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In cancer patients, a high pre-treatment neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival outcomes. Significant variation in the magnitude of this association has been observed between studies, but sources of this variation are poorly understood. Here, we explore differences in the prognostic potential of NLR between patient subgroups stratified by demographic and clinical characteristics using a retrospective cohort of 5,363 patients treated at Moffitt Cancer Center (Tampa, FL). We identify patients for whom NLR has maximum prognostic potential via adjusted hazard ratios (HRs) calculated using multivariable Cox proportional hazards models and area under the curve analysis. NLR demonstrates stronger associations (HRs > 2) with survival among African-American patients, patients receiving radiation therapy, stage IV patients, and melanoma patients when compared with the overall study population (HR = 1.58). Sensitivity and specificity of NLR as a prognostic marker are also higher in these patient subgroups, and increase further with combinations of multiple “high-risk” demographic or clinical characteristics. In summary, NLR may have greater prognostic value in patients with certain demographic and clinical features. Future prospective studies could validate this hypothesis, after further characterization of populations in which NLR has maximum prognostic potential and the identification of meaningful thresholds for risk stratification.

Background/aim Gastric adenocarcinoma is the fourth most common cancer worldwide. While gastric cancer prevalence varies globally and incidence rates are decreasing in the West, many cases continue to be diagnosed at an advanced stage and the 5-year survival rate still falls below 30%. Early treatment of gastric cancer by endoscopic and/or surgical therapy may decrease mortality; yet reliable, universally applicable biomarkers for early detection of gastric cancer have still not been established. Materials and methods The present work compares the expression of CD133 (prominin-1), a potential biomarker of disease progression in gastric cancer, between independent cohorts of H. pylori (+) and H. pylori (-) patients at each respective stage of carcinogenesis. H. pylori (-) patients (N=45) who underwent gastric biopsy at the Moffitt Cancer Center (MCC) in Tampa, Florida, and H. pylori (+) patients (N=59) who underwent gastric biopsy at the Instituto de Patologia Mejia Jimenez (IPMJ) in Cali, Colombia were evaluated and immunostained for CD133. Results A statistically significant increase in CD133 expression (in terms of the Allred score) was observed between all stages of progression (normal mucosa, inflammation/metaplasia, low-grade dysplasia and gastric adenocarcinoma) for each respective patient cohort. No statistically significant difference in CD133 expression at each respective stage of disease was observed between the H. pylori-positive and negative-cohorts. Conclusion The observation of distinct stepwise increases in CD133 expression in both patient cohorts, and the lack of any significant difference between groups, suggests that CD133 expression may serve as a biomarker for early detection of gastric cancer independent of bacterial status and strain, and corresponding differences in disease histomorphology and classification. This warrants further validation on larger independent cohorts across multiple geographic regions and incorporating multiple bacterial strain types.

“Deprescribing – is less more?” was the theme of this year's annual scientific meeting organised by the Prescribing and Research in Medicines Management (PRIMM) group, held in London in January. The meeting covered a range of topics relating to deprescribing, including a seven-step deprescribing model, identifying patients with polypharmacy problems, and providing individualised prescribing.

High pre-treatment values of the neutrophil-to-lymphocyte ratio (NLR) are strongly associated with poorer survival outcomes in cancer patients. Here, we assess heterogeneity in the magnitude of this association and the prognostic potential of the NLR between patient subgroups. We conducted a random effects meta-analysis of 228 published studies (N=75,555 patients) relating NLR with overall survival across 18 cancer types. Cochran’s Q test and Higgins I2 statistic were used to assess study heterogeneity. Pooled hazard ratios were compared between groups of studies classified by cancer type, geographic region, therapy type, and cut-off for high NLR to identify study-level characteristics associated with increased prognostic potential of the NLR. Pooled hazard ratios are highest in studies of melanoma and breast cancer and lowest in studies of brain cancer and lung cancer. Radiation as primary treatment also demonstrates a large pooled effect size as compared to other therapies. The NLR has greater prognostic value in certain cancer types and therapeutic regimens. Efforts are needed to comprehensively examine populations in which NLR has maximum prognostic power. Clinically meaningful thresholds for risk stratification should be identified within these patient subgroups to permit prospective validation of the prognostic potential of the NLR.

Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation with established prognostic value in patients with cancer. Although high NLR is associated with poorer clinical outcomes, factors that influence the magnitude of NLR independently of disease are poorly understood. Methods We identified 48,023 adults who participated in the National Health and Nutrition Examination Survey (1999-2016). Demographic, socioeconomic, and lifestyle factors associated with the magnitude of NLR after adjusting for comorbidities including heart disease, cancer, diabetes, and hypertension, and medications including aspirin, were identified. Effect modification by comorbidity status and demographics was explored. Results Female gender, age less than 60 years, and non-Hispanic black race/ethnicity were associated with lower NLR. Marital statuses of widowed, separated, or never married demonstrated increased NLR as compared with those who were currently married. Never-smoking and moderate alcohol consumption were associated with lower NLR. Participation in physical activity was associated with decreased NLR after adjustment for potential confounders, primarily among non-Hispanic whites. Conclusions Multiple demographic and lifestyle factors are independently associated with NLR. Sex, age, race, marital status, body mass index, physical activity, smoking history, and alcohol consumption should all be routinely collected and adjusted for to improve the accuracy of assessment of the prognostic power of NLR.

Immune checkpoint inhibitors (ICIs) have improved overall survival for cancer patients, however, optimal duration of ICI therapy has yet to be defined. Given ICIs were first used to treat patients with metastatic melanoma, a condition that at the time was incurable, little attention was initially paid to how much therapy would be needed for a durable response. As the early immunotherapy trials have matured past 10 years, a significant per cent of patients have demonstrated durable responses; it is now time to determine whether patients have been overtreated, and if durable remissions can still be achieved with less therapy, limiting the physical and financial toxicity associated with years of treatment. Well-designed trials are needed to identify optimal duration of therapy, and to define biomarkers to predict who would benefit from shorter courses of immunotherapy. Here, we outline key questions related to health, financial and societal toxicities of over treating with ICI and present four unique clinical trials aimed at exposing criteria for early cessation of ICI. Taken together, there is a serious liability to overtreating patients with ICI and future work is warranted to determine when it is safe to stop ICI.

