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ABSTRACT Uveal melanoma (UM) and nonacral cutaneous melanoma (CM) are distinct entities with varied genetic landscapes despite both arising from melanocytes. There are, however, similarities in that they most frequently affect people of European ancestry, and high penetrance germline variants in BAP1, POT1 and CDKN2A have been shown to predispose to both UM and CM. This study aims to further explore germline variants in patients affected by both UM and CM, shedding light on the underlying genetic mechanism causing these diseases. Using exome sequencing we analysed germline DNA samples from a cohort of 83 Australian patients diagnosed with both UM and CM. Eight (10%) patients were identified that carried pathogenic mutations in known melanoma predisposition genes POT1, MITF, OCA2, SLC45A2 and TYR. Three (4%) patients carried pathogenic variants in genes previously linked with other cancer syndromes (ATR, BRIP1 and MSH6) and another three cases carried monoallelic pathogenic variants in recessive cancer genes (xeroderma pigmentosum and Fanconi anaemia), indicating that reduced penetrance of phenotype in these individuals may contribute to the development of both UM and CM. These findings highlight the need for further studies characterising the role of these genes in melanoma susceptibility. [ABSTRACT FROM AUTHOR]

Aim: To explore spouses' experiences of living with a partner suffering from non‐cardiac chest pain (NCPP). Design: An inductive qualitative study. Methods: Individual interviews (n = 10) were performed with spouses of partners having NCCP and cardiac anxiety. The analysis was performed according to Patton's guide for content analysis of qualitative data. Results: Three categories and seven subcategories were identified. First, 'a feeling of being neglected', where spouses felt ignored by healthcare professionals and excluded by their partners. Secondly, 'a tension between hope and despair' encompassed feelings of faith, support, unpreparedness for chest pain and situational frustration. Lastly, in 'a threat to ordinary life', spouses noted chest pain‐induced changes impacting daily life, finances, leisure and relationships. To conclude, NCCP in partners significantly affects their spouses emotionally and practically. Spouses felt neglected and isolated, oscillating between hope and despair and experiencing faith, powerlessness and frustration. They also faced challenges in daily life and relationships. [ABSTRACT FROM AUTHOR]

Summary: Accelerometers placed on the thigh provide accurate measures of daily physical activity types, postures and sedentary behaviours, over 24 h and across consecutive days. However, the ability to estimate sleep duration or quality from thigh‐worn accelerometers is uncertain and has not been evaluated in comparison with the 'gold‐standard' measurement of sleep polysomnography. This study aimed to develop an algorithm for sleep estimation using the raw data from a thigh‐worn accelerometer and to evaluate it in comparison with polysomnography. The algorithm was developed and optimised on a dataset consisting of 23 single‐night polysomnography recordings, collected in a laboratory, from 15 asymptomatic adults. This optimised algorithm was then applied to a separate evaluation dataset, in which, 71 adult males (mean [SD] age 57 [11] years, height 181 [6] cm, weight 82 [13] kg) wore ambulatory polysomnography equipment and a thigh‐worn accelerometer, simultaneously, whilst sleeping at home. Compared with polysomnography, the algorithm had a sensitivity of 0.84 and a specificity of 0.55 when estimating sleep periods. Sleep intervals were underestimated by 21 min (130 min, Limits of Agreement Range [LoAR]). Total sleep time was underestimated by 32 min (233 min LoAR). Our results evaluate the performance of a new algorithm for estimating sleep and outline the limitations. Based on these results, we conclude that a single device can provide estimates of the sleep interval and total sleep time with sufficient accuracy for the measurement of daily physical activity, sedentary behaviour, and sleep, on a group level in free‐living settings. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have fundamentally improved survival from advanced cutaneous melanoma. Significant efforts have been made to understand the ICI response to identify ways to further improve outcomes. One such approach has been to investigate gene expression associated with response to ICI, which has identified various immune‐related mRNA signatures, including a six‐gene IFN‐γ signature (IFN‐γ6), an expanded immune signature (IFN‐γ18), an effector T‐cell gene signature (Teff), and a Teff‐associated and IFN‐γ‐associated gene signature (Teff + IFN‐γ). Given that these signatures appear to reflect expression from T cells and the level of tumour‐infiltrating immune cells has been associated with survival, we hypothesised that the prognostic value of the signatures is not limited to ICI treatment and investigated if they were associated with survival also in patients who never received ICI. The signatures were not present in melanoma cell lines when compared with tumour samples, confirming that the signatures were likely derived from the samples' non‐tumour (immune) components. We acquired expression and survival data from five melanoma cohorts with a wide range of disease stages, treatments and metrics for survival, and correlated the expression signatures with survival. All four signatures were significantly associated (p <.05) with survival in four of five cohorts, with hazard ratios ranging from 0.69 to 0.92. We conclude that these immune signatures' association with survival is not specific to ICI‐treated patients, but present in a number of settings. [ABSTRACT FROM AUTHOR]

Acral melanoma (AM) tumors arise on the palms, soles, fingers, toes, and nailbeds. A comprehensive systematic meta‐analysis of AM genomic aberrations has not been conducted to date. A literature review was carried out to identify studies sequencing AM. Whole‐genome/exome data from 181 samples were identified. Targeted panel sequencing data from MSK‐IMPACT were included as a validation cohort (n = 92), and studies using targeted hot spot sequencing were also collated for BRAF (n = 26 studies), NRAS (n = 21), and KIT (n = 32). Statistical analysis indicated BRAF, NRAS, PTEN, TYRP1, and KIT as significantly mutated genes. Frequent copy‐number aberrations were also found for important cancer genes, such as CDKN2A, KIT, MDM2, CCND1, CDK4, and PAK1, among others. Mapping genomic alterations within the context of the hallmarks of cancer identified four components frequently altered, including (i) sustained proliferative signaling and (ii) evading growth suppression, (iii) genome instability and mutation, and (iv) enabling replicative immortality. This analysis provides the largest analysis of genomic aberrations in AM in the literature to date and highlights pathways that may be therapeutically targetable. [ABSTRACT FROM AUTHOR]

The present study aims to describe accelerometer‐assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle‐aged men and women, and to study differences between subgroups of socio‐demographic, socio‐economic, and lifestyle‐related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle‐aged men and women with at least four days of valid hip‐worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X‐BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All‐year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty‐eight percent was defined as having an "at‐risk" behavior, which included both high sedentary time and low vigorous PA. In this large population‐based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice. [ABSTRACT FROM AUTHOR]

