Content analysis of Advance Directives completed by patients with advanced cancer as part of an Advance Care Planning intervention : insights gained from the ACTION trial

Purpose Writing an Advance Directive (AD) is often seen as a part of Advance Care Planning (ACP). ADs may include specific preferences regarding future care and treatment and information that provides a context for healthcare professionals and relatives in case they have to make decisions for the patient. The aim of this study was to get insight into the content of ADs as completed by patients with advanced cancer who participated in ACP conversations. Methods A mixed methods study involving content analysis and descriptive statistics was used to describe the content of completed My Preferences forms, an AD used in the intervention arm of the ACTION trial, testing the effectiveness of the ACTION Respecting Choices ACP intervention. Results In total, 33% of 442 patients who received the ACTION RC ACP intervention completed a My Preferences form. Document completion varied per country: 10.4% (United Kingdom), 20.6% (Denmark), 29.2% (Belgium), 41.7% (the Netherlands), 61.3% (Italy) and 63.9% (Slovenia). Content analysis showed that 'maintaining normal life' and 'experiencing meaningful relationships' were important for patients to live well. Fears and worries mainly concerned disease progression, pain or becoming dependent. Patients hoped for prolongation of life and to be looked after by healthcare professionals. Most patients preferred to be resuscitated and 44% of the patients expressed maximizing comfort as their goal of future care. Most patients preferred 'home' as final place of care. Conclusions My Preferences forms provide some insights into patients' perspectives and preferences. However, understanding the reasoning behind preferences requires conversations with patients

Reproducibility, and sensitivity to motor unit loss in amyotrophic lateral sclerosis, of a novel MUNE method: MScanFit MUNE

OBJECTIVE: To examine inter- and intra-rater reproducibility and sensitivity to motor unit loss of a novel motor unit number estimation (MUNE) method, MScanFit MUNE (MScan), compared to two traditional MUNE methods; Multiple point stimulation MUNE (MPS) and Motor Unit Number Index (MUNIX). METHODS: Twenty-two ALS patients and 20 sex- and age-matched healthy controls were included. MPS, MUNIX, and MScan were performed twice each by two blinded physicians. Reproducibility of MUNE values was assessed by coefficient of variation (CV) and intra class correlation coefficient (ICC). Ability to detect motor unit loss was assessed by ROC curves and area under the curve (AUC). The times taken for each of the methods were recorded. RESULTS: MScan was more reproducible than MPS and MUNIX both between and within operators. The mean CV for MScan (12.3%) was significantly lower than for MPS (24.7%) or MUNIX (21.5%). All methods had ICC>0.94. MScan and Munix were significantly quicker to perform than MPS (6.3mvs. 13.2m). MScan (AUC=0.930) and MPS (AUC=0.899) were significantly better at discriminating between patients and healthy controls than MUNIX (AUC=0.831). CONCLUSIONS: MScan was more consistent than MPS or MUNIX and better at distinguishing ALS patients from healthy subjects. SIGNIFICANCE: MScan may improve detection and assessment of motor unit loss

Variation in the use of chemotherapy in lung cancer

Factors influencing the use of chemotherapy for the initial (6 months) treatment of lung cancer in South East England were investigated. The variables explored as possibly influencing the use of chemotherapy were sex, age, the year of diagnosis, the type of lung cancer, the stage, the index of multiple deprivation and the cancer network of residence. χ2 analysis and multivariate logistic regression models were used to examine the effect of each of the variables on the use of chemotherapy. The results showed a highly significant trend in use of chemotherapy over time; the adjusted proportion of patients receiving chemotherapy increasing from 13.6% in 1994 to 29.3% in 2003. However, age, cancer network and type of lung cancer had the strongest influence on the use of chemotherapy. This finding is important when we consider that the NHS Cancer Plan aims at improving inequalities in cancer care in the UK

International variation in oesophageal and gastric cancer survival 2012–2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study)

Objective To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. Methods As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012–2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. Results Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. Conclusion Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future

Testing association of rare genetic variants with resistance to three common antiseizure medications

OBJECTIVE: Drug resistance is a major concern in the treatment of individuals with epilepsy. No genetic markers for resistance to individual antiseizure medication (ASM) have yet been identified. We aimed to identify the role of rare genetic variants in drug resistance for three common ASMs: levetiracetam (LEV), lamotrigine (LTG), and valproic acid (VPA). METHODS: A cohort of 1622 individuals of European descent with epilepsy was deeply phenotyped and underwent whole exome sequencing (WES), comprising 575 taking LEV, 826 LTG, and 782 VPA. We performed gene- and gene set-based collapsing analyses comparing responders and nonresponders to the three drugs to determine the burden of different categories of rare genetic variants. RESULTS: We observed a marginally significant enrichment of rare missense, truncating, and splice region variants in individuals who were resistant to VPA compared to VPA responders for genes involved in VPA pharmacokinetics. We also found a borderline significant enrichment of truncating and splice region variants in the synaptic vesicle glycoprotein (SV2) gene family in nonresponders compared to responders to LEV. We did not see any significant enrichment using a gene-based approach. SIGNIFICANCE: In our pharmacogenetic study, we identified a slightly increased burden of damaging variants in gene groups related to drug kinetics or targeting in individuals presenting with drug resistance to VPA or LEV. Such variants could thus determine a genetic contribution to drug resistance