Introduction Cancer patients often choose complementary and alternative medicine (CAM) in palliative care, often in addition to conventional treatment and without medical advice or approval. Herbal medicines (HM) are the most commonly used type of CAM, but rarely available on an in-patient basis for palliative care. The motivations which lead very ill patients to travel far to receive such therapies are not clear. A qualitative study was therefore carried out to investigate influences on choosing to attend a CAM herbal hospice, to identify cancer patients’ main concerns about end-of-life care. Methods Semi-structured interviews with 32 patients were conducted and analysed using thematic analysis. Patients were recruited from Arokhayasala, a Buddhist cancer hospice in Thailand which provides CAM, in the form of HM, a restricted diet, Thai yoga, deep-breathing exercises, meditation, chanting, Dhamma, laughter and music therapy, free-of-charge. Results The main factors influencing decision-making were a positive attitude towards HMs and previous use of them, dissatisfaction with conventional treatment, the home environment and their relationships with hospital doctors. Conclusions Patients’ own perceptions and experiences were more important in making the decision to use CAM, and especially HM, in palliative cancer care than referral by healthcare professionals or scientific evidence of efficacy. Patients were prepared to travel far and live away from home to receive such care, especially as it was cost-free. In view of patients’ previously stated satisfaction with the regime at the Arokhayasala, these findings may be relevant to the provision of in-patient cancer palliative care to other patients.

Ethnopharmacological relevance Cancer patients in all cultures are high consumers of herbal medicines (HMs) usually as part of a regime consisting of several complementary and alternative medicine (CAM) modalities, but the type of patient, the reasons for choosing such HM-CAM regimes, and the benefits they perceive from taking them are poorly understood. There are also concerns that local information may be ignored due to language issues. This study investigates aspects of HM-CAM use in cancer patients using two different abstracting sources: Medline, which contains only peer-reviewed studies from SCI journals, and in order to explore whether further data may be available regionally, the Thai national databases of HM and CAM were searched as an example. Materials and methods The international and Thai language databases were searched separately to identify relevant studies, using key words chosen to include HM use in all traditions. Analysis of these was undertaken to identify socio-demographic and clinical factors, as well as sources of information, which may inform the decision to use HMs. Results Medline yielded 5638 records, with 49 papers fitting the criteria for review. The Thai databases yielded 155, with none relevant for review. Factors associated with HM-CAM usage were: a younger age, higher education or economic status, multiple chemotherapy treatment, late stage of disease. The most common purposes for using HM-CAM cited by patients were to improve physical symptoms, support emotional health, stimulate the immune system, improve quality of life, and relieve side-effects of conventional treatment. Conclusions Several indicators were identified for cancer patients who are most likely to take HM-CAM. However, interpreting the clinical reasons why patients decide to use HM-CAM is hampered by a lack of standard terminology and thematic coding, because patients' own descriptions are too variable and overlapping for meaningful comparison. Nevertheless, fears that the results of local studies published regionally are being missed, at least in the case of Thailand, appeared to be unfounded.

Introduction: Much of the information in electronic medical records (EMRs) required for the practice of clinical oncology is contained in unstructured text. While natural language processing (NLP) has been used to extract information from EMR text, accuracy is suboptimal. In late 2018 a powerful new deep-learning NLP algorithm was published: Bidirectional Encoder Representations from Transformers (BERT). BERT set new accuracy records and for the first time achieved human-level performance on several NLP benchmarks. Our goal was to train BERT to extract clinically relevant data from pathology reports with high accuracy. Procedures: Like many cancer centers nationwide, Moffitt Cancer Center employs Certified Tumor Registrars (CTRs) to collect and report data about cancer patients to state and federal agencies. The CTR extracted data are labels that identify, with high accuracy, important information in each pathology report. Consequently, we used this data to tune BERT to perform a question-and-answering (Q&A) task. Our system sought the answers to 2 predetermined questions in each pathology report: “What organ contains the tumor?”, and “What is the kind of tumor or carcinoma?” To achieve this, we matched surgical pathology reports created at Moffitt from January 1, 2007 onwards with structured data extracted by CTRs. The resulting dataset was randomly divided into training (80%) and testing (20%) subsets. After Q&A training, model performance was assessed using the test dataset. Two metrics were calculated for each question: a true-or-false indication of a perfect word-for-word match between the BERT-extracted data and CTR-extracted data; and, the F1 statistic. The latter produces a value between 0% and 100% indicating the degree of overlap between words in the BERT-extracted data and words in the CTR-extracted data. Results: The final dataset contained 14,143 pathology reports (11,520 for training, 2,623 for testing). This dataset included tumors from 228 organ sites involving 232 histological classifications. The three most common organ sites / histological classifications were: Prostate Gland / Adenocarcinoma (6.7%); Breast / Invasive Carcinoma (6.1%); and, Breast Overlapping Lesion / Invasive Carcinoma (5.9%). Our BERT-based Q&A system searched for answers to both questions in each test report. Thus, a total of 5,246 answers were generated. Of these, 4,667 (89%) were a perfect word-for-word match with the corresponding CTR extracted phrases. The mean F1 statistic between the BERT answers and the CTR extracted phrases was 92%. Conclusions: Future efforts will focus on improving performance via unsupervised training of the BERT language model using 484,000 Moffitt pathology reports. We will also extract additional data fields with CTR-matched ground truth labels. Ultimately new NLP transformer models could aid extraction of information from pathology reports and other EMR documents. This, in turn, could greatly facilitate personalized medicine. Citation Format: Ross Mitchell, Rachel Howard, Patricia Lewis, Katie Fellows, Jennie Jones, Phillip Reisman, Brooke Fridley, Dana Rollison. Deep learning for automatic extraction of tumor site and histology from unstructured pathology reports [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2101.

