Ontological analysis of SNOMED CT

Background

SNOMED CT is the most comprehensive medical terminology. However, its use for intelligent services based on formal reasoning is questionable.

Methods

The analysis of the structure of SNOMED CT is based on the formal top-level ontology DOLCE.

Results

The analysis revealed several ontological and knowledge-engineering errors, the most important are errors in the hierarchy (mostly from an ontological point of view, but also regarding medical aspects) and the mixing of subsumption relations with other types (mostly 'part of').

Conclusion

The found errors impede formal reasoning. The paper presents a possible way to correct these problems.

     

Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer

Background

Endometrial cancer (EC) is a major health concern due to its rising incidence. Whilst early stage disease is generally cured by surgery, advanced EC has a poor prognosis with limited treatment options. Altered energy metabolism is a hallmark of malignancy. Cancer cells drive tumour growth through aerobic glycolysis and must export lactate to maintain intracellular pH. The aim of this study was to evaluate the expression of the lactate/proton monocarboxylate transporters MCT1 and MCT4 and their chaperone CD147 in EC, with the ultimate aim of directing future drug development.

Methods

MCT1, MCT4 and CD147 expression was examined using immunohistochemical analysis in 90 endometrial tumours and correlated with clinico-pathological characteristics and survival outcomes.

Results

MCT1 and MCT4 expression was observed in the cytoplasm, the plasma membrane or both locations. CD147 was detected in the plasma membrane and associated with MCT1 (p =?0.003) but not with MCT4 (p =?0.207) expression. High MCT1 expression was associated with reduced overall survival (p =?0.029) and remained statistically significant after adjustment for survival covariates (p =?0.017).

Conclusion

Our data suggest that MCT1 expression is an important marker of poor prognosis in EC. MCT1 inhibition may have potential as a treatment for advanced or recurrent EC.

     

Nearest neighbor imputation algorithms: a critical evaluation

Background

Nearest neighbor (NN) imputation algorithms are efficient methods to fill in missing data where each missing value on some records is replaced by a value obtained from related cases in the whole set of records. Besides the capability to substitute the missing data with plausible values that are as close as possible to the true value, imputation algorithms should preserve the original data structure and avoid to distort the distribution of the imputed variable. Despite the efficiency of NN algorithms little is known about the effect of these methods on data structure.

Methods

Simulation on synthetic datasets with different patterns and degrees of missingness were conducted to evaluate the performance of NN with one single neighbor (1NN) and with k neighbors without (kNN) or with weighting (wkNN) in the context of different learning frameworks: plain set, reduced set after ReliefF filtering, bagging, random choice of attributes, bagging combined with random choice of attributes (Random-Forest-like method).

Results

Whatever the framework, kNN usually outperformed 1NN in terms of precision of imputation and reduced errors in inferential statistics, 1NN was however the only method capable of preserving the data structure and data were distorted even when small values of k neighbors were considered; distortion was more severe for resampling schemas.

Conclusions

The use of three neighbors in conjunction with ReliefF seems to provide the best trade-off between imputation error and preservation of the data structure. The very same conclusions can be drawn when imputation experiments were conducted on the single proton emission computed tomography (SPECTF) heart dataset after introduction of missing data completely at random.

     

Integration of tools for binding archetypes to SNOMED CT

Background

The Archetype formalism and the associated Archetype Definition Language have been proposed as an ISO standard for specifying models of components of electronic healthcare records as a means of achieving interoperability between clinical systems. This paper presents an archetype editor with support for manual or semi-automatic creation of bindings between archetypes and terminology systems.

Methods

Lexical and semantic methods are applied in order to obtain automatic mapping suggestions. Information visualisation methods are also used to assist the user in exploration and selection of mappings.

Results

An integrated tool for archetype authoring, semi-automatic SNOMED CT terminology binding assistance and terminology visualization was created and released as open source.

Conclusion

Finding the right terms to bind is a difficult task but the effort to achieve terminology bindings may be reduced with the help of the described approach. The methods and tools presented are general, but here only bindings between SNOMED CT and archetypes based on the openEHR reference model are presented in detail.

     

Defining electronic-prescribing and infusion-related medication errors in paediatric intensive care – a Delphi study

Background

The use of health information technology (HIT) to improve patient safety is widely advocated by governmental and safety agencies. Electronic-prescribing and smart-pump technology are examples of HIT medication error reduction strategies. The introduction of new errors on HIT implementation is, however, also recognised. To determine the impact of HIT interventions, clear medication error definitions are required. This study aims to achieve consensus on defining as medication errors a range of either technology-generated, or previously unaddressed infusion-related scenarios, common in the paediatric intensive care setting.

