Primer Part 1 - Preparing a laboratory quality improvement project.

Quality in laboratory medicine encompasses multiple components related to total quality management, including quality control (QC), quality assurance (QA), quality indicators, and quality improvement (QI). Together, they contribute to minimizing errors (pre-analytical, analytical, or post-analytical) in clinical service delivery and improving process appropriateness and efficiency. In contrast to static quality benchmarks (QC, QA, quality indicators), the QI paradigm is a continuous approach to systemic process improvement for optimizing patient safety, timeliness, effectiveness, and efficiency. Healthcare institutions have placed emphasis on applying the QI framework to identify and improve healthcare delivery. Despite QI's increasing importance, there is a lack of guidance on preparing, executing, and sustaining QI initiatives in the field of laboratory medicine. This has presented a significant barrier for clinical laboratorians to participate in and lead QI initiatives. This three-part primer series will bridge this knowledge gap by providing a guide for clinical laboratories to implement a QI project that issuccessful and sustainable. In the first article, we introduce the steps needed to prepare a QI project with focus on relevant methodology and tools related to problem identification, stakeholder engagement, root cause analysis (e.g., fishbone diagrams, Pareto charts and process mapping), and SMART aim establishment. Throughout, we describe a clinical vignette of a real QI project completed at our institution focused on serum protein electrophoresis (SPEP) utilization. This primer series is the first of its kind in laboratory medicine and will serve as a useful resource for future engagement of clinical laboratory leaders in QI initiatives.

Vitalizing the evaluation of curricular implementation: a framework for attending to the "how and whys" of curriculum evolution.

As curricular reforms are implemented, there is often urgency among scholars to swiftly evaluate curricular outcomes and establish whether desired impacts have been realized. Consequently, many evaluative studies focus on summative program outcomes without accompanying evaluations of implementation. This runs the risk of Type III errors, whereby outcome evaluations rest on unverified assumptions about the appropriate implementation of prescribed curricular activities. Such errors challenge the usefulness of the evaluative studies, casting doubt on accumulated knowledge about curricular innovations, and posing problems for educational systems working to mobilize scarce resources. Unfortunately, however, there is long-standing inattention to the evaluation of implementation in health professions education (HPE). To address this, we propose an accessible framework that provides substantive guidance for evaluative research on implementation of curricular innovations. The Prescribed-Intended-Enacted-Sustainable (PIES) framework that is articulated in this paper, introduces new concepts to HPE-with a view to facilitating more nuanced examination of the evolution of curricula as they are implemented. Critically, the framework is theoretically grounded, integrating evaluation and implementation science as well as education theory. It outlines when, how, and why evaluators need to direct attention to curricular implementation, providing guidance on how programs can map out meaningful evaluative research agendas. Ultimately, this work is intended to support evaluators and educators, seeking to design evaluation studies that provide more faithful, useful representations of the intricacies of curricular change implementation.

Choosing Wisely for Medical Education: Six Things Medical Students and Trainees Should Question.

PROBLEM: Physician behaviors that promote overuse of health care resources develop early in training, and the medical education environment helps foster such behaviors. The authors describe the development of a Choosing Wisely list for medical students aimed at helping to curb overuse. APPROACH: The list was developed in 2015 by Choosing Wisely Canada (CWC) in partnership with the Canadian Federation of Medical Students and the Fédération médicale étudiante du Québec, which together represent all medical students in Canada. CWC convened a student-led taskforce to develop recommendations targeting medical student behaviors with respect to resource stewardship practices. Students at all 17 Canadian medical schools were consulted via an online questionnaire to solicit feedback on a list of 10 candidate recommendations. The taskforce used this student feedback in finalizing the list. OUTCOMES: The final list of "Six Things That Medical Students and Trainees Should Question" highlights both behaviors students should avoid (e.g., "Don't suggest ordering the most invasive test before considering other less invasive options") and behaviors related to aspects of medical training that may promote overuse, such as the hierarchical nature of clinical supervision (e.g., "Don't hesitate to ask for clarification on tests, treatments, or procedures that you believe may be ordered inappropriately"). Based on student requests for illustrative examples, clinical vignettes were developed. NEXT STEPS: This list highlights medical student behaviors and aspects of the academic environment that drive overuse. It is also relevant to faculty, whose behaviors and supervision practices influence trainees.

A survey of primary care patients' readiness to engage in the de-adoption practices recommended by Choosing Wisely Canada.