The vast wealth of medical data collected over the last decade holds great promise for accelerating novel research, discovery, and clinical translation. Specifically, the rapid expansion of genomic testing provides new opportunities for the clinical management of cancer patients, influencing diagnosis, risk stratification, and treatment planning. Moffitt Cancer Center's Personalized Medicine Clinical Service integrates next-generation sequencing test results into patient care, using the data to guide individualized treatment plans. To maximize the efficiency and efficacy of this service, creative solutions for data harmonization, storage, and management are required. We implemented a commercial molecular data warehouse (MDW), directly linked to our existing clinical data warehouse, to store and manage molecular data ranging from genotypic alterations to annotations from public resources (HUGO, COSMIC, Ensembl) and clinically actionable targets (4,256 records currently loaded). A centralized, cloud-based data and analytics platform is also being implemented at Moffitt that will integrate a broad range of multi-modal data. In the cloud environment, the data from the MDW will be linked to typically siloed data streams from the electronic health record, cancer registry management system, biospecimen management system, billing and scheduling systems, patient-reported information and outcomes, and patient-generated health data, creating a unique and customized Personalized Medicine Curated Data Mart (CDM). In addition to describing the features of the MDW and the challenges faced during its implementation, we will provide an overview of the extensive data cleaning and curation required to facilitate such a CDM. This includes the extraction of disease characteristics from unstructured clinical text via natural language processing, creation of new derived data fields, approaches to extracting and managing complex treatment data, and the inclusion of detailed, manually-abstracted recurrence and outcomes data for historical patients from existing institutional datasets such as the Clinical Genomics Action Committee (CGAC) database. Finally, we will present prototypes of analytics dashboards that will interface directly with our CDM, facilitating intuitive data exploration for all members of our personalized medicine teams. Citation Format: Rachel Howard, Kevin Hicks, Jamie Teer, Phillip Reisman, Mandy O'Leary, Steven Eschrich, Ross Mitchell, Howard McLeod, Dana Rollison. Facilitating personalized medicine with cloud-based storage and analytics [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3226.

As precision medicine research and its clinical applications continue to advance, it is critical for pharmacists to be involved in these developments to deliver optimal, tailored drug therapies for patients. To ensure pharmacists remain leaders in the field, the annual Pharmaceutical Sciences Conference convened by the University of North Carolina at Chapel Hill Eshelman School of Pharmacy focused on the role of pharmacy within precision medicine. This is a summary of the conference, highlighting the major challenges and solutions that will help advance individualized pharmacological methods within practice and research.

Pharmacogenomics provides a personalized approach to pharmacotherapy by using genetic information to guide drug dosing and selection. However, partly due to lack of education, pharmacogenomic testing has not been fully implemented in clinical practice. With pharmacotherapy training and patient accessibility, pharmacists are ideally suited to apply pharmacogenomics to patient care. Student pharmacists (n = 222) participated in an educational intervention that included voluntary personal genotyping using 23andMe. Of these, 31% of students completed both pre- and post-educational interventions to evaluate their attitudes and confidence towards the use of pharmacogenomics data in clinical decision making, and 55% of this paired subset obtained personal genotyping. McNemar&rsquo, s test and the Wilcoxon signed-rank test were used to analyze responses. Following the educational intervention, students regardless of genotyping were more likely to recommend personal genotyping (36% post-educational intervention versus 19% pre-educational intervention, p = 0.0032), more confident in using pharmacogenomics in the management of drug therapy (51% post-educational intervention versus 29% pre-educational intervention, p = 0.0045), and more likely to believe that personalized genomics would have an important role in their future pharmacy career (90% post-educational intervention versus 51% pre-educational intervention, p = 0.0072) compared to before receiving the educational intervention. This educational intervention positively influenced students&rsquo, attitudes and confidence regarding pharmacogenomics in the clinical setting. Future studies will examine the use of next-generation sequencing assays that selectively examine pharmacogenes in the education of student pharmacists.

PURPOSE/OBJECTIVES We set out to predict response and progression risk in recurrent high-grade glioma patients treated with hypofractionated stereotactic radiation plus pembrolizumab and bevacizumab (NCT02313272). At present RANO criteria define progression as 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement (either at baseline or best response) or significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids. To this extent, a predictive model is needed to adaptively learn and forecast individual response to therapy. We evaluate if early tumor volume evolution can train a mathematical model to predict subsequent response to therapy. MATERIALS/METHODS We develop a mathematical model that describes patient-uniform tumor growth rate and initial pembrolizumab and bevacizumab responses, and patient-specific treatment response dynamics. A total of 154 radiology scans were delineated to derive longitudinal tumor volumes of 26 patients. In a leave-one-out study, patient-uniform model parameters are derived and then applied to the left-out patient to adaptively learn treatment response dynamics to forecast tumor volume evolution and progression risk. Model prediction performance is evaluated based on classification accuracy, including sensitivity and specificity. RESULTS Patient-uniform glioma growth rate and initial treatment response rates are estimated to achieve acceptable fits to the longitudinal data of all untrained patients with R2 = 0.81 [0.75, 0.89]. Response dynamics are predicted with high accuracy (0.78 [0.76, 0.79]), with positive and negative predictive values of 0.90 [0.86, 0.92] and 0.81 [0.78, 0.86], and sensitivity and specificity of 0.71 [0.69, 0.73] and 0.88 [0.83, 0.91] respectively. CONCLUSIONS Two patient-specific parameters in a mathematical model can be adaptively learned from early tumor volume evolution to predict subsequent response to therapy and progression risk for individual patients. Future validation is required in an independent dataset and prospective evaluation in another clinical trial.

Objectives To explore factors affecting communication between Foundation Year (FY) 1 doctors and hospital pharmacists about prescribing from the junior doctors’ perspective.Methods Trained interviewers (n=4) conducted semistructured interviews with FY1 doctors who were purposively sampled from three hospitals in England. FY1 doctors were asked about their experiences of communication with hospital pharmacists about their prescribing; instances where they disagreed with or did not implement a hospital pharmacist’s recommendation; and their preferences for communicating with hospital pharmacists about prescribing. Interviews were audiorecorded, transcribed verbatim and analysed thematically.Results A total of 27 FY1 doctors were interviewed. Findings were categorised into four main themes: (1) nature and context of communication; (2) FY1 doctors’ perceptions of communication with hospital pharmacists; (3) factors influencing FY1 doctors’ decision whether to act on pharmacists’ prescribing recommendations; and (4) suggestions to improve communication with pharmacists. FY1 doctors and hospital pharmacists generally communicated well. FY1 doctors appreciated and frequently acted on pharmacists’ advice yet there was deference to senior medical staff when advice differed. Joint ward rounds, pharmacist-led teaching sessions and a standardised approach to communication were all suggested as ways to improve communication and may increase the likelihood of pharmacists’ recommendations being acted on.Conclusions FY1 doctors and hospital pharmacists communicated frequently about medication prescribing. Issues occurred when there were differences in professional judgement between senior medical staff and pharmacists but these were usually resolved satisfactorily for the FY1 doctor. Further interventions to improve communication and safe prescribing could involve a multidisciplinary and systems approach.

