Patient perspectives on key symptoms and preferences for follow-up after upper gastro-intestinal cancer surgery.

PURPOSE: Long-lasting symptoms and reductions in quality of life are common after oesophago-gastric surgery. Post-operative follow-up has traditionally focussed on tumour recurrence and survival, but there is a growing need to also identify and treat functional sequelae to improve patients' recovery. METHODS: An electronic survey was circulated via a British national charity for patients undergoing oesophago-gastric surgery and their families. Patients were asked about post-operative symptoms they deemed important to their quality of life, as well as satisfaction and preferences for post-operative follow-up. Differences between satisfied and dissatisfied patients with reference to follow-up were assessed. RESULTS: Among 362 respondents with a median follow-up of 58 months since surgery (range 3-412), 36 different symptoms were reported as being important to recovery and quality of life after surgery, with a median of 13 symptoms per patient. Most (84%) respondents indicated satisfaction with follow-up. Satisfied patients were more likely to have received longer follow-up (5-year or longer follow-up 60% among satisfied patients vs 27% among unsatisfied, p < 0.001). These were also less likely to have seen a dietitian as part of routine follow-up (37% vs 58%, p = 0.005). CONCLUSION: This patient survey highlights preferences regarding follow-up after oesophago-gastrectomy. Longer follow-up and dietician involvement improved patient satisfaction. Patients reported being concerned by a large number of gastrointestinal and non-gastrointestinal symptoms, highlighting the need for multidisciplinary input and a consensus on how to manage the poly-symptomatic patient.

Bereavement support effectiveness for parents of infants and children: a systematic review.

OBJECTIVES: This systematic review aims to assess the effectiveness of bereavement support interventions (BSIs) for parents of an infant or a child who has died from a medical condition or in unforeseen circumstances. METHODS: A systematic search of MEDLINE, PsycINFO, Embase and CINAHL (1980 to January 2018) was performed to identify studies investigating BSIs for the parents of children who died between the ages of 24 weeks gestation and 30 years. Due to significant clinical and methodological heterogeneity between studies, a narrative synthesis was performed. RESULTS: The database searches returned 24 550 records, with a further 6 identified through other sources. Of these, eight studies, reported in nine papers, met the inclusion criteria. Most studies were conducted in the USA (n=5) and in perinatal/neonatal deaths (n=6). Five of the included studies were randomised controlled trials and three were non-randomised comparative studies. Interventions were delivered to groups, individuals or families. Outcomes of interest were grief, mental health, physical health and 'others'. There were major concerns over the quality of study methods and reporting. Only three of the nine studies reported a significant difference between experimental and control arm participants in any outcomes, despite a total of 23 outcomes being measured. CONCLUSIONS: Poor methodology and reporting of the few studies which have assessed BSIs for parents limit any conclusions on their effectiveness. Agreement on core outcomes and more robust study methodology are required in this neglected area of research.

A South African review of routinely-collected health data of psychogenic nonepileptic seizure patients referred to psychiatrists in Johannesburg.

Patients with psychogenic nonepileptic seizures (PNES) are often referred to psychiatrists for treatment of functional neurological symptom disorder (FNSD). However, not all patients with FNSD have an identified psychiatric comorbidity [1]. The aim of this observational study was to characterize the clinical and psychiatric features of patients with PNES from Johannesburg, South Africa, where a high frequency of PNES has been reported [2], and compare these findings to other reports. We hypothesized that patient outcomes regarding treatment adherence and episode frequency would improve when treated within a closed multidisciplinary team. The data included a retrospective record review of patients diagnosed with PNES from an epilepsy monitoring unit and referred for psychiatric assessment and treatment between November 2013 and July 2017. Fifty-nine cases met the criteria for the study. There were 7 male and 52 female participants, aged between 14 and 72 years (M = 33.76, SD = 13.88). The most frequently reported comorbid symptoms were anxiety (90%); dissociative symptoms (51%); headaches (76%) and gastrointestinal symptoms (36%). Important patient characteristics included past substance abuse (76%); impaired attachment (86%); past trauma (69%) and sexual trauma (29%). Generalized anxiety disorder (76%), major depressive disorder (64%) and PTSD (22%) were the most prevalent psychiatric diagnoses. After receiving psychiatric treatment, 47% of patients experienced a decrease in the frequency of episodes, while 86% became aware of the precipitants of their episodes. Psychiatric data can valuably inform current theories of PNES management. This study contributes to the understanding of comorbid, aetiological, and prognostic factors that are crucial to refining coherent models that will guide practice.

The social dynamics of lung cancer talk on Twitter, Facebook and Macmillan.org.uk.

