Search

CNS small vessel disease (CSVD) causes 25% of strokes and contributes to 45% of dementia cases. Prevalence increases with age, affecting about 5% of people aged 50 years to almost 100% of people older than 90 years. Known causes and risk factors include age, hypertension, branch atheromatous disease, cerebral amyloid angiopathy, radiation exposure, immune-mediated vasculitides, certain infections, and several genetic diseases. CSVD can be asymptomatic; however, depending on location, lesions can cause mild cognitive dysfunction, dementia, mood disorders, motor and gait dysfunction, and urinary incontinence. CSVD is diagnosed on the basis of brain imaging biomarkers, including recent small subcortical infarcts, white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy. Advanced imaging modalities can detect signs of disease even earlier than current standard imaging techniques. Diffusion tensor imaging can identify altered white matter connectivity, and blood oxygenation level-dependent imaging can identify decreased vascular reactivity. Pathogenesis is thought to begin with an etiologically specific insult, with or without genetic predisposition, which results in dysfunction of the neurovascular unit. Uncertainties regarding pathogenesis have delayed development of effective treatment. The most widely accepted approach to treatment is to intensively control well-established vascular risk factors, of which hypertension is the most important. With better understanding of pathogenesis, specific therapies may emerge. Early identification of pathologic characteristics with advanced imaging provides an opportunity to forestall progression before emergence of symptoms.

Objective As the globe endures the coronavirus disease 2019 (COVID-19) pandemic, we developed a hybrid Shewhart chart to visualize and learn from day-to-day variation in a variety of epidemic measures over time. Context Countries and localities have reported daily data representing the progression of COVID-19 conditions and measures, with trajectories mapping along the classic epidemiological curve. Settings have experienced different patterns over time within the epidemic: pre-exponential growth, exponential growth, plateau or descent and/ or low counts after descent. Decision-makers need a reliable method for rapidly detecting transitions in epidemic measures, informing curtailment strategies and learning from actions taken. Methods We designed a hybrid Shewhart chart describing four ‘epochs’ ((i) pre-exponential growth, (ii) exponential growth, (iii) plateau or descent and (iv) stability after descent) of the COVID-19 epidemic that emerged by incorporating a C-chart and I-chart with a log-regression slope. We developed and tested the hybrid chart using international data at the country, regional and local levels with measures including cases, hospitalizations and deaths with guidance from local subject-matter experts. Results The hybrid chart effectively and rapidly signaled the occurrence of each of the four epochs. In the UK, a signal that COVID-19 deaths moved into exponential growth occurred on 17 September, 44 days prior to the announcement of a large-scale lockdown. In California, USA, signals detecting increases in COVID-19 cases at the county level were detected in December 2020 prior to statewide stay-at-home orders, with declines detected in the weeks following. In Ireland, in December 2020, the hybrid chart detected increases in COVID-19 cases, followed by hospitalizations, intensive care unit admissions and deaths. Following national restrictions in late December, a similar sequence of reductions in the measures was detected in January and February 2021. Conclusions The Shewhart hybrid chart is a valuable tool for rapidly generating learning from data in close to real time. When used by subject-matter experts, the chart can guide actionable policy and local decision-making earlier than when action is likely to be taken without it.

Synesthesia literally means a "union of the senses" whereby two or more of the five senses that are normally experienced separately are involuntarily and automatically joined together in experience (1, 2, 3). For example, some synesthetes experience a color when they hear a sound, although many instances of synesthesia also occur entirely within the visual sense. In this paper, I first mainly engage critically with Sollberger's view that there is reason to think that at least some synesthetic experiences can be viewed as truly veridical perceptions, and not as illusions or hallucinations (4). Among other things, I explore the possibility that many forms of synesthesia can be understood as experiencing what I will call "second-order secondary properties," that is, experiences of properties of objects induced by the secondary qualities of those objects. In doing so, I shed some light on why synesthesia is typically one-directional and its relation to some psychopathologies such as autism.

Objective Motivated by the coronavirus disease 2019 (covid-19) pandemic, we developed a novel Shewhart chart to visualize and learn from variation in reported deaths in an epidemic. Context Without a method to understand if a day-to-day variation in outcomes may be attributed to meaningful signals of change—rather than variability we would expect—care providers, improvement leaders, policy-makers, and the public will struggle to recognize if epidemic conditions are improving. Methods We developed a novel hybrid C-chart and I-chart to detect within a geographic area the start and end of exponential growth in reported deaths. Reported deaths were the unit of analysis owing to erratic reporting of cases from variability in local testing strategies. We used simulation and case studies to assess chart performance and define technical parameters. This approach also applies to other critical measures related to a pandemic when high-quality data are available. Conclusions The hybrid chart detected the start of exponential growth and identified early signals that the growth phase was ending. During a pandemic, timely reliable signals that an epidemic is waxing or waning may have mortal implications. This novel chart offers a practical tool, accessible to system leaders and frontline teams, to visualize and learn from daily reported deaths during an epidemic. Without Shewhart charts and, more broadly, a theory of variation in our epidemiological arsenal, we lack a scientific method for a real-time assessment of local conditions. Shewhart charts should become a standard method for learning from data in the context of a pandemic or epidemic.