Objectives Using strong structuration theory, we aimed to understand the adoption and implementation of an electronic clinical audit and feedback tool to support medicine optimisation for patients in primary care.Design This is a qualitative study informed by strong structuration theory. The analysis was thematic, using a template approach. An a priori set of thematic codes, based on strong structuration theory, was developed from the literature and applied to the transcripts. The coding template was then modified through successive readings of the data.Setting Clinical commissioning group in the south of England.Participants Four focus groups and five semi-structured interviews were conducted with 18 participants purposively sampled from a range of stakeholder groups (general practitioners, pharmacists, patients and commissioners).Results Using the system could lead to improved medication safety, but use was determined by broad institutional contexts; by the perceptions, dispositions and skills of users; and by the structures embedded within the technology. These included perceptions of the system as new and requiring technical competence and skill; the adoption of the system for information gathering; and interactions and relationships that involved individual, shared or collective use. The dynamics between these external, internal and technological structures affected the adoption and implementation of the system.Conclusions Successful implementation of information technology interventions for medicine optimisation will depend on a combination of the infrastructure within primary care, social structures embedded in the technology and the conventions, norms and dispositions of those utilising it. Future interventions, using electronic audit and feedback tools to improve medication safety, should consider the complexity of the social and organisational contexts and how internal and external structures can affect the use of the technology in order to support effective implementation.

BACKGROUND: Monitoring for potentially hazardous prescribing is increasingly important to improve medication safety. Healthcare information technology can be used to achieve this aim, for example by providing access to prescribing data through surveillance of patients' electronic health records. The aim of our study was to examine the implementation and adoption of an electronic medicines optimisation system that was intended to facilitate clinical audit in primary care by identifying patients at risk of an adverse drug event. We adopted a sociotechnical approach that focuses on how complex social, organisational and institutional factors may impact upon the use of technology within work settings.METHODS: We undertook a qualitative realist evaluation of the use of an electronic medicines optimisation system in one Clinical Commissioning Group in England. Five semi-structured interviews, four focus groups and one observation were conducted with a range of stakeholders. Consistent with a realist evaluation methodology, the analysis focused on exploring the links between context, mechanism and outcome to explain the ways the intervention might work, for whom and in what circumstances.RESULTS: Using the electronic medicines optimisation system could lead to a number of improved patient safety outcomes including pre-emptively reviewing patients at risk of adverse drug events. The effective use of the system depended upon engagement with the system, the flow of information between different health professionals centrally placed at the Clinical Commissioning Group and those locally placed at individual general practices, and upon variably adapting work practices to facilitate the use of the system. The use of the system was undermined by perceptions of ownership, lack of access, and lack of knowledge and awareness.CONCLUSIONS: The use of an electronic medicines optimisation system may improve medication safety in primary care settings by identifying those patients at risk of an adverse drug event. To fully realise the potential benefits for medication safety there needs to be better utilisation across primary care and with a wider range of stakeholders. Engaging with all potential stakeholders and users prior to implementation of such systems might allay perceptions that the system is owned centrally and increase knowledge of the potential benefits.

Herbal medicines and dietary supplements are commonly taken by patients with cancer, leading to concern over interactions with conventional medicines. A literature search was carried out to identify published studies exploring supplement use by patients with a cancer diagnosis. A total of 818 articles were retrieved using the key words, but only 41 are judged to be relevant based on title. Following the review of the abstracts, ten papers were considered to be potentially relevant, but of these, only two met the selection criteria, and three additional papers were identified from published reviews. Of 806 patients surveyed, 433 (53.7%) were reported to be taking combinations of supplements and drugs, and 167 incidents of risk were identified, affecting 60 patients (13.9%). The interactions identified were mainly theoretical and not supported by clinical data. No studies reported any adverse events associated with these combinations; most did not record the actual drug combinations taken, and the risk potential of some supplements appears to have been over-estimated. More effort should be made to investigate supplement use in this vulnerable patient group, based on sound evidence of plausible interaction, not only to avoid harm but also to provide reassurance where appropriate if the patient wishes to take a particular supplement. Copyright © 2014 John Wiley & Sons, Ltd.

Background: The neutrophil-to-lymphocyte ratio (NLR) is an established marker of subclinical inflammation, and a high NLR is associated with poorer clinical outcomes in cancer patients. Despite this, factors that influence the magnitude of NLR independently of disease are poorly understood. Here, we systematically assess the influence of socio-demographic and lifestyle factors on NLR to identify a) potential confounders and effect modifiers in the relationship between NLR and cancer outcomes, and b) possible targets for intervention in patients with high NLR at diagnosis. Methods: Based on a total participant cohort of 48,023 adults with available NLR data, we identified 20 factors of interest relating to patient demographics, socioeconomic status and lifestyle that were included in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2016. Multivariable regression analysis identified factors significantly associated with the magnitude of NLR after adjusting for comorbidities and medications. Interactions between factors of interest were evaluated, and effect modification by demographic characteristics including age, sex and race was quantified. Results: Seven demographic and lifestyle factors were found to be significantly and independently associated with NLR: age, sex, race, marital status, physical activity, smoking history and alcohol use. Females, under 60s and non-Hispanic blacks demonstrated significantly lower NLR than males, over 60s and non-Hispanic whites. Participation in vigorous activity for at least ten minutes at a time was associated with decreased NLR, as was never-smoker status. Moderate drinking was also associated with a decreased NLR as compared to complete abstinence from alcohol. Conclusions: Multiple demographic and lifestyle factors are independently associated with elevated NLR. For an accurate assessment of the prognostic power of the NLR in the clinical setting, these factors should be routinely adjusted for in studies of the association between NLR and cancer outcomes. The present study reiterates that physical activity may have the potential to improve clinical outcomes by way of reducing systemic inflammation. Citation Format: Rachel Howard, Aaron Scheiner, Kathleen M. Egan. Socio-demographic and lifestyle factors associated with the neutrophil-to-lymphocyte ratio: A systematic evaluation of the United States National Health and Nutrition Examination Survey [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3299.

