Using data mining techniques to explore physicians' therapeutic decisions when clinical guidelines do not provide recommendations: methods and example for type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Clinical guidelines carry medical evidence to the point of practice. As evidence is not always available, many guidelines do not provide recommendations for all clinical situations encountered in practice. We propose an approach for identifying knowledge gaps in guidelines and for exploring physicians' therapeutic decisions with data mining techniques to fill these knowledge gaps. We demonstrate our method by an example in the domain of type 2 diabetes.</p> <p>Methods</p> <p>We analyzed the French national guidelines for the management of type 2 diabetes to identify clinical conditions that are not covered or those for which the guidelines do not provide recommendations. We extracted patient records corresponding to each clinical condition from a database of type 2 diabetic patients treated at Avicenne University Hospital of Bobigny, France. We explored physicians' prescriptions for each of these profiles using C5.0 decision-tree learning algorithm. We developed decision-trees for different levels of detail of the therapeutic decision, namely the type of treatment, the pharmaco-therapeutic class, the international non proprietary name, and the dose of each medication. We compared the rules generated with those added to the guidelines in a newer version, to examine their similarity.</p> <p>Results</p> <p>We extracted 27 rules from the analysis of a database of 463 patient records. Eleven rules were about the choice of the type of treatment and thirteen rules about the choice of the pharmaco-therapeutic class of each drug. For the choice of the international non proprietary name and the dose, we could extract only a few rules because the number of patient records was too low for these factors. The extracted rules showed similarities with those added to the newer version of the guidelines.</p> <p>Conclusion</p> <p>Our method showed its usefulness for completing guidelines recommendations with rules learnt automatically from physicians' prescriptions. It could be used during the development of guidelines as a complementary source from practice-based knowledge. It can also be used as an evaluation tool for comparing a physician's therapeutic decisions with those recommended by a given set of clinical guidelines. The example we described showed that physician practice was in some ways ahead of the guideline.</p

An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up

Attitudes Toward the Ethics of Research Using Social Media: A Systematic Review.

BACKGROUND: Although primarily used for social networking and often used for social support and dissemination, data on social media platforms are increasingly being used to facilitate research. However, the ethical challenges in conducting social media research remain of great concern. Although much debated in the literature, it is the views of the public that are most pertinent to inform future practice. OBJECTIVE: The aim of our study was to ascertain attitudes on the ethical considerations of using social media as a data source for research as expressed by social media users and researchers. METHODS: A systematic review was conducted, wherein 16 databases and 2 Internet search engines were searched in addition to handsearching, reference checking, citation searching, and contacting authors and experts. Studies that conducted any qualitative methods to collect data on attitudes on the ethical implications of research using social media were included. Quality assessment was conducted using the quality of reporting tool (QuaRT) and findings analyzed using inductive thematic synthesis. RESULTS: In total, 17 studies met the inclusion criteria. Attitudes varied from overly positive with people expressing the views about the essential nature of such research for the public good, to very concerned with views that social media research should not happen. Underlying reasons for this variation related to issues such as the purpose and quality of the research, the researcher affiliation, and the potential harms. The methods used to conduct the research were also important. Many respondents were positive about social media research while adding caveats such as the need for informed consent or use restricted to public platforms only. CONCLUSIONS: Many conflicting issues contribute to the complexity of good ethical practice in social media research. However, this should not deter researchers from conducting social media research. Each Internet research project requires an individual assessment of its own ethical issues. Guidelines on ethical conduct should be based on current evidence and standardized to avoid discrepancies between, and duplication across, different institutions, taking into consideration different jurisdictions

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis : an international, multidisciplinary Delphi-based consensus

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.Peer reviewe

Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon: A Semi - longitudinal study.