In the current omics-age of research, major developments have been made in technologies that attempt to survey the entire repertoire of genes, transcripts, proteins, and metabolites present within a cell. While genomics has led to a dramatic increase in our understanding of such things as disease morphology and how organisms respond to medications, it is critical to obtain information at the proteome level since proteins carry out most of the functions within the cell. The primary tool for obtaining proteome-wide information on proteins within the cell is mass spectrometry (MS). While it has historically been associated with the protein identification, developments over the past couple of decades have made MS a robust technology for protein quantitation as well. Identifying quantitative changes in proteomes is complicated by its dynamic nature and the inability of any technique to guarantee complete coverage of every protein within a proteome sample. Fortunately, the combined development of sample preparation and MS methods have made it capable of quantitatively comparing many thousands of proteins obtained from cells and organisms.

The recommended starting dose of bosutinib is 500 mg/day for chronic-phase (CP) or accelerated-/blast-phase Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy. However, some patients may require dose reductions to manage the occurrences of adverse events (AEs). Bosutinib efficacy and safety were evaluated following dose reductions in a phase I/II study of Ph+ patients with CP CML resistant/intolerant to imatinib or imatinib plus dasatinib and/or nilotinib, and those with accelerated-/blast-phase CML or acute lymphoblastic leukemia after at least imatinib treatment. In all, 570 patients with ≥4 years’ follow-up were included in this analysis. Among 144 patients who dose-reduced to bosutinib 400 mg/day (without reduction to 300 mg/day), 22 (15 %) had complete cytogenetic response (CCyR) before and after reduction, 40 (28 %) initially achieved CCyR after reduction, and 4 (3 %) only had CCyR before reduction. Among 95 patients who dose-reduced to bosutinib 300 mg/day, 23 (24 %) had CCyR before and after reduction, 13 (14 %) initially achieved CCyR after reduction, and 3 (3 %) only had CCyR before reduction. Results were similar to matched controls who remained on 500 mg/day, indicating dose reductions had not substantially affected efficacy. The incidence of treatment-emergent AEs was lower after dose reductions, particularly for gastrointestinal events. The incidence of hematologic toxicities generally was similar before and after dose reduction. The management of AEs with bosutinib through dose reduction can lead to improved/maintained efficacy and better tolerability; still, approximately half of patients on treatment at year 4 maintained a dose of ≥500 mg/day. ClinicalTrials.gov: NCT00261846.

The lapatinib–taxane combination led to shorter PFS than trastuzumab–taxane in HER2+ metastatic breast cancer. We investigated the prognostic and predictive effects of pretreatment serum HER2, CAIX, and TIMP-1. MA.31 accrued 652 patients; 537 (82%) were centrally confirmed HER2+. Biomarkers were categorized for univariate and multivariable predictive investigations with a median cut-point, ULN cut-points (15 ng/ml for HER2; 506 pg/ml for CAIX; 454 pg/ml for TIMP-1), and custom cut-points (30 and 100 ng/ml for HER2). Stratified step-wise forward Cox multivariable analysis examined continuous and categorical effects of biomarkers on PFS in the ITT and central HER2+ populations; central HER2+ biomarker results are shown. Serum was banked for 472 (72%) of 652 patients. Higher serum HER2 (>median; >15; >30; or >100 ng/ml; p = 0.05–0.002); higher CAIX (>median; >506 pg/ml; p = 0.02; p = 0.001); and higher TIMP-1 (> median; > 454 pg/ml; p = 0.001; p = 0.02) had shorter univariate PFS. In multivariable analysis, higher continuous TIMP-1 was associated with significantly shorter PFS: HR = 1.001 (95% CI = 1.00–01.002; p = 0.004). Continuous serum HER2 and CAIX were not significantly associated with PFS. HER2 of 15 ng/ml or higher had shorter PFS (p = 0.02); higher categorical CAIX had shorter PFS (p = 0.01–0.08). Interaction terms of HER2, CAIX, and TIMP-1 with treatment were not significant; the predictive test power was low. Higher levels of serum TIMP-1, CAIX, and HER2 were significant prognostic biomarkers of shorter PFS. We found no significant interaction between serum biomarkers and response to lapatinib versus trastuzumab. Evaluation of TIMP-1 and CAIX-targeted therapy in addition to HER2-targeted therapy appears warranted in patients with elevated serum levels of these biomarkers.