Aim: To test the effect of nurse‐led Internet‐based cognitive behavioural therapy for insomnia (I‐CBTI), tailored for patients with cardiovascular disease (CVD), with a 6‐month follow‐up. Design: A two‐arm parallel‐group randomized controlled trial (RCT) registered at clinicaltrials.gov (NTC03938805) and reported according to the CONSORT checklist. Methods: Forty‐eight patients (mean age 72 years, 65% men) diagnosed with CVD and insomnia were randomized to either 9‐week nurse‐led I‐CBTI with support, or an Internet‐based self‐study programme without support (control group). Insomnia Severity Index (ISI) and Short Form Health Survey (SF‐12) were used as primary and secondary outcomes. Results: ISI showed a significant treatment effect of I‐CBTI compared to the control group at 9‐week follow‐up. The mean ISI score in the I‐CBTI group at 9 weeks post‐treatment was maintained at the 6‐month follow‐up. Patients' adherence to I‐CBTI was associated with a better effect on both the ISI and SF‐12. [ABSTRACT FROM AUTHOR]

Aim: To undertake a cost‐effectiveness analysis of dapagliflozin in treating high‐risk patients with type 2 diabetes mellitus (T2DM), using both directly observed events in the DECLARE‐TIMI 58 trial and surrogate risk factors to predict endpoints not captured within the trial. Methods: An established T2DM model was adapted to integrate survival curves derived from the DECLARE‐TIMI 58 trial, and extrapolated over a lifetime for all‐cause mortality, hospitalization for heart failure, stroke, myocardial infarction, hospitalization for unstable angina, and end‐stage kidney disease. The economic analysis considered the overall DECLARE trial population, as well as reported patient subgroups. Total and incremental costs, life‐years and quality‐adjusted life‐years associated with dapagliflozin versus placebo were estimated from the perspective of the UK healthcare payer. Results: In the UK setting, treatment with dapagliflozin compared to placebo was estimated to be dominant, with an expected increase in quality‐adjusted life‐years from 10.43 to 10.48 (+0.06) and a reduction in lifetime total costs from £39 451 to £36 899 (−£2552). Across all patient subgroups, dapagliflozin was estimated to be dominant, with the greatest absolute benefit in the prior heart failure subgroup (incremental lifetime costs −£4150 and quality‐adjusted life‐years +0.11). Conclusions: The results of this study demonstrate that dapagliflozin compared to placebo appears to be cost‐effective, when considering evidence reported from the DECLARE‐TIMI 58 trial, at established UK willingness‐to‐pay thresholds. The findings highlight the potential of dapagliflozin to have a meaningful impact in reducing the economic burden of T2DM and its associated complications across a broad T2DM population. [ABSTRACT FROM AUTHOR]

Protection of telomeres 1 (POT1) is a component of the shelterin complex of six subunits encoded by adrenocortical dysplasia protein homologue ( I ACD i ; also known as TPP1), I POT1 i , telomeric repeat binding factor 1 ( I TERF1 i ), telomeric repeat binding factor 2 ( I TERF2 i ), TERF1-interacting nuclear factor 2 ( I TINF2 i ) and TERF2 interacting protein ( I TERF2IP i ), which binds to single-stranded telomeric DNA to regulate telomere elongation and integrity.1 The telomerase and shelterin complexes play specific roles in telomere maintenance and prevention of activation of DNA damage response pathways at telomeres, by protecting single-stranded DNA (ssDNA) overhangs.1 Conserved oligonucleotide/oligosaccharide-binding (OB) domains in I POT1 i recognise specific ssDNA motifs with high affinity and are required for I POT1 i function.1 Acquired and inherited variants in I POT1 i that alter these OB folds are associated with longer telomeres due to disruption of shelterin function.2 Rare germline pathogenic variants in I POT1 i predispose to chronic leucocyte leukaemia (CLL), glioma, angiosarcoma, osteosarcoma, thyroid cancer, colorectal cancer and cutaneous melanoma (CM), collectively termed the POT1-tumour predisposition syndrome (POT1-TPDS; Fig 1). Proband II:1 was the only individual chosen for whole-genome sequencing (WGS) due to their extensive personal cancer history (MCC AUS244) to assess the burden of cancer risk alleles among individuals with multiple primary cancers. [Extracted from the article]

Aims: To evaluate comprehensively the safety of dapagliflozin in patients with type 2 diabetes (T2DM), with emphasis placed on potential safety concerns related to the sodium‐glucose co‐transporter‐2 inhibitor class. Methods: In the Dapagliflozin Effect on Cardiovascular Events – Thrombolysis in Myocardial Infarction 58 (DECLARE‐TIMI 58) study, 17 160 patients with T2DM were randomized to dapagliflozin or placebo and followed for a median of 4.2 years. Safety was evaluated in 17 143 patients receiving at least one dose of study drug. Results: Acute kidney injury occurred less frequently with dapagliflozin, and adverse events suggestive of volume depletion were balanced between treatment groups, both irrespective of baseline estimated glomerular filtration rate, blood pressure, diuretic or loop diuretic use (interaction P values >0.05). Fractures and malignancies were balanced between the groups, irrespective of sex, diabetes duration or smoking (interaction P values >0.05) and fewer cases of bladder cancer occurred in the dapagliflozin versus the placebo group. Diabetic ketoacidosis was very rare, but more frequent with dapagliflozin versus placebo (27 vs. 12 patients with events; P = 0.02), yet signs, symptoms and contributing factors were similar in the two groups. Major hypoglycaemia occurred less frequently with dapagliflozin versus placebo, regardless of baseline use of either insulin or sulphonylureas (interaction P values >0.05). There were more adverse events of genital infections leading to discontinuation of study drug in the dapagliflozin versus the placebo group, but serious genital infections were few and balanced between treatment groups. Urinary tract infections, acute pyelonephritis and urosepsis were also balanced between treatment groups. Conclusions: Dapagliflozin was well tolerated. The long duration and large number of patient‐years in DECLARE‐TIMI 58 comprehensively addressed previous safety questions, confirming the robust safety profile of dapagliflozin. [ABSTRACT FROM AUTHOR]

