Defining patterns of care in the management of patients with brain metastases in a large oncology centre: A single‐centre retrospective audit of 236 cases

Aims: The role of selected treatments for brain metastases (BM) is well documented; however the prevalence of these is not. We report on the patterns of care in the management of BM in a large Oncology centre. Materials and methods: We retrospectively audited 236 cases of newly diagnosed BM from January 2016 to December 2017 by looking at 2 years of radiology reports and gathered data on primary site, survival, treatment received, palliative care input and brain metastases related admissions. Results Eighty-two percent of cases were related to lung, breast and melanoma primaries. Half of patients received a form of treatment with the other half receiving best supportive care. Of these, whole brain radiotherapy (39%) and stereotactic radiosurgery (40%) were the most common treatment modalities. Most common reasons for admissions were headaches, seizures, weakness and confusion. Conclusion: This is the first study in the UK that gives an in-depth overview of the real world management of brain metastases. We have demonstrated the prevalence of treatment across the spectrum of brain metastases patients. Radiotherapy is the mainstay of treatment in nearly 80% of cases; however care needs to be taken in ensuring that SRS is offered to those who are suitable

Lung cancer diagnosed following an emergency admission: mixed methods study of the management, outcomes and needs and experiences of patients and carers

Background In the UK, although 40% of patients with lung cancer are diagnosed following an emergency admission (EA), data is limited on their needs and experiences as they progress through diagnostic and treatment pathways. Methods Prospective data collection using medical records, questionnaires and in-depth interviews. Multivariate logistic regression explored associations between diagnosis following EA and aspects of interest. Questionnaire responses with 95% confidence intervals were compared with local and national datasets. A grounded theory approach identified patient and carer themes. Results Of 401 patients, 154 (38%) were diagnosed following EA; 37 patients and six carers completed questionnaires and 13 patients and 10 carers were interviewed. Compared to those diagnosed electively, EA patients adjusted results found no difference in treatment recommendation, treatment intent or place of death. Time to diagnosis, review, or treatment was 7–14 days quicker but fewer EA patients had a lung cancer nurse present at diagnosis (37% vs. 62%). Palliative care needs were high (median [IQR] 21 [13–25] distressing or bothersome symptoms/issues) and various information and support needs unmet. Interviews highlighted in particular, perceived delays in obtaining investigations/specialist referral and factors influencing success or failure of the cough campaign. Conclusions Presentation as an EA does not appear to confer any inherent disadvantage regarding progress through lung cancer diagnostic and treatment pathways. However, given the frequent combination of advanced disease, poor performance status and prognosis, together with the high level of need and reported short-fall in care, we suggest that a specialist palliative care assessment is routinely offered

Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility)

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. New treatments are required for severe breathlessness in advanced disease. We conducted a randomised feasibility trial of mirtazapine over 28 days in adults with a modified medical research council breathlessness scale score ≥3. Sixty-four patients were randomised (409 screened), achieving our primary feasibility endpoint of recruitment. Most patients had COPD or interstitial lung disease; 52 (81%) completed the trial. There were no differences between placebo and mirtazapine in tolerability or safety, and blinding was maintained. Worst breathlessness ratings at day 28 (primary clinical activity endpoint) were, 7.1 (SD 2.3, placebo) and 6.3 (SD 1.8, mirtazapine). A phase III trial of mirtazapine is indicated. Trial registration: ISRCTN 32236160; European Clinical Trials Database (EudraCT no: 2015-004064-11)

Family and health-care professionals managing medicines for patients with serious and terminal illness at home: a qualitative study