Background: In the phase 3 BFORE trial (NCT02130557), treatment with bosutinib resulted in a significantly higher major molecular response rate at 12months versus imatinib in the modified intent-to-treat (mITT) population of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). Assessment of patient-reported outcomes (PROs) was an exploratory objective. Methods: Patients with newly diagnosed CP CML were randomized 1:1 to receive once-daily bosutinib 400mg or imatinib 400mg as first-line therapy. Patients completed the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL-5 Dimensions (EQ-5D) questionnaires at baseline, every 3 months for the first 24 months of treatment, every 6 months thereafter, and at treatment completion. We report PRO results at month 12 in the mITT population (bosutinib: n = 246; imatinib: n = 241). Results: Mean FACT-Leu combined and subscale scores were similar at baseline in the bosutinib and imatinib arms; at month 12, all scores demonstrated improvement or maintenance of health-related quality of life (HRQoL) in both treatment arms. Repeated-measures mixed-effects models showed no significant difference between bosutinib and imatinib for any FACT-Leu score. Functional health status, as measured by EQ-5D, also demonstrated improvement or maintenance with bosutinib and imatinib at month 12. Conclusions: Similar improvements in PROs compared with baseline were seen after 12 months of treatment with first-line bosutinib or imatinib in the BFORE trial. Newly diagnosed patients with CP CML receiving bosutinib or imatinib can preserve or improve HRQoL during treatment, although clinical efficacy was superior with bosutinib

A 46-year-old previously healthy man presented with 1 week of headache, nausea, vomiting and dizziness. He was found to have cranial nerve deficits, his cerebrospinal fluid (CSF) demonstrated a lymphocytic pleocytosis and brain MRI suggested rhombencephalitis. Although Gram stains and cultures of his CSF did not identify a pathogen, Listeria monocytogenes DNA was detected by the FilmArray Meningitis/Encephalitis panel within 2 hours of performing a lumbar puncture. He was treated with ampicillin and gentamicin and had a near-complete recovery. This case highlights the importance of recognising L. monocytogenes infection as a cause of acute cranial nerve impairment with MRI findings suggestive of brainstem encephalitis. It also highlights the frequently atypical CSF profile and low yield of culture in L. monocytogenes rhombencephalitis and the value of multiplex PCR testing of CSF to rapidly identify this pathogen and permit targeted therapy.

This review highlights current management of patients with concomitant cerebral amyloid angiopathy (CAA) and atrial fibrillation (AF). We review quantifying risk of ischemic and hemorrhagic stroke as well as treatments to minimize future risk. Ischemic stroke risk in AF can be quantified by CHA2DS2-VASc and assessing left atrial echocardiographic characteristics. Patients deemed not low risk by CHA2DS2-VASC should be anticoagulated. CAA increases intracranial hemorrhage risk. CAA biomarkers include cortical microbleeds (CMBs), cortical superficial siderosis (cSS), convexal subarachnoid hemorrhage (cSAH), and lobar intracerebral hemorrhage (ICH). CAA with prior lobar ICH has an annual recurrence rate of 8.9%. CAA with cSAH carries an even higher annual lobar ICH risk of 19%. CMBs are associated with a dose-dependent risk of ICH, which rises with OACs. In patients with AF, antithrombotics should be avoided in CAA with predominant ICH, cSS, or cSAH features. Those with ≥ 2 CMB require in-depth risk-benefit analysis using a multidisciplinary approach.

The US health care system has recently begun to account for patients’ unmet social needs in care delivery and payment reform. This article presents a twenty-year qualitative case study of five stages of diffusion—testing and learning, standardization, replication, shifting from doing to enabling, and catalyzing broad adoption—of a practical approach for integrating social needs into clinical care. This case study of Health Leads and its funders confirms the importance of focusing on a clear aim, investing in model testing and standardization to enable subsequent responsiveness to the market, and the willingness of innovators and their investors to cede control of a model to allow local adaption and accelerate broad adoption.

Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Philadelphia positive chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase I/II study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow up and treatment durations were 54.8 (range 0.6-96.3) and 25.6 (0.2-96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytogenetic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5. Kaplan-Meier probability of maintaining major and complete cytogenetic response was 76% and 78%, respectively, at year 2 and 71% and 69% at year 5. Cumulative incidence of on-treatment disease progression/death was similar at years 5 (19%) and 2 (15%); Kaplan-Meier overall survival was 91% at year 2 and 84% at year 5. Of 169 patients who had discontinued bosutinib by year 5, 38 did so after year 2, most commonly for disease progression (n=11). Most adverse events initially occurred within two years. Overall, gastrointestinal events were the most common (diarrhea 86%, nausea 46%, vomiting 37%); the most common grade 3/4 toxicity was thrombocytopenia (25%). None of the 4 on-treatment deaths in years 3-5 were related to bosutinib. Bosutinib demonstrated durable efficacy and manageable toxicity through year 5 confirming its importance in the treatment of chronic phase chronic myeloid leukemia patients resistant/intolerant to prior imatinib. This trial was registered at clinicaltrials.gov identifier: 00261846.

