Improvements In Clinical Care Research Articles

Implementation of Provider-Based Electronic Medical Records and Improvement of the Quality of Data in a Large HIV Program in Sub-Saharan Africa

IntroductionStarting in June 2010 the Infectious Diseases Institute (IDI) clinic (a large urban HIV out-patient facility) switched to provider-based Electronic Medical Records (EMR) from paper EMR entered in the database by data-entry clerks. Standardized clinics forms were eliminated but providers still fill free text clinical notes in physical patients’ files. The objective of this study was to compare the rate of errors in the database before and after the introduction of the provider-based EMR.Methods and FindingsData in the database pre and post provider-based EMR was compared with the information in the patients’ files and classified as correct, incorrect, and missing. We calculated the proportion of incorrect, missing and total error for key variables (toxicities, opportunistic infections, reasons for treatment change and interruption). Proportions of total errors were compared using chi-square test. A survey of the users of the EMR was also conducted. We compared data from 2,382 visits (from 100 individuals) of a retrospective validation conducted in 2007 with 34,957 visits (from 10,920 individuals) of a prospective validation conducted in April–August 2011. The total proportion of errors decreased from 66.5% in 2007 to 2.1% in 2011 for opportunistic infections, from 51.9% to 3.5% for ART toxicity, from 82.8% to 12.5% for reasons for ART interruption and from 94.1% to 0.9% for reasons for ART switch (all P<0.0001). The survey showed that 83% of the providers agreed that provider-based EMR led to improvement of clinical care, 80% reported improved access to patients’ records, and 80% appreciated the automation of providers’ tasks.ConclusionsThe introduction of provider-based EMR improved the quality of data collected with a significant reduction in missing and incorrect information. The majority of providers and clients expressed satisfaction with the new system. We recommend the use of provider-based EMR in large HIV programs in Sub-Saharan Africa.

Microbial analysis of the upper respiratory tract to support the development of effective vaccine policy: a population-based pilot study

BackgroundRespiratory infections cause 7% of deaths globally. Microbial upper respiratory tract (URT) carriage is a precursor to respiratory disease, meningitis, and septicaemia. Understanding carriage of URT pathogens is crucial to understanding the spread of respiratory disease. Vaccination against respiratory pathogens has reduced invasive disease rates but also profoundly modified carriage. Previous work shows the importance of individual URT pathogens, especially Streptococcus pneumoniae, and the effects of vaccination on carriage and disease. We aimed to assess carriage of multiple respiratory pathogens within a population benefitting from pneumococcal, Haemophilus influenzae b and meningitis C vaccines. This assessment will enable us to decipher the role of URT community dynamics. MethodsWe undertook a population-based respiratory carriage pilot study with 1574 participants, 1171 of whom were aged 5 years or older and 385 aged younger than 5 years (18 participants of age unknown because they did not return questionnaire). Patients registered at one of 19 Hampshire general practices, of any age and health status, were randomly selected using the ralloc command in Stata 12. Optimum sample collection method and carriage rates of the above species were assessed in two study groups: a self-swab group, in which participants did their own nose and mouth swabs; and a healthcare professional (HCP) group, in which HCPs did participants' nasopharyngeal and mouth swabs. Participant response rates in each study arm were compared. SPSS and a confidence interval calculator were used in the analysis. FindingsPreliminary data suggest that nasal swabbing gave the greatest bacterial recovery at 40%. Nasal carriage rates of S pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, H influenzae, and Neisseria meningitidis were 10·3%, 2·5%, 1·6%, 21·3%, 2·6%, and 1·7%, respectively. Carriage of S pneumoniae and H influenzae were associated with young children whereas S aureus was associated with adults (p<0·0001). Carriage of S pneumoniae and H influenzae were associated with recent respiratory infection (p<0·0001 and p=0·0003, respectively). Co-colonisation of S pneumoniae with other species was common, especially H influenzae. Polymicrobial carriage occurred in 2·5% (n=80) samples. Response rates were higher for self-swabbing (22·3%, 95% CI 21·2–23·4) versus HCP-swabbing (6·6%, 5·9–7·3). However, isolation rates were greater for HCP-swabbing (36·0%, 30·7–41·3) versus self-swabbing (20·2%, 18·0–22·4). InterpretationPreliminary data show URT diversity and will aid continuation of the study in future years. We hope to use molecular methods to further understand the genetic composition and diversity of the URT community. Continuation of such studies will enable us to track changes in the rates of these interacting pathogens with ever-changing use of vaccines and antibiotics within the population. These studies are essential for enabling future improvements in clinical care by informing vaccine and antibiotic development and policy against infections causing meningitis, sepsis, and respiratory disease. FundingBupa Foundation, The Rosetree's Trust.