BACKGROUND: Strategies such as Choosing Wisely have been established to identify the overuse of interventions considered as low-value. Reduction of low-value practices will require patients to understand why certain interventions are no longer recommended. The objective of this study was to determine whether older adults accept the rationale for and perceive themselves ready to de-adopt annual electrocardiogram testing, imaging for low back pain, the use of antibiotics for sinusitis, the use of sedative-hypnotics for insomnia, and the use of antipsychotics to treat behavioural symptoms of dementia. METHODS: A self-administered iPad survey was distributed to consecutive patients aged 50 years and older, presenting to three primary care outpatient practices in Ontario, Canada. Data from patients who were able and willing to complete the survey while waiting to see their physician were included. The survey queried knowledge, attitudes and behaviours around the targeted low-value interventions, before and after exposure to a Choosing Wisely Canada patient educational brochure on one of these five topics. A subset of patients agreed to participate in a semi-structured interview after their clinic visit. RESULTS: Three-hundred and forty-four patients (mean age 63, range 50-88, 59 % female) read the materials and completed the survey. Forty-eight percent (95 % CI 43-53 %) intended to discuss the information with a healthcare provider. Forty-five percent (95 % CI 40-51 %) expressed a desire to change current low-value practices. Approximately two-thirds of those who indicated they would not change future behaviours explained that it was because they were already espousing the Choosing Wisely values. After reading the Choosing Wisely brochures, knowledge improved independent of age, sex and education in 48 % (95 % CI 38-57 %) of participants about electrocardiogram testing, in 74 % (95 % CI 65-82 %) about use of antipsychotics, in 66 % (95 % CI 52-78 %) about use of antibiotics for sinusitis, in 60 % (95 % CI 46-72 %) about imaging for low back pain, and in 40 % (95 % CI 26-55 %) about sedative-hypnotic use in the elderly. CONCLUSIONS: The majority of primary care patients seem ready to de-adopt low-value practices. Provision of education in clinic waiting rooms can help improve knowledge around unnecessary care.

Robust effects of genetic background on responses to subarachnoid hemorrhage in mice.

Outcome varies among patients with subarachnoid hemorrhage but known prognostic factors explain only a small portion of the variation in outcome. We hypothesized that individual genetic variations influence brain and vascular responses to subarachnoid hemorrhage and investigated this using inbred strains of mice.Subarachnoid hemorrhage was induced in seven inbred and a chromosome 7 substitution strain of mouse. Cerebral blood flow, vasospasm of the middle cerebral artery, and brain injury were assessed. After 48 h of subarachnoid hemorrhage, mice showed significant middle cerebral artery vasospasm that correlated positively with reduction in cerebral blood flow at 45 min. Mice also had increased neuronal injury compared to sham controls; A/J and C57BL/6 J strains represented the most and least severe, respectively. However, brain injury did not correlate with cerebral blood flow reduction at 45 min or with vasospasm at 48 h. Chromosome 7 substitution did not influence the degree of vasospasm or brain injury.Our data suggested that mouse genetic background influences outcome of subarachnoid hemorrhage. Investigations into the genetic factors causing these inter-strain differences may provide insight into the etiology of the brain damage following subarachnoid hemorrhage. These findings also have implications for animal modeling of disease and suggest that genetic differences may also modulate outcome in other cardiovascular diseases.

Mouse genetic background is associated with variation in secondary complications after subarachnoid hemorrhage.

Spontaneous subarachnoid hemorrhage (SAH) is a form of hemorrhagic stroke that accounts for approximately 7 % of all strokes worldwide and is associated with mortality in approximately 35 % of cases and morbidity in many of the survivors. Studies have suggested that genetic variations may affect the pathophysiology of SAH. The goal of this study was to investigate the effect of mouse genetic background on brain injury and large artery vasospasm after SAH. SAH was induced in seven inbred strains of mice, and the degree of large artery vasospasm and brain injury was assessed. After 48 h, SAH mice showed a significant reduction in middle cerebral artery diameter and increased neuronal injury in the cerebral cortex compared with sham-operated controls. Mouse strains also demonstrated variable degrees of vasospasm and brain injury. This data suggests that different genetic factors influence how much brain injury and vasospasm occur after SAH. Future investigations may provide insight into the causes of these differences between strains and into which genetic contributors may be responsible for vasospasm and brain injury after SAH.

Valproic Acid treatment after experimental subarachnoid hemorrhage.

INTRODUCTION: Subarachnoid hemorrhage (SAH) can result in significant brain injury. Valproic acid (VPA), a widely-used anti-epileptic drug, was investigated as a possible neuroprotective drug in a prechiasmatic injection model of SAH in mice. METHODS: Mice were randomized to the following experimental groups: SAH, SAH + VPA, Sham, and Sham + VPA. VPA (400 mg/kg) or saline was administered within 30 min of SAH induction and every 12 h thereafter for 48 h. Neurobehavioral assessments using the modified Garcia Score were conducted at 24 and 48 h. Brain injury was assessed at 48 h with fluoro-jade b and caspase-3/NeuN histo- and immunohistochemistry. Vasospasm was assessed in the MCA branches using hematoxylin & eosin histology. RESULTS: SAH mice treated with VPA appeared to have improved neurobehavioral assessments at both 24 and 48 h compared to untreated SAH mice. VPA treatment in SAH mice also significantly decreased the number of degenerating neurons on fluoro-jade b staining. In VPA-treated SAH mice, there was a trend toward a decrease in the number of apoptotic neurons on caspase-3/NeuN immunohistochemistry. VPA did not significantly affect vasospasm. CONCLUSION: This study demonstrated that VPA improves neurological outcome and decreases brain injury in a mouse model of SAH.

Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage.