BackgroundMore effective ways of managing symptoms of chronic and terminal illness enable patients to be cared for, and to die, at home. This requires patients and family caregivers to manage complex medicines regimens, including powerful painkillers that can have serious side effects. Little is known about how patients and family caregivers manage the physical and emotional work of managing medicines in the home or the support that they receive from health-care professionals and services.ObjectiveTo investigate how patients with serious and terminal illness, their family caregivers and the health-care professionals manage complex medication regimens and routines of care in the domestic setting.DesignA qualitative study involving (1) semistructured interviews and group discussions with 40 health-care professionals and 21 bereaved family caregivers, (2) 20 patient case studies with up to 4 months’ follow-up and (3) two end-of-project stakeholder workshops.SettingThis took place in Nottinghamshire and Leicestershire, UK.ResultsAs patients’ health deteriorated, family caregivers assumed the role of a care co-ordinator, undertaking the everyday work of organising and collecting prescriptions and storing and administering medicines around other care tasks and daily routines. Participants described the difficulties of navigating a complex and fragmented system and the need to remain vigilant about medicines prescribed, especially when changes were made by different professionals. Access to support, resilience and coping capacity are mediated through the resources available to patients, through the relationships that they have with people in their personal and professional networks, and, beyond that, through the wider connections – or disconnections – that these links have with others. Health-care professionals often lacked understanding of the practical and emotional challenges involved. All participants experienced difficulties in communication and organisation within a health-care system that they felt was complicated and poorly co-ordinated. Having a key health professional to support and guide patients and family caregivers through the system was important to a good experience of care.LimitationsThe study achieved diversity in the recruitment of patients, with different characteristics relating to the type of illness and socioeconomic circumstances. However, recruitment of participants from ethnically diverse and disadvantaged or hard-to-reach populations was particularly challenging, and we were unable to include as many participants from these groups as had been originally planned.ConclusionsThe study identified two key and inter-related areas in which patient and family caregiver experience of managing medicines at home in end-of-life care could be improved: (1) reducing work and responsibility for medicines management and (2) improving co-ordination and communication in health care. It is important to be mindful of the need for transparency and open discussion about the extent to which patients and family caregivers can and should be co-opted as proto-professionals in the technically and emotionally demanding tasks of managing medicines at the end of life.Future workPriorities for future research include investigating how allocated key professionals could integrate and co-ordinate care and optimise medicines management; the role of domiciliary home care workers in supporting medicines management in end-of-life care; patient and family perspectives and understanding of anticipatory prescribing and their preferences for involvement in decision-making; the experience of medicines management in terminal illness among minority, disadvantaged and hard-to-reach patient groups; and barriers to and facilitators of increased involvement of community pharmacists in palliative and end-of-life care

20 questions on Adaptive Dynamics

Abstract Adaptive Dynamics is an approach to studying evolutionary change when fitness is density or frequency dependent. Modern papers identifying themselves as using this approach first appeared in the 1990s, and have greatly increased up to the present. However, because of the rather technical nature of many of the papers, the approach is not widely known or understood by evolutionary biologists. In this review we aim to remedy this situation by outlining the methodology and then examining its strengths and weaknesses. We carry this out by posing and answering 20 key questions on Adaptive Dynamics. We conclude that Adaptive Dynamics provides a set of useful approximations for studying various evolutionary questions. However, as with any approximate method, conclusions based on Adaptive Dynamics are valid only under some restrictions that we discuss

Is clarithromycin a potential treatment for cachexia in people with lung cancer?: a feasibility study

Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250 mg twice daily or placebo for eight weeks. Aspects of trial feasibility recorded included numbers eligible, approached and recruited, together with adherence and completion of treatment and assessments. Over 6 months, none of 125 patients identified fulfilled the entry criteria. The commonest reasons for ineligibility were the use of an excluded concurrent drug (45, 36%), brain metastases (22, 18%), poor performance status (21, 17%) and current chemotherapy (15, 12%). A phase III trial of clarithromycin using these entry criteria is not feasible in this setting. Other macrolides that have a lower risk of a drug–drug interaction may be more practical to pursue

Next-generation sequencing identifies the natural killer cell microRNA transcriptome