The North of England Survey of Twin and Multiple Pregnancy

The population-based Northern Survey of Twin and Multiple Pregnancy (NorSTAMP, formerly the Multiple Pregnancy Register) has collected data since 1998 on all multiple pregnancies in North of England (UK) from the earliest point of ascertainment in pregnancy. This paper updates recent developments to the NorSTAMP and presents some early mortality data from the first 10 years of data collection (1998-2007). Since 2005, mothers have been asked to give explicit consent for their identifiable data to be held by the survey, in line with changing guidance and legal frameworks for identifiable data. In 2009, regional standards of care for multiple pregnancies were developed, agreed, and disseminated. During 1998-2007, 4,865 twin maternities (pregnancies with at least one live birth or stillbirth) were registered, with an average twinning rate of 14.9 per 1,000 maternities. The overall stillbirth and neonatal mortality rates in twins were 18.0/1,000 births and 23.0/1,000 live births respectively. Stillbirth and neonatal mortality rates were significantly higher in monochorionic than dichorionic twins: 44.4 versus 12.2 per 1,000 births (relative risk [RR] 3.6, 95% Confidence Intervals [CI] 2.6-5.1), and 32.4 versus 21.4 per 1,000 live births (RR 1.5, 95% CI 1.04-2.2) respectively. There was no significant improvement during this period in either stillbirth or neonatal mortality rates in either chorionicity group. This population-based survey is an important source of data on multiple pregnancies, which allows monitoring of trends in multiple birth rates and pregnancy losses, providing essential information to support improvements in clinical care and for epidemiological research.

Making Connections: Using TeleHealth to Improve the Diagnosis and Treatment of Complex Regional Pain Syndrome, an Underrecognized Neuroinflammatory Disorder

Complex Regional Pain Syndrome (CRPS) is a common and complex, but often underrecognized neuroinflammatory disorder. This syndrome can cause significant intractable pain, worsening motor changes, negative sensory symptoms as well as autonomic, vasomotor and trophic changes. Primary care providers and specialists are frequently challenged with patients who present with unusual symptoms and are unsure of the differential diagnosis and best practices treatment options for CRPS. The Project ECHO Pain Team leverages tele-health technologies to connect clinician specialists and primary care providers in order to increase awareness and create knowledge networks regarding improvement in clinical care for patients with CRPS.

Assessment of a pay-for-performance program in primary care designed by target users

Evidence for pay-for-performance (P4P) has been searched for in the last decade as financial incentives increased to influence behaviour of health care professionals to improve quality of care. The effectiveness of P4P is inconclusive, though some reviews reported significant effects. To assess changes in performance after introducing a participatory P4P program. An observational study with a pre- and post-measurement. Setting and subjects. Sixty-five general practices in the south of the Netherlands. Intervention. A P4P program designed by target users containing indicators for chronic care, prevention, practice management and patient experience (general practitioner's [GP] functioning and organization of care). Quality indicators were calculated for each practice. A bonus with a maximum of 6890 Euros per 1000 patients was determined by comparing practice performance with a benchmark. Quality indicators for clinical care (process and outcome) and patient experience. We included 60 practices. After 1 year, significant improvement was shown for the process indicators for all chronic conditions ranging from +7.9% improvement for cardiovascular risk management to +11.5% for asthma. Five outcome indicators significantly improved as well as patients' experiences with GP's functioning and organization of care. No significant improvements were seen for influenza vaccination rate and the cervical cancer screening uptake. The clinical process and outcome indicators, as well as patient experience indicators were affected by baseline measures. Smaller practices showed more improvement. A participatory P4P program might stimulate quality improvement in clinical care and improve patient experiences with GP's functioning and the organization of care.

Genome-wide association study of glioma and meta-analysis.