OBJECT: Glutamate is important in the pathogenesis of brain damage after cerebral ischemia and traumatic brain injury. Notably, brain extracellular and cerebrospinal fluid as well as blood glutamate concentrations increase after experimental and clinical trauma. While neurons are one potential source of glutamate, platelets also release glutamate as part of their recruitment and might mediate neuronal damage. This study investigates the hypothesis that platelet microthrombi release glutamate that mediates excitotoxic brain injury and neuron dysfunction after subarachnoid hemorrhage (SAH). METHODS: The authors used two models, primary neuronal cultures exposed to activated platelets, as well as a whole-animal SAH preparation. Propidium iodide was used to evaluate neuronal viability, and surface glutamate receptor staining was used to evaluate the phenotype of platelet-exposed neurons. RESULTS: The authors demonstrate that thrombin-activated platelet-rich plasma releases glutamate, at concentrations that can exceed 300 µM. When applied to neuronal cultures, this activated plasma is neurotoxic, and the toxicity is attenuated in part by glutamate receptor antagonists. The authors also demonstrate that exposure to thrombin-activated platelets induces marked downregulation of the surface glutamate receptor glutamate receptor 2, a marker of excitotoxicity exposure and a possible mechanism of neuronal dysfunction. Linear regression demonstrated that 7 days after SAH in rats there was a strong correlation between proximity to microthrombi and reduction of surface glutamate receptors. CONCLUSIONS: The authors conclude that platelet-mediated microthrombosis contributes to neuronal glutamate receptor dysfunction and might mediate brain injury after SAH.

Increased incidence of tuberculosis in zimbabwe, in association with food insecurity, and economic collapse: an ecological analysis.

BACKGROUND: Zimbabwe underwent a socioeconomic crisis and resultant increase in food insecurity in 2008-9. The impact of the crisis on Tuberculosis (TB) incidence is unknown. METHODS: Prospective databases from two mission hospitals, which were geographically widely separated, and remained open during the crisis, were reviewed. RESULTS: At the Howard Hospital (HH) in northern Zimbabwe, TB incidence increased 35% in 2008 from baseline rates in 2003-2007 (p<0.01) and remained at that level in 2009. Murambinda Hospital (MH) in Eastern Zimbabwe also demonstrated a 29% rise in TB incidence from 2007 to 2008 (p<0.01) and remained at that level in 2009. Data collected post-crisis at HH showed a decrease of 33% in TB incidence between 2009 to 2010 (p<0.001) and 2010/2011 TB incidence remained below that of the crisis years of 2008/2009 (p<0.01). Antenatal clinic HIV seroprevalence at HH decreased between 2001(23%) to 2011(11%) (p<0.001). Seasonality of TB incidence was analyzed at both MH and HH. There was a higher TB incidence in the dry season when food is least available (September-November) compared to post harvest (April-June) (p<0.001). CONCLUSION: This study suggests that an epidemic of TB mirrored socioeconomic collapse and recovery in Zimbabwe. The seasonal data suggests that food security may have been associated with TB incidence both annually and during the crisis in this high HIV prevalence country.

Genetic elimination of eNOS reduces secondary complications of experimental subarachnoid hemorrhage.

Delayed complications of subarachnoid hemorrhage (SAH) such as angiographic vasospasm, cortical spreading ischemia, microcirculatory dysfunction, and microthrombosis are reported in both patients and animal models of SAH. We demonstrated previously that SAH is associated with increased oxidative stress in the brain parenchyma, and that this correlates with dysfunction of endothelial nitric oxide synthase (eNOS) (homodimeric uncoupling). Uncoupling of eNOS exacerbated oxidative stress and enhanced nitric oxide (NO) depletion, and was associated with multiple secondary complications such as microthrombosis, neuronal apoptosis, and release of reactive oxygen species. Thus, we hypothesized that genetic abbrogation of eNOS would confer a beneficial effect on the brain after SAH. Using a prechiasmatic injection model of SAH, we show here that eNOS knockout (KO) significantly alleviates vasospasm of the middle cerebral artery and reduces superoxide production. Endothelial nitric oxide synthase KO also affected other nitric oxide synthase isoforms. It significantly increases neuron nitric oxide synthase expression but has no effect on inducible nitric oxide synthase. Endothelial nitric oxide synthase KO decreases Zn(2+) release after SAH, reduces microthrombi formation, and prevent neuronal degeneration. This work is consistent with our findings where, after SAH, increased oxidative stress can uncouple eNOS via Zn(2+) thiolate oxidation, or theoretically by depletion or oxidation of tetrahydrobiopterin, resulting in a paradoxical release of superoxide anion radical, further exacerbating oxidative stress and microvascular damage.

Early brain injury: a common mechanism in subarachnoid hemorrhage and global cerebral ischemia.

Early brain injury (EBI) has become an area of extreme interest in the recent years and seems to be a common denominator in the pathophysiology of global transient ischemia and subarachnoid hemorrhage (SAH). In this paper, we highlight the importance of cerebral hypoperfusion and other mechanisms that occur in tandem in both pathologies and underline their possible roles in triggering brain injury after hemorrhagic or ischemic strokes.