The current guidelines for malaria prevention and control during pregnancy in Africa is predicated on the prevention of infection and/or disease through intermittent preventive treatment in pregnancy (IPTp), insecticide-treated nets (ITNs) and effective malaria case diagnosis and management. Concerns that increasing SP resistance in some areas of SSA may have compromised IPTp-SP efficacy prompted this contemporaneous study, designed to assess the prevalence and risk factors of sub-microscopic infection in parturient women during the low transmission season in Mutengene, a rapidly growing semi-urban area in Southwest Region, Cameroon. Pregnant women originally reporting for the establishment of antenatal clinic care during the dry season were followed-up to term and their pregnancy outcomes recorded. About 2 ml of venous blood was collected for malaria diagnosis using PfHRP2/pLDH malaria rapid diagnostic kit and light microscopy. DNA was extracted from dried blood spots by the Chelex-100 method and the Plasmodium falciparum status detected by nested PCR amplification of the 18SrRNA gene using specific predesigned primers. Of the 300 women enrolled, the proportion of malaria parasite infected as determined by microscopy, RDT and PCR was 12.9%, 16.4% and 29.4% respectively, with 39.9% overall infected with P. falciparum by microscopy and/or RDT and/or PCR and a very low-density infection, averaging 271 parasites per microliter of blood. About 25.0% (68/272) of women who were negative by microscopy were positive by PCR (submicroscopic P. falciparum infection), with primigravidae and IPTp-SP non usage identified as independent risk factors for submicroscopic P. falciparum parasitaemia while fever history (aOR = 4.83, 95% CI = 1.28-18.22, p = 0.020) was associated with risk of malaria parasite infection overall. IPTp-SP use (p = 0.007) and dosage (p = 0.005) significantly influenced whether or not the participant will be malaria parasite negative or carry submicroscopic or microscopic infection. Although Infant birthweight and APGAR score were independent of the mother's P. falciparum infection and submicroscopic status, infant's birthweight varied with the gravidity status (p = 0.001) of the mother, with significantly lower birthweight neonates born to primigravidae compared to secundigravidae (p = 0.001) and multigravidae (p = 0.003). Even in holo-endemic dry season, there exists a large proportion of pregnant women with very low density parasitaemia. IPTp-SP seems to be relevant in controlling submicroscopic P. falciparum infections, which remains common in pregnant women, and are hard to diagnose, with potentially deleterious consequences for maternal and fetal health. Future studies should be carried out in hyperendemic malaria foci where the parasitemia levels are substantially higher in order to confirm the efficacy of IPTp-SP

Towards computerizing intensive care sedation guidelines: design of a rule-based architecture for automated execution of clinical guidelines

<p>Abstract</p> <p>Background</p> <p>Computerized ICUs rely on software services to convey the medical condition of their patients as well as assisting the staff in taking treatment decisions. Such services are useful for following clinical guidelines quickly and accurately. However, the development of services is often time-consuming and error-prone. Consequently, many care-related activities are still conducted based on manually constructed guidelines. These are often ambiguous, which leads to unnecessary variations in treatments and costs.</p> <p>The goal of this paper is to present a semi-automatic verification and translation framework capable of turning manually constructed diagrams into ready-to-use programs. This framework combines the strengths of the manual and service-oriented approaches while decreasing their disadvantages. The aim is to close the gap in communication between the IT and the medical domain. This leads to a less time-consuming and error-prone development phase and a shorter clinical evaluation phase.</p> <p>Methods</p> <p>A framework is proposed that semi-automatically translates a clinical guideline, expressed as an XML-based flow chart, into a Drools Rule Flow by employing semantic technologies such as ontologies and SWRL. An overview of the architecture is given and all the technology choices are thoroughly motivated. Finally, it is shown how this framework can be integrated into a service-oriented architecture (SOA).</p> <p>Results</p> <p>The applicability of the Drools Rule language to express clinical guidelines is evaluated by translating an example guideline, namely the sedation protocol used for the anaesthetization of patients, to a Drools Rule Flow and executing and deploying this Rule-based application as a part of a SOA. The results show that the performance of Drools is comparable to other technologies such as Web Services and increases with the number of decision nodes present in the Rule Flow. Most delays are introduced by loading the Rule Flows.</p> <p>Conclusions</p> <p>The framework is an effective solution for computerizing clinical guidelines as it allows for quick development, evaluation and human-readable visualization of the Rules and has a good performance. By monitoring the parameters of the patient to automatically detect exceptional situations and problems and by notifying the medical staff of tasks that need to be performed, the computerized sedation guideline improves the execution of the guideline.</p

Cancer recurrence times from a branching process model

As cancer advances, cells often spread from the primary tumor to other parts of the body and form metastases. This is the main cause of cancer related mortality. Here we investigate a conceptually simple model of metastasis formation where metastatic lesions are initiated at a rate which depends on the size of the primary tumor. The evolution of each metastasis is described as an independent branching process. We assume that the primary tumor is resected at a given size and study the earliest time at which any metastasis reaches a minimal detectable size. The parameters of our model are estimated independently for breast, colorectal, headneck, lung and prostate cancers. We use these estimates to compare predictions from our model with values reported in clinical literature. For some cancer types, we find a remarkably wide range of resection sizes such that metastases are very likely to be present, but none of them are detectable. Our model predicts that only very early resections can prevent recurrence, and that small delays in the time of surgery can significantly increase the recurrence probability.Comment: 26 pages, 9 figures, 4 table