Summary : Polycythaemia vera (PV) patients have an overall comparatively favourable prognosis, but disease progression is very heterogeneous and life‐threatening thrombosis and bleedings are frequent complications in untreated disease. Moreover, transformation to more severe secondary myelofibrosis and acute myeloid leukaemia can occur. The aim of this study was to identify gene mutations that could be used together with clinical data as prognostic markers to guide treatment decisions in PV patients. A well‐characterized WHO‐defined cohort of PV patients was used. Clinical data and blood values were evaluated and a myeloid sequencing panel was used to screen for additional mutations other than the diagnostic JAK2 V617F and JAK2 exon 12 mutations. In 78% of the PV patients, at least one mutation additional to JAK2 V617F was detected. Additional mutations in genes coding for epigenetic modifiers, like TET2, DNMT3A and ASXL1, were most frequent. When correlated to overall survival, mutations in ASXL1 were significantly associated with inferior survival. In an attempt to obtain prognostic guidance in a larger number of patients, the presence of ASXL1 mutations was combined with age and vascular complications prior to diagnosis. Based on these data we were able to define three risk groups that predicted survival. [ABSTRACT FROM AUTHOR]

Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population‐based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean ± SD EPO was 11.5 ± 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR ≥60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = −0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10‐year follow‐up, 164 men had an X‐ray–verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35–1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08–1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00–2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function. © 2019 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Approximately 1%–2% of cutaneous melanoma (CM) is classified as strongly familial. We sought to investigate unexplained CM predisposition in families negative for the known susceptibility genes using next‐generation sequencing of affected individuals. Segregation of germline variants of interest within families was assessed by Sanger sequencing. Several heterozygous variants in oculocutaneous albinism (OCA) genes: TYR, OCA2, TYRP1 and SLC45A2, were present in our CM cohort. OCA is a group of autosomal recessive genetic disorders, resulting in pigmentation defects of the eyes, hair and skin. Missense variants classified as pathogenic for OCA were present in multiple families and some fully segregated with CM. The functionally compromised TYR p.T373K variant was present in three unrelated families. In OCA2, known pathogenic variants: p.V443I and p.N489D, were present in three families and one family, respectively. We identified a likely pathogenic SLC45A2 frameshift variant that fully segregated with CM in a family of four cases. Another four‐case family harboured cosegregating variants (p.A24T and p.R153C) of uncertain functional significance in TYRP1. We conclude that rare, heterozygous variants in OCA genes confer moderate risk for CM. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma accounts for at least >10% of all cancers in adolescents and young adults (AYA, 15–30 years of age) in Western countries. To date, little is known about the correlations between germline variants and somatic mutations and mutation signatures in AYA melanoma patients that might explain why they have developed a cancer predominantly affecting those over 65 years of age. We performed genomic analysis of 50 AYA melanoma patients (onset 10–30 years, median 20); 25 underwent whole genome sequencing (WGS) of both tumor and germline DNA, exome data were retrieved from 12 TCGA AYA cases, and targeted DNA sequencing was conducted on 13 cases. The AYA cases were compared with WGS data from 121 adult cutaneous melanomas. Similar to mature adult cutaneous melanomas, AYA melanomas showed a high mutation burden and mutation signatures of ultraviolet radiation (UVR) damage. The frequencies of somatic mutations in BRAF (96%) and PTEN (36%) in the AYA WGS cohort were double the rates observed in adult melanomas (Q < 6.0 × 10−6 and 0.028, respectively). Furthermore, AYA melanomas contained a higher proportion of non‐UVR‐related mutation signatures than mature adult melanomas as a proportion of total mutation burden (p = 2.0 × 10−4). Interestingly, these non‐UVR mutation signatures relate to APOBEC or mismatch repair pathways, and germline variants in related genes were observed in some of these cases. We conclude that AYA melanomas harbor some of the same molecular aberrations and mutagenic insults occurring in older adults, but in different proportions. Germline variants that may have conferred disease susceptibility correlated with somatic mutation signatures in a subset of AYA melanomas. What's new? Melanoma is a leading cause of cancer death in adolescents and young adults (AYA) in Western countries. Little is known, however, about the contribution of genetic factors to AYA melanoma risk. Here, genomic analyses show that AYA melanomas, similar to adult cutaneous melanomas, have a high mutation burden, with mutations indicative of ultraviolet radiation (UVR) damage. AYA tumors further exhibited increased somatic mutation rates in key melanoma driver genes and had a higher proportion of non‐UVR mutation signatures relative to adult melanomas. Germline variants identified in an AYA patient subset suggests a role for dysfunctional DNA maintenance in AYA melanoma susceptibility. [ABSTRACT FROM AUTHOR]

Abstract: Objective: In myeloproliferative neoplasms (MPN), interferon‐alpha (IFN‐α) is an effective treatment with disease‐modifying properties but currently with no clear predictors of treatment outcome. Recent genomewide association studies in chronic hepatitis C have found a strong influence of genetic polymorphism near the IL28B (IFNL3) gene in response to IFN‐α treatment. In this study, we sought to evaluate the prognostic impact of IL28B rs12979860, rs8099917, and rs12980275 on IFN‐α treatment response in myeloproliferative neoplasms. Method: We retrospectively evaluated 100 patients with MPN treated with IFN‐α. The hematologic treatment response on IFN‐α was compared between patients and correlated with host genetic variations in IL28B. The genotypes of IL28B were determined by allelic discrimination assays. Results: The CC genotype of rs12979860 was found significantly associated with hematologic response in polycythemia vera (PV) with a complete response (CR) in 79% (CC) compared to 48% (non‐CC), (P = .036). No association between the genotypes and treatment response on hydroxyurea was found. Conclusion: These results imply an effect of IL28B genotype on the outcome of IFN‐α treatment in MPN. [ABSTRACT FROM AUTHOR]