People with lung cancer and others affected by the condition are using social media to share information and support, but little is known about how these behaviours vary between different platforms. To investigate this, we extracted posts from Twitter (using relevant hashtags), the Lung Cancer Support Group on Facebook and the Macmillan.org.uk lung cancer discussion forum for a single month. Interaction Process Analysis revealed that all three platforms were used more for giving than seeking information, opinion or suggestions. However, interaction types (including sentiment) varied between platforms, reflecting their digital architectures, user-base and inclusion of a moderator. For example, a higher percentage of information-seeking and sentiment marked the Macmillan.org.uk, compared with Twitter and the Facebook Group. Further analysis of the messages using a four-dimensional typology of social support revealed that emotional and informational support types were most prevalent on the Macmillan.org.uk forum, closely followed by the Facebook Group. Contrary to expectations, Twitter posts showed the most companionship support, reflecting the use of hashtags as user-generated signals of community belonging and interests. Qualitative analysis revealed an unanticipated sub-category of spiritual support, which featured uniquely in the Lung Cancer Support Group on Facebook. There was little evidence of trolling or stigma, although some users remarked that lung cancer was unfairly resourced compared with other cancers. These findings provide new insights about how people affected by lung cancer use social media and begin to elucidate the value of different platforms as channels for patient engagement and support, or as potential research data sources.

The utility of geodemographic indicators in small area estimates of limiting long-term illness.

Small area health data are not always available on a consistent and robust routine basis across nations, necessitating the employment of small area estimation methods to generate local-scale data or the use of proxy measures. Geodemographic indicators are widely marketed as a potential proxy for many health indicators. This paper tests the extent to which the inclusion of geodemographic indicators in small area estimation methodology can enhance small area estimates of limiting long-term illness (LLTI). The paper contributes to international debates on small area estimation methodologies in health research and the relevance of geodemographic indicators to the identification of health care needs. We employ a multilevel methodology to estimate small area LLTI prevalence in England, Scotland and Wales. The estimates were created with a standard geographically-based model and with a cross-classified model of individuals nested separately in both spatial groupings and non-spatial geodemographic clusters. LLTI prevalence was estimated as a function of age, sex and deprivation. Estimates from the cross-classified model additionally incorporated residuals relating to the geodemographic classification. Both sets of estimates were compared against direct estimates from the 2011 Census. Geodemographic clusters remain relevant to understanding LLTI even after controlling for age, sex and deprivation. Incorporating a geodemographic indicator significantly improves concordance between the small area estimates and the Census. Small area estimates are however consistently below the equivalent Census measures, with the LLTI prevalence in urban areas characterised as 'blue collar' and 'struggling families' being markedly lower. We conclude that the inclusion of a geodemographic indicator in small area estimation can improve estimate quality and enhance understanding of health inequalities. We recommend the inclusion of geodemographic indicators in public releases of survey data to facilitate better small area estimation but caution against assumptions that geodemographic indicators can, on their own, provide a proxy measure of health status.

Comprehensive scoping review of health research using social media data.

INTRODUCTION: The rising popularity of social media, since their inception around 20 years ago, has been echoed in the growth of health-related research using data derived from them. This has created a demand for literature reviews to synthesise this emerging evidence base and inform future activities. Existing reviews tend to be narrow in scope, with limited consideration of the different types of data, analytical methods and ethical issues involved. There has also been a tendency for research to be siloed within different academic communities (eg, computer science, public health), hindering knowledge translation. To address these limitations, we will undertake a comprehensive scoping review, to systematically capture the broad corpus of published, health-related research based on social media data. Here, we present the review protocol and the pilot analyses used to inform it. METHODS: A version of Arksey and O'Malley's five-stage scoping review framework will be followed: (1) identifying the research question; (2) identifying the relevant literature; (3) selecting the studies; (4) charting the data and (5) collating, summarising and reporting the results. To inform the search strategy, we developed an inclusive list of keyword combinations related to social media, health and relevant methodologies. The frequency and variability of terms were charted over time and cross referenced with significant events, such as the advent of Twitter. Five leading health, informatics, business and cross-disciplinary databases will be searched: PubMed, Scopus, Association of Computer Machinery, Institute of Electrical and Electronics Engineers and Applied Social Sciences Index and Abstracts, alongside the Google search engine. There will be no restriction by date. ETHICS AND DISSEMINATION: The review focuses on published research in the public domain therefore no ethics approval is required. The completed review will be submitted for publication to a peer-reviewed, interdisciplinary open access journal, and conferences on public health and digital research.

#Deathbedlive: the end-of-life trajectory, reflected in a cancer patient's tweets.