The commonness of rarity: Global and future distribution of rarity across land plants

A key feature of life’s diversity is that some species are common but many more are rare. Nonetheless, at global scales, we do not know what fraction of biodiversity consists of rare species. Here, we present the largest compilation of global plant diversity to quantify the fraction of Earth’s plant biodiversity that are rare. A large fraction, ~36.5% of Earth’s ~435,000 plant species, are exceedingly rare. Sampling biases and prominent models, such as neutral theory and the k-niche model, cannot account for the observed prevalence of rarity. Our results indicate that (i) climatically more stable regions have harbored rare species and hence a large fraction of Earth’s plant species via reduced extinction risk but that (ii) climate change and human land use are now disproportionately impacting rare species. Estimates of global species abundance distributions have important implications for risk assessments and conservation planning in this era of rapid global change

Low Variation in the Polymorphic Clock Gene Poly-Q Region Despite Population Genetic Structure across Barn Swallow (Hirundo rustica) Populations

Recent studies of several species have reported a latitudinal cline in the circadian clock gene, Clock, which influences rhythms in both physiology and behavior. Latitudinal variation in this gene may hence reflect local adaptation to seasonal variation. In some bird populations, there is also an among-individual association between Clock poly-Q genotype and clutch initiation date and incubation period. We examined Clock poly-Q allele variation in the Barn Swallow (Hirundo rustica), a species with a cosmopolitan geographic distribution and considerable variation in life-history traits that may be influenced by the circadian clock. We genotyped Barn Swallows from five populations (from three subspecies) and compared variation at the Clock locus to that at microsatellite loci and mitochondrial DNA (mtDNA). We found very low variation in the Clock poly-Q region, as >96% of individuals were homozygous, and the two other alleles at this locus were globally rare. Genetic differentiation based on the Clock poly-Q locus was not correlated with genetic differentiation based on either microsatellite loci or mtDNA sequences. Our results show that high diversity in Clock poly-Q is not general across avian species. The low Clock variation in the background of heterogeneity in microsatellite and mtDNA loci in Barn Swallows may be an outcome of stabilizing selection on the Clock locus

Prevalence and anatomical location of muscle tenderness in adults with nonspecific neck/shoulder pain

<p>Abstract</p> <p>Background</p> <p>Many adults experience bothersome neck/shoulder pain. While research and treatment strategies often focus on the upper trapezius, other neck/shoulder muscles may be affected as well. The aim of the present study is to evaluate the prevalence and anatomical location of muscle tenderness in adults with nonspecific neck/shoulder pain.</p> <p>Methods</p> <p>Clinical neck/shoulder examination at two large office workplaces in Copenhagen, Denmark. 174 women and 24 men (aged 25-65 years) with nonspecific neck/shoulder pain for a duration of at least 30 days during the previous year and a pain intensity of at least 2 on a modified VAS-scale of 0-10 participated. Exclusion criteria were traumatic injuries or other serious chronic disease. Using a standardized finger pressure of 2 kg, palpable tenderness were performed of eight anatomical neck/shoulder locations in the left and right side on a scale of 'no tenderness', 'some tenderness' and 'severe tenderness'.</p> <p>Results</p> <p>In women, the levator scapulae, neck extensors and infraspinatus showed the highest prevalence of severe tenderness (18-30%). In comparison, the prevalence of severe tenderness in the upper trapezius, occipital border and supraspinatus was 13-19%. Severe tenderness of the medial deltoid was least prevalent (0-1%). In men, the prevalence of severe tenderness in the levator scapulae was 13-21%, and ranged between 0-8% in the remainder of the examined anatomical locations.</p> <p>Conclusions</p> <p>A high prevalence of tenderness exists in several anatomical locations of the neck/shoulder complex among adults with nonspecific neck/shoulder pain. Future research should focus on several neck/shoulder muscles, including the levator scapulae, neck extensors and infraspinatus, and not only the upper trapezius.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN60264809">ISRCTN60264809</a></p

Knee-clicks and visual traits indicate fighting ability in eland antelopes: multiple messages and back-up signals

Abstract Background Given the costs of signalling, why do males often advertise their fighting ability to rivals using several signals rather than just one? Multiple signalling theories have developed largely in studies of sexual signals, and less is known about their applicability to intra-sexual communication. We here investigate the evolutionary basis for the intricate agonistic signalling system in eland antelopes, paying particular attention to the evolutionary phenomenon of loud knee-clicking. Results A principal components analysis separated seven male traits into three groups. The dominant frequency of the knee-clicking sound honestly indicated body size, a main determinant of fighting ability. In contrast, the dewlap size increased with estimated age rather than body size, suggesting that, by magnifying the silhouette of older bulls disproportionately, the dewlap acts as an indicator of age-related traits such as fighting experience. Facemask darkness, frontal hairbrush size and body greyness aligned with a third underlying variable, presumed to be androgen-related aggression. A longitudinal study provided independent support of these findings. Conclusion The results show that the multiple agonistic signals in eland reflect three separate components of fighting ability: (1) body size, (2) age and (3) presumably androgen-related aggression, which is reflected in three backup signals. The study highlights how complex agonistic signalling systems can evolve through the simultaneous action of several selective forces, each of which favours multiple signals. Specifically, loud knee-clicking is discovered to be an honest signal of body size, providing an exceptional example of the potential for non-vocal acoustic communication in mammals.</p