Aim: To describe the baseline characteristics of participants randomized in the Dapagliflozin Effect on CardiovascuLAR Events (DECLARE‐TIMI 58) trial, the pivotal study conducted to assess cardiovascular (CV) outcomes with dapagliflozin. Methods: The DECLARE‐TIMI 58 trial will analyse 17 160 patients with type 2 diabetes randomized to treatment with dapagliflozin (10 mg/d) or matching placebo. We analysed their baseline characteristics. Results: The participants’ mean ± SD age was 63.8 ± 6.8 years, 62.6% were male, and their mean ± SD diabetes duration was 11.8 ± 7.8 years, glycated haemoglobin 8.3% ± 1.2% (67 mmol/mol ± 9.7 mmol/mol) and body mass index 32.1 ± 6.0 kg/m2. Randomization included 6971 (40.6%) patients with atherosclerotic CV disease (CVD), and 10 189 (59.4%) patients with multiple risk factors (MRF) for CVD (defined as men age ≥ 55 years or women ≥60 years, with at least one of dyslipidaemia, hypertension or smoking). Patients with CVD compared with patients with MRF were younger (62.5 ± 8.1 vs 64.7 ± 5.6 years), more frequently male (72.1% vs 56.1%), less often used metformin (74.6% vs 81.2%), more often used insulin (44.2% vs 36.4%), and more frequently used statins, aspirin, clopidogrel and β‐blockers (82.2%, 71.1%, 24.7% and 66.6% vs 63.7%, 39.1%, 1.5% and 32.3%, respectively). Conclusion: The DECLARE‐TIMI 58 trial is expected to provide conclusive data on the effect of treatment with dapagliflozin in addition to standard of care, on CV outcomes in a broad patient population with type 2 diabetes and CVD or MRF for CVD. [ABSTRACT FROM AUTHOR]

Abstract: Background: In an intervention study where 221 healthy elderly persons received selenium and coenzyme Q10 as a dietary supplement, and 222 received placebo for 4 years we observed improved cardiac function and reduced cardiovascular mortality. As fibrosis is central in the aging process, we investigated the effect of the intervention on biomarkers of fibrogenic activity in a subanalysis of this intervention study. Material and Methods: In the present subanalysis 122 actively treated individuals and 101 controls, the effect of the treatment on eight biomarkers of fibrogenic activity were assessed. These biomarkers were: Cathepsin S, Endostatin, Galectin 3, Growth Differentiation Factor‐15 (GDF‐15), Matrix Metalloproteinases 1 and 9, Tissue Inhibitor of Metalloproteinases 1 (TIMP 1) and Suppression of Tumorigenicity 2 (ST‐2). Blood concentrations of these biomarkers after 6 and 42 months were analyzed by the use of T‐tests, repeated measures of variance, and factor analyses. Results: Compared with placebo, in those receiving supplementation with selenium and coenzyme Q10, all biomarkers except ST2 showed significant decreased concentrations in blood. The changes in concentrations, that is, effects sizes as given by partial eta2 caused by the intervention were considered small to medium. Conclusion: The significantly decreased biomarker concentrations in those on active treatment with selenium and coenzyme Q10 compared with those on placebo after 36 months of intervention presumably reflect less fibrogenic activity as a result of the intervention. These observations might indicate that reduced fibrosis precedes the reported improvement in cardiac function, thereby explaining some of the positive clinical effects caused by the intervention. © 2017 BioFactors, 44(2):137–147, 2018 [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to explore whether associations between self‐reported sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness differed in older community‐dwelling men and women. Design: Cross‐sectional. Methods: A community‐dwelling sample of 675 older men and women (mean age 77.7 years, SD 3.8 years) was used. All participants underwent a clinical examination by a cardiologist. Validated questionnaires were used to investigate sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness. Subjects were divided into short sleepers (≤6 hours), n = 231; normal sleepers (7–8 hours), n = 338; and long sleepers (≥9 hours), n = 61. ancovas were used to explore sex‐specific effects. Results: Depressive symptoms were associated with short sleep in men, but not in women. Fatigue was associated with both short and long sleep duration in men. No sex‐specific associations of sleep duration with daytime sleepiness or anxiety were found. Conclusion: Nurses investigating sleep duration and its correlates, or effects, in clinical practice need to take sex into account, as some associations may be sex specific. Depressive symptoms and fatigue can be used as indicators to identify older men with sleep complaints. [ABSTRACT FROM AUTHOR]

Objective The study mainly aimed at investigating possible correlations between peripheral blood counts, erythropoietin ( EPO), JAK2 V617F mutation, and vascular complications prior to diagnosis of a population-based cohort of newly diagnosed patients with myeloproliferative neoplasms ( MPN). Method The study comprises 1105 patients with polycythemia vera ( PV) and 1284 patients with essential thrombocythemia ( ET) registered in the Swedish MPN Registry. Results Vascular complications, prior to diagnosis, were registered in 37% of PV patients. In multivariate analysis, low hemoglobin was the only significant risk factor ( P=.0120). Among ET patients, 35% had encountered a vascular complication. Risk factors for thromboembolic complications in ET were identified as age>65 years, white cell count>12×109/L, and the presence of JAK2 V617F mutation ( P=.0004, P=.0038, and P=.0016, respectively). A JAK2 V617F mutation was present in 71% of ET patients with vascular complications, compared to 60% in patients without. A majority of complications were thromboembolic, in both PV and ET. Conclusion We conclude that vascular complications among newly diagnosed patients had affected more than one-third of our study population. Risk factors for vascular complications prior to diagnosis were lower hemoglobin in PV, and the presence of JAK2 V617F mutation, higher age, and leukocytosis in ET. [ABSTRACT FROM AUTHOR]

Vascular and non-vascular complications are common in patients with polycythaemia vera. This retrospective study of 217 patients with polycythaemia vera aimed to determine whether blood counts with respect to different treatments influenced the complication rate and survival. We found that 78 (36%) patients suffered from at least one complication during follow-up. Older age and elevated lactate dehydrogenase at diagnosis were found to be risk factors for vascular complications. When the vascular complication occurred, 41% of the patients with a complication had elevated white blood cells ( WBC) compared with 20% of patients without a complication ( P = 0·042). Patients treated with hydroxycarbamide ( HC; also termed hydroxyurea) experienced significantly fewer vascular complications (11%) than patients treated with phlebotomy only (27%) ( P = 0·013). We also found a survival advantage for patients treated with HC, when adjusted for age, gender and time period of diagnosis (Hazard ratio for phlebotomy-treated patients compared to HC-treated patients at 5 years was 2·42, 95% confidence interval 1·03-5·72, P = 0·043). Concerning survival and vascular complications, HC-treated patients who needed at least one phlebotomy per year were not significantly different from HC-treated patients with a low phlebotomy requirement. We conclude that complementary phlebotomy in HC-treated patients in order to maintain the haematocrit, is safe. [ABSTRACT FROM AUTHOR]