Methods

This study was conducted in a 23-bed paediatric intensive care unit (PICU) of an Irish tertiary paediatric hospital. A modified Delphi technique was employed: previously undefined medication-incidents were identified by retrospective review of voluntary incident reports and clinical pharmacist interventions; a multidisciplinary expert panel scored each incident using a 9-point Likert scale over a number of iterative rounds; levels of agreement were assessed to produce a list of medication errors. Differences in scoring between healthcare professionals were assessed.

Results

Seventeen potential errors or ‘scenarios’ requiring consensus were identified, 13 of which related to technology recently implemented into the PICU. These were presented to a panel of 37 participants, comprising of doctors, nurses and pharmacists. Consensus was reached to define as errors all reported smart-pump scenarios (n =?6) and those pertaining to the pre-electronic process of prescribing weight-based paediatric infusions (n =?4). Of 7 electronic-prescribing scenarios, 4 were defined as errors, 2 were deemed not to be and consensus could not be achieved for the last. Some differences in scoring between healthcare professionals were found, but were only significant (p <?0.05) for two and three scenarios in consensus rounds 1 and 2 respectively.

Conclusion

The list of medication errors produced using the Delphi technique highlights the diversity of previously undefined medication errors in PICU. The increased complexity of electronic-prescribing processes is evident from the difficulty in achieving consensus on those scenarios. Reducing ambiguity in defining medication errors should assist future research on the impact of HIT medication safety initiatives in critical care. The increasing use of HIT and associated new errors will necessitate further similar studies.

     

Lightweight predicate extraction for patient-level cancer information and ontology development

Background

Knowledge engineering for ontological knowledgebases is resource and time intensive. To alleviate these issues, especially for novices, automated tools from the natural language domain can assist in the development process of ontologies. We focus towards the development of ontologies for the public health domain and use patient-centric sources from MedlinePlus related to HPV-causing cancers.

Methods

This paper demonstrates the use of a lightweight open information extraction (OIE) tool to derive accurate knowledge triples that can lead to the seeding of an ontological knowledgebase. We developed a custom application, which interfaced with an information extraction software library, to help facilitate the tasks towards producing knowledge triples from textual sources.

Results

The results of our efforts generated accurate extractions ranging from 80–89% precision. These triples can later be transformed to OWL/RDF representation for our planned ontological knowledgebase.

Conclusions

OIE delivers an effective and accessible method towards the development ontologies.

     

Hypnotic relaxation results in elevated thresholds of sensory detection but not of pain detection

Background

Many studies show an effectiveness of hypnotic analgesia. It has been discussed whether the analgesic effect is mainly caused by the relaxation that is concomitant to hypnosis. This study was designed to evaluate the effects of hypnotic relaxation suggestion on different somatosensory detection and pain thresholds.

Methods

Quantitative sensory testing (QST) measurements were performed before and during hypnosis in twenty-three healthy subjects on the dorsum of the right hand. Paired t-test was used to compare threshold changes. The influence of hypnotic susceptibility was evaluated by calculating correlation coefficients for threshold changes and hypnotic susceptibility (Harvard group scale).

Results

During hypnosis significantly changed somatosensory thresholds (reduced function) were observed for the following sensory detection thresholds: Cold Detection Threshold (CDT), Warm Detection Threshold (WDT), Thermal Sensory Limen (TSL) and Mechanical Detection Threshold (MDT). The only unchanged sensory detection threshold was Vibration Detection Threshold (VDT). No significant changes were observed for the determined pain detection thresholds (Cold Pain Thresholds, Heat Pain Thresholds, Mechanical Pain Sensitivity, Dynamic Mechanical Allodynia, Wind-up Ratio and Pressure Pain Threshold). No correlation of hypnotic susceptibility and threshold changes were detected.

Conclusion

Hypnotic relaxation without a specific analgesic suggestion results in thermal and mechanical detection, but not pain threshold changes. We thus conclude that a relaxation suggestion has no genuine effect on sensory pain thresholds.

Trial Registration

ClinicalTrials.gov, Identifier:NCT02261155 (9^th October 2014).

     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

Ethical Assessment of Human Embryonic Stem Cell Research According to Turkish Muslim Scholars: First Critical Analysis and Some Reflections

Background

Turkey, with a Muslim population of officially over 99 %, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people’s attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals.

Objective(s)

To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos.

Design

Qualitative study.

Setting

Muslim scholars located in different parts of Turkey.

