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Hanna Sandelowsky,1– 3 Björn Ställberg,4 Fredrik Wiklund,5 Gunilla Telg,6 Sofie de Fine Licht,6 Christer Janson7 1Karolinska Institutet, Department of Medicine, Division of Clinical Epidemiology, Solna, Sweden; 2Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Solna, Sweden; 3Academic Primary Health Care Centre, Region Stockholm, Sweden; 4Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 5Statisticon AB, Uppsala, Sweden; 6AstraZeneca Nordic, Södertälje, Sweden; 7Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, SwedenCorrespondence: Hanna Sandelowsky, Karolinska Institutet, Department of Medicine, Division of Clinical Epidemiology, Solna, Sweden, Tel +46738902565, Email hanna.sandelowsky@ki.seBackground: Symptom control has not improved in Swedish asthma patients during the last two decades. Guidelines recommend annual reviews for asthma patients treated with maintenance inhaled corticosteroids (ICS). We aimed to describe how visit patterns in an ICS-treated asthma population in Sweden were related to applicable asthma guidelines.Methods: Swedish electronic health data for incident asthma patients, ≥ 18 years, with at least one ICS collection (index date) between 2006 and 2017 were included. Exacerbations were defined as hospitalizations, emergency visits, or collection of oral corticosteroids (OCS). Probability of an asthma-related regular follow-up visit and probability of a follow-up visit after an exacerbation, both within 15 months, were estimated using the cumulative incidence function, time-to-event analysis, and incident rate ratios.Results: In 51,349 asthma patients (mean age 47.6 years, 63% females), 17,573 had a regular asthma visit in primary or secondary care within 15 months after the index, yielding an overall probability of a visit of 37.4%. Patients with a follow-up visit had higher ICS collection and lower OCS collection than patients without regular visits. Among 22,097 patients with acute exacerbations, the probability of a visit within 15 months after an exacerbation was 31.0%. The probability of having a visit increased during the study period.Conclusion: Only one-third of ICS-treated asthma patients, regardless of asthma severity, had a regular or post-exacerbation follow-up visit within a 15-month period. The consequences of this lack of adherence to guidelines need further evaluation to secure optimal asthma management.Keywords: asthma, disease management, follow-up visit, exacerbation

Abstract Background Elder abuse is underreported and undertreated. Methods for prevention and intervention are being developed, but the knowledge guiding such measures is often insufficiently based on the victims’ own voices due to a paucity of studies. The aim of this study was therefore to explore experiences of elder abuse among the victims themselves. Methods Consecutive inpatients ≥ 65 years of age at a hospital clinic in Sweden were invited to participate, and 24 victims of elder abuse were identified. Semi-structured qualitative interviews were conducted, and transcripts were analyzed using qualitative content analysis. Results The analysis generated four themes that together give a comprehensive picture of elder abuse from the participants’ subjective perspectives. The participants’ experiences of abuse were similar to previous third-party descriptions of elder abuse and to descriptions of abuse among younger adults, but certain aspects were substantially different. Vulnerability due to aging and diseases led to dependance on others and reduced autonomy. Rich descriptions were conveyed of neglect, psychological abuse, and other types of abuse in the contexts of both care services and family relations. Conclusions Elder abuse is often associated with an individual vulnerability mix of the aging body, illnesses, and help dependence in connection with dysfunctional surroundings. As individual differences of vulnerability, exposure to violence, and associated consequences were so clear, this implies that components of prevention and intervention should be individually tailored to match the needs and preferences of older victims.