BACKGROUND: Understanding physical and psycho-social illness trajectories towards the end of life can help in the planning of palliative and supportive care. With terminal patients increasingly seeking and sharing health information and support via social media, it is timely to examine whether these trajectories are reflected in their digital narratives. In this exploratory study, we analysed the Twitter feed of prominent cancer sufferer and physician, Kate Granger, over the final 6 months of her life. METHODS: With the consent of Kate's widower, Chris Pointon, 1628 Twitter posts from @GrangerKate were manually screened. The 550 tweets judged relevant to her disease were qualitatively content analysed with reference to the six modifiable dimensions of the patient experience in Emanuel and Emanuel's 'framework for a good death'. The frequency of each tweet category was charted over time and textual content was examined and cross-referenced with key events, to obtain a deeper understanding of its nature and significance. RESULTS: Tweets were associated with physical symptoms (N = 270), psychological and cognitive symptoms (N = 213), social relationships and support (N = 85), economic demands and care giving needs (N = 85), hopes and expectations (N = 51) and spiritual beliefs (N = 7). While medical treatments and procedures were discussed in detail, medical information-seeking was largely absent, likely reflecting Kate clinical expertise. Spirituality was expressed more as hope in treatments or "someone out there listening", than in religious terms. The high value of Kate's palliative care team was a dominant theme in the support category, alongside the support she received from her online community of fellow sufferers, friends, family and colleagues. Significant events, such as medical procedures and hospital stays generated the densest Twitter engagement. Transitions between trajectory phases were marked by changes in the relative frequency of tweet-types. CONCLUSIONS: In Kate's words, "the power of patient narrative cannot be underestimated". While this analysis spanned only 6 months, it yielded rich insights. The results reflect theorised end-of-life dimensions and reveal the potential of social media data and digital bio-ethnography to shine a light on terminal patients' lived experiences, coping strategies and support needs, suggesting new opportunities for enhancing personalised palliative care and avenues for further research.

Integrating national surveys to estimate small area variations in poor health and limiting long-term illness in Great Britain.

OBJECTIVES: This study aims to address, for the first time, the challenges of constructing small area estimates of health status using linked national surveys. The study also seeks to assess the concordance of these small area estimates with data from national censuses. SETTING: Population level health status in England, Scotland and Wales. PARTICIPANTS: A linked integrated dataset of 23 374 survey respondents (16+ years) from the 2011 waves of the Health Survey for England (n=8603), the Scottish Health Survey (n=7537) and the Welsh Health Survey (n=7234). PRIMARY AND SECONDARY OUTCOME MEASURES: Population prevalence of poorer self-rated health and limiting long-term illness. A multilevel small area estimation modelling approach was used to estimate prevalence of these outcomes for middle super output areas in England and Wales and intermediate zones in Scotland. The estimates were then compared with matched measures from the contemporaneous 2011 UK Census. RESULTS: There was a strong positive association between the small area estimates and matched census measures for all three countries for both poorer self-rated health (r=0.828, 95% CI 0.821 to 0.834) and limiting long-term illness (r=0.831, 95% CI 0.824 to 0.837), although systematic differences were evident, and small area estimation tended to indicate higher prevalences than census data. CONCLUSIONS: Despite strong concordance, variations in the small area prevalences of poorer self-rated health and limiting long-term illness evident in census data cannot be replicated perfectly using small area estimation with linked national surveys. This reflects a lack of harmonisation between surveys over question wording and design. The nature of small area estimates as 'expected values' also needs to be better understood.

How Neurolinguistic Psychotherapy (NLPt) could Help to Improve Psychological Wellbeing within the Dental Profession.

This article is an exploration of some of the causes of stress within the dental profession and a discussion on how some of the models and philosophies of NLPt could help improve the levels of psychological wellbeing within the profession. Some of the fundamental concepts of NLPt are explored, with particular reference to their application in regard to stress. It is concluded that NLPt could provide a robust methodology for reducing psychological distress within the profession, by helping dentists to understand the concept of unuseful constructs, to improve behavioural choice and to discover the possibility of a more resourceful way of being. CPD/Clinical Relevance: Dentists under stress do not perform well; judgement is impaired, motivation is reduced and poor decisions can be made which impact directly on patient care.

Using geocoded survey data to improve the accuracy of multilevel small area synthetic estimates.