Methods

Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis.

Results

Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments.

Conclusion

Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.

     

Experiences mapping a legacy interface terminology to SNOMED CT

Background

SNOMED CT is being increasingly adopted as the standard clinical terminology for health care applications. Existing clinical applications that use legacy interface terminology need to migrate to the preferred SNOMED CT standard. In this paper, we describe our experience and methodology for mapping concepts from a legacy system to SNOMED CT.

Methods

Our approach includes the establishment of mapping rules between terminologists and back and forth collaboration of the mapped results through one or more iterations in order to reach consensus on the final maps.

Results

We highlight our results not only in terms of the number of matches, quality of maps, use of post-coordination, and multiple maps but also include our observations about SNOMED CT including inconsistencies, redundancies and omissions related to our legacy mapping.

Conclusion

Our methodology and lessons learned from this mapping exercise may be helpful to other terminologists who may be similarly challenged to migrate their legacy terminology to SNOMED CT. This mapping process and resulting discoveries about SNOMED CT may further contribute to refinement of this dynamic, clinical terminology standard.

     

Novel Mutation in <Emphasis Type="Italic">CECR1</Emphasis> Leads to Deficiency of ADA2 with Associated Neutropenia

Purpose

Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2.

Methods

We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives.

Results

Genetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives.

Conclusion

This is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.

     

Glücklich als Paar – glücklicher Schlaf?

Background

Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.

Objectives

To identify and discuss connections between relationship and sleep quality.

Methods

Review of the literature in electronic databases.

Results

Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.

Conclusions

Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.

     

The Course of Quality of Life in Patients on Peritoneal Dialysis: A 12-month Prospective Observational Cohort Study

Background

Quality of life (QOL) impairments are common in patients undergoing dialysis, and have been strongly associated with significant clinical outcomes like mortality and morbidity. Despite this, little is known about the course of QOL over time, especially for patients on peritoneal dialysis (PD).

Purpose

This prospective study was set to explore course and determinants of QOL over 12 months in PD patients.

Methods

A total of 115 PD patients completed the SF-12 and Kidney Disease Quality of Life Short Form (KDQOL-SF) at baseline and 12 months later. Intra-individual changes in physical (physical component summary, PCS), mental (mental component summary, MCS), and Kidney Disease Component Summary scores (KDCS) were identified based on the minimally important clinical difference threshold. Clinical information was extracted from medical records.

Results

Of the patients, 74–80 % reported physical QOL impairments, as compared to 29–33 % who reported mental/emotional QOL impairments. PCS and MCS scores remained stable across 12 months. Significant deterioration was noted in the domains of patient satisfaction, staff encouragement, and social support, while there were significant increases in the perceived effects of kidney disease. Intra-individual trajectory analyses indicated that one in three patients reported deteriorating QOL. No sociodemographic or clinical variables were found to be associated with course of outcomes.

Conclusions

Although PD offers the convenience of home-based care, it is associated with persisting QOL impairments and diminishing QOL over time, especially in domains related to quality of care and support. This highlights the need for improving or maintaining standards of care and support for PD patients as they become increasingly established on their regimes.

     

The Role of Mindfulness in the Insomnia Severity of Female Chronic Hypnotic Users

Purpose

To investigate dispositional mindfulness, psychiatric symptoms, and their relationship with insomnia severity among female chronic hypnotic users.

Methods

Observational, cross-sectional study, including 76 women with chronic hypnotic use. Participants completed several self-report questionnaires: sociodemographic characteristics, depressive symptoms (CES-D), anxiety levels (STAI-T), dispositional mindfulness (FFMQ), and insomnia severity (ISI). Exploratory linear regression models were used to identify factors related to insomnia severity.

Results

Multiple linear regression models showed that, for the total sample (N?=?76), age (B?=???0.14, p?=?0.003), depressive symptoms (B?=?0.16, p =?0.005), and the mindfulness facets “observe” (B?=?0.21. p?=?0.013) and “act with awareness—auto pilot” (B?=???0.48, p =?0.017) were correlated to insomnia severity.

Conclusion

Results confirm a relationship between mindfulness and insomnia among female chronic hypnotic users, specifically regarding the ability to observe and act with awareness. A higher score on the “observe” facet was positively correlated with insomnia. This may be because the skill of observing itself, isolated from other mindfulness precepts, does not provide sufficient strategies to cope with the observed discomfort. Increased “acting with awareness—autopilot” was negatively correlated with insomnia severity, arguably because it stimulates breaking automatic patterns of thoughts and behaviors that contribute to the perpetuation of the insomnia cycle.