Aims To develop a list of prescribing indicators specific for the hospital setting that would facilitate the prospective collection of high-severity and/or high-frequency prescribing errors, which are also amenable to electronic clinical decision support. Methods A two-stage consensus technique (electronic Delphi) was carried out with 20 experts across England. Participants were asked to score prescribing errors using a five-point Likert scale for their likelihood of occurrence and the severity of the most likely outcome. These were combined to produce risk scores, from which median scores were calculated for each indicator across the participants in the study. The degree of consensus between the participants was defined as the proportion that gave a risk score in the same category as the median. Indicators were included if a consensus of 80% or more was achieved. Results A total of 80 prescribing errors were identified by consensus as being high or extreme risk. The most common drug classes named within the indicators were antibiotics (n = 13), antidepressants (n = 8), nonsteroidal anti-inflammatory drugs (n = 6) and opioid analgesics (n = 6). The most frequent error type identified as high or extreme risk were those classified as clinical contraindications (n = 29 of 80). Conclusions Eighty high-risk prescribing errors in the hospital setting have been identified by an expert panel. These indicators can serve as a standardized, validated tool for the collection of prescribing data in both paper-based and electronic prescribing processes. This can assess the impact of safety improvement initiatives, such as the implementation of electronic clinical decision support.

Background: Few detailed studies exist of the underlying causes of prescribing errors in the UK. Aim: To examine the causes of prescribing and monitoring errors in general practice and provide recommendations for how they may be overcome. Design and setting: Qualitative interview and focus group study with purposive sampling of English general practices. Method: General practice staff from 15 general practices across three PCTs in England participated in a combination of semi-structured interviews (n = 34) and six focus groups (n = 46). Thematic analysis informed by Reason’s Accident Causation Model was used. Results: Seven categories of high-level error-producing conditions were identified: the prescriber, the patient, the team, the working environment, the task, the computer system, and the primary–secondary care interface. These were broken down to reveal various error-producing conditions: the prescriber’s therapeutic training, drug knowledge and experience, knowledge of the patient, perception of risk, and their physical and emotional health; the patient’s characteristics and the complexity of the individual clinical case; the importance of feeling comfortable within the practice team was highlighted, as well as the safety implications of GPs signing prescriptions generated by nurses when they had not seen the patient for themselves; the working environment with its extensive workload, time pressures, and interruptions; and computer-related issues associated with mis-selecting drugs from electronic pick-lists and overriding alerts were all highlighted as possible causes of prescribing errors and were often interconnected. Conclusion: Complex underlying causes of prescribing and monitoring errors in general practices were highlighted, several of which are amenable to intervention.

Background Relatively little is known about prescribing errors in general practice, or the factors associated with error. Aim To determine the prevalence and nature of prescribing and monitoring errors in general practices in England. Design and setting Retrospective case-note review of unique medication items prescribed over a 12-month period to a 2% random sample of patients. Fifteen general practices across three primary care trusts in England. Method A total of 6048 unique prescription items prescribed over the previous 12 months for 1777 patients were examined. The data were analysed by mixed effects logistic regression. The main outcome measures were prevalence of prescribing and monitoring errors, and severity of errors, using validated definitions. Results Prescribing and/or monitoring errors were detected in 4.9% (296/6048) of all prescription items (95% confidence interval [CI] = 4.4% to 5.5%). The vast majority of errors were of mild to moderate severity, with 0.2% (11/6048) of items having a severe error. After adjusting for covariates, patient-related factors associated with an increased risk of prescribing and/or monitoring errors were: age 64 years (OR = 1.68, 95% CI = 1.04 to 2.73, P = 0.035), and higher numbers of unique medication items prescribed (OR = 1.16, 95% CI = 1.12 to 1.19, P Conclusion Prescribing and monitoring errors are common in English general practice, although severe errors are unusual. Many factors increase the risk of error. Having identified the most common and important errors, and the factors associated with these, strategies to prevent future errors should be developed, based on the study findings.

This is the fourth in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist-initiated palliative-care medicines. Here, the authors summarise the key issues around the use of apid onset opioids in palliative care.

Background\ud Herb/Dietary Supplements (HDS) are the most popular Complementary and Alternative Medicine (CAM) modality used by cancer patients and the only type which involves the ingestion of substances which may interfere with the efficacy and safety of conventional medicines. This study aimed to assess the level of use of HDS in cancer patients undergoing treatment in the UK, and their perceptions of their effects, using 127 case histories of patients who were taking HDS. Previous studies have evaluated the risks of interactions between HDS and conventional drugs on the basis on numbers of patient using HDSs, so our study aimed to further this exploration by examining the actual drug combinations taken by individual patients and their potential safety.\ud \ud Method\ud Three hundred seventy-five cancer patients attending oncology departments and centres of palliative care at the Oxford University Hospitals Trust (OUH), Duchess of Kent House, Sobell House, and Nettlebed Hospice participated in a self-administered questionnaire survey about their HDS use with their prescribed medicines. The classification system of Stockley’s Herbal Medicine’s Interactions was adopted to assess the potential risk of herb-drug interactions for these patients.\ud \ud Results\ud 127/375 (34 %; 95 % CI 29, 39) consumed HDS, amounting to 101 different products. Most combinations were assessed as ‘no interaction’, 22 combinations were categorised as ‘doubt about outcomes of use’, 6 combinations as ‘Potentially hazardous outcome’, one combination as an interaction with ‘Significant hazard’, and one combination as an interaction of “Life-threatening outcome”. Most patients did not report any adverse events.\ud \ud Conclusion\ud Most of the patients sampled were not exposed to any significant risk of harm from interactions with conventional medicines, but it is not possible as yet to conclude that risks in general are over-estimated. The incidence of HDS use was also less than anticipated, and significantly less than reported in other areas, illustrating the problems when extrapolating results from one region (the UK), in one setting (NHS oncology) in where patterns of supplement use may be very different to those elsewhere.

This is the third in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist-initiated palliative-care drugs. Here, the authors summarise the key issues around the shortterm use of psychostimulants in palliative care.

This is the first in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist-initiated palliative-care drugs. This first article summarises the key issues for patients receiving ketamine.