Abstract Background Individuals describe both short and long term consequences after an anterior cruciate ligament (ACL) injury. Functional impairments are well documented while psychological, social and contextual factors need to be further investigated. By the use of a qualitative method incorporating a biopsychosocial lens, we aimed to explore individuals’ experiences of living and coping with an ACL rupture with a specific focus on experiences significant to overall life, activity in daily living and physical activity more than one year after injury. Methods Twelve participants were chosen strategically by a purposive sampling. Four men and eight women (19–41 years) with an ACL rupture 2–25 years ago, were included. Semi-structured interviews were used and analysed with qualitative content analysis. Results The results consisted of one overarching theme: ‘A strenuous process towards regaining balance’ which built on three categories ‘Disrupted knee’, ‘Disrupted me’ and ‘Moving forward with new insights’. The overarching theme captures the participants’ experiences of a strenuous process towards regaining both physical and mental balance in the aftermath of an ACL injury. The results illuminate how participants were forced to cope with a physically ‘disrupted knee’, as well as facing mental challenges, identity challenges and a ‘disrupted me’. By gradual acceptance and re-orientation they were moving forward with new insights – although still struggling with the consequences of the injury. Conclusions Individuals with an ACL injury experience both physical, psychological, and social challenges several years after injury. In addition to the functional impairments, diverse psychological, social and contextual ‘disruptions’ and struggles may also be present and influence the rehabilitation process. It is important that physiotherapists identify individuals who face such challenges and individually tailor the rehabilitation and support. A biopsychosocial approach is recommended in the clinical practice and future studies focusing on psychosocial processes in the context of ACL rehabilitation are warranted.

Background: For females undergoing cystectomy and urinary diversion, decreases in sexual and urinary functions can have a significant impact on quality of life. Pelvic organ–preserving (POP) radical cystectomy (RC) has been proposed as an approach to improve postoperative functional outcomes. Objective: To evaluate postoperative functional outcomes of a robotic approach for female POP RC with intracorporeal urinary diversion. Design, setting, and participants: This was a multicenter retrospective study evaluating sexual, urinary, and oncological outcomes for sexually active females undergoing POP robot-assisted RC for ≤T2 bladder cancer. Exclusion criteria included multifocal, trigonal, or locally advanced tumors. Surgical procedure: We describe a step-by-step technique for POP robot-assisted RC with intracorporeal urinary diversion. Measurements: The primary outcome of the study was evaluation of sexual and urinary functions following surgery. Oncological outcomes were evaluated as a secondary endpoint. Results and limitations: Our study included 23 females who underwent POP robot-assisted RC between 2008 and 2020 with intracorporeal neobladder (87%) or ileal conduit (13%) reconstruction. The median follow-up was 20 mo. A postoperative sexual function questionnaire was completed by 15 patients (65%). Of those, 13 (87%) resumed sexual activity at a median of 6 mo after surgery. Of the patients with a neobladder, 14 (70%) achieved daytime continence and 16 (80%) achieved nighttime continence. Cancer-specific and overall survival were both 91%. The results are limited by their retrospective nature. Conclusions: POP robot-assisted RC with orthotopic neobladder allows a majority of female patients to return to sexual activity after surgery. This approach should be considered for selected sexually active women. Patient summary: We evaluated 23 women with bladder cancer who underwent surgical removal of the bladder with preservation of their reproductive organs. Following this surgery, a majority of patients resumed sexual activity. For selected patients, this technique can be performed without compromising cancer control.

ABSTRACT Forming therapeutic relationships is considered important within psychiatric and mental health nursing. One way of achieving this is through social interaction when engaging in joint activities. However, introducing and using nursing interventions based on joint activities in psychiatric inpatient care has proven challenging. Since staff motivation is important, researching the meaning of engaging in joint activities from the nursing professional's point of view can provide information that is relevant in this area. This study aims to illuminate the meaning of participating in joint activities with patients as narrated by nursing professionals in psychiatric inpatient care. Narrative interviews with 14 nursing professionals with experience from psychiatric inpatient care were conducted. Data were analysed using phenomenological hermeneutics and reported following the consolidated criteria for reporting qualitative research (COREQ) guidelines. Results illuminate that engaging in joint activities means being open to a process of learning. Four themes contributed to this understanding: Struggling with uncertainty, discovering aspects of the other, unfolding paths to self‐fulfilment and sharing personhood. Being open to a process of learning means being willing to face uncertainty when engaging in activities as well as being open to learning about oneself as well as the other. Through openness to this process of learning, a sharing of personhood can be achieved, where the nursing professional and the patient approach becoming two persons. Illuminating the meaning of joint activities from the nursing professionals' perspective may provide valuable insights related to introducing and using interventions focusing on joint activities. [ABSTRACT FROM AUTHOR]

