Improving search filter development: a study of palliative care literature

Background It is difficult to systematically search for literature relevant to palliative care in general medical journals. A previously developed search filter for use on OVID Medline validated using a gold standard set of references identified through hand searching, achieved an unacceptably low sensitivity (45.4%). Retrieving relevant literature is integral to support evidence based practice, and understanding the nature of the incorrectly excluded citations (false negatives) using the filter may lead to improvement in the filter's performance. Methods The objectives were to describe the nature of subjects reflected in the false negative citations and to empirically improve the sensitivity of the search filter. A thematic analysis of MeSH terms by three independent reviewers was used to describe the subject coverage of the missed records. Using a frequency analysis of MeSH terms, those headings which could individually contribute at least 2.5% to sensitivity (occurring 19 or more times) were added to the search filter. All previously run searches were rerun at the same time as the revised filter, and results compared. Results Thematic analysis of MeSH terms identified thirteen themes reflected in the missing records, none of them intrinsically palliative. The addition of six MeSH terms to the existing search filter (physician-patient relations, prognosis, quality of life, survival rate, treatment outcome and attitude to health) led to an increase in sensitivity from 46.3% to 64.7%, offset by a decrease in precision from 72.6% to 21.9%. Conclusion The filter's sensitivity was successfully increased using frequency analysis of MeSH terms, offset by a decrease in precision. A thematic analysis of MeSH terms for the false negative citations confirmed the absence of any intrinsically palliative theme or term, suggesting that future improvements to search filters for palliative care literature will first depend on better identifying how clinicians and researchers conceptualise palliative care. It is suggested that a constellation of parameters: stage of disease (advanced or active), prospect of cure (little or none), and treatment goals (primarily quality of life) may ultimately inform search strategies. This may be similarly true for chronic diseases, which share the inherent passage of time which marks them apart from acute, and therefore more readily identifiable, episodes of care

Comparison of Two Porcine-Derived Materials for Repairing Abdominal Wall Defects in Rats

OBJECTIVE: The purpose of this study was to compare the mechanical properties, host responses and incorporation of porcine small intestine submucosa (PSIS) and porcine acellular dermal matrix (PADM) in a rat model of abdominal wall defect repair. MATERIALS AND METHODS: Prior to implantation, PSIS and PADM were prepared and evaluated in terms of structure and mechanical properties. Full-thickness abdominal wall defects were created in 50 Sprague-Dawley rats, and were repaired using either PSIS or PADM. Rats were sacrificed 1, 2, 4, 8 and 12 weeks post-repair and examined for herniation, infection, adhesions, contraction, and changes in the thickness and strength of the tissues incorporated at the defect sites. Histopathology and immunohistochemistry were performed to analyze inflammatory responses, collagen deposition and vascularization. RESULTS: PADM showed more dense collagen deposition and stronger mechanical properties than PSIS prior to implantation (P<0.01). However, the mechanical properties observed after integration with the surrounding native tissues was similar for PADM and PSIS. Both PADM and PSIS showed significant contraction by week 12. However, PADM tissue induced less adhesion and increased in thickness more slowly, and showed less infiltration by foreign giant cells, polymorphonuclear cells, and mononuclear cells. Improved remodeling of host tissue was observed after PSIS implantation, which was apparent from the orientation of bands of fibrous connective tissue, intermixed with newly formed blood vessels by Week 12. CONCLUSION: PSIS showed weaker mechanical properties prior to implantation. However, after implantation PSIS induced more pronounced host responses and showed better incorporation into host tissues than PADM

Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits

PURPOSE: The use of novel and often expensive drugs offering limited survival benefit in advanced disease is controversial. Treatment recommendations are influenced by patient characteristics and trial data showing overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). PFS is frequently the primary outcome in licencing studies. PATIENTS AND METHODS: As part of a longitudinal study Assessing the 'VALue' to patients of PROgression Free Survival (AVALPROFS), oncologists completed checklists at baseline following consultations with patients. Questions probed perceived clinical benefits of the drugs to populations in general. Patients completed study-specific interview schedules at baseline, 6 weeks into treatment, and at withdrawal due to toxicity or progression. Patients also completed tumour- and treatment-specific quality of life questionnaires monthly for their time in the study. Only baseline results are reported here. RESULTS: Thirty-two UK oncologists discussed management options with 90 patients with heterogeneous advanced cancers. Oncologists' estimates of medical benefit in general from treatment varied between 10 and 80 %. They expected 46/90 (51 %) of their patients to derive some clinical benefit from the prescribed treatment but were either unsure or expected none for 44/90 (49 %). Predictions of life expectancy were variable but 62 % (56/90) of patients were expected to survive longer with treatment. A majority of patients 51/90 (57 %) had 'no idea' or were 'unclear' what PFS meant and 45/90 (50 %) thought extension of life was the primary therapeutic aim of treatment. CONCLUSION: Discussions between doctors and patients with metastatic disease about future management plans and likely therapeutic gains are challenging. Factors influencing decisions about putative benefits of novel drugs are often applied inconsistently can be overly optimistic and may even contradict published data

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Fluorescence in-situ hybridisation on biopsies from clam ileocystoplasties and on a clam cancer