This paper examines the secondary data requirements for multilevel small area synthetic estimation (ML-SASE). This research method uses secondary survey data sets as source data for statistical models. The parameters of these models are used to generate data for small areas. The paper assesses the impact of knowing the geographical location of survey respondents on the accuracy of estimates, moving beyond debating the generic merits of geocoded social survey datasets to examine quantitatively the hypothesis that knowing the approximate location of respondents can improve the accuracy of the resultant estimates. Four sets of synthetic estimates are generated to predict expected levels of limiting long term illnesses using different levels of knowledge about respondent location. The estimates were compared to comprehensive census data on limiting long term illness (LLTI). Estimates based on fully geocoded data were more accurate than estimates based on data that did not include geocodes.

Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives.

Optimization of KDM6B (JMJD3) HTS hit 12 led to the identification of 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic acid 39 that are inhibitors of the KDM4 (JMJD2) family of histone lysine demethylases. Compounds 34 and 39 possess activity, IC50 ≤ 100 nM, in KDM4 family biochemical (RFMS) assays with ≥ 50-fold selectivity against KDM6B and activity in a mechanistic KDM4C cell imaging assay (IC50 = 6-8 µM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM).

Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives.

Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDM5C biochemical and target-specific, cellular mechanistic assays.

Small area synthetic estimates of smoking prevalence during pregnancy in England.

BACKGROUND: Complete and accurate data on maternal smoking prevalence during pregnancy are not available at a local geographical scale in England. We employ a synthetic estimation approach to predict the expected prevalence of smoking during pregnancy and smoking at delivery by Primary Care Trust (PCT). METHODS: Multilevel logistic regression models were used with data from the 2010 Infant Feeding Survey and 2011 Census to predict the probability of mothers (a) smoking at any point during pregnancy and (b) smoking at delivery, according to age, deprivation, and the ethnic profile of the home area. These probabilities were applied to demographic information on mothers giving birth from 2010/11 Hospital Episode Statistics data to produce expected counts, and prevalence figures, of smokers by PCT, with Bayesian 95 % credible intervals. The expected prevalence of smoking at delivery by PCT was compared with midwife-collected Smoking at the Time of Delivery (SATOD) data using a Bland-Altman plot. RESULTS: The expected prevalence of smoking during pregnancy by PCT ranged from 8.1 % (95 % CI 5.6-1.0) to 31.6 % (27.5-34.8). The expected prevalence of smoking at delivery ranged from 2.5 % (1.4-4.0) to 17.1 % (13.7-20.4). Figures for expected smoking prevalence at delivery showed some agreement with SATOD, though SATOD data were generally higher than the synthetic estimates (mean difference 2.99 %). CONCLUSIONS: It is possible to derive good estimates of expected smoking prevalence during pregnancy for small areas, potentially at much lower cost than conducting large surveys. Such data may be useful to help plan and commission smoking cessation services and monitor their effectiveness.

The convergent validity of three surveys as alternative sources of health information to the 2011 UK census.

Censuses have traditionally been a key source of localised information on the state of a nation's health. Many countries are now adopting alternative approaches to the traditional census, placing such information at risk. The purpose of this paper is to inform debate about whether existing social surveys could provide an adequate 'base' for alternative model-based small area estimates of health data in a post traditional census era. Using a case study of 2011 UK Census questions on self-assessed health and limiting long term illness, we examine the extent to which the results from three large-scale surveys - the Health Survey for England, the Crime Survey for England and Wales and the Integrated Household Survey - conform to census output. Particularly in the case of limiting long term illness, the question wording renders comparisons difficult. However, with the exception of the general health question from the Health Survey for England all three surveys meet tests for convergent validity.

Configuration of a high-content imaging platform for hit identification and pharmacological assessment of JMJD3 demethylase enzyme inhibitors.

The biological complexity associated with the regulation of histone demethylases makes it desirable to configure a cellular mechanistic assay format that simultaneously encompasses as many of the relevant cellular processes as possible. In this report, the authors describe the configuration of a JMJD3 high-content cellular mechanistic imaging assay that uses single-cell multiparameter measurements to accurately assess cellular viability and the enzyme-dependent demethylation of the H3K27(Me)3 mark by exogenously expressed JMJD3. This approach couples robust statistical analyses with the spatial resolving power of cellular imaging. This enables segregation of expressing and nonexpressing cells into discrete subpopulations and consequently pharmacological quantification of compounds of interest in the expressing population at varying JMJD3 expression levels. Moreover, the authors demonstrate the utility of this hit identification strategy through the successful prosecution of a medium-throughput focused campaign of an 87 500-compound file, which has enabled the identification of JMJD3 cellular-active chemotypes. This study represents the first report of a demethylase high-content imaging assay with the ability to capture a repertoire of pharmacological tools, which are likely both to inform our mechanistic understanding of how JMJD3 is modulated and, more important, to contribute to the identification of novel therapeutic modalities for this demethylase enzyme.