This study explores the adoption of robot process automation (RPA) technology among micro and small audit entities. Whereas studies on RPA adoption have focused on the Big 4, this study contributes by examining (1) micro and small independent audit firms and (2) small, provincial offices affiliated with large audit firms such as the Big 4. The contribution also includes insight into the autonomy of RPA adoption of these small, provincial-affiliated offices. By drawing upon innovation adoption theory, we analyze interview data concerning partners' and managers' assessments of adoption decisions. The nonadoption of RPA is explained by three lags: a standardization–regulation lag, a supply side (auditor) lag, and a demand side (audit client) lag. The small, provincial offices affiliated with large audit firms experience autonomy regarding RPA adoption when they carry out audit assignments on their local clients: "Big 4 auditor" is not a homogenous concept in this respect. [ABSTRACT FROM AUTHOR]

The faster-Z/X hypothesis predicts that sex-linked genes should diverge faster than autosomal genes. However, studies across different lineages have shown mixed support for this effect. So far, most analyses have focused on old and well-differentiated sex chromosomes, but less is known about the divergence of more recently acquired neo-sex chromosomes. In Lepidoptera (moths and butterflies), Z-autosome fusions are frequent, but the evolutionary dynamics of neo-Z chromosomes have not been explored in detail. Here, we analyzed the faster-Z effect in Leptidea sinapis , a butterfly with three Z chromosomes. We show that the neo-Z chromosomes have been acquired stepwise, resulting in strata of differentiation and masculinization. While all Z chromosomes showed evidence of the faster-Z effect, selection for genes on the youngest neo-Z chromosome (Z3) appears to have been hampered by a largely intact, homologous neo-W chromosome. However, the intermediately aged neo-Z chromosome (Z2), which lacks W gametologs, showed fewer evolutionary constraints, resulting in particularly fast evolution. Our results therefore support that neo-sex chromosomes can constitute temporary hot-spots of adaptation and divergence. The underlying dynamics are likely causally linked to shifts in selective constraints, evolution of gene expression, and degeneration of W-linked gametologs which gradually expose Z-linked genes to selection. [ABSTRACT FROM AUTHOR]

Background α1-Adrenergic receptor antagonists are commonly used to treat benign prostatic hyperplasia. Preclinical studies suggest that they induce cell death and inhibit tumor growth. This study evaluated the risk of prostate cancer death in men using α1-adrenergic receptor antagonists. Methods A population-based cohort study in Stockholm, Sweden (January 1, 2007, to December 31, 2019) included 451 779 men with a prostate-specific antigen test result. Study entry was 1 year after the first prostate-specific antigen test. Men were considered exposed at their second filled prescription. The primary outcome was prostate cancer mortality. Secondary outcomes were all-cause mortality and prostate cancer incidence. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all outcomes. Inverse-probability weighting with marginal structural models accounted for time-dependent confounders. Results Of 351 297 men in the final cohort, 39 856 (11.3%) were exposed to α1-adrenergic receptor antagonists. Median (interquartile range) follow-up for prostate cancer mortality was 8.9 (5.1-10.9) years; median (interquartile range) exposure time to α1-adrenergic receptor antagonists was 4.4 (2.0-7.6) years. There was no evidence of an association between α1-adrenergic receptor antagonist use and prostate cancer mortality, all-cause mortality, or high-grade prostate cancer. α1-Adrenergic receptor antagonist use was associated with an increased risk of prostate cancer (HR = 1.11, 95% CI = 1.06 to 1.17) and low-grade prostate cancer (HR = 1.22, 95% CI = 1.11 to 1.33). Men whose prostate cancer was treated with α1-adrenergic receptor antagonists underwent more frequent prostate-specific antigen testing. Conclusions Our findings show no significant association between α1-adrenergic receptor adrenoceptor antagonist exposure and prostate cancer mortality or high-grade prostate cancer. Although the preclinical evidence indicates a potential chemopreventive effect, this study's findings do not support it. [ABSTRACT FROM AUTHOR]