Gliomas account for approximately 80% of all primary malignant brain tumors and, despite improvements in clinical care over the last 20years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

Evaluation of risk equations for prediction of short-term coronary heart disease events in patients with long-standing type 2 diabetes: the Translating Research into Action for Diabetes (TRIAD) study

BackgroundTo evaluate the U.K. Prospective Diabetes Study (UKPDS) and Framingham risk equations for predicting short-term risk of coronary heart disease (CHD) events among adults with long-standing type 2 diabetes, including those with and without preexisting CHD.MethodsProspective cohort of U.S. managed care enrollees aged ≥ 18 years and mean diabetes duration of more than 10 years, participating in the Translating Research into Action for Diabetes (TRIAD) study, was followed for the first occurrence of CHD events from 2000 to 2003. The UKPDS and Framingham risk equations were evaluated for discriminating power and calibration.ResultsA total of 8303 TRIAD participants, were identified to evaluate the UKPDS (n = 5914, 120 events), Framingham-initial (n = 5914, 218 events) and Framingham-secondary (n = 2389, 374 events) risk equations, according to their prior CHD history. All of these equations exhibited low discriminating power with Harrell’s c-index <0.65. All except the Framingham-initial equation for women and the Framingham-secondary equation for men had low levels of calibration. After adjsusting for the average values of predictors and event rates in the TRIAD population, the calibration of these equations greatly improved.ConclusionsThe UKPDS and Framingham risk equations may be inappropriate for predicting the short-term risk of CHD events in patients with long-standing type 2 diabetes, partly due to changes in medications used by patients with diabetes and other improvements in clinical care since the Frmaingham and UKPDS studies were conducted. Refinement of these equations to reflect contemporary CHD profiles, diagnostics and therapies are needed to provide reliable risk estimates to inform effective treatment.

Clinical ethics consultation in oncology.

9121 Background: There is limited empirical research exploring the nature of clinical ethical consultations within the oncology population. Our objective is to review, describe and compare clinical ethics consultations at two NCI-designated comprehensive cancer centers, in order to identify opportunities for systems improvement in clinical care. Methods: This case series is derived from prospectively-maintained clinical ethics consultation databases at each institution. All adult oncology patients receiving ethics consultation from 2007 through 2011 were included as eligible cases. Both qualitative and quantitative analyses were undertaken. Demographic and clinical information were obtained from the databases for all patients, and verified via chart abstraction. Additional variables studied included the reason for and context of the ethical consultation, the patient’s code status before and after consultation, and involvement of palliative care or other adjuvant services. Opportunities for systems-level improvements and/or educational initiatives were identified. Results: A total of 207 eligible cases were identified. The most common primary issues leading to ethics consultation were code status and advance directives (25%), surrogate decision-making (17%), and medical futility (13%). Communication lapses were identified in 41%, and interpersonal conflict arose in 51%. Prior to ethics consultation, 26% of patients were DNR; 60% were DNR after ethics consultation. Palliative care consultation occurred in 41% of cases. Opportunities for systems improvement and professional education related to goals of care at the end of life, the role of palliative care involvement, and improved communication. Conclusions: Ethics consultations among cancer patients reflect the realities inherent to their clinical management. Appropriately addressing advance directives within the context of overall goals of care is crucial. Thoughtful consideration of communication barriers, sources of interpersonal conflict, symptom control, and end-of-life care are paramount to optimal management strategies in this patient population.

Risk categories and refractory CLL in the era of chemoimmunotherapy

AbstractStandardized criteria for diagnosis and response evaluation in chronic lymphocytic leukemia (CLL) are essential to achieve comparability of results and improvement of clinical care. With the increasing range of therapeutic options, the treatment context is important when defining refractory CLL. Refractory CLL has been defined as no response or response lasting ≤ 6 months from last therapy. This subgroup has a very poor outcome, and many trials use this group as an entry point for early drug development. With the intensification of first-line regimens, the proportion of patients with refractory CLL using these criteria decreases. This has immediate consequences for recruitment of patients into trials as well as salvage strategies. Conversely, patients who are not refractory according to the traditional definition but who have suboptimal or short response to intense therapy also have a very poor outcome. In this Perspective, we discuss recent results that may lead to a reassessment of risk categories in CLL focusing on fit patients who are eligible for all treatment options. We cover aspects of the history and biologic basis for refractory CLL and will focus on how emerging data on treatment failure from large trials using chemoimmunotherapy may help to define risk groups in CLL.

