Learning to detect and understand drug discontinuation events from clinical narratives

OBJECTIVE: Identifying drug discontinuation (DDC) events and understanding their reasons are important for medication management and drug safety surveillance. Structured data resources are often incomplete and lack reason information. In this article, we assessed the ability of natural language processing (NLP) systems to unlock DDC information from clinical narratives automatically. MATERIALS AND METHODS: We collected 1867 de-identified providers\u27 notes from the University of Massachusetts Medical School hospital electronic health record system. Then 2 human experts chart reviewed those clinical notes to annotate DDC events and their reasons. Using the annotated data, we developed and evaluated NLP systems to automatically identify drug discontinuations and reasons at the sentence level using a novel semantic enrichment-based vector representation (SEVR) method for enhanced feature representation. RESULTS: Our SEVR-based NLP system achieved the best performance of 0.785 (AUC-ROC) for detecting discontinuation events and 0.745 (AUC-ROC) for identifying reasons when testing this highly imbalanced data, outperforming 2 state-of-the-art non-SEVR-based models. Compared with a rule-based baseline system for discontinuation detection, our system improved the sensitivity significantly (57.75% vs 18.31%, absolute value) while retaining a high specificity of 99.25%, leading to a significant improvement in AUC-ROC by 32.83% (absolute value). CONCLUSION: Experiments have shown that a high-performance NLP system can be developed to automatically identify DDCs and their reasons from providers\u27 notes. The SEVR model effectively improved the system performance showing better generalization and robustness on unseen test data. Our work is an important step toward identifying reasons for drug discontinuation that will inform drug safety surveillance and pharmacovigilance

A Pill for the Ill? : Depression, Medicalization and Public Health

Mental disorders, especially depression, have been increasingly described as a growing burden to global public health. Critics argue, however, that the use of mental health surveys, underlying these descriptions, tends to overestimate the prevalence of mental disorders by not distinguishing everyday experiences of distress from pathological conditions. This medicalization of public health is believed to narrow the focus of public health practices. The aim of this thesis is twofold. The first objective is to describe and analyze experiences with antidepressant treatment for depression as expressed in adverse drug reaction (ADR) reports from patients, i.e. “consumers reports.” A second goal is to conduct a theoretical discussion, by looking at broad societal changes, and analyzing the consequences of mental ill health as a significant public health problem. Special attention will be given to medicalization. Reports of suspected adverse reactions regarding antidepressant mediations were submitted from 2002 to 2009 to an open Internet-based reporting system in Sweden. These were analyzed according to common psychiatric reactions and narrative experiences. Furthermore, a literature overview in a broad and general sense was performed to underpin a theoretical discussion on health, public health, mental ill health and medicalization. The main findings of this thesis were that patients reporting to an open Internet-based system in Sweden seemed, to a large extent, to experience psychiatric ADR symptoms of mental disturbances (sometimes severe), which affected them in many different ways, especially during discontinuation. These reports also suggested a negative doctor-patient interaction from the patient’s perspective. Risks leading to increased medicalization as a result of overdiagnoses of depression were found. Pharmaceuticalization resulting from overprescribed antidepressants was also deemed problematic. According to a theoretical discussion on public health and medicalization, increased medicalization as a result of excessive diagnosing risks individualizing mental problems and may divert the focus from the social and political context of public health. According to patient reports, there seems to be a potential problem as to how patients are diagnosed with depression and prescribed antidepressant medication in the medical encounter. Increased drug treatment risks lead to increased health care costs and potential harm from adverse drug reactions. Overdiagnosis and overtreatment may in turn lead to diminished trust in the health system. If depression is going to be viewed as a growing public health problem, it, therefore, calls for a distinction between ill health problems that are medical and those that are not. Arguments for increased medication must be related to a possible danger of medicalizing social problems and life crises

Patient-Reported Reasons for Switching or Discontinuing Statin Therapy : A Mixed Methods Study Using Social Media

INTRODUCTION: Statin discontinuation can have major negative health consequences. Studying the reasons for discontinuation can be challenging as traditional data collection methods have limitations. We propose an alternative approach using social media. METHODS: We used natural language processing and machine learning to extract mentions of discontinuation of statin therapy from an online health forum, WebMD ( http://www.webmd.com ). We then extracted data according to themes and identified key attributes of the people posting for themselves. RESULTS: We identified 2121 statin reviews that contained information on discontinuing at least one named statin. Sixty percent of people posting declared themselves as female and the most common age category was 55-64 years. Over half the people taking statins did so for < 6 months. By far the most common reason given (90%) was patient experience of adverse events, the most common of which were musculoskeletal and connective tissue disorders. The rank order of adverse events reported in WebMD was largely consistent with those reported to regulatory agencies in the US and UK. Data were available on age, sex, duration of statin use, and, in some instances, adverse event resolution and rechallenge. In some instances, details were presented on resolution of the adverse event and rechallenge. CONCLUSION: Social media may provide data on the reasons for switching or discontinuation of a medication, as well as unique patient perspectives that may influence continuation of a medication. This information source may provide unique data for novel interventions to reduce medication discontinuation

Loa loa Alben Trial data

Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001-50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas

An empirical and theoretical investigation of psychodynamic psychotherapy and neuroleptic medication for the treatment of schizophrenia