Vertebral compression fractures (VCFs) are common and indicate a high future risk of additional osteoporotic fractures. However, many VCFs are unreported by radiologists, and even if reported, many patients do not receive treatment. The purpose of the study was to evaluate a new artificial intelligence (AI) algorithm for the detection of VCFs and to assess the prevalence of reported and unreported VCFs. This retrospective cohort study included patients over age 60 yr with an abdominal CT between January 18, 2019 and January 18, 2020. Images and radiology reports were reviewed to identify reported and unreported VCFs, and the images were processed by an AI algorithm. For reported VCFs, the electronic health records were reviewed regarding subsequent osteoporosis screening and treatment. Totally, 1112 patients were included. Of these, 187 patients (16.8%) had a VCF, of which 62 had an incident VCF and 49 had a previously unknown prevalent VCF. The radiologist reporting rate of these VCFs was 30% (33/111). For moderate and severe (grade 2–3) VCF, the AI algorithm had 85.2% sensitivity, 92.3% specificity, 57.8% positive predictive value, and 98.1% negative predictive value. Three of 30 patients with reported VCFs started osteoporosis treatment within a year. The AI algorithm had high accuracy for the detection of VCFs and could be very useful in increasing the detection rate of VCFs, as there was a substantial underdiagnosis of VCFs. However, as undertreatment in reported cases was substantial, to fully realize the potential of AI, changes to the management pathway outside of the radiology department are imperative. Lay Summary: Vertebral compression fractures (VCFs) are the most common osteoporotic fractures. However, they often go undetected leading to a high risk of further fractures. In this study, we tested a new artificial intelligence (AI) algorithm to detect VCFs in abdominal CT scans in patients over 60 yr of age and assessed how often VCFs were missed by radiologists. We found that VCFs were underreported, with only 30% being identified by the radiologists. The AI algorithm showed promising results and had high accuracy for detecting VCFs. However, many patients with a detected VCF still did not receive treatment. The results suggest that AI could increase the detection rate of VCFs, but also highlight the need for changes beyond radiology to ensure that patients with detected fractures are appropriately treated. [ABSTRACT FROM AUTHOR]

The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium‐induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200‐fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo‐oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation. [ABSTRACT FROM AUTHOR]

Given previous findings on test enhanced learning, the present study examined the implementation of this practice in terms of quizzing, during the progress of a course. After completing the university course, 88 Swedish teacher students were asked to answer an adapted Retrieval Practice and Test Anxiety Survey. The results showed that students perceived quizzing to improve learning, and reduce test anxiety. Nonetheless, based on students' misconceptions regarding why quizzing actually enhances learning, it is suggested that implications of test enhanced learning was not fully conveyed. It is for educational purpose imperative to not forget this application.

Branched-chain amino acids are critical metabolic intermediates that can indicate increased risk of cardiometabolic disease when levels are elevated or, alternatively, suggest sufficient mitochondrial energy metabolism and reserve in old age. The interpretation of BCAA levels can be context-dependent, and it remains unclear whether abnormal levels can inform prognosis. This prospective longitudinal study aimed to determine the interrelationship between mortality hazard and fasting serum BCAA levels among older men and women aged ≥65 years with or without hypertension and diabetes mellitus. At baseline (0Y), fasting serum BCAA concentration in 2997 community-living older men and women were measured. Approximately 14 years later (14Y), 860 study participants returned for repeat measurements. Deaths were analysed and classified into cardiovascular and non-cardiovascular causes using International Classification of Diseases codes. Survival analysis and multivariable Cox regression were performed. During a median follow-up of 17Y, 971 (78.6%) non-cardiovascular and 263 (21.4%) cardiovascular deaths occurred among 1235 (41.2%) deceased (median age, 85.8 years [IQR 81.7–89.7]). From 0Y to 14Y, BCAA levels declined in both sexes, whereas serum creatinine concentration increased (both p < 0.0001). In older adults without hypertension or diabetes mellitus, the relationship between mortality hazard and BCAA level was linear and above-median BCAA levels were associated with improved survival, whereas in the presence of cardiometabolic disease the relationship was U-shaped. Overall, adjusted Cox regression determined that each 10% increment in BCAA concentration was associated with a 7% (p = 0.0002) and 16% (p = 0.0057) reduction in mortality hazard estimated at 0Y and 14Y, respectively. Our findings suggested that abnormally high or low (dyshomeostatic) BCAA levels among older adults with hypertension and/or diabetes mellitus were associated with increased mortality, whereas in those with neither disease, increased BCAA levels was associated with improved survival, particularly in the oldest-old.