Whole-genome sequencing of matched germline and tumour pairs in a well-characterized cohort of melanoma patients allowed investigation of associations between melanoma body site, age at melanoma onset and MC1R variant status with overall mutation burden and specific base pair changes observed in the corresponding melanoma. We observed statistically significant associations between mutation burden in melanoma and body site, age at onset and MC1R genotype, for both ultraviolet radiation ( UVR) signature changes (C>T and CC> TT) and non- UVR base pair substitutions, as well as with overall variant load. [ABSTRACT FROM AUTHOR]

Intervention with selenium and coenzyme Q10 have recently been found to reduce mortality and increase cardiac function. The mechanisms behind these effects are unclear. As selenium and coenzyme Q10 is involved in the anti-oxidative defence, the present study aimed to evaluate effects of selenium and coenzyme Q10 on copeptin and adrenomedullin as oxidative stress biomarkers. Therefore 437 elderly individuals were included and given intervention for 4 years. Clinical examination and blood samples were undertaken at start and after 18 and 48 months. Evaluations of copeptin and MRproADM changes were performed using repeated measures of variance. Cardiovascular mortality was evaluated using a 10-year-period of follow-up, and presented in Kaplan-Meier plots. A significant increase in copeptin level could be seen in the placebo group during the intervention period (from 9.4 pmol/L to 15.3 pmol/L), compared to the active treatment group. The difference between the groups was confirmed in the repeated measurement of variance analyses (P=0.031) with less copeptin increase in the active treatment group. Furthermore, active treatment appeared to protect against cardiovascular death both in those with high and with low copeptin levels at inclusion. Less increase of MR-proADM could also be seen during the intervention in the active treatment group compared to controls (P=0.026). Both in those having an MR-proADM level above or below median level, significantly less cardiovascular mortality could be seen in the active treatment group (P=0.0001, and P=0.04 respectively). In conclusion supplementation with selenium and coenzyme Q10 during four years resulted in less concentration of both copeptin and MRproADM. A cardioprotective effect of the supplementation was registered, irrespective of the initial levels of these biomarkers, and this protection was recognized also after 10 years of observation. [ABSTRACT FROM AUTHOR]

The article discusses the performance of a molecular diagnostics assay which detects MPL mutations in a single reaction. Topics discussed include multiplex polymerase chain reaction (PCR) and capillary electrophoresis for MPL mutation screening, the inclusion of a mutation-specific primer for W515R gene and the variable sensitivity of the assay for different MPL mutations.

ABSTRACT Thermal degradation of poly[( R)−3-hydroxybutyric acid] (PHB) during melt mixing results in random chain scission that produces shorter polymer chains containing crotonic and carboxyl end groups. One way of preventing this serious reduction of molar mass is to add agents that react with at least two of the newly generated end groups. Different types of commercially available additives known to react with carboxyl group, namely bis(3,4-epoxycyclohexylmethyl) adipate (BECMA), 2,2'-bis(2-oxazoline) (BOX), trimethylolpropane tris(2-methyl-1-aziridinepropionate) (PETAP), triphenyl phosphate (TPP), tris(nonylphenyl) phosphate (TNPP), polycarbodiimide (PCDI), and poly(methyl metharylate- co-glycidyl methacrylate) (GMA.MMA) were mixed with PHB by cocasting from solution in chloroform. Dynamic rheology as well as measurements of molar masses before and after dynamic analysis was used to evaluate the effect of the additives on the melt stability of PHB. Measurements of the dynamic shear modulus and the molar mass of molten PHB with the additives PCDI and GMA.MMA showed a minor improvement on the thermal stability. Furthermore, TPP and TNPP did not affect the thermal stability of PHB, whereas the presence of BECMA, BOX, and PETAP gave a strong decrease of the dynamic modulus compared with neat PHB. © 2014 The Authors Journal of Applied Polymer Science Published by Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41836. [ABSTRACT FROM AUTHOR]

We evaluate the detection performance of several commercial interference detectors and of a detector that uses the automatic gain control (AGC) level as a test statistic. The evaluations are based on actual measurements of GPS signals and different types of jamming signals, and were performed at the Vidsel test range in northern Sweden. The AGC detector and the Chronos CTL-3500 were shown to work well for all types of jamming signals. The J-alert was able to detect a wideband (20 MHz) signal but not the narrow band (<2 MHz) signals. By contrast, the jamming indicator on a Ublox 6H receiver was only able to detect a slowly varying modulated CW signal, but not signals with larger bandwidth (>2 MHz). We confirmed that C/N0-based Android application detectors could work well in static scenarios but are not suitable in dynamic scenarios, since they cannot distinguish between decreased GPS signal strength and increased interference. Copyright © 2015 Institute of Navigation [ABSTRACT FROM AUTHOR]

The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients ( n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population ( n = 9 340 682). Median overall survival for non-high-dose treated patients was 2·8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4·9 years) compared to conventional treatment (2·3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6·9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment. [ABSTRACT FROM AUTHOR]

Melanoma of unknown primary ( MUP) is an uncommon phenomenon whereby patients present with metastatic disease without an evident primary site. To determine their likely site of origin, we combined exome sequencing from 33 MUPs to assess the total rate of somatic mutations and degree of UV mutagenesis. An independent cohort of 91 archival MUPs was also screened for 46 hot spot mutations highly prevalent in melanoma including BRAF, NRAS, KIT, GNAQ, and GNA11. Results showed that the majority of MUPs exhibited high somatic mutation rates, high ratios of C>T/G>A transitions, and a high rate of BRAF (45 of 101, 45%) and NRAS (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun-exposed melanomas. These data suggest that a significant proportion of MUPs arise from regressed or unrecognized primary cutaneous melanomas or arise de novo in lymph nodes from nevus cells that have migrated from the skin. [ABSTRACT FROM AUTHOR]

Three hundred and twenty-seven patients from two population-based cohorts with an established diagnosis of polycythaemia vera were studied for prognostic risk factors for survival and leukaemia in a long-term survey. The relative survival ( RS) was 72% and 46% at 10 and 20 years respectively, from the time of diagnosis. Multivariate analysis identified age >70 years, white blood cell count >13 × 109/l and thrombo-embolism at diagnosis as independent risk factors. Patients with two or three of these factors had a 10 year RS of 26%, compared with 59% and 84% in patients with one and no risk factors, respectively. Age and leucocyte count are the main predicting factors for survival in polycythaemia vera. [ABSTRACT FROM AUTHOR]