Sampling in improvement work can pose challenges. How is it different from the sampling strategies many use with research, clinical trials, or regulatory programs? What should improvement teams consider when determining a useful approach to sampling and a useful sample size? The aim of this article is to introduce some of the concepts related to sampling for improvement. We give specific guidance related to determining a useful sample size to a wider health care audience so that it can be applied to improvement projects in hospitals and health systems.

Hospitals often have limited ability to obtain primary clinical data from electronic health records to use in assessing quality and safety. We outline a new model that uses administrative data to gauge the safety of care at the hospital level. The model is based on a set of highly undesirable events (HUEs) defined using administrative data and can be customized to address the priorities and needs of different users. Patients with HUEs were identified using discharge abstracts from July 1, 2008 through June 30, 2010. Diagnoses were classified as HUEs based on the associated present-on-admission status. The 2-year study population comprised more than 6.5 million discharges from 161 hospitals. The proportion of hospitalizations including at least one HUE during the 24-month study period varied greatly among hospitals, with a mean of 7.74% (SD 2.3%) and a range of 13.32% (max, 15.31%; min, 1.99%). The whole-patient measure of safety provides a global measure to use in assessing hospitals with the patient's entire care experience in mind. As administrative and clinical datasets become more consistent, it becomes possible to use administrative data to compare the rates of HUEs across organizations and to identify opportunities for improvement.

An extracardiac Fontan operation through a right thoracotomy incision is an alternative approach in children who have an ascending aorta that is in close proximity to the sternum, as in aortic atresia or transposed great vessels, and in those who have had prior mediastinitis.

Limb-shaking transient ischemic attacks (LSTIAs) are a phenomenon that occurs due to transient hypoperfusion to a cerebral motor territory with a chronically outstripped autoregulatory vascular reserve. First described in 1962 by Miller Fisher, the pathogenesis and the global understanding of this presentation have undergone a significant advancement throughout the years. Typically, patients will present with this syndrome of transient hypoperfusion in the context of extracranial carotid intrinsic vessel stenosis or by intracranial vascular stenosis to select motor pathways. We present within this case report a novel mechanism by which LSTIAs may emerge. Through this knowledge, clinicians may need to consider expansion of their diagnostic breadth to include proximal vasculature luminal integrity.

Combining the use of employee perception surveys with sound analytical techniques and models is critical to capturing high quality data from which effective decisions can be made in complex healthcare settings. This study used the Baldrige Award companion surveys with an analysis of variance (ANOVA) framework to identify discordant perceptions of hospital staff and leadership in the areas of customer focus, knowledge management, and results that were significant at the 0.05 and 0.01 levels. Senior leaders in the organization found the ANOVA framework helpful as they interpreted results from the Baldrige companion surveys and planned future improvement activities. During the execution of our study a number of difficulties and challenges arose that are not uncommon to survey administration in smaller settings, such as community hospitals, or in larger hospital settings with no research staff or research staff with relevant psychometric expertise. Our experience suggests that the Baldrige companion survey process would be enhanced by providing organizations with general guidance and protocols for optimal survey administration and data analysis. The purpose of this article is to outline the ANOVA model we used with the Baldrige companion surveys and to provide guidance related to the administration and analysis of these companion surveys for those that use them.

Context: Good health is the most important outcome of health care, and healthy life expectancy (HLE), an intuitive and meaningful summary measure combining the length and quality of life, has become a standard in the world for measuring population health. Methods: This article critically reviews the literature and practices around the world for measuring and improving HLE and synthesizes that information as a basis for recommendations for the adoption and adaptation of HLE as an outcome measure in the United States. Findings: This article makes the case for adoption of HLE as an outcome measure at the national, state, community, and health care system levels in the United States to compare the effectiveness of alternative practices, evaluate disparities, and guide resource allocation. Conclusions: HLE is a clear, consistent, and important population health outcome measure that can enable informed judgments about value for investments in health care.

Purpose. A case of elevated creatine phosphokinase (CPK) levels associated with linezolid therapy in a patient on chronic antihyperlipidemic therapy is presented. Summary. A 79-year-old Caucasian man with a primary diagnosis of acute hemoptysis secondary to pneumonia was admitted to the medical–surgical intensive care unit. A chest radiograph showed a large, right, lower-lobe infiltrate with alveolar consolidation. The patient’s medical history included hyperlipidemia that was chronically treated with lovastatin and gemfibrozil. Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was suspected and confirmed. Vancomycin 1 g i.v. every 12 hours was administered for approximately 10 days into the admission and switched to linezolid 600 mg i.v. every 12 hours after a lack of response to vancomycin. On hospital day 11, the patient’s CPK concentration was 47 units/L. Seven days later, his CPK concentration was 2584 units/L and his lovastatin and gemfibrozil were discontinued on that day. The patient’s CPK concentration peaked at 5369 units/L on the following day, and linezolid was discontinued at that point. One week later, his CPK concentration was 28 units/L. Approximately two weeks after the patient’s CPK levels normalized, he developed numerous complications. The patient died as a result of respiratory failure 11 days after being extubated, which occurred about 38 days after his admission. Although concomitant use of statins and gemfibrozil is known to increase the risk for CPK elevations, the continued rise in CPK levels after discontinuation of antihyperlipidemic therapy and the rapid time course for normalization after linezolid discontinuation are more consistent with an event associated with linezolid initiation. Conclusion. A patient on chronic antihyperlipidemic therapy developed elevated CPK levels after receiving linezolid for the treatment of MRSA pneumonia.