An increased interest in health, diet, and physical activity exist among young people, in this study termed 'fitness hype'. Viewing the body and health as commodities can be understood as part of a healthism discourse. In this study, we explored how Swedish high school students perceive and negotiate the trend regarding exercise, diet and body ideals. Semi-structured interviews were conducted with ten high school students, aged 16-18 years, from various educational programs and with varying levels of physical activity. Using qualitative content analysis, we developed one overarching theme "navigating life satisfaction in the face of an 'unhealthy fitness hype'". Four additional, interrelated categories showed how the young people negotiated this developing trend through: (1) the quest for social recognition and value, (2) social media sets the standards, (3) the paradox of strong and skinny as the new standard, and (4) the need for new safety nets. Our results highlight the young people's perceptions of an excessive and influential focus on health and exercise in contemporary society. They described a fitness hype as exorbitant and unhealthy ideals of body and exercise, and understood this as problematic. Social media was seen as contributing to this hype as a powerful arena for 'the quest for social recognition and value'. While not all the young people felt negatively affected by the fitness hype, they perceived its influence on their lives. Further, body and fitness ideals were gendered. Teenage girls faced the paradox of shaping themselves as 'strong "and" skinny'. Social ties were recognized as an important safety net, particularly classmates, sports mates, and coaches. Knowledge of these problems from the perspective of young people is crucially needed among health professionals and educators. Further research should explore additional support strategies, and young people's experiences of fitness hype among additional youth groups.

Abstract Background Physiotherapists need to use pedagogical approaches and strategies in their work. However, there is no previous definition of what a pedagogical approach in physiotherapy means neither in general nor specifically to dementia. The purpose of this study was therefore to gain greater insight into physiotherapists’ pedagogical approach to dementia by investigating physiotherapists’ views and working methods in contact with older people with dementia, relatives, and nursing staff in elderly care. Methods This was a qualitative study with an inductive approach. Semi-structured individual interviews were conducted with 15 physiotherapists with experience of working with older people with dementia in elderly care. The interviews were analyzed with qualitative content analysis. Results The term “pedagogical approach” could sometimes be experienced as “vague” or “hard to grasp”. Our research nonetheless identified one overarching theme To see, meet and adapt which is based on insights from the interviews grouped in to five categories. This theme can be seen as an expression of the physiotherapists’ pedagogical approach in contact with older people with dementia, relatives, and nursing staff. It captures the participants’ desire to always see the person in front of them, meet them where they are and adapt their own way of working accordingly. Creating a trusting relationship was described as important and made it easier for the participants to adapt their working methods. The participants’ adaptations could apply to the way they communicated with people with dementia, and how they organized tutoring/education of relatives and nursing staff to maximize learning. Learning through experience and reflection was described as a key to advancing the pedagogical approach and the participants experienced their own learning as constantly ongoing. Conclusions This study provides increased understanding into physiotherapists’ pedagogical approach in contact with older people with dementia, relatives, and nursing staff in elderly care and shows that learning through experience and reflection can contribute to the development of the pedagogical approach. Thus, opportunity for reflection should be accommodated in the physiotherapists’ work. The importance of more pedagogical education for physiotherapists both in bachelor and master level were also highlighted. Increasing mobility and physical activity in older people with dementia is important since physical inactivity and sedentary behavior is common. Future research may be directed at further exploring physiotherapists’ pedagogical approach in tutoring/education of nursing staff, with the aim of increasing physical activity among older people with dementia.

Abstract Background It is important to support ageing home care nurses (HCNs) to remain in work for longer, since the need for home care services is increasing. Personal resources such as self-efficacy belief contribute to work ability, as does work motivation. Few studies have targeted the ageing workers’ self-efficacy belief to manage their final working years. This study explores ageing HCNs’ work motivation, and occupational self-efficacy, i.e. belief in one’s capabilities, to continue working until expected retirement age. Methods The design of the study is exploratory using a mixed method with a qualitative to quantitative approach. A total of 234 HCNs answered four open-ended questions from a cross-sectional survey, regarding their work motivation and self-efficacy beliefs. First, data was analysed using manifest qualitative content analysis. Next, a quantitative analysis was performed based on the results of the qualitative study, and the categories that emerged were quantitatively ranked. Results The open-ended questions yielded 2339 utterances. The findings showed that several categories concurrently affected both work motivation and self-efficacy belief. When they were well-functioning, they positively affected both work motivation and self-efficacy belief, and when they were insufficient, they negatively affected either or both motivation and/or belief. Meaningfulness, job satisfaction, social support, and work environmental and organizational characteristics affected work motivation most. Perceived health highly affected the self-efficacy belief to continue working until expected retirement age, as well as meaningfulness of work, support from colleagues and home care managers, and work characteristics. Conclusions Through highlighting the meaningfulness of work, and supporting the perceived health, the work community and leadership, both work motivation and self-efficacy belief to continue working might be facilitated among ageing HCNs. However, the still present draining workload must be handled.