Aims Heart failure (HF) patients frequently suffer from episodes of deterioration and may need medical treatment. An adequate reaction from the patient is needed to decrease the delay between the onset of deterioration and consulting a medical professional (i.e. consulting behaviour). The aim of the present study was to evaluate whether depressive symptoms are associated with the duration of the delay between the onset of symptoms of worsening HF and hospitalization, and to examine how consulting behaviour correlates to depressive symptoms and delay in HF patients. Methods and results Data on the time between the onset of symptoms of worsening HF and hospitalization, depressive symptoms, and self-care behaviour were collected in 958 HF patients (37% female; age 71 ± 11 years; New York Heart Association functional class II–IV), using validated questionnaires. The median delay time of the total sample was 72 h (ranging from 0 to 243 days). Patients with depressive symptoms delayed longer compared with those without depressive symptoms (120 vs. 54 h, P= 0.001). Patients with depressive symptoms had a 1.5 times higher risk for a delay of ≥72 h, independent of demographic and clinical variables (P= 0.008). Consulting behaviour did not correlate with depressive symptoms but was weakly associated with delay (r= −0.07, P= 0.03). Conclusions Heart failure patients with depressive symptoms have a significantly longer delay between HF deterioration and hospital admission. Interventions designed to improve the consulting behaviour in HF patients with depressive symptoms may have a limited effect on delay. Further research is needed to obtain more insight into the mechanisms underlying the relationship between delay and depression. [ABSTRACT FROM AUTHOR]

The Philadelphia chromosome-negative (Ph-) chronic myeloproliferative neoplasms include the three well-known clinical entities polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Over time, patients with ET and PV may develop myelofibrosis (MF), and all three entities carry a risk of transformation into acute myeloid leukemia (AML). In a population-based survey during 1983-1999, we studied a total of 358 patients who were diagnosed with ET and PV in the city of Gothenburg, Sweden. At the time of diagnosis, evaluable bone marrow biopsy material was available from 280 of these patients. The current work was aimed at investigating the impact of peripheral blood counts, spleen size, and bone marrow biopsy findings at diagnosis on long-term survival and the risk of development of AML or MF in this well-defined unselected population. The variables evaluated were venous blood hemoglobin concentration, packed cell volume, white blood cell count, platelet count, and splenic enlargement; as to bone marrow biopsies, interest was focused on reticulin content, focal or generalized collagen formation, bone marrow cellularity, and megakaryocyte profile number. Over the median observation time of 15 yr, the patients with ET did not demonstrate any significant difference as to survival compared to the normal Swedish population (hazard ratio, 1.23; 95% confidence interval, 0.97-1.51; p = 0.089). The patients with PV, on the other hand, had a significantly shorter survival compared to general population (hazard ratio, 1.66; 95% confidence interval, 1.38-1.99; p < 0.001). A lower hemoglobin concentration at diagnosis of ET predicted poorer survival ( p = 0.0281), whereas patients with PV with splenic enlargement at diagnosis had a shorter survival ( p = 0.037). In the patients with ET, the risk of transformation to either MF or AML was significantly associated with low hemoglobin concentration and high white cell count at diagnosis ( p = 0.0037 and 0.0306, respectively). An increased reticulin content and hypercellularity in the bone marrow at diagnosis were also independent risk factors ( p = 0.0359 and 0.0103, respectively). The risk of transformation in patients with PV was significantly associated with splenic enlargement and increase in bone marrow reticulin content ( p = 0.0028 and 0.0164, respectively). [ABSTRACT FROM AUTHOR]

Aims: It is unknown whether there is an interaction between aspirin and angiotensin receptor blockers on outcomes in patients with heart failure (HF). [ABSTRACT FROM PUBLISHER]

Öhman D, Björk Y, Bratel J, Kristiansson C, Johansson P, Johansson J-E, Brune M, Hasséus B. Partially erupted third molars as a potential source of infection in patients receiving peripheral stem cell transplantation for malignant diseases: a retrospective study. Eur J Oral Sci 2010; 118: 53–58. © 2010 The Authors. Journal compilation© 2010 Eur J Oral Sci Forty-four patients with malignant diseases for which they received peripheral stem cell transplant therapy (PSCT) were retrospectively studied regarding local and systemic infection originating from around partially erupted third molars (PEMs). Twenty-two patients had one or more PEMs, while 22 patients had none. Data were retrieved from medical and dental records. Systemic and local signs of infection and treatment were assessed. We recorded the number of transplanted CD34+ blood stem cells, days with white blood cell counts < 0.5 × 109 l−1, days until engraftment, maximum level of C-reactive protein (CRP), days with fever, positive blood cultures, days taking antibiotics, days drinking < 0.5 l, days of total parenteral nutrition, days receiving intravenously administered analgesics, and number of admission days. No statistically significant difference was detected between patients with PEMs and those without PEMs regarding any of the studied parameters. Of patients with PEMs, 36% (8 of 22) developed local infections around PEMs during the PSCT period. The study indicates that PEMs pose no significant risk of causing systemic infection in patients receiving PSCT for malignant diseases but increase the risk of developing a local infection, justifying close supervision and early treatment in cases of local infection during PSCT treatment. [ABSTRACT FROM AUTHOR]