Squamous cell carcinoma (SCC) can arise from different anatomical sites including the skin, head and neck, lung, esophagus, genital area, and so on. Despite the same histopathologic features and immunohistochemistry profile, the SCCs of different body sites can show tremendous differences in their presenting symptoms, risk factor associations, natural history, prognosis, and response to treatment. This may reflect the fact that SCCs are heterogenous and likely have unique molecular characteristics at different anatomical sites. Recurrent somatic mutations in the TERT promoter region were first reported in human melanomas. Subsequently, other tumors including cutaneous SCC were found to demonstrate high frequencies of the same mutations. However, the incidences of TERT promoter mutation in noncutaneous SCCs have not been systemically studied. We investigated the TERT promoter mutation status among SCCs from different sites. We collected 84 cases of SCC from the skin (27), head and neck (12), lung (25), and cervix (10), as well as 10 cases of urothelial carcinoma with squamous differentiation (UC-SqD). We found that the frequencies of TERT promoter mutation among SCC of different sits are quite heterogenous: ~70% in skin SCC and UC-SqD, 16.67% in head and neck SCC, and 0% in lung and cervix SCC. These results may support the hypothesis of different carcinogenesis mechanisms of SCC in different sites. It also indicates that TERT promoter mutation could be a biomarker for distinguishing skin SCC or UC-SqD vs pulmonary SCC.

In 4 experiments, the authors examined how several variables influence the quality and quantity of information that people use to make judgments about other people. The results showed that when possible, participants consistently responded appropriately to variables that influenced information that they used to make inferences about other minds. The results also suggested that under circumstances with no opportunity to contrast behavior in different situations, people might not be sensitive to the quality and quantity of information present. The authors interpreted results to mean that under most circumstances, people make inferences in a way that efficiently uses information about the causes of behavior.

Background Advanced predictive analytical techniques are being increasingly applied to clinical risk assessment. This study compared a neural network model to several other models in predicting the length of stay (LOS) in the cardiac surgical intensive care unit (ICU) based on pre-incision patient characteristics. Methods Thirty six variables collected from 185 cardiac surgical patients were analyzed for contribution to ICU LOS. The Automatic Linear Modeling (ALM) module of IBM-SPSS software identified 8 factors with statistically significant associations with ICU LOS; these factors were also analyzed with the Artificial Neural Network (ANN) module of the same software. The weighted contributions of each factor (“trained” data) were then applied to data for a “new” patient to predict ICU LOS for that individual. Results Factors identified in the ALM model were: use of an intra-aortic balloon pump; O2 delivery index; age; use of positive cardiac inotropic agents; hematocrit; serum creatinine ≥ 1.3 mg/deciliter; gender; arterial pCO2. The r2 value for ALM prediction of ICU LOS in the initial (training) model was 0.356, p

Risk-adjusted hospital-wide mortality has been proposed as a key indicator of system-level quality. Several risk-adjusted measures are available, and one-the hospital standardized mortality ratio (HSMR) - is publicly reported in a number of countries, but not in the United States. This paper reviews potential uses of such measures. We conclude that available methods are not suitable for interhospital comparisons or rankings and should not be used for pay-for-performance or value-based purchasing/payment. Hospital-wide mortality is a relatively imprecise, crude measure of quality, but disaggregation into condition- and service-line-specific mortality can facilitate targeted improvement efforts. If tracked over time, both observed and expected mortality rates should be monitored to ensure that apparent improvement is not due to increasing expected mortality, which could reflect changes in case mix or coding. Risk-adjusted mortality can be used as an initial signal that a hospital's mortality rate is significantly higher than statistically expected, prompting further inquiry.

Objectives Engaging physicians in quality and patient safety initiatives is a well-described challenge. Barriers include time constraints, lack of defined common purpose and leadership support, poorly communicated goals, and scarcity of supporting data (references 1, 2, 3).With reference to strengthening a culture of safety while meeting regulatory and performance standards, health-care systems face a difficult twin objective: educate the medical staff and its trainees and maintain high levels of compliance across inpatient, ambulatory clinic, and procedural areas.In 2010, our institution identified opportunities for improvement in physician performance related to several important patient safety standards. These issues had not been previously corrected by didactic sessions, written communication, and the chain of command. Methods To help address these general and site-specific problems, we developed and deployed a set of medical record audit tools entitled "physician-led audits" (PLAs). We trained providers in leadership positions to use the tools and to teach their use to others. We designed a system to capture data on frequency of use and results. The PLA process is distinctive in that it holds physicians accountable for the auditing and for follow-up afterward. Results With support from department chairs, division chiefs, residency program directors, and other leaders, close to 2000 PLAs were performed over a 10-month study period. Conclusions The audits engaged physician leaders and the at-large medical staff, making them key participants in a system-wide improvement campaign. The tool was customized for use in a broad range of clinical settings and was widely and rapidly adopted, leading to important dialogue and a substantive contribution to our safety culture.