Geophysical monitoring and reactive transport modeling of ureolytically-driven calcium carbonate precipitation.

Ureolytically-driven calcium carbonate precipitation is the basis for a promising in-situ remediation method for sequestration of divalent radionuclide and trace metal ions. It has also been proposed for use in geotechnical engineering for soil strengthening applications. Monitoring the occurrence, spatial distribution, and temporal evolution of calcium carbonate precipitation in the subsurface is critical for evaluating the performance of this technology and for developing the predictive models needed for engineering application. In this study, we conducted laboratory column experiments using natural sediment and groundwater to evaluate the utility of geophysical (complex resistivity and seismic) sensing methods, dynamic synchrotron x-ray computed tomography (micro-CT), and reactive transport modeling for tracking ureolytically-driven calcium carbonate precipitation processes under site relevant conditions. Reactive transport modeling with TOUGHREACT successfully simulated the changes of the major chemical components during urea hydrolysis. Even at the relatively low level of urea hydrolysis observed in the experiments, the simulations predicted an enhanced calcium carbonate precipitation rate that was 3-4 times greater than the baseline level. Reactive transport modeling results, geophysical monitoring data and micro-CT imaging correlated well with reaction processes validated by geochemical data. In particular, increases in ionic strength of the pore fluid during urea hydrolysis predicted by geochemical modeling were successfully captured by electrical conductivity measurements and confirmed by geochemical data. The low level of urea hydrolysis and calcium carbonate precipitation suggested by the model and geochemical data was corroborated by minor changes in seismic P-wave velocity measurements and micro-CT imaging; the latter provided direct evidence of sparsely distributed calcium carbonate precipitation. Ion exchange processes promoted through NH4+ production during urea hydrolysis were incorporated in the model and captured critical changes in the major metal species. The electrical phase increases were potentially due to ion exchange processes that modified charge structure at mineral/water interfaces. Our study revealed the potential of geophysical monitoring for geochemical changes during urea hydrolysis and the advantages of combining multiple approaches to understand complex biogeochemical processes in the subsurface.

Evaluating the potential of native ureolytic microbes to remediate a 90Sr contaminated environment.

This study was a preliminary evaluation of ureolytically driven calcite precipitation and strontium coprecipitation for remediating (90)Sr contamination at the Hanford 100-N Area in Washington; in particular the approach is suitable for treating sorbed (90)Sr that could otherwise be a long-term source for groundwater contamination. Geochemical conditions at the site are compatible with long-term calcite stability, and therefore groundwater and sediment samples were examined to assess the ureolytic capabilities of the native microbiota. Quantitative assays detected up to 2 × 10(4) putative ureC gene copies mL(-1) in water and up to 9 × 10(5) copies g(-1) in sediment. The ureC assays and laboratory-based estimates of ureolytic activity indicated that the distribution of in situ ureolytic potential was very heterogeneous with depth and also that the ureolytic activity was predominantly associated with attached organisms. A mixed kinetic-equilibrium model was developed for the 100-N site to simulate urea treatment and predict strontium removal. Together, the microbial characterization data and modeling suggest that the site has the requisite biogeochemical characteristics for application of the calcite precipitation remediation approach for (90)Sr.

Stimulation of microbial urea hydrolysis in groundwater to enhance calcite precipitation.

Addition of molasses and urea was tested as a means of stimulating microbial urea hydrolysis in the Eastern Snake River Plain Aquifer in Idaho. Ureolysis is an integral component of a novel remediation approach for divalent trace metal and radionuclide contaminants in groundwater and associated geomedia, where the contaminants are immobilized by coprecipitation in calcite. Generation of carbonate alkalinity from ureolysis promotes calcite precipitation. In calcite-saturated aquifers, this represents a potential long-term contaminant sequestration mechanism. In a single-well experiment, dilute molasses was injected three times over two weeks to promote overall microbial growth, followed by one urea injection. With molasses addition, total cell numbers in the groundwater increased 1-2 orders of magnitude. Estimated ureolysis rates in recovered groundwater samples increased from < 0.1 to > 25 nmol L(-1) hr(-1). A quantitative PCR assay for the bacterial ureC gene indicated that urease gene numbers increased up to 170 times above pre-injection levels. Following urea injection, calcite precipitates were recovered. Estimated values for an in situ first order ureolysis rate constant ranged from 0.016 to 0.057 d(-1). Although collateral impacts such as reduced permeability were observed, overall results indicated the viability of manipulating biogeochemical processes to promote contaminant sequestration.