The Philadelphia chromosome-negative (Ph−) chronic myeloproliferative disorders (MPD) have an inherent tendency for transformation into acute myelogenous leukaemia (AML). The long-term rate of leukaemic transformation in unselected MPD patients was studied in well-defined MPD populations in Gothenburg, Sweden and the Côte d′Or area, Burgundy, France, respectively. Over a median observation time of 15 yr, 56 subjects (7%) out of a total of 795 patients with Ph− MPD transformed to AML. The yearly incidence of AML transformation was 0.38% in polycythaemia vera (PV), 0.37% in essential thrombocythaemia (ET) and 1.09% in idiopathic myelofibrosis (IMF). The incidence of AML development was significantly higher in IMF as compared with both PV and ET ( P = 0.002 and P = 0.02, respectively). Six of the patients who developed AML had never been treated with cytoreductive agents and two had only been exposed to interferon. In IMF, the average time from diagnosis to AML transformation was 42 ± 33 months, which was significantly shorter than for both PV and ET (88 ± 56 and 76 ± 57 months; P = 0.0075 and P = 0.027, respectively). The time from diagnosis to AML transformation appears to be a continuous event as regards all three MPD entities. It was shown that 17 out of the 18 patients with PV who developed AML were females; this was true despite the fact that the male/female ratio for the whole PV group was 146/171 (0.85). As regards ET and IMF patients who transformed to AML, the gender ratio showed slight male predominance (1.33 and 1.13, respectively). The average survival time for the 56 MPD patients who developed AML was 4.6 ± 5.5 (range 0–28) months and did not differ with respect to the three subtypes of pre-AML MPD. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Although multi-item health-related quality of life (HRQoL) instruments provide prognostic information, they are rarely used in routine clinical practice. Aim: To examine whether a single question about global perceived health (GPH) was a prognostic indicator of cardiovascular (CV) mortality over 10 years of follow-up in elderly patients with possible heart failure (HF) in primary care. Method: GPH was measured using the first question on the Short-Form-36 concerning current health status. Of the 510 patients who underwent baseline evaluation, 448 patients were included. Results: Cox proportional regression hazard analysis controlled for age, sex, NYHA class, diabetes, ischaemic heart disease, left ventricular ejection fraction and B-type natriuretic peptide plasma concentrations, showed that patients with GPH rated as “poor” or “good” were at four (HR 4.1 CI 95% 1.8–9.4) and three times (HR 3.4 CI 95% 1.4–7.8) the risk of CV mortality, respectively. Conclusion: GPH is an independent predictor of CV mortality in elderly patients with possible HF. As a complement to clinical factors when evaluating severity of HF, GPH could be an important tool for identifying patients at risk of adverse CV events and in need of improved treatment. [Copyright &y& Elsevier]

Mutations in the BRAF oncogene occur in the majority of melanomas, leading to the activation of the mitogen-activated protein kinase pathway and the transcription of downstream effectors. As BRAF and its effectors could be good melanoma therapy targets, defining the repertoire of genes that are differentially regulated because of BRAF mutational activation is an important objective. Towards this goal, we and others have attempted to determine whether a BRAF mutation-associated gene expression profile exists. Results have been mixed, with some groups reporting a BRAF-signature and another group not. Here we resolve this issue and confirm that while gene-by-gene correlations fail to reveal a specific gene(s) whose expression correlates with BRAF status, a BRAF signature can be distinguished by analysis of global expression patterns. Specifically, we have here applied support vector machine (SVM) analysis to Affymetrix microarray data from a panel of 63 melanoma cell lines. SVMs found a BRAF signature in training samples and predicted BRAF mutation status with high accuracy (AUC = 0.840) in the remaining samples. We verified this is a generalized BRAF signature by repeating the analysis in three published microarray datasets, and again found that SVMs predicted BRAF mutation well (Philadelphia: AUC = 0.788; Zurich: AUC = 0.688; Mannheim: AUC = 0.686). An ensemble of 300 SVMs trained on our data also predicted BRAF mutation status in two of the three published datasets (Philadelphia AUC = 0.778; Zurich AUC = 0.719; Mannheim AUC = 0.564). Taken together, these data support the existence of a BRAF mutation-specific expression signature. [ABSTRACT FROM AUTHOR]

Title. Obstructive sleep apnoea syndrome – patients' perceptions of their sleep and its effects on their life situation Aim. This paper reports a descriptive study of how untreated patients with obstructive sleep apnoea syndrome perceived their sleep situation and how the syndrome affected their life situation. Background. Obstructive sleep apnoea syndrome is a prevalent problem independently associated with an increased risk for hypertension, cardiovascular disease, chronic heart failure and mortality. Increased consumption of healthcare resources can often be seen among patients over a long period of time since many have been undiagnosed and untreated. Methods. A phenomenographic approach was employed. Data were collected by interviews during 2005 with 20 purposively selected participants with untreated obstructive sleep apnoea syndrome. Findings. Participants described loud snoring, frequent awakenings, dyspnoea, frustration over nocturia, fear of dying during sleep and partners’ anxiety about the apnoea, as being night-time effects of obstructive sleep apnoea syndrome. They described dry and sore throats, tiredness and daytime sleepiness, shame about falling asleep and snoring, thoughts about complications and depressed mood as daytime effects. Needs, such as increased alertness, improved ability to concentrate, improved relationship, adequate information as well as effective treatment, were described. Participants tried self-care strategies such as information-seeking about sleep disturbances and treatment, adapted sleeping routines, change of bedroom arrangements, adapted daily schedules, hyperactivity and avoidance of difficult situations. Conclusion. The perceived effects and needs, as well as tried self-care actions by the patients with obstructive sleep apnoea syndrome in this study, could be used to identify and evaluate concerns of other patients with obstructive sleep apnoea syndrome waiting for treatment. [ABSTRACT FROM AUTHOR]

Depression is common among patients with chronic heart failure (HF) and leads to more symptoms of HF, decreased quality of life, and an increased risk for premature death. Depressed HF patients also use more health care resources, which increases the economic burden on the health care system. The assessment of risk factors of depression such as age younger than 60-65 years, poor physical functioning, previous depression, poor self-efficacy, living alone, and distressful relationships, in combination with the use of depression instruments, can be helpful in detecting depression in HF patients. Unfortunately, interventions on how to relieve depression in patients with HF have not been investigated thoroughly; however, depression agents as well as HF education, social support, exercise therapy, stress management, and relaxation have been shown to be useful interventions. Because of poor outcomes, studies that examine the effectiveness and/or side effects of pharmacologic as well as nonpharmacologic interventions on depressed patients with HF are needed. [ABSTRACT FROM AUTHOR]

Chronic heart failure is a common disease accompanied by poor mental health and depression. The diagnosis of depression is based on the presence of affective, cognitive, and somatic symptoms assessed by categoric or dimensional instruments. Depression is prominent and high rates are found with dimensional instruments in hospitalized heart failure patients. Categoric instruments seem to be more reliable but are more complex to use. Because of poor outcomes, attention should also be paid to subthreshold depression. In screening for such cases, dimensional instruments might be preferable because of the risk for underestimation by categoric instruments. Dimensional instruments might also be easier to implement in daily practice but, to reduce bias, cutoff scores might need refinement according to the clinical setting. Therefore, studies that evaluate different cutoff values are needed to find a critical level of burden from a depressive symptomatology on outcomes such as mortality, hospitalizations, and quality of life. [ABSTRACT FROM AUTHOR]