Neurovascular disorders in children: a 21st century challenge for paediatric neurologists

Neurovascular disorders have been poorly understood within paediatric neurology and perceived as rare and untreatable. However, clinical and research advances argue for the development of this neurological subspecialty. Key examples are better understanding of risk factors for childhood stroke, recognition of cerebrovascular complications of genetic disorders, and the potential for multimodal therapy for complex cerebrovascular disease. Arterial ischaemic stroke (AIS) in adults is now a medical emergency; however, the distinct causes and consequences in children make adult ‘stroke pathways’ (e.g. for hyperacute thrombolysis) inappropriate for most children. The significant delays in diagnosis of childhood AIS reflect lack of clinical awareness and access to acute neuroimaging – the latter is essential because of the wide differential diagnosis. Management of childhood stroke is supported by international clinical guidelines,1 but these also reflect the urgent need for high quality research to underpin recommendations, currently based on expert consensus. Specialist clinical expertise can help to target investigations and potential interventions in individual children, as these are much more diverse than in adults. The International Pediatric Stroke Study group (https://app3.ccb.sickkids.ca/cstrokestudy/) has provided key insights into childhood stroke and developed an important collaborative research framework. International networks, such as the International Child Neurology Association (ICNA; http://www.icnapedia.org), have an important role in facilitating clinical and research infrastructure, as well as the resources to consider global variations in disease profiles and medical practice. Sickle-cell disease is one of the most common severe monogenic disorders; a quarter of affected people will have ischaemic brain injury in childhood. Transcranial Doppler ultrasound (TCD) screening, and prophylactic blood transfusion if this is abnormal, is effective in AIS prevention2 and is being implemented in many countries. The UK National Institute for Health and Clinical Excellence (NICE) guidelines (http://sct.screening.nhs.uk/cms.php?folder=2493) recommend neuroimaging in children with abnormal TCD studies, as well as those with a range of neurological symptoms. Interpretation of neuroimaging in sickle-cell disease and putting this into an appropriate clinical context is complex, and argues for involvement of a child neurologist. Other neurological issues include assessment for surgical revascularization, concurrent cerebrovascular pathologies (including dissection3), and AIS risk factors. The issue of cerebrovascular screening in asymptomatic children with genetic disorders is complex and contentious. Examples include children whose parents have hereditary haemorrhagic telangiectasia4 (frequency 1:5 000) and microcephalic osteodysplastic primordial dwarfism type II – even where there are guidelines, the evidence underpinning these is scanty. The ethical and health economic issues merit separate consideration; however counselling, imaging, and managing such patients and their cerebrovascular disease is complex, requiring specialist expertise and access to a multidisciplinary neurovascular team. The literature on treatment of paediatric brain arteriovenous malformations is strongly biased by proponents of specific treatment approaches (surgical resection/endovascular treatment/stereotactic radiosurgery) and it is impossible to derive conclusions about relative efficacy or factors influencing this. Increasing realization that vascular malformations are commonly genetic or systemic means that a detailed clinical assessment and identification of medically treatable factors is essential. In this regard the neurologist can act as an honest broker in the multidisciplinary forum. Excitingly, genetic advances have elucidated some underlying disease mechanisms and targeted medical interventions are likely to become available in the palpable future.5 Rapid developments in endovascular devices (stents/angioplasty) mean that the neurologist within such teams also has a key role in identifying children with occlusive cerebrovascular diseases who could benefit from these novel interventions, akin to established practice for evaluating children with moyamoya for surgical revascularization. Organizations such as ICNA, are key to achieving improvements in clinical care and facilitating research on paediatric neurovascular disorders on a global scale. In the upcoming May 2012 ICNA meeting in Brisbane (http://www.icnc2012.com) there will be four neurovascular sessions, including 11 lectures from an international faculty, promoting both clinical and research agendas. Paediatric neurovascular disorders are clinically significant and now often treatable. The development of networks, that include specialist multidisciplinary teams to consider complex or novel interventions and systematically accrue high quality clinical evidence is an essential requirement.

Introduction of county-wide electronic palliative care notes system improves quality and efficiency

BackgroundA partnership of the five different Specialist Palliative Care service providers in Worcestershire came together to implement a county-wide clinical notes system for specialist palliative care patients. The SystmOne electronic...

