Patient and professional experiences of palliative care referral discussions from cancer services : a qualitative interview study

Objectives The aim of this paper was to identify current barriers, facilitators and experiences of raising and discussing palliative care with people with advanced cancer. Methods Semi‐structured interviews were conducted with patients with advanced cancer and healthcare professionals (HCPs). Patients were included who had and had not been referred to palliative care. Transcripts were analysed using framework analysis. Results Twenty‐four patients and eight HCPs participated. Two overarching themes and five sub‐themes emerged: Theme one—referral process: timing and triggers, responsibility. Theme two—engagement: perception of treatment, prognosis and palliative care, psychological and emotional preparedness for discussion, and understanding how palliative care could benefit present and future care. Conclusion There is a need to identify suitable patients earlier in their cancer trajectory, address misconceptions about palliative care, treatment and prognosis, and better prepare patients and HCPs to have meaningful conversations about palliative care. Patients and HCPs need to establish and communicate the relevance of palliative care to the patient's current and future care, and be clear about the referral process

Observational studies of depression in primary care: what do we know?

<p>Abstract</p> <p>Background</p> <p>We undertook a systematic review of observational studies of depression in primary care to determine 1) the nature and scope of the published studies 2) the methodological quality of the studies; 3) the identified recovery and risk factors for persistent depression and 3) the treatment and health service use patterns among patients.</p> <p>Methods</p> <p>Searches were conducted in MEDLINE, CINAHL and PsycINFO using combinations of topic and keywords, and Medical Subject Headings in MEDLINE, Headings in CINAHL and descriptors in PsycINFO. Searches were limited to adult populations and articles published in English during 1985–2006.</p> <p>Results</p> <p>40 articles from 17 observational cohort studies were identified, most were undertaken in the US or Europe. Studies varied widely in aims and methods making it difficult to meaningfully compare the results. Methodological limitations were common including: selection bias of patients and physicians; small sample sizes (range 35–108 patients at baseline and 20–59 patients at follow-up); and short follow-up times limiting the extent to which these studies can be used to inform our understanding of recovery and relapse among primary care patients with depression. Risk factors for the persistence of depression identified in this review were: severity and chronicity of the depressive episode, the presence of suicidal thoughts, antidepressant use, poorer self-reported quality of life, lower self-reported social support, experiencing key life events, lower education level and unemployment.</p> <p>Conclusion</p> <p>Despite the growing interest in depression being managed as a chronic illness, this review identified only 17 observational studies of depression in primary care, most of which have included small sample sizes and been relatively short-term. Future research should be large enough to investigate risk factors for chronicity and relapse, and should be conducted over a longer time frame.</p

Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1) activity and increase airway smooth muscle contraction in asthma

Airway remodelling describes the histopathological changes leading to fixed airway obstruction in patients with asthma and includes extra-cellular matrix (ECM) deposition. Matrix metalloproteinase-1 (MMP-1) is present in remodelled airways but its relationship with ECM proteins and the resulting functional consequences are unknown. We used airway smooth muscle cells (ASM) and bronchial biopsies from control donors and patients with asthma to examine the regulation of MMP-1 by ECM in ASM cells and the effect of MMP-1 on ASM contraction. Collagen-I and tenascin-C induced MMP-1 protein expression, which for tenascin-C, was greater in asthma derived ASM cells. Tenascin-C induced MMP-1 expression was dependent on ERK1/2, JNK and p38 MAPK activation and attenuated by function blocking antibodies against the β1 and β3 integrin subunits. Tenascin-C and MMP-1 were not expressed in normal airways but co-localised in the ASM bundles and reticular basement membrane of patients with asthma. Further, ECM from asthma derived ASM cells stimulated MMP-1 expression to a greater degree than ECM from normal ASM. Bradykinin induced contraction of ASM cells seeded in 3D collagen gels was reduced by the MMP inhibitor ilomastat and by siRNA knockdown of MMP-1. In summary, the induction of MMP-1 in ASM cells by tenascin-C occurs in part via integrin mediated MAPK signalling. MMP-1 and tenascin-C are co-localised in the smooth muscle bundles of patients with asthma where this interaction may contribute to enhanced airway contraction. Our findings suggest that ECM changes in airway remodelling via MMP-1 could contribute to an environment promoting greater airway narrowing in response to broncho-constrictor stimuli and worsening asthma symptoms

The RESET project: constructing a European tephra lattice for refined synchronisation of environmental and archaeological events during the last c. 100 ka

This paper introduces the aims and scope of the RESET project (. RESponse of humans to abrupt Environmental Transitions), a programme of research funded by the Natural Environment Research Council (UK) between 2008 and 2013; it also provides the context and rationale for papers included in a special volume of Quaternary Science Reviews that report some of the project's findings. RESET examined the chronological and correlation methods employed to establish causal links between the timing of abrupt environmental transitions (AETs) on the one hand, and of human dispersal and development on the other, with a focus on the Middle and Upper Palaeolithic periods. The period of interest is the Last Glacial cycle and the early Holocene (c. 100-8 ka), during which time a number of pronounced AETs occurred. A long-running topic of debate is the degree to which human history in Europe and the Mediterranean region during the Palaeolithic was shaped by these AETs, but this has proved difficult to assess because of poor dating control. In an attempt to move the science forward, RESET examined the potential that tephra isochrons, and in particular non-visible ash layers (cryptotephras), might offer for synchronising palaeo-records with a greater degree of finesse. New tephrostratigraphical data generated by the project augment previously-established tephra frameworks for the region, and underpin a more evolved tephra 'lattice' that links palaeo-records between Greenland, the European mainland, sub-marine sequences in the Mediterranean and North Africa. The paper also outlines the significance of other contributions to this special volume: collectively, these illustrate how the lattice was constructed, how it links with cognate tephra research in Europe and elsewhere, and how the evidence of tephra isochrons is beginning to challenge long-held views about the impacts of environmental change on humans during the Palaeolithic. © 2015 Elsevier Ltd.RESET was funded through Consortium Grants awarded by the Natural Environment Research Council, UK, to a collaborating team drawn from four institutions: Royal Holloway University of London (grant reference NE/E015905/1), the Natural History Museum, London (NE/E015913/1), Oxford University (NE/E015670/1) and the University of Southampton, including the National Oceanography Centre (NE/01531X/1). The authors also wish to record their deep gratitude to four members of the scientific community who formed a consultative advisory panel during the lifetime of the RESET project: Professor Barbara Wohlfarth (Stockholm University), Professor Jørgen Peder Steffensen (Niels Bohr Institute, Copenhagen), Dr. Martin Street (Romisch-Germanisches Zentralmuseum, Neuwied) and Professor Clive Oppenheimer (Cambridge University). They provided excellent advice at key stages of the work, which we greatly valued. We also thank Jenny Kynaston (Geography Department, Royal Holloway) for construction of several of the figures in this paper, and Debbie Barrett (Elsevier) and Colin Murray Wallace (Editor-in-Chief, QSR) for their considerable assistance in the production of this special volume.Peer Reviewe