Natural killer (NK) cells are innate lymphocytes important for early host defense against infectious pathogens and surveillance against malignant transformation. Resting murine NK cells regulate the translation of effector molecule mRNAs (e.g., granzyme B, GzmB) through unclear molecular mechanisms. MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate the translation of their mRNA targets, and are therefore candidates for mediating this control process. While the expression and importance of miRNAs in T and B lymphocytes have been established, little is known about miRNAs in NK cells. Here, we used two next-generation sequencing (NGS) platforms to define the miRNA transcriptomes of resting and cytokine-activated primary murine NK cells, with confirmation by quantitative real-time PCR (qRT-PCR) and microarrays. We delineate a bioinformatics analysis pipeline that identified 302 known and 21 novel mature miRNAs from sequences obtained from NK cell small RNA libraries. These miRNAs are expressed over a broad range and exhibit isomiR complexity, and a subset is differentially expressed following cytokine activation. Using these miRNA NGS data, miR-223 was identified as a mature miRNA present in resting NK cells with decreased expression following cytokine activation. Furthermore, we demonstrate that miR-223 specifically targets the 3′ untranslated region of murine GzmB in vitro, indicating that this miRNA may contribute to control of GzmB translation in resting NK cells. Thus, the sequenced NK cell miRNA transcriptome provides a valuable framework for further elucidation of miRNA expression and function in NK cell biology

Multiscale climate emulator of multimodal wave spectra: MUSCLE-spectra

Characterization of multimodal directional wave spectra is important for many offshore and coastal applications, such as marine forecasting, coastal hazard assessment, and design of offshore wave energy farms and coastal structures. However, the multivariate and multiscale nature of wave climate variability makes this complex problem tractable using computationally expensive numerical models. So far, the skill of statistical-downscaling model-based parametric (unimodal) wave conditions is limited in large ocean basins such as the Pacific. The recent availability of long-term directional spectral data from buoys and wave hindcast models allows for development of stochastic models that include multimodal sea-state parameters. This work introduces a statistical downscaling framework based on weather types to predict multimodal wave spectra (e.g., significant wave height, mean wave period, and mean wave direction from different storm systems, including sea and swells) from large-scale atmospheric pressure fields. For each weather type, variables of interest are modeled using the categorical distribution for the sea-state type, the Generalized Extreme Value (GEV) distribution for wave height and wave period, a multivariate Gaussian copula for the interdependence between variables, and a Markov chain model for the chronology of daily weather types. We apply the model to the southern California coast, where local seas and swells from both the Northern and Southern Hemispheres contribute to the multimodal wave spectrum. This work allows attribution of particular extreme multimodal wave events to specific atmospheric conditions, expanding knowledge of time-dependent, climate-driven offshore and coastal sea-state conditions that have a significant influence on local nearshore processes, coastal morphology, and flood hazards.We thank Jorge Perez for the ESTELA code. A.R., J.A.A.A., and F.J.M. acknowledge the support of the Spanish ‘‘Ministerio de Economia y Competitividad’’ under grant BIA2014-59643-R. P.C. acknowledges the support of the Spanish ‘‘Ministerio de Economia y Competitividad’’ under grant BIA2015-70644-R. J.A.A.A. is indebted to the MEC (Ministerio de Educacion, Cultura y Deporte, Spain) for the funding provided in the FPU (Formacion del ProfesoradoUniversitario) studentship (BOE-A-2013-12235). This material is based upon work supported by the U.S. Geological Survey under grant/cooperative agreement G15AC00426. P.R. acknowledges the support of the National Oceanic and Atmospheric Administration Climate Program Office via award NA15OAR4310145. Support was provided from the US DOD Strategic Environmental Research and Development Program (SERDP Project RC-2644) through the NOAA National Centers for Environmental Information (NCEI). Atmospheric data from CFSR are available online at https://climatedataguide.ucar.edu/climatedata/climate-forecast-system-reanalysis-cfsr. Marine data from global reanalysis are lodge with the IHData center from IHCantabria and are available for research purposes upon request (contact: [email protected])