of accessibility, bullying, or unwanted attention in public, and negative effects on self‐esteem. Caregivers were concerned about accessing appropriate medical care for their child, and also reported experiencing financial, relational, and emotional challenges in their families. Achondroplasia also affected individuals and their families in positive ways, including increasing empathy, receiving positive attention, and feeling supported by the achondroplasia community. Conclusions These findings underscore the importance of regular assessments of HRQoL and the provision of psychosocial support to affected children and families.

Abstract This is the protocol for a Campbell review. The objectives are as follows: To investigate the evidence on the effectiveness of education programmes in improving the knowledge of back health, ergonomics and postural behaviour in University students.

Background Women with a history of obstetric complications are at increased risk of cardiovascular disease, but whether they should be specifically targeted for cardiovascular disease (CVD) risk screening is unknown. Methods and Results We used linked data from the Norwegian HUNT (Trøndelag Health) Study and the Medical Birth Registry of Norway to create a population‐based, prospective cohort of parous women. Using an established CVD risk prediction model (A Norwegian risk model for cardiovascular disease), we predicted 10‐year risk of CVD (nonfatal myocardial infarction, fatal coronary heart disease, and nonfatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and high‐density lipoprotein cholesterol, smoking, antihypertensive use, and family history of myocardial infarction). Predicted 10‐year CVD risk scores in women aged between 40 and 60 years were consistently higher in those with a history of obstetric complications. For example, when aged 40 years, women with a history of preeclampsia had a 0.06 percentage point higher mean risk score than women with all normotensive deliveries, and when aged 60 years this difference was 0.86. However, the differences in the proportion of women crossing established clinical thresholds for counseling and treatment in women with and without a complication were modest. Conclusions Findings do not support targeting parous women with a history of pregnancy complications for CVD screening. However, pregnancy complications identify women who would benefit from primordial and primary prevention efforts such as encouraging and supporting behavioral changes to reduce CVD risk in later life.

Abstract Objective Antitumor viral vaccines, and more particularly poxviral vaccines, represent an active field for clinical development and translational research. To improve the efficacy and treatment outcome, new viral vectors are sought, with emphasis on their abilities to stimulate innate immunity, to display tumor antigens and to induce a specific T‐cell response. Methods We screened for a new poxviral backbone with improved innate and adaptive immune stimulation using IFN‐α secretion levels in infected PBMC cultures as selection criteria. Assessment of virus effectiveness was made in vitro and in vivo. Results The bovine pseudocowpox virus (PCPV) stood out among several poxviruses for its ability to induce significant secretion of IFN‐α. PCPV produced efficient activation of human monocytes and dendritic cells, degranulation of NK cells and reversed MDSC‐induced T‐cell suppression, without being offensive to activated T cells. A PCPV‐based vaccine, encoding the HPV16 E7 protein (PCPV‐E7), stimulated strong antigen‐specific T‐cell responses in TC1 tumor‐bearing mice. Complete regression of tumors was obtained in a CD8+ T‐cell‐dependent manner after intratumoral injection of PCPV‐E7, followed by intravenous injection of the cancer vaccine MVA‐E7. PCPV also proved active when injected repeatedly intratumorally in MC38 tumor‐bearing mice, generating tumor‐specific T‐cell responses without encoding a specific MC38 antigen. From a translational perspective, we demonstrated that PCPV‐E7 effectively stimulated IFN‐γ production by T cells from tumor‐draining lymph nodes of HPV+‐infected cancer patients. Conclusion We propose PCPV as a viral vector suitable for vaccination in the field of personalised cancer vaccines, in particular for heterologous prime‐boost regimens.

Abstract Early‐onset Alzheimer's disease (EOAD) is generally known as a dominant disease due to highly penetrant pathogenic mutations in the amyloid precursor protein, presenilin 1 and 2. However, they explain only a fraction of EOAD patients (5% to 10%). Furthermore, only 10% to 15% of EOAD families present with clear autosomal dominant inheritance. Studies showed that only 35% to 60% of EOAD patients have at least one affected first‐degree relative. Parent–offspring concordance in EOAD was estimated to be

Abstract Aim The aim of this systematic review is to evaluate and synthesize published and unpublished literature on the effectiveness of a diverse range of exercise programs on back shape/posture, balance, falling and fear of falling in older people with hyperkyphosis. Objectives The objective of this systematic review is to determine the effects of difference exercise programs on back shape/posture, balance, falling and fear of falling in older adults with hyperkyphosis.

Background Women with hypertensive pregnancy disorders have adverse levels of cardiovascular risk factors. It is unclear how this adverse risk factor profile evolves during adult life. We compared life course trajectories of cardiovascular risk factors in women with preeclampsia or gestational hypertension in their first pregnancy to normotensive women. Methods and Results We linked information on cardiovascular risk factors from the population‐based HUNT (Nord‐Trøndelag Health Study) surveys with pregnancy information from the Medical Birth Registry of Norway. Trajectories of cardiovascular risk factors were constructed for 22 308 women with a normotensive first pregnancy; 1092 with preeclampsia, and 478 with gestational hypertension in first pregnancy. Already before first pregnancy, women with preeclampsia in their first pregnancy had higher measures of adiposity, blood pressure, heart rate, and serum lipids and glucose compared with women with a normotensive first pregnancy. After first pregnancy, there was a parallel development in cardiovascular risk factor levels, but women with a normotensive first pregnancy had a time lag of >10 years compared with the preeclampsia group. There were no clear differences in risk factor trajectories between women with gestational hypertension and women with preeclampsia. Conclusions Women with hypertensive pregnancy disorders in their first pregnancy had an adverse cardiovascular risk factor profile before pregnancy compared with normotensive women, and the differences persisted beyond 50 years of age. Hypertensive disorders in pregnancy signal long‐term increases in modifiable cardiovascular risk factors, and may be used to identify women who would benefit from early prevention strategies.