The diagnosis of polycythaemia vera (PV) has been established upon sets of clinical criteria, which require the presence of absolute erythrocytosis (AE). The most recent clinical criteria for PV, published by the World Health Organization (WHO) in 2001, also required AE, and stated that the measured red cell mass (RCM) could be replaced by a surrogate marker for AE; a haemoglobin (Hb) value of>18·5 g/dl in males and>16·5 g/dl in females. The present study evaluated the potential of venous haematocrit (Hct) and Hb values as possible surrogate markers for AE in a series of 77 consecutive patients with PV and 66 patients with apparent polycythaemia (AP), in all of whom the RCM had been previously determined. In only 35% of the male PV patients would Hb values>18·5 g/dl indicate the presence of AE. Conversely, 14% of male AP patients would be misdiagnosed as having AE. A Hb > 16·5 g/dl would predict the presence of AE in 63% of the female PV patients, but 35% of female AP cases would be misdiagnosed as having AE. However, when the Hct was≥0·60 an AE was always present, and this was true for both male and female subjects. [ABSTRACT FROM AUTHOR]

Essential thrombocythaemia (ET) is a heterogeneous disorder with respect to plasma erythropoietin concentration at diagnosis and clonality of haematopoiesis. Polycythaemia rubra vera-1 (PRV-1) positivity, i.e. PRV-1 mRNA overexpression, is known to be present in the vast majority of patients with polycythaemia vera and also in some patients with ET. In the present study, PRV-1 expression was quantified by real-time polymerase chain reaction in 70 ET patients; 17 of them (24%) were found to be PRV-1 positive. Ten of the 17 PRV-1 positive ET patients had experienced thromboembolic complications compared with 14 of 53 PRV-1 negative patients, the difference between the two groups being statistically significant ( P = 0·02). In addition, the frequency of total vascular complications, thromboembolic events and major bleedings, was significantly higher in the group of PRV-1 positive as compared with PRV-1 negative ET patients ( P = 0·03). The time from diagnosis of ET to the requirement of platelet-lowering therapy was significantly shorter in PRV-1 positive compared with PRV-1 negative ET patients ( P = 0·014). It can be concluded that PRV-1 positive patients appear to suffer from a more aggressive disorder with increased risk for vascular complications and a greater need for platelet-lowering therapy, compared with PRV-1 negative ET patients. [ABSTRACT FROM AUTHOR]

Abstract: Approximately 45% of newly diagnosed patients with essential thrombocythaemia (ET) demonstrate subnormal plasma erythropoietin (EPO) concentrations, which constitutes a risk factor for occlusive vascular events. In 58 ET patients, a possible association between polycythaemia rubra vera-1 (PRV-1) overexpression and subnormal plasma EPO was investigated, which was always measured prior to the institution of platelet lowering agents. At the time when PRV-1 expression was measured, 28 of 58 (48%) ET patients had received platelet lowering treatment. PRV-1 expression was measured by quantitative real-time reverse transcription–polymerase chain reaction assay of mRNA extracted from purified peripheral blood buffy coat. The cycle threshold (CT) value of PRV-1 was determined and was divided with the CT value for the housekeeping GAPDH gene transcript. A quotient <0.93 was defined as PRV-1 positive. Of the ET patients 12 of 58 (21%) were PRV-1 positive and 19 of 58 (33%) demonstrated subnormal plasma EPO. In the 58 ET patients there was a significant association between low plasma EPO and PRV-1 positive results (P = 0.001). The 30 ET patients who had not received any platelet lowering treatment showed a significant (P = 0.005) relation between PRV-1 positivity and subnormal plasma EPO. No such relationship was present in the 28 ET patients who had received prior treatment with the above drugs (P = 0.147). [ABSTRACT FROM AUTHOR]

To evaluate and improve the quality of care provided, it is of vital importance to investigate the quality of care in the context of health care. Patient satisfaction is a significant indicator of the quality of care. Consequently, quality work includes investigations that map out patient satisfaction with nursing care. To improve the quality of nursing care, the nurse needs to know what factors influence patient satisfaction. The aim of this literature study was to describe the influences on patient satisfaction with regard to nursing care in the context of health care. In the description of nursing care, we have used Henderson's nursing care model. The results describe eight domains that have an influence on patient satisfaction with nursing care: the socio-demographic background of the patients, patients' expectations regarding nursing care, the physical environment, communication and information, participation and involvement, interpersonal relations between nurse and patient, nurses' medical–technical competence, and the influence of the health care organization on both patients and nurses. The bulk of the literature included in the study came from the UK, Sweden and the USA. This means that the results should be applicable to health care in the western world. An important implication for future research is to continue to elucidate the factors that influence satisfaction with nursing care, as seen from the patient's perspective. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions To report the clinicopathological features and epidemiology of iris melanoma in Queensland, Australia.This was a retrospective study of 86 patients with iris melanoma treated between 2001 and 2022 at the Queensland Ocular Oncology Service, Brisbane, Australia. Main outcome measures included demographics, clinical and phenotypic features, age‐adjusted incidence and relative survival.Eighty‐six patients (63% female) were included. Mean age was 54 years (range 17–82 years). The majority of patients (97%) were Caucasian, with blue eyes, fair skin and Fitzpatrick Skin Type I or II. Demographic features and clinical history showed a tendency for high ultraviolet radiation (UVR) exposure in the cohort. Histopathology was available in 69 cases (82%), and of these, 77% tumours were of spindle cell origin, with low‐risk genetic profiles. Patients were followed for a mean of 8 years (median 7, range 1–21 years) after diagnosis, and only one case of metastasis was documented.The association of iris freckles, history of UVR exposure and dermatologic findings supports the role of UVR in iris melanoma. Occupation and avocation history, as well as evaluation of iris freckles may offer an easily accessible way of stratifying the risk of an individual for development of UVR‐related uveal melanoma. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the accumulation of celecoxib with a seven-fold higher drug exposure in individuals homozygous for cytochrome P-450 allele.