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Collaborative care for patients with bipolar disorder: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Bipolar disorder is a severe mental illness with serious consequences for daily living of patients and their caregivers. Care as usual primarily consists of pharmacotherapy and supportive treatment. However, a substantial number of patients show a suboptimal response to treatment and still suffer from frequent episodes, persistent interepisodic symptoms and poor social functioning. Both psychiatric and somatic comorbid disorders are frequent, especially personality disorders, substance abuse, cardiovascular diseases and diabetes. Multidisciplinary collaboration of professionals is needed to combine all expertise in order to achieve high-quality integrated treatment. 'Collaborative Care' is a treatment method that could meet these needs. Several studies have shown promising effects of these integrated treatment programs for patients with bipolar disorder. In this article we describe a research protocol concerning a study on the effects of Collaborative Care for patients with bipolar disorder in the Netherlands.</p> <p>Methods/design</p> <p>The study concerns a two-armed cluster randomised clinical trial to evaluate the effectiveness of Collaborative Care (CC) in comparison with Care as usual (CAU) in outpatient clinics for bipolar disorder or mood disorders in general. Collaborative Care includes individually tailored interventions, aimed at personal goals set by the patient. The patient, his caregiver, the nurse and the psychiatrist all are part of the Collaborative Care team. Elements of the program are: contracting and shared decision making; psycho education; problem solving treatment; systematic relapse prevention; monitoring of outcomes and pharmacotherapy. Nurses coordinate the program. Nurses and psychiatrists in the intervention group will be trained in the intervention. The effects will be measured at baseline, 6 months and 12 months. Primary outcomes are psychosocial functioning, psychiatric symptoms, and quality of life. Caregiver outcomes are burden and satisfaction with care.</p> <p>Discussion</p> <p>Several ways to enhance the quality of this study are described, as well as some limitations caused by the complexities of naturalistic treatment settings where not all influencing factors on an intervention and the outcomes can be controlled.</p> <p>Trial Registration</p> <p>The Netherlands Trial Registry, <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2600">NTR2600</a>.</p

Assessing changes in global fire regimes

PAGES, Past Global Changes, is funded by the Swiss Academy of Sciences and the Chinese Academy of Sciences and supported in kind by the University of Bern, Switzerland. Financial support was provided by the U.S. National Science Foundation award numbers 1916565, EAR-2011439, and EAR-2012123. Additional support was provided by the Utah Department of Natural Resources Watershed Restoration Initiative. SSS was supported by Brigham Young University Graduate Studies. MS was supported by National Science Centre, Poland (grant no. 2018/31/B/ST10/02498 and 2021/41/B/ST10/00060). JCA was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 101026211. PF contributed within the framework of the FCT-funded project no. UIDB/04033/2020. SGAF acknowledges support from Trond Mohn Stiftelse (TMS) and University of Bergen for the startup grant ‘TMS2022STG03’. JMP participation in this research was supported by the Forest Research Centre, a research unit funded by Fundação para a Ciência e a Tecnologia I.P. (FCT), Portugal (UIDB/00239/2020). A.-LD acknowledge PAGES, PICS CNRS 06484 project, CNRS-INSU, Région Nouvelle-Aquitaine, University of Bordeaux DRI and INQUA for workshop support.Background The global human footprint has fundamentally altered wildfire regimes, creating serious consequences for human health, biodiversity, and climate. However, it remains difficult to project how long-term interactions among land use, management, and climate change will affect fire behavior, representing a key knowledge gap for sustainable management. We used expert assessment to combine opinions about past and future fire regimes from 99 wildfire researchers. We asked for quantitative and qualitative assessments of the frequency, type, and implications of fire regime change from the beginning of the Holocene through the year 2300. Results Respondents indicated some direct human influence on wildfire since at least ~ 12,000 years BP, though natural climate variability remained the dominant driver of fire regime change until around 5,000 years BP, for most study regions. Responses suggested a ten-fold increase in the frequency of fire regime change during the last 250 years compared with the rest of the Holocene, corresponding first with the intensification and extensification of land use and later with anthropogenic climate change. Looking to the future, fire regimes were predicted to intensify, with increases in frequency, severity, and size in all biomes except grassland ecosystems. Fire regimes showed different climate sensitivities across biomes, but the likelihood of fire regime change increased with higher warming scenarios for all biomes. Biodiversity, carbon storage, and other ecosystem services were predicted to decrease for most biomes under higher emission scenarios. We present recommendations for adaptation and mitigation under emerging fire regimes, while recognizing that management options are constrained under higher emission scenarios. Conclusion The influence of humans on wildfire regimes has increased over the last two centuries. The perspective gained from past fires should be considered in land and fire management strategies, but novel fire behavior is likely given the unprecedented human disruption of plant communities, climate, and other factors. Future fire regimes are likely to degrade key ecosystem services, unless climate change is aggressively mitigated. Expert assessment complements empirical data and modeling, providing a broader perspective of fire science to inform decision making and future research priorities.Peer reviewe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701