Background. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are established markers of systemic inflammation, and they are believed to have prognostic value in various diseases including many common cancers. These indicators of the cellular-mediated inflammatory response are easily obtained from patient blood samples and hold promise as simple and inexpensive tools for risk stratification. Methods. In the present study, 4509 patients spanning multiple cancer types (breast N=979; colorectal N=1024; esophageal N=594; hepatocellular N=287; melanoma N=349 and pancreatic N=1276) treated at Moffitt Cancer Center and with valid hematology lab values, demographic information, clinical disease characteristics, and outcome data were identified. We compared marker counts and ratios across all cancer types to identify disease-specific patterns in pre-treatment host immune response and evaluated the similarities with other established measures of disease-specific immunogenicity. An initial evaluation of the association between pre-treatment NLR, PLR (and corresponding absolute counts of lymphocytes (L), neutrophils (N) and platelets (P)) and disease-specific survival was conducted, controlling for age, sex, race, disease stage, treatment modality, and additionally for primary site and histological and molecular subtypes as appropriate. Results. Mean levels of N, L, P, NLR, and PLR all demonstrated significant differences across cancer types. Pre-treatment NLR was significantly associated with disease-specific death in four of our six cancer sites (colorectal: hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.21-1.79; esophageal: HR = 1.38, 95% CI = 1.05-1.82; melanoma: HR = 1.87, 95% CI = 1.18-2.95; pancreatic: HR = 1.69, 95% CI = 1.43-1.99). Pre-treatment PLR was significantly associated with disease-specific death in two sites (colorectal: HR = 1.34, 95% CI = 1.10-1.64; pancreatic: HR = 1.53, 95% CI = 1.30-1.79). This suggests that the utilization of markers of the cellular-mediated inflammatory response for clinical prognosis and decision-making may require disease-specific risk classification criteria. Citation Format: Rachel Howard, Kathleen Egan, Peter Kanetsky. Pretreatment markers of cellular-mediated inflammation and association with survival vary significantly among cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4206.

A collaboration between the University of Louisville's Dwight Anderson Music Library and Digital Initiatives Department has resulted in the digitization of the University of Louisville School of Music Guest Book. Begun in 1949, the book contains signatures and handwritten messages from many of the most well-known musicians of the twentieth and twenty-first centuries. This article describes the approach to scanning, cataloging, indexing, and providing full-text searchable online access to the Guest Book using CONTENTdm digital media management software. It addresses resource and technical challenges encountered and overcome.

Ethnobotanical relevance Cancer patients commonly use traditional medicines (TM) and in Thailand these are popular for both self-medication and as prescribed by TM practitioners, and are rarely monitored. A study was conducted at Wat Khampramong, a Thai Buddhist temple herbal medicine hospice, to document some of these practices as well as the hospice regime. Materials and methods Cancer patients (n=286) were surveyed shortly after admission as to which TMs they had previously taken and perceptions of effects experienced. They were also asked to describe their current symptoms. Treatment at the hospice is built upon an 11-herb anti-cancer formula, yod-ya-mareng, prescribed for all patients, and ideally, its effects would have been evaluated. However other herbal medicines and holistic practices are integral to the regime, so instead we attempted to assess the value of the patients׳ stay at the hospice by measuring any change in symptom burden, as they perceived it. Surviving patients (n=270) were therefore asked to describe their symptoms again just before leaving. Results 42% of patients (120/286; 95% CI 36.4%, 47.8%) had used herbal medicines before their arrival, with 31.7% (38/120; 95% CI 24%, 40.4%) using several at once. Mixed effects were reported for these products. After taking the herbal regime at Khampramong, 77% (208/270 95% CI; 71.7%, 81.7%) reported benefit, and a comparison of the incidence of the most common (pain, dyspepsia, abdominal or visceral pain, insomnia, fatigue) showed statistical significance (χ2 57.1, df 7, p Conclusions A wide range of TMs is taken by cancer patients in Thailand and considered to provide more benefit than harm, and this perception extends to the temple regime. Patients reported a significant reduction in symptoms after staying at Khampramong, indicating an improvement in quality of life, the aim of hospices everywhere. Based on this evidence, it is not possible to justify the use of TM for cancer in general, but this study suggests that further research is warranted. The uncontrolled use of TMs, many of which are uncharacterised, raises concerns, and this work also highlights the fact that validated, robust methods of assessing holistic medical regimes are urgently needed.

Objective: To describe the drugs and types of medicine management problems most frequently associated with preventable drug related admissions to an acute medical admissions unit. Design: Observation study. Setting: Medical admissions unit in a teaching hospital in Nottingham, UK. Participants: 4093 patients seen by pharmacists on the medical admissions unit between 1 January and 30 June 2001. Main outcome measures: Proportion of admissions that were drug related and preventable, classification of the underlying causes of preventable drug related admissions, and identification of drugs most commonly associated with preventable drug related admissions. Results: Of the admissions seen by pharmacists, 265 (6.5%) were judged to be drug related and 178 (67%) of these were judged to be preventable. Preventable admissions were mainly due to problems with prescribing (63 cases (35%)), monitoring (46 cases (26%)), and adherence to medication (53 cases (30%)). The drugs most commonly implicated were NSAIDs, antiplatelets, antiepileptics, hypoglycaemics, diuretics, inhaled corticosteroids, cardiac glycosides, and beta-blockers. Conclusions: Potentially preventable drug related morbidity was associated with 4.3% of admissions to a medical admissions unit. In 91% of cases these admissions were related to problems with either prescribing, monitoring, or adherence.

Magnesium sulphate has been demonstrated to be an effective neuroprotectant for babies delivered prematurely (under 37 weeks’ gestational age). Antenatal administration reduces infant mortality and cerebral palsy (CP); however, uptake in the UK has been significantly lower than other countries. A quality improvement (QI) project (PReventing Cerebral palsy in Pre Term labour (PReCePT)) was carried out in the West of England, UK, to raise awareness of evidence and to improve the uptake of magnesium sulphate as neuroprotectant in preterm deliveries. Five National Health Service (NHS) Trusts and the West of England Academic Health Science Network participated in the QI project. The project was underpinned by a multifaceted QI approach that included: patient and clinical coproduction of resources; recruitment of clinical champions to support the local microsystems and create a stimulating/supporting environment for change; Plan, Do, Study, Act cycles; training for over 600 NHS staff and awareness raising and strategic influencing of key leaders. A baseline audit and regular measurement of the number of eligible women receiving magnesium sulphate was undertaken at each hospital site, and the overall programme was evaluated using data from an international benchmarking organisation for neonatal care outcomes—the Vermont Oxford Network. During the project 664 staff received magnesium sulphate training. The use of magnesium sulphate increased across the West of England from an average baseline of 21% over the 2 years preceding the project to 88% by the conclusion of the project. The project was also able to influence the development of a national data collection process for benchmarking the use of magnesium sulphate for neuroprotection in preterm deliveries in the U.K. PReCePT appears to have had a favourable effect on the uptake of magnesium sulphate across the West of England. The project has also provided learning about how to stimulate adoption and spread of evidence using a QI approach across a network.