The incidence of carcinoma following an enterocystoplasty increases with time and is a major concern after such procedures. The aim of this study was to investigate genetic instability (in the form of numerical chromosomal aberrations) at the enterovesical anastomosis in patients who had undergone a clam ileocystoplasty using fluorescent in-situ hybridisation (FISH). Fluorescent in-situ hybridisation was performed on touch preparation samples prepared from fresh endoscopic biopsies obtained from the enterovesical anastomosis and native bladder remnant (control specimens) of 15 patients who had undergone a clam ileocystoplasty. Fluorescent in-situ hybridisation was also performed on one squamous cell cancer specimen. Significant aneusomic changes were found at the enterovesical anastomosis in all 15 patients. Alterations in chromosome 18 copy number were the most frequent abnormal finding (trisomy 18, n=8; monosomy 18, n=7). Nine patients were monosomic for chromosome 9. Isolated monosomy 8 and trisomy 8 were each found in one patient. The control specimens were all normal. An unusually high incidence of polysomic cells was found in the clam tumour specimen, reflecting the aggressive nature of this cancer. Chromosomal numerical abnormalities occur at the enterovesical anastomosis following a clam ileocystoplasty and chromosome 18 appears to be a particularly good marker of genetic instability. The results of this study indicate that morphologically normal tissue obtained from the enterovesical anastomosis displays evidence of chromosomal instability that may predispose to tumour formation. However, further prospective, blinded, longitudinal studies are required to establish whether predetermined FISH signal patterns in enterocystoplasty cells in urine or obtained by biopsy predict the presence or absence of tumour

Vigorous lateral export of the meltwater outflow from beneath an Antarctic ice shelf

The instability and accelerated melting of the Antarctic Ice Sheet are among the foremost elements of contemporary global climate change1, 2. The increased freshwater output from Antarctica is important in determining sea level rise1, the fate of Antarctic sea ice and its effect on the Earth’s albedo4, 5, ongoing changes in global deep-ocean ventilation6, and the evolution of Southern Ocean ecosystems and carbon cycling7, 8. A key uncertainty in assessing and predicting the impacts of Antarctic Ice Sheet melting concerns the vertical distribution of the exported meltwater. This is usually represented by climate-scale models3–5, 9 as a near-surface freshwater input to the ocean, yet measurements around Antarctica reveal the meltwater to be concentrated at deeper levels10, 11, 12, 13, 14. Here we use observations of the turbulent properties of the meltwater outflows from beneath a rapidly melting Antarctic ice shelf to identify the mechanism responsible for the depth of the meltwater. We show that the initial ascent of the meltwater outflow from the ice shelf cavity triggers a centrifugal overturning instability that grows by extracting kinetic energy from the lateral shear of the background oceanic flow. The instability promotes vigorous lateral export, rapid dilution by turbulent mixing, and finally settling of meltwater at depth. We use an idealized ocean circulation model to show that this mechanism is relevant to a broad spectrum of Antarctic ice shelves. Our findings demonstrate that the mechanism producing meltwater at depth is a dynamically robust feature of Antarctic melting that should be incorporated into climate-scale models

West Antarctic Ice Sheet retreat in the Amundsen Sea driven by decadal oceanic variability

Mass loss from the Amundsen Sea sector of the West Antarctic Ice Sheet has increased in recent decades, suggestive of sustained ocean forcing or an ongoing, possibly unstable, response to a past climate anomaly. Lengthening satellite records appear to be incompatible with either process, however, revealing both periodic hiatuses in acceleration and intermittent episodes of thinning. Here we use ocean temperature, salinity, dissolved-oxygen and current measurements taken from 2000 to 2016 near the Dotson Ice Shelf to determine temporal changes in net basal melting. A decadal cycle dominates the ocean record, with melt changing by a factor of about four between cool and warm extremes via a nonlinear relationship with ocean temperature. A warm phase that peaked around 2009 coincided with ice-shelf thinning and retreat of the grounding line, which re-advanced during a post-2011 cool phase. These observations demonstrate how discontinuous ice retreat is linked with ocean variability, and that the strength and timing of decadal extremes is more influential than changes in the longer-term mean state. The nonlinear response of melting to temperature change heightens the sensitivity of Amundsen Sea ice shelves to such variability, possibly explaining the vulnerability of the ice sheet in that sector, where subsurface ocean temperatures are relatively high

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response

Mild cognitive impairment following chemotherapy is one of the most commonly reported post treatment symptoms by breast cancer survivors. This deterioration in cognitive function, commonly referred to as “chemobrain” or “chemofog,” was largely unacknowledged by the medical community until recent years. Although chemobrain has now become the subject of more vigorous exploration, little is known about this specific phenomenon’s psychosocial impact on breast cancer survivors. This research documents in-depth the effects that cognitive impairment has on women’s personal and professional lives, and our data suggest that greater attention needs to be focused on this arena of survivorship. The results are based on an in-depth qualitative study of 74 white and African American breast cancer survivors in California who experience post-treatment side effects. The data reported herein were obtained through the use of focus groups and in-depth interviews. Our data indicate that cognitive impairment can be problematic for survivors, with many asserting that it is their most troublesome post treatment symptom. Survivors report diminished quality of life and daily functioning as a result of chemobrain. Respondents detail a range of coping strategies that they are forced to employ in order to manage their social and professional lives. Chemobrain significantly impairs a proportion of cancer survivors, at great cost to them economically, emotionally, and interpersonally. This suggests that more research needs to be conducted on the psychosocial ramifications of post treatment symptoms in order to inform the efforts of the medical and mental health communities as well as the support networks of survivors. A better and broader understanding of the effects of cognitive impairment both in the medical community and among lay people could pave the way for improved social and psychological services for this population