BackgroundSwimming is a genotype-specific trigger in long QT syndrome type 1 (LQT1).ObjectiveTo examine the autonomic response to water activities in children and adolescents with LQT1.MethodsIn this cross-sectional study, LQT1 patients were age and sex matched to one healthy control subject. Electrocardiograms (ECGs) were recorded during face immersion (FI), swimming, diving, and whole-body submersion (WBS). Heart rate (HR) and heart rate variability (HRV) was measured. The high frequency (HF) component of HRV was interpreted to reflect parasympathetic activity, while the low frequency (LF) component was interpreted as reflecting the combined influence of sympathetic and parasympathetic activity on autonomic nervous modulation of the heart.ResultsFifteen LQT1 patients (aged 7-19 years, all on beta-blocker therapy) and fifteen age and sex matched non-medicated controls were included. No significant ventricular arrhythmias were observed in the LQT1 population during the water activities. Out of these 15 matched pairs, 12 pairs managed to complete FI and WBS for more than 10 seconds and were subsequently included in HR and HRV analyses. In response to FI, the LQT1 group experienced a drop in HR of 48 bpm, compared to 67 bpm in the control group (p = 0.006). In response to WBS, HR decreased by 48 bpm in the LQT1 group and 70 bpm in the control group (p = 0.007). A significantly lower PTOT (p < 0.001) and HF (p = 0.011) component was observed before, during and after FI in LQT1 patients compared with the controls. Before, during and after WBS, a significantly lower total power (p < 0.001), LF (p = 0.002) and HF (p = 0.006) component was observed in the LQT1 patients.ConclusionA significantly lower HR decrease in response to water activities was observed in LQT1 subjects on beta-blocker therapy, compared to matched non-medicated controls. The data suggests an impaired parasympathetic response in LQT1 children and adolescents. An aberrant autonomic nervous system (ANS) response may cause an autonomic imbalance in this patient group.

AimsTo objectively appraise evidence for possible adverse effects of long-term statin therapy on glucose homeostasis, cognitive, renal and hepatic function, and risk for haemorrhagic stroke or cataract.Methods and resultsA literature search covering 2000-2017 was performed. The Panel critically appraised the data and agreed by consensus on the categorization of reported adverse effects. Randomized controlled trials (RCTs) and genetic studies show that statin therapy is associated with a modest increase in the risk of new-onset diabetes mellitus (about one per thousand patient-years), generally defined by laboratory findings (glycated haemoglobin ≥6.5); this risk is significantly higher in the metabolic syndrome or prediabetes. Statin treatment does not adversely affect cognitive function, even at very low levels of low-density lipoprotein cholesterol and is not associated with clinically significant deterioration of renal function, or development of cataract. Transient increases in liver enzymes occur in 0.5-2% of patients taking statins but are not clinically relevant; idiosyncratic liver injury due to statins is very rare and causality difficult to prove. The evidence base does not support an increased risk of haemorrhagic stroke in individuals without cerebrovascular disease; a small increase in risk was suggested by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels study in subjects with prior stroke but has not been confirmed in the substantive evidence base of RCTs, cohort studies and case-control studies.ConclusionLong-term statin treatment is remarkably safe with a low risk of clinically relevant adverse effects as defined above; statin-associated muscle symptoms were discussed in a previous Consensus Statement. Importantly, the established cardiovascular benefits of statin therapy far outweigh the risk of adverse effects.