Within Sight of a Rational Pipeline for Development of Protein Diagnostics

Given the paucity of new clinical tests emerging from proteomics research on the one hand (1) and the large and increasing levels of NIH funding devoted to biomarker research on the other (2), important questions have been raised about our strategy for translating basic research into clinical diagnostics. At a fundamental level, it has been unclear whether the lack of clinical results from numerous biomarker discovery efforts is due to our having exhausted the low-hanging fruit (or all fruit?) in years past, or to defects in the approaches being used in the search for new markers. It seems unlikely that all useful clinical protein tests have been discovered; therefore, discussion has focused on the defects in the “biomarker pipeline” that should be conveying candidate biomarker proteins toward a clinical application. The ultimate importance of this debate is not academic: Improvements in clinical care and in basic health economics increasingly depend on the development of new tests (including companion diagnostics that allow personalization of therapy) and markers addressing the long-standing list of unmet clinical diagnostic needs in such areas as Alzheimer disease, chronic obstructive pulmonary disease, and cancer. Fortunately, recent publications (3, 4) suggest that progress is being made in implementing biomarker pipeline concepts that work: approaches that link a “discovery” process that uses a small number of particularly favorable samples with one or more “qualification” and/or “verification” steps that focus on testing the resulting candidate biomarkers with independent sets of real clinical samples. The work of Addona et al. (3) serves as a useful benchmark in this context because it is focused on a clinical indication (cardiac damage markers) in which numerous proteins, such as creatine kinase isoenzyme MB, troponins, and B-type natriuretic peptide, have achieved undisputed clinical success. One can thus ask whether such a modern systematic approach …

Clinical Care Improvement with Use of Health Information Technology Focusing on Evidence Based Medicine

ObjectivesHealthcare institutions need timely patient information from various sources at the point-of-care. Evidence-based medicine (EBM) is a tool for proper and efficient incorporation of the results of research in decision-making. Characteristics of medical treatment processes and practical experience concerning the effect of EBM in the clinical process are surveyed.MethodsA cross sectional survey conducted in Tehran hospitals in February-March 2012 among 51 clinical residents. The respondents were asked to apply EBM in clinical decision-making to answer questions about the effect of EBM in the clinical process. A valid and reliable questionnaire was used in this study.ResultsEBM provides a framework for problem solving and improvement of processes. Most residents (76%) agreed that EBM could improve clinical decision making. Eighty one percent of the respondents believed that EBM resulted in quick updating of knowledge. They believed that EBM was more useful for diagnosis than for treatment. There was a significant association between out-patients and in-patients in using electronic EBM resources.ConclusionsResearch findings were useful in clinical practice and decision making. The computerized guidelines are important tools for improving clinical process quality. When learning how to use IT, methods of search and evaluation of evidence for diagnosis, treatment and medical education are necessary. Purposeful use of IT in clinical processes reduces workload and improves decision-making.

Internet-Based Learning and Applications for Critical Care Medicine

Recent changes in duty hour allowances and economic constraints are forcing a paradigm shift in graduate medical education in the United States. Internet-based learning is a rapidly growing component of postgraduate medical education, including the field of critical care medicine. Here, we define the key concepts of Internet-based learning, summarize the current literature, and describe how Internet-based learning may be uniquely suited for the critical care provider. A MEDLINE/PubMed search from January 2000 to July 2011 using the search terms: "e-learning," "Web-based learning," "computer-aided instruction," "adult learning," "knowledge retention," "intensive care," and "critical care." The growth of the Internet is marked by the development of new technologies, including more user-derived tools. Nonmedical fields have embraced Internet-based learning as a valuable teaching tool. A recent meta-analysis described Internet-based learning in the medical field as being more effective than no intervention and likely as efficacious as traditional teaching methods. Web sites containing interactive features are aptly suited for the adult learner, complementing the paradigm shift to more learner-centered education. Interactive cases, simulators, and games may allow for improvement in clinical care. The total time spent utilizing Internet-based resources, as well as the frequency of returning to those sites, may influence educational gains. Internet-based learning may provide an opportunity for assistance in the transformation of medical education. Many features of Web-based learning, including interactivity, make it advantageous for the adult medical learner, especially in the field of critical care medicine, and further work is necessary to develop a robust learning platform incorporating a variety of learning modalities for critical care providers.