Since the early 1950s, biopsychiatric conceptualizations have dominated empirical, theoretical and therapeutic efforts to understand the treatment of schizophrenia. The contemporary preeminence of biopsychiatric conceptualizations of schizophrenia have overshadowed other perspectives that might contribute fruitfully to our capacity to understand and aid individuals suffering with this devastating emotional disorder. The origin of modern biopsychiatric conceptualizations is deconstructed by illuminating the non-epistemic underpinnings of Emil Kraeplin\u27s dementia praecox concept, which is the forerunner of the modern schizophrenia construct. Two widely held assumptions of the biomedical model, namely: 1) that schizophrenia is a degenerative, organic brain disease; and 2) that neuroleptic medications are the most effective and safest treatment of schizophrenia are empirically reviewed. Psychodynamic theory and therapy alternatives are also reviewed empirically and theoretically.The comparative effectiveness of Psychodynamic Psychotherapy-only (n = 9) and Medication-only (n = 12) was investigated using an experimental design (Karon & VandenBos, 1981). All patients were administered the Thematic Apperception Test (TAT) at pre- and post-treatment (20 months). Westen\u27s (1995; Hilsenroth, Stein, & Pinsker, 2004) Social Cognition and Object Relations Scale (SCORS) was used to rate pre- and post-treatment TAT narratives in order to assess changes in the cognitive and affective aspects of patients\u27 object relations throughout treatment. Jacobson and Truax\u27 (1991) Clinical Significance methodology was used to detect clinically significant change for each individual patient. Results show the SCORS is a reliable and valid instrument for use with a schizophrenia sample.Treatment outcome results suggest that patients receiving psychodynamic psycotherapy exhibit clinically significant change in a variety of object relations domains when assessed at the group and individual levels. Comparative analyses indicated that Psychodynamic Psychotherapy-only patients outperformed Medication-only patients in regard to changes in a variety of object relations domains. Medication-only patients did not outperform Psychodynamic Psychotherapy-only patients in any domain of object relations. Significantly more Medication-only patients exhibited clinical regression compared to patients receiving psychodynamic psychotherapy. (Dr. Leonard Handler served as the chairperson of this dissertation committee.

Women’s Experiences of Discontinuing Hormone Therapy: A Dissertation

Although many women find relief from menopause through hormone therapy (HT), current guidelines recommend that HT be used only for short-term relief of symptoms. Women who attempt to stop HT often encounter troublesome recurrent symptoms leading to a diminished quality of life (QoL); 25% of women who discontinue eventually resume HT. Unfortunately, there is little information for women and their health care providers as to the best way to discontinue HT or how to prepare and guide women through this process. An in-depth description of women‘s experiences during HT discontinuation and the factors influencing recurrent symptoms, QoL and discontinuation outcome would provide knowledge to develop much needed counseling and support interventions. The purpose of this study was to explore women‘s experiences discontinuing hormone therapy for menopause. This Internet-based mixed-methods study used a dominant Qualitative Descriptive design with embedded quantitative QoL measurements. Participants completed the quantitative questionnaires online while open-ended questions were completed either online or by telephone. Interview data were analyzed through Qualitative Content Analysis; descriptive statistics were used to explore the quantitative measures. Participants were stratified by discontinuation status for comparison of variations in discontinuation experiences, QoL and influencing factors. Thirty-four women (20 stopped, 9 resumed, 4 tapering) were enrolled. One overarching theme--\u27a solitary journey\u27--emerged: although all women embarked on this journey, each woman traveled her own path. Two subthemes--\u27burden and interference\u27 and \u27appraising risk\u27--encompassed the symptom factors (severity, interference and sensitivity) that influenced women\u27s experiences and the manner in which women evaluated their options. Other influencing factors included: readiness viii and reasons for stopping HT, beliefs about menopause and roles. QoL was strongly connected to symptoms for many but not all women. Information from health care providers was inconsistent; women desired more support from providers and other women. The rich description of women\u27s experiences stopping HT highlights the need for providers to assess women\u27s sensitivity to symptoms and readiness to discontinue to determine which women might benefit from more support. Greater health literacy would enhance women\u27s understanding of HT risks. More research is needed on symptom clusters and interference and strategies for minimizing their impact

Study protocol for THINK : a multinational open-label phase I study to assess the safety and clinical activity of multiple administrations of NKR-2 in patients with different metastatic tumour types

Introduction: NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3 zeta signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells. In preclinical studies, NKR-2 demonstrated long-term antitumour activity towards a breadth of tumour indications, with maximum efficacy observed after multiple NKR-2 administrations. Importantly, NKR-2 targeted tumour cells and tumour neovasculature and the local tumour immunosuppressive microenvironment and this mechanism of action of NKR-2 was established in the absence of preconditioning. Methods and analysis: This open-label phase I study will assess the safety and clinical activity of NKR-2 treatment administered three times, with a 2-week interval between each administration in different tumour types. The study will contain two consecutive segments: a dose escalation phase followed by an expansion phase. The dose escalation study involves two arms, one in solid tumours (five specific indications) and one in haematological tumours (two specific indications) and will include three dose levels in each arm: 3x10(8), 1x10(9) and 3x10(9) NKR-2 per injection. On the identification of the recommended dose in the first segment, based on dose-limiting toxicity occurrences, the study will expand to seven different cohorts examining the seven different tumour types separately. Clinical responses will be determined according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria for solid tumours or international working group response criteria in haematological tumours. Ethics approval and dissemination: Ethical approval has been obtained at all sites. Written informed consent will be taken from all participants. The results of this study will be disseminated through presentation at international scientific conferences and reported in peer-reviewed scientific journals