Over the past 10 years our team has been involved in a wide range of studies of prescribing in general practice, but one we feel that has really made a difference is the PRACtICe study, which was funded by the General Medical Council.1,2 In this study we took a sample of 15 general practices across England and did a retrospective review of the clinical records of a random sample of over 1700 patients, and over 6000 prescription items. Using a definition of error that focused on clinically important problems,1 we found that one in 20 (5%) prescription items was associated with one or more prescribing or monitoring errors, and that one in 550 prescription items contained what we regarded as a severe error1 (with seriously inadequate monitoring of patients taking warfarin the biggest culprit). We found that per prescription item, errors were more common in children and older people, and that nearly half of patients receiving >10 items over the course of a year were the recipients of an error. The commonest types of error related to incomplete information on the prescription, dose-strength errors, and timing-frequency errors. Using interviews, root cause analyses and focus groups, we explored the underlying causes of the errors and, not surprisingly, found them to be multifactorial.2 Of the various underlying causes, we felt that several were amenable to intervention, including improving safety systems in general practices; making best use of our electronic prescribing systems, including computerised clinical decision support; improving prescribing and monitoring at the interface between primary and secondary care, and better training for GPs in therapeutics and safe prescribing (accepting that most GPs already have good therapeutic knowledge and are highly committed to patient safety). We made a number of recommendations from our research and have taken …

CONTEXT Recent surveys indicate that approximately 40% of graduates from schools of public health are employed within the private sector or have an employer charged with regulating the private sector. These data suggest that schools of public health should provide curricular opportunities for their students--the future public health workforce--to learn about the relationship between the private sector and the public's health. OBJECTIVE To identify opportunities for graduate students in schools of public health to select course work that educates them about the relationship between the private sector and public health. DESIGN We systematically identified and analyzed data gathered from publicly available course titles and descriptions on the Web sites of accredited schools of public health. SETTING Data were collected in the United States. PARTICIPANTS The sample consisted of accredited schools of public health. MAIN OUTCOME MEASURES Descriptions of the number and types of courses that schools of public health offer about the private sector and identification of how course descriptions frame the private sector relative to public health. RESULTS We identified 104 unique courses with content about the private sector's relationship to public health. More than 75% of accredited schools of public health offered at least 1 such course. Nearly 25% of identified courses focused exclusively on the health insurance industry. Qualitative analysis of the data revealed 5 frames used to describe the private sector, including its role as a stakeholder in the policy process. CONCLUSIONS Schools of public health face a curricular gap, with relatively few course offerings that teach students about the relationship between the private sector and the public's health. By developing new courses or revising existing ones, schools of public health can expose the future public health workforce to the varied ways public health professionals interact with the private sector, and potentially influence students' career paths.

Summary Background Medication errors are common in primary care and are associated with considerable risk of patient harm. We tested whether a pharmacist-led, information technology-based intervention was more effective than simple feedback in reducing the number of patients at risk of measures related to hazardous prescribing and inadequate blood-test monitoring of medicines 6 months after the intervention. Methods In this pragmatic, cluster randomised trial general practices in the UK were stratified by research site and list size, and randomly assigned by a web-based randomisation service in block sizes of two or four to one of two groups. The practices were allocated to either computer-generated simple feedback for at-risk patients (control) or a pharmacist-led information technology intervention (PINCER), composed of feedback, educational outreach, and dedicated support. The allocation was masked to researchers and statisticians involved in processing and analysing the data. The allocation was not masked to general practices, pharmacists, patients, or researchers who visited practices to extract data. Primary outcomes were the proportions of patients at 6 months after the intervention who had had any of three clinically important errors: non-selective non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to those with a history of peptic ulcer without co-prescription of a proton-pump inhibitor; β blockers prescribed to those with a history of asthma; long-term prescription of angiotensin converting enzyme (ACE) inhibitor or loop diuretics to those 75 years or older without assessment of urea and electrolytes in the preceding 15 months. The cost per error avoided was estimated by incremental cost-effectiveness analysis. This study is registered with Controlled-Trials.com, number ISRCTN21785299. Findings 72 general practices with a combined list size of 480 942 patients were randomised. At 6 months' follow-up, patients in the PINCER group were significantly less likely to have been prescribed a non-selective NSAID if they had a history of peptic ulcer without gastroprotection (OR 0·58, 95% CI 0·38–0·89); a β blocker if they had asthma (0·73, 0·58–0·91); or an ACE inhibitor or loop diuretic without appropriate monitoring (0·51, 0·34–0·78). PINCER has a 95% probability of being cost effective if the decision-maker's ceiling willingness to pay reaches £75 per error avoided at 6 months. Interpretation The PINCER intervention is an effective method for reducing a range of medication errors in general practices with computerised clinical records. Funding Patient Safety Research Portfolio, Department of Health, England.

Background Medication errors are an important cause of morbidity and mortality in primary care. The aims of this study are to determine the effectiveness, cost effectiveness and acceptability of a pharmacist-led information-technology-based complex intervention compared with simple feedback in reducing proportions of patients at risk from potentially hazardous prescribing and medicines management in general (family) practice. Methods Research subject group: "At-risk" patients registered with computerised general practices in two geographical regions in England. Design: Parallel group pragmatic cluster randomised trial. Interventions: Practices will be randomised to either: (i) Computer-generated feedback; or (ii) Pharmacist-led intervention comprising of computer-generated feedback, educational outreach and dedicated support. Primary outcome measures: The proportion of patients in each practice at six and 12 months post intervention: - with a computer-recorded history of peptic ulcer being prescribed non-selective non-steroidal anti-inflammatory drugs - with a computer-recorded diagnosis of asthma being prescribed beta-blockers - aged 75 years and older receiving long-term prescriptions for angiotensin converting enzyme inhibitors or loop diuretics without a recorded assessment of renal function and electrolytes in the preceding 15 months. Secondary outcome measures; These relate to a number of other examples of potentially hazardous prescribing and medicines management. Economic analysis: An economic evaluation will be done of the cost per error avoided, from the perspective of the UK National Health Service (NHS), comparing the pharmacist-led intervention with simple feedback. Qualitative analysis: A qualitative study will be conducted to explore the views and experiences of health care professionals and NHS managers concerning the interventions, and investigate possible reasons why the interventions prove effective, or conversely prove ineffective. Sample size: 34 practices in each of the two treatment arms would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a 50% reduction in error rates for each of the three primary outcome measures in the pharmacist-led intervention arm compared with a 11% reduction in the simple feedback arm. Discussion At the time of submission of this article, 72 general practices have been recruited (36 in each arm of the trial) and the interventions have been delivered. Analysis has not yet been undertaken. Trial registration Current controlled trials ISRCTN21785299