To analyze the extent of academic interest in quality improvement (QI) initiatives in medical practice, annual publication trends for the most well-known QI methodologies being used in health care settings were analyzed. A total of 10 key medical- and business-oriented library databases were examined: PubMed, Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, ISI Web of Science, Scopus, the Cochrane Central Register of Controlled Trials, ABI/INFORM, and Business Source Complete. A total of 13 057 articles were identified that discuss at least 1 of 10 well-known QI concepts used in health care contexts, 8645 (66.2%) of which were classified as original research. "Total quality management" was the only methodology to demonstrate a significant decline in publication over time. "Continuous quality improvement" was the most common topic of study across all publication years, whereas articles discussing Lean methodology demonstrated the largest growth in publication volume over the past 2 decades. Health care QI publication volume increased substantially beginning in 1991.

Prointerleukin-1 beta (pro-IL-1 beta) is the only known physiologic substrate of the interleukin-1 beta (IL-1 beta)-converting enzyme (ICE), the founding member of the ICE/ced-3 cell death gene family. Since secreted mature IL-1 beta has been detected after apoptosis, we investigated whether this cytokine, when produced endogenously, plays a role in cell death. We found that hypoxia-induced apoptosis can be inhibited by either the IL-1 receptor antagonist (IL-1Ra) or by neutralizing antibodies to IL-1 or to its type 1 receptor. IL-1Ra also inhibits apoptosis induced by trophic factor deprivation in primary neurons, as well as by tumor necrosis factor alpha in fibroblasts. In addition, during the G1/S phase arrest, mature IL-1 beta induces apoptosis through a pathway independent of CrmA-sensitive gene activity. We also demonstrate that Ice, when expressed in COS cells, requires the coexpression of pro-IL-1 beta for the induction of apoptosis, which is inhibited by IL-1Ra. Interestingly, we found that mature IL-1 beta has antiapoptotic activity when added exogenously before the onset of hypoxia, which we found is caused in part by its ability to downregulate the IL-1 receptor. Our findings demonstrate that pro-IL-1 beta is a substrate of ICE relevant to cell death, and depending on the temporal cellular commitment to apoptosis, mature IL-1 beta may function as a positive or negative mediator of cell death.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by autoantibody production and inflammatory disease involving multiple organs. Premature atherosclerosis is a common complication of SLE and results in substantial morbidity and mortality from cardiovascular disease (CVD). The reasons for the premature atherosclerosis in SLE are incompletely understood, although chronic inflammation is thought to play an important role. There is currently no known preventative treatment of premature atherosclerosis in SLE. Mycophenolate mofetil (MMF) is an immunosuppressive agent that is commonly used for treatment of patients with SLE. In order to study the impact of this drug on murine lupus disease including premature atherosclerosis development, we treated gld.apoE(-/-) mice, a model of SLE and accelerated atherosclerosis, with MMF. We maintained seven-week old gld.apoE(-/-) mice on a high cholesterol Western diet with or without MMF. After 12 weeks on diet, mice receiving MMF showed decreased atherosclerotic lesion area compared to the control group. MMF treatment also improved the lupus phenotype, indicated by a significant decrease circulating autoantibody levels and ameliorating lupus nephritis associated with this model. This data suggests that the effects of MMF on the immune system may not only be beneficial for lupus, but also for inflammation driving lupus-associated atherosclerosis.

Sampling plays a major role in quality improvement work. Random sampling (assumed by most traditional statistical methods) is the exception in improvement situations. In most cases, some type of "judgment sample" is used to collect data from a system. Unfortunately, judgment sampling is not well understood. Judgment sampling relies upon those with process and subject matter knowledge to select useful samples for learning about process performance and the impact of changes over time. It many cases, where the goal is to learn about or improve a specific process or system, judgment samples are not merely the most convenient and economical approach, they are technically and conceptually the most appropriate approach. This is because improvement work is done in the real world in complex situations involving specific areas of concern and focus; in these situations, the assumptions of classical measurement theory neither can be met nor should an attempt be made to meet them. The purpose of this article is to describe judgment sampling and its importance in quality improvement work and studies with a focus on health care settings.

The purpose of this article is to examine the relationship between sample size and cost using a benefit to cost ratio in the context of hospital accountability measures. We argue that the decision to use larger samples should include an assessment of the marginal benefit in terms of the cost to obtain the samples. Our main conclusion is that without recognizing and balancing the cost of different sampling schemes and developing reasonable cost limits we lose an opportunity at efficiency.