     

Deficiencies in elements involved in TLR4-receptor signalling in RBL-2H3 cells

Objective

RBL-2H3 cells express Toll-like receptors, including TLR4. This study aims to assess various aspects of the TLR4 pathway.

Methods

RBL-2H3 cells were indirectly stained for cell surface TLR4, 25 CD14 and intracellular MyD88 proteins and analysed through flow cytometry for single-colour staining.

Results

While TLR4-receptors are expressed in RBL-2H3 cells, associated elements involved in the signaling pathway, CD14 and MyD88, are not.

Conclusion

Care should be taken if RBL-2H3 cells are used to study aspects of the innate immune system in mast cells.

     

Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study

Background

Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample.

Methods

A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores.

Results

The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10^-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10^-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 (GATA11A06), previously linked to dyslexia (LOD scores = 2.2 and 5.1).

Conclusion

Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies.

     

Micronized palmitoylethanolamide reduces joint pain and glial cell activation

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.

     

Public responses to the sharing and linkage of health data for research purposes: a systematic review and thematic synthesis of qualitative studies

Background

The past 10 years have witnessed a significant growth in sharing of health data for secondary uses. Alongside this there has been growing interest in the public acceptability of data sharing and data linkage practices. Public acceptance is recognised as crucial for ensuring the legitimacy of current practices and systems of governance. Given the growing international interest in this area this systematic review and thematic synthesis represents a timely review of current evidence. It highlights the key factors influencing public responses as well as important areas for further research.

Methods

This paper reports a systematic review and thematic synthesis of qualitative studies examining public attitudes towards the sharing or linkage of health data for research purposes. Twenty-five studies were included in the review. The included studies were conducted primarily in the UK and North America, with one study set in Japan, another in Sweden and one in multiple countries. The included studies were conducted between 1999 and 2013 (eight studies selected for inclusion did not report data collection dates). The qualitative methods represented in the studies included focus groups, interviews, deliberative events, dialogue workshops and asynchronous online interviews.

Results

Key themes identified across the corpus of studies related to the conditions necessary for public support/acceptability, areas of public concern and implications for future research. The results identify a growing body of evidence pointing towards widespread general—though conditional—support for data linkage and data sharing for research purposes. Whilst a variety of concerns were raised (e.g. relating to confidentiality, individuals’ control over their data, uses and abuses of data and potential harms arising) in cases where participants perceived there to be actual or potential public benefits from research and had trust in the individuals or organisations conducting and/or overseeing data linkage/sharing, they were generally supportive. The studies also find current low levels of awareness about existing practices and uses of data.

Conclusions

Whilst the results indicate widespread (conditional) public support for data sharing and linkage for research purposes, a range of concerns exist. In order to ensure public support for future research uses of data greater awareness raising combined with opportunities for public engagement and deliberation are needed. This will be essential for ensuring the legitimacy of future health informatics research and avoiding further public controversy.

     

Picture perfect—how seeking perfection influences sleep and romantic relationships

Background

Studies have shown that sleep quality is negatively affected by perfectionism. Moreover, partner- or relationship-oriented perfectionism negatively influences relationship quality.

Objective

This paper aims to investigate the association of general perfectionism with sleep quality and relationship quality.

Materials and methods

A study assessing perfectionism, sleep quality, and relationship quality was performed via analyzing online questionnaires completed by 489 German adults from the general population.

Results

Participants with impaired sleep showed a higher level of maladaptive perfectionism (concern over mistakes and doubts, parental expectations, and criticism) than participants with good sleep, whereby the severity of sleep problems was not determining. Relationship quality is affected by perfectionism. However, this association is mediated by sleep quality.

Conclusion

Perfectionism is associated with worse sleep quality but not with worse relationship quality when sleep quality is integrated into the model as a mediator.

     

Histamine intolerance: a metabolic disease?

Objective

To evaluate the evidence regarding the disease concept of histamine intolerance as a state of inadequate histamine inactivation.

Methods

Keyword-based systematic screening of the scientific literature and of public websites focusing on diagnostic and therapeutic procedures.

Results

Histamine intolerance is commonly diagnosed based solely on subjective reporting of symptoms instead of following systematic diagnostic procedures based on objective laboratory and physical parameters. The only effective long-term therapy is avoidance of histamine-containing food.

Conclusions

The concept of histamine intolerance as a metabolic disease is in need of more experimental and clinical evidence and affected patients will benefit from a clear, evidence-based diagnostic and therapeutic regime.