Preclinical Studies for Sickle Cell Disease Gene Therapy Using Bone Marrow CD34+ Cells Modified with a βAS3-Globin Lentiviral Vector

Abstract 3119 BACKGROUND:Sickle cell disease (SCD) affects approximately 80, 000 Americans, and causes significant neurologic, pulmonary, and renal injury, as well as severe acute and chronic pain that adversely impacts quality of life. Because SCD results from abnormalities in red blood cells, which in turn are produced from adult hematopoietic stem cells, hematopoietic stem cell transplant (HSCT) from a healthy (allogeneic) donor can benefit patients with SCD, by providing a source for life-long production of normal red blood cells. However, allogeneic HSCT is limited by the availability of well-matched donors and by immunological complications of graft rejection and graft-versus-host disease. Thus, despite major improvements in clinical care, SCD continues to cause significant morbidity and early mortality. HYPOTHESIS:We hypothesize that autologous stem cell gene therapy for SCD has the potential to treat this illness without the need for immune suppression of current allogeneic HSCT approaches. Previous studies have demonstrated that addition of a β-globin gene, modified to have the anti-sickling properties of fetal (γ-) globin (βAS3), to bone marrow (BM) stem cells in murine models of SCD normalizes RBC physiology and prevents the manifestations of sickle cell disease (Levassuer Blood 102 :4312–9, 2003). The present work seeks to provide pre-clinical evidence of efficacy for SCD gene therapy using human BM CD34+ cells modified with the bAS3 lentiviral (LV) vector. RESULTS:The βAS3 globin expression cassette was inserted into the pCCL LV vector backbone to confer tat-independence for packaging. The FB (FII/BEAD-A) composite enhancer-blocking insulator was inserted into the 3’ LTR (Ramezani, Stem Cells 26 :32–766, 2008). Assessments were performed transducing human BM CD34+ cells from healthy or SCD donors with βAS3 LV vectors. Efficient (1–3 vector copies/cell) and stable gene transmission were determined by qPCR and Southern Blot. CFU assays demonstrated that βAS3 gene modified SCD CD34+ cells are fully capable of maintaining their hematopoietic potential. To demonstrate the effectiveness of the erythroid-specific bAS3 gene in the context of human HSPC (Hematopoietic Stem and Progenitor Cells), we optimized an in vitro model of erythroid differentiation of huBM CD34+ cells. We successfully obtained an expansion up to 700 fold with >80% fully mature enucleated RBC derived from CD34+ cells obtained from healthy or SCD BM donors. We then assessed the expression of the βAS3 globin gene by isoelectric focusing: an average of 18% HbAS3 over the total globin present (HbS, HbA2) per Vector Copy Number (VCN) was detected in RBC derived from SCD BM CD34+. A qRT-PCR assay able to discriminate HbAS3 vs. HbA RNA, was also established, confirming the quantitative expression results obtained by isoelectric focusing. Finally, we show morphologic correction of in vitro differentiated RBC obtained from SCD BM CD34+ cells after βAS3 LV transduction; upon induction of deoxygenation, cells derived from SCD patients showed the typical sickle shape whereas significantly reduced numbers were detected in βAS3 gene modified cells. Studies to investigate risks of insertional oncogenesis from gene modification of CD34+ cells by βAS3 LV vectors are ongoing as are in vivo studies to demonstrate the efficacy of βAS3 LV vector in the NSG mouse model. CONCLUSIONS:This work provides initial evidence for the efficacy of the modification of human SCD BM CD34+ cells with βAS3 LV vector for gene therapy of sickle cell disease.This work was supported by the California Institute for Regenerative Medicine Disease Team Award (DR1-01452). Disclosures:No relevant conflicts of interest to declare.

Queensland Health – a leadership development journey

PurposeThis paper is a descriptive case study which seeks to outline how leadership development is being utilised across Queensland Health (Queensland Department of Health, Australia) to achieve improvements in workplace culture and ultimately improvements in clinical care and patient outcomes.Design/methodology/approachQueensland Health has been implementing a comprehensive organisation‐wide suite of leadership development programs since 2006. This includes a range of specific leadership development programs conducted over a period of time for clinical and non‐clinical staff. It also includes specialist leadership development workshops of shorter duration, online leadership modules, web‐based support, executive coaching and 360‐degree feedback. The programs are based upon experiential learning which engages participants in critical thinking and self‐reflection based upon in‐context experiences relevant to themselves. Ongoing leadership program development has been evidence‐based and identified through 360‐degree feedback outcomes, staff opinion survey outcomes and program evaluation outcomes.FindingsThe 360‐degree feedback survey results of participants have improved. This demonstrates that the leadership development programs have impacted positively on participants' workplace behaviour. The culture and climate survey results have improved which demonstrates positive cultural change has taken place. The programs have been evaluated very highly by participants.Originality/valueThis is one of the most comprehensive and innovative leadership development initiatives ever undertaken within the Australian health sector, with over 10,000 participants to date.