Objective: To explore the causes of preventable drug-related admissions (PDRAs) to hospital. Design: Qualitative case studies using semi-structured interviews and medical record review; data analysed using a framework derived from Reason’s model of organisational accidents and cascade analysis. Participants: 62 participants, including 18 patients, 8 informal carers, 17 general practitioners, 12 community pharmacists, 3 practice nurses and 4 other members of healthcare staff, involved in events leading up to the patients’ hospital admissions. Setting: Nottingham, UK. Results: PDRAs are associated with problems at multiple stages in the medication use process, including prescribing, dispensing, administration, monitoring and help seeking. The main causes of these problems are communication failures (between patients and healthcare professionals and different groups of healthcare professionals) and knowledge gaps (about drugs and patients’ medical and medication histories). The causes of PDRAs are similar irrespective of whether the hospital admission is associated with a prescribing, monitoring or patient adherence problem. Conclusions: The causes of PDRAs are multifaceted and complex. Technical solutions to PDRAs will need to take account of this complexity and are unlikely to be sufficient on their own. Interventions targeting the human causes of PDRAs are also necessary—for example, improving methods of communication.

Aim: Previous systematic reviews have found that drug-related morbidity accounts for 4.3% of preventable hospital admissions. None, however, has identified the drugs most commonly responsible for preventable hospital admissions. The aims of this study were to estimate the percentage of preventable drug-related hospital admissions, the most common drug causes of preventable hospital admissions and the most common underlying causes of preventable drug-related admissions. Methods: Bibliographic databases and reference lists from eligible articles and study authors were the sources for data. Seventeen prospective observational studies reporting the proportion of preventable drug-related hospital admissions, causative drugs and/or the underlying causes of hospital admissions were selected. Included studies used multiple reviewers and/or explicit criteria to assess causality and preventability of hospital admissions. Two investigators abstracted data from all included studies using a purpose-made data extraction form. Results: From 13 papers the median percentage of preventable drug-related admissions to hospital was 3.7% (range 1.4-15.4). From nine papers the majority (51%) of preventable drug-related admissions involved either antiplatelets (16%), diuretics (16%), nonsteroidal anti-inflammatory drugs (11%) or anticoagulants (8%). From five studies the median proportion of preventable drug-related admissions associated with prescribing problems was 30.6% (range 11.1-41.8), with adherence problems 33.3% (range 20.9-41.7) and with monitoring problems 22.2% (range 0-31.3). Conclusions: Four groups of drugs account for more than 50% of the drug groups associated with preventable drug-related hospital admissions. Concentrating interventions on these drug groups could reduce appreciably the number of preventable drug-related admissions to hospital from primary care.

Aim: To describe how quantitative data obtained from applying a series of indicators for preventable drug related morbidity (PDRM) in the electronic patient record in English general practice can be used to facilitate changes aimed at helping to improve medicines management. Design: A multidisciplinary discussion forum held at each practice facilitated by a clinical researcher. Subjects and setting: Eight English general practices. Outcome measures: Issues discussed at the multidisciplinary discussion forum and ideas generated by practices for tackling these issues. Progress made by practices after 1, 3, and 6 months. Results: A number of clinical issues were raised by the practices and ideas for moving them forward were discussed. The issues that were easiest and most straightforward to deal with (for example, reviewing specific patient groups) were quickly addressed in most instances. Practices were less likely to have taken steps towards addressing issues at a systems level. Conclusions: Data generated from applying PDRM indicators can be used to facilitate practice-wide discussion on medicines management. Different practices place different priority levels on the issues they wish to pursue. Individual practice “ownership” of these, together with having a central committed figure at the practice, is key to the success of the process.

Item does not contain fulltext BACKGROUND: This study was carried out as part of a European Union funded project (PharmDIS-e+), to develop and evaluate software aimed at assisting physicians with drug dosing. A drug that causes particular problems with drug dosing in primary care is digoxin because of its narrow therapeutic range and low therapeutic index. OBJECTIVES: To determine (i) accuracy of the PharmDIS-e+ software for predicting serum digoxin levels in patients who are taking this drug regularly; (ii) whether there are statistically significant differences between predicted digoxin levels and those measured by a laboratory and (iii) whether there are differences between doses prescribed by general practitioners and those suggested by the program. METHODS: We needed 45 patients to have 95% Power to reject the null hypothesis that the mean serum digoxin concentration was within 10% of the mean predicted digoxin concentration. Patients were recruited from two general practices and had been taking digoxin for at least 4 months. Exclusion criteria were dementia, low adherence to digoxin and use of other medications known to interact to a clinically important extent with digoxin. RESULTS: Forty-five patients were recruited. There was a correlation of 0.65 between measured and predicted digoxin concentrations (P < 0.001). The mean difference was 0.12 microg/L (SD 0.26; 95% CI 0.04, 0.19, P = 0.005). Forty-seven per cent of the patients were prescribed the same dose as recommended by the software, 44% were prescribed a higher dose and 9% a lower dose than recommended. CONCLUSION: PharmDIS-e+ software was able to predict serum digoxin levels with acceptable accuracy in most patients.

Focal points The study involved used a two-round Delphi questionnaire survey of a total of 17 general practitioners and pharmacists, to assess the face and content validity and develop consensus for 31 indicators for preventable drug-related morbidity (PDRM) Consensus that an indicator represented a PDRM was achieved for 15 indicators Combining these results with that from previous work has identified 34 PDRM indicators suitable for use in the UK This study has highlighted the difficulty of identifying the process of care needed to prevent specific drug-related morbidities The results of operationalising these indicators will help focus an intervention to facilitate improvements in medicines usage in UK primary care