Context The goal of this article is to provide a succinct scan of the literature as it relates to the current thinking and practice in large-scale improvement initiatives in healthcare. Method We employed a scan of the literature using a modified Delphi technique. A standard review form was used. The scan was limited to large-scale spread efforts in hospitals and healthcare systems. Each of the main factors that emerged during the scan was linked to secondary factors and organized using a driver diagram. Findings Four primary drivers (factors) emerged during our scan that inform large-scale change initiatives in healthcare: Planning and Infrastructure; Individual, Group, Organizational, and System Factors; The Process of Change; and Performance Measures and Evaluation. Conclusion Our scan identified a tremendous amount of work being done around the world to improve healthcare. In general, our findings suggest these initiatives tend to be fragmented from an implementation standpoint. We identified primary and secondary drivers (factors) that can be used by those responsible for implementing large-scale improvement initiatives both at a strategy level and in their daily work. These drivers could serve as a “checklist” of ideas to consider in different testing and implementation situations.

Background Those working in healthcare today are challenged more than ever before to quickly and efficiently learn from data to improve their services and delivery of care. There is broad agreement that healthcare professionals working on the front lines benefit greatly from the visual display of data presented in time order. Aim To describe the run chart—an analytical tool commonly used by professionals in quality improvement but underutilised in healthcare. Methods A standard approach to the construction, use and interpretation of run charts for healthcare applications is developed based on the statistical process control literature. Discussion Run charts allow us to understand objectively if the changes we make to a process or system over time lead to improvements and do so with minimal mathematical complexity. This method of analyzing and reporting data is of greater value to improvement projects and teams than traditional aggregate summary statistics that ignore time order. Because of its utility and simplicity, the run chart has wide potential application in healthcare for practitioners and decision-makers. Run charts also provide the foundation for more sophisticated methods of analysis and learning such as Shewhart (control) charts and planned experimentation.

Although TLR9 was originally thought to specifically recognize microbial DNA, it is now evident that mammalian DNA can be an effective TLR9 ligand. However, the DNA sequence required for TLR9 activation is controversial, as studies have shown conflicting results depending on the nature of the DNA backbone, the route of DNA uptake, and the cell type being studied. In systemic lupus erythematosus, a major route whereby DNA gains access to intracellular TLR9, and thereby activates dendritic cells (DCs), is through uptake as a DNA-containing immune complex. In this report, we used defined dsDNA fragments with a natural (phosphodiester) backbone and show that unmethylated CpG dinucleotides within dsDNA are required for murine DC TLR9 activation induced by a DNA-containing immune complex. The strongest activation is seen with dsDNA fragments containing optimal CpG motifs (purine-purine-CpG-pyrimidine-pyrimidine) that are common in microbial DNA but rare in mammalian DNA. Importantly, however, activation can also be induced by CpG-rich DNA fragments that lack these optimal CpG motifs and that we show are plentiful in CpG islands within mammalian DNA. No activation is induced by DNA fragments lacking CpG dinucleotides, although this CpG-free DNA can induce DC activation if internalized by liposomal transfection instead of as an immune complex. Overall, the data suggest that the release of CpG-rich DNA from mammalian DNA may contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus and psoriasis in which activation of TLR9 in DCs by self DNA has been implicated in disease pathogenesis.

This article presents a logistic model that describes the mean number of unique methicillin-resistant Staphylococcus aureus (MRSA) isolates collected daily at a 150-bed community hospital in central Massachusetts. The model is used to derive a long-term forecast of the mean MRSA isolate frequency.The mean number of MRSA isolates collected daily was found for each quarter from the first quarter of 1996 to the first quarter of 2008. A logistic model was fit to the data and then extrapolated to obtain a long-term forecast.Data was collected at a one-hundred-fifty bed community hospital in central Massachusetts.The coefficient of determination indicates that 87% of the variation in transformed data is explained by the model. The extrapolated logistic model prediction is that the mean number of MRSA isolates collected daily approaches 1.42 MRSA isolates per day.Logistic modeling of empirical data using modest mathematical assumptions is an effective way to understand, visualize, and forecast MRSA daily frequencies over time. The advantage for laboratorians and epidemiologists is that logistic models provide reliable trending and long-term prediction ability of multi-drug resistant organism frequencies. Moreover, as additional data is obtained, the logistic model assumptions can be checked, the model updated, and forecasts improved.