Abstract PL04-01: Early Detection Research Network: Biomarker discovery and validation - A team approach

Abstract While the principle of early detection and treatment of cancer through the use of diagnostic tests including biomarkers may seem to be a straightforward process, the rate of registration of new cancer-related biomarkers (approximately one per year) illustrates the substantial challenges to this science. Essential elements of a successful biomarker include sensitivity in the face of cancer, specificity in the cancer-free state as well as in the face of disease which may clinically mimic cancer or which is associated with a higher cancer risk, a reproducible, accurate, and portable assay, and, more recently, evidence that the specifics of the cancer detected (stage and prognosis, for example) leads to reductions in morbidity, mortality, or, possibly, cost. There is possibly no greater opportunity for team science to merge discovery, validation, and clinical efficacy than in cancer biomarkers. The EDRN, now 11 years old, envisioned such a collaboration, including Biomarker Development Laboratories, Biomarker Reference Laboratories, Clinical Validation Centers, an Informatics Center, and a Data Management and Coordinating Center. EDRN member institutions participate in organ working groups including Breast and Ovarian, GI, Prostate and GU, and Lung. Organ working groups function as teams, all focused on collaborative science with the ultimate goal of validation of biomarkers for the purpose of improvements in clinical care. Cross-organ-site team collaborations also occur as biomarkers or concepts that are applicable to multiple organ sites are evaluated. Teams include biostatistical expertise that has developed new methods for biomarker evaluation and validation. Finally, the EDRN is an open organization that seeks to partner with non-EDRN investigators through sharing of biospecimens, clinical data, and new analysis techniques to further the goal of early cancer detection. Citation Information: Cancer Prev Res 2011;4(10 Suppl):PL04-01.

Pathways for cervical metastasis in malignant neoplasms of the head and neck region

There have been significant changes in the evaluation and management of lymphatic metastases in the neck during the past several decades, and knowledge of the functional anatomy of the cervical lymphatics is fundamental to the clinical management of metastasis in this region. This review provides a comprehensive description of the cervical lymphatics and discusses how this knowledge is used in the modern management of the neck lymphatics in the setting of common cancers of the head and neck. The patterns of tumor spread can be delineated based on the well-studied functional anatomy of the lymphatic networks in the cervical region. The characteristics and patterns of metastatic spread for two common cancers found in this region, squamous cell carcinoma and cutaneous malignant melanoma, are discussed in this review. Significant improvements in clinical care, namely, selective neck dissection and sentinel lymph node biopsy aided by lymphoscintigraphy, have been developed and are based upon detailed studies of the pathways of metastatic spread. These advances have significantly decreased the morbidity associated with the evaluation and treatment of metastatic disease to the neck.

Effects of a clinical pathway 3 years after implementation in breast surgery

The aim of the present study is to evaluate the effects of the implementation of clinical pathways into routine practice of breast surgery. We implemented a clinical pathway for breast surgery in 2006 and analysed for the following 3 years its path in respect to hospital stay, total costs per case, readmission rate, and patients' satisfaction. The mean hospital stay decreased significantly from 4.5 days in 2006 to 3.7 days in 2007 and revealed 3.4 days in 2008. This is a decrease by 24.4% for the duration of hospital stay. The total cost per case between 2006 and 2007 showed a significant decrease of 23.4%. The total costs increased by 13.4% in 2008. Readmission rate was under 5% and remained constant. Patients' satisfaction remained constant, whereby more than 90% of the expected good results were attained. There is substantial evidence that clinical pathways lead to various improvements in clinical care in surgery. We show a constantly significant effect on duration of hospital stay without any increase in the number of readmissions. In our view, it is not only an economic benefit which prevails here, but also especially a transparency of treatment which leads to higher compliance, better outcome and a shorter length of stay.

Safe Opioid Prescribing: A Long Way to Go

Safe Opioid Prescribing: A Long Way to Go