ContextRadical cystectomy continues to be associated with a significant risk of morbidity and all-cause mortality (ACM). Practice pattern data demonstrating underuse of surgery for patients with muscle-invasive and high-risk non-muscle invasive bladder cancer (BC) have been linked to the advanced age and higher comorbidity status of such patients, which suggests that rates of ACM as well as cancer-specific mortality should be incorporated into patient counseling and guideline recommendations.ObjectiveTo review the literature on risk assessment tools for preoperative comorbidity in BC that may aid in treatment decision-making.Evidence acquisitionA systematic search was conducted using Ovid and Medline according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2017 reporting on comorbidity risk assessment (CRA) tools for BC. Prospective and retrospective studies were included.Evidence synthesisThere are no published randomized control trials comparing CRA tools for BC. Patients undergoing radical cystectomy with combined high-risk comorbidity and performance scores may face up to a sevenfold greater risk of other-cause mortality compared to those with low scores. The Charlson Comorbidity Index is one of the most widely studied indices for 90-d perioperative mortality and overall and cancer-specific survival, with an area under the receiver operating characteristic curve of up to 0.810. Prospective studies of CRA tools for BC have consistently shown that patients with higher comorbidity have worse outcomes. While not specific for BC, comorbidity indices provide useful assessment of competing risks. Competing-risks assessment tools are lacking, with limited studies assessing the impact of these tools on treatment decision-making by patients and providers. We provide the impetus for incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients.ConclusionsCRA tools should be incorporated into preoperative treatment counseling and the assessment of postoperative outcomes. While retrospective evidence supports the use of CRA tools for BC, further comparative studies evaluating the effectiveness of these tools and identifying the patients most likely to benefit from a treatment according to competing-risks assessment are needed.Patient summaryIn this review we explored the clinical evidence for comorbidity risk assessment tools in bladder cancer. We found evidence to support incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients.

ObjectivesTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DesignAnalysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SettingMultiple institutions that were members of international PRACTICAL consortium.ParticipantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.Main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.ResultsIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.ConclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.

Abstract Background Children report that they do not participate in their healthcare as much as they want, despite having the lawful right to form their own views and the right to express those views freely in all matters affecting them. Children and parents appeared to be more satisfied when healthcare professionals (HCP) use a participatory style in healthcare encounters. Aim To explore how children, adolescents and young adults with Juvenile Idiopathic Arthritis (JIA) and parents of children with JIA view their participation and communication in healthcare encounters with healthcare professionals. Methods Using a qualitative study design, participatory workshops were held separately for children and young adults with JIA and parents of children with JIA. The workshop data were analysed with Graneheim and Lundman’s Qualitative Content Analysis resulting in one main theme and two subthemes. Results The theme “Feeling alienated or familiar with healthcare encounters” illuminates how children felt alienated at healthcare encounters if they found the encounters emotionally distressing. Children could withhold information regarding their health and function from both HCPs and their family and friends. The subtheme “Distancing oneself from healthcare” describe why children felt reluctant to engage in the healthcare encounters and experienced difficulty expressing how they really felt. The subtheme “Being a normal event in life” describe how children felt more comfortable over time engaging with HCPs when they knew what would happen, and felt that HCPs gave them the necessary support they needed to participate. Conclusions Children’s participation in healthcare encounters varied depending if children felt alienated or familiar to the healthcare situations. Children distance themselves and are reluctant to engage in healthcare encounters if they find them emotionally distressing and feel disregarded. Over time, children can become more familiar and at ease with healthcare situations when they feel safe and experience personal and positive encounters. When the children are prepared for the encounter, provided with the space and support they want and receive tailored help they are more enabled to participate.

Abstract Objectives The PROSE trial purpose is to investigate whether the incidence of thromboembolic—related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.—On-X) compared with a previous generation mechanical prosthesis (St Jude Medical—SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. Methods The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. Results The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. Conclusions The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Abstract Background In the current study, the approach of ‘utopia as method’ was combined with the concept ‘landscapes of care’ to explore collective imaginaries of caring landscapes in relation to young people living in rural northern Sweden, while focusing specifically on what such landscapes should ideally look like, and how various strategies could help to realise the visions. Methods The research was conducted using a modified concept mapping methodology comprising three phases of data collection and analysis. This facilitated the integration of tacit knowledge and utopian visions of young people, professionals and policymakers living and working in various parts of northern Sweden. Results The results indicated that caring landscapes should: ‘provide services responsive to young people’s wishes and needs’, ‘be organised around values of safety, equity and youth participation’, and ‘rework metro-centredness’ in order to care for, with and about rural youth. Conclusions The findings can be viewed as an imaginary reconstitution of communities in rural northern Sweden, but also as hypothetical building blocks to be used for developing caring landscapes and a ‘good countryside’ where young people have the possibility to live a good life in decent health.