This study was designed to demonstrate that the number of methicillin-resistant Staphylococcus aureus (MRSA) isolates collected daily in a community hospital is Poisson distributed and that using a one-sided Poisson control table is a fast and easy way to recognize unusually high numbers of MRSA isolates collected daily that may signal possible outbreaks.A retrospective analysis of MRSA isolates collected daily over a three year period (2005-2007, N = 934) was performed. Observed MRSA isolate frequencies are compared to Poisson frequencies using chi-square goodness-of-fit tests. A regression equation on the mean number of MRSA isolates collected daily for the years 2005, 2006, and 2007 is used to predict the mean number of MRSA isolates for 2008. A warning system for MRSA isolates collected daily is presented and a one-tailed, mean + 2 sigma control table is provided.One-hundred-fifty bed community hospital in central Massachusetts.Goodness-of-fit tests showed close agreement between actual MRSA isolates collected daily and Poisson frequencies for 2005 (chi4(2) = 4.045, p = 0.39), 2006 (chi4(2) = 2.807, p = 0.59), and 2007 (chi4(2) = 1.494, p = 0.83).Theoretical and empirical support is provided for the Poisson probability model. The model can be used to identify unusually high occurrences ofMRSA isolates collected daily. This study was limited to a single community healthcare system but the results may be generalized to other types of healthcare settings.

Government-mandated reporting of health care-associated infections (HAIs) and new reimbursement regulations place a premium on accurate and reliable detection of HAIs. This commentary addresses the challenges and opportunities of having consistent, well-defined, and continuous methods in place to ensure the reliability and validity of HAI detection and reporting. In addition, such procedures could support the development and expertise of infection preventionists. A Web-based clinical vignette model is suggested for improving HAI reporting for hospitals participating in the Centers for Disease Control and Prevention's National Healthcare Safety Network.

Background: Management of malignant renal tumors involving the inferior vena cava (IVC) depends on tumor extension within the cava. Methods: Of 295 patients treated for renal cancer, propagation of tumor mass through the renal vein to IVC was seen in 22 (7%) patients. Cephalad extension of the tumor was suprarenal: infrahepatic in 12, retrohepatic in 6, and within the right atrium in 4 patients. All patients had radical nephrectomy, cavotomy, and complete resection of tumors except 1 with diffuse peritoneal metastasis. Results: Twenty-one patients had curative resections. No operative deaths and no instances of pulmonary embolism or exsanguination occurred. Seventeen patients were alive at 2 years and 12 at 5 years, resulting in 77% and 55% survival rates, respectively. Conclusions: An aggressive approach for vena cava involvement from malignant renal neoplasms resulted in prevention of tumor embolus, minimization of blood loss, and maintenance of venous return to the heart.

We argue that analyzing everyday memory failures in terms of the "unity of consciousness" can elucidate the bases of such failures. A perfect unity amongst one's mental states is rare. In extreme cases the unity of consciousness can breakdown in dramatic fashion (e.g., in Dissociative Identity Disorder), but such breakdowns also occur in less dramatic ways that affect us in everyday life. For example, disruptions in the unity of consciousness can result in everyday memory failures, such as forgetting to put on a tie for an important formal meeting. After providing some philosophical background into the notions of "unity of consciousness" and "functionalism," we offer preliminary analyses of three examples of everyday memory failure. We then introduce and develop what we call the "unity model" of memory failure and show how it explains the examples. We also describe different ways that unity can break down which, in turn, can lead to memory failure and inappropriate behavior. We then show how slips of action and other kinds of cognitive failures (e.g., memory blocks) differ from everyday memory failures. Finally, we examine alternative models (e.g., Absentmindedness and Multimodal) arguing that the unity model is preferable, and then show how our model is consistent with some experimental results.

Background Inadequate data exist regarding the management of acute major pulmonary embolism. Various modalities that are used, including thrombolytics and embolectomy, have not been shown to conclusively improve mortality when compared to heparin. In the past, open pulmonary embolectomy was reserved for patients with severe hemodynamic instability because of its high mortality rate. Our objective was to analyze our experience with early embolectomy as an alternative for the treatment of major pulmonary embolism. Methods A retrospective review of charts of all patients undergoing pulmonary embolectomy at our institution over the last two years was performed. Patients were followed until their discharge from hospital. Results There were 13 patients (7 women and 6 men). Four had massive and 9 had submassive pulmonary embolism. There was one mortality. Postoperative echocardiography showed no evidence of pulmonary hypertension in 7. Conclusions Open pulmonary embolectomy can be performed in patients with major pulmonary embolism with minimal mortality and morbidity. It may prevent the development of chronic thromboembolic pulmonary hypertension and should be a part of the algorithm in the treatment of major pulmonary embolism.

Pseudoaneurysms in the ascending aorta most commonly occur as a complication of surgical procedures at this site. They have also been reported in association with trauma, infection, aortitis, and other disorders. Pseudoaneurysm formation in the descending aorta or arch may occur as a result of penetrating ulcers in the presence of severe atherosclerotic plaque. Pseudoaneurysm as a result of atherosclerotic disease has only rarely been noted in the ascending aorta, where complex plaque is less common. We report here the finding with transesophageal echocardiography of a pseudoaneurysm in the ascending aorta as a result of atherosclerotic disease and penetrating ulcer.

We describe two cases of immediate structural valve deterioration of the 27-mm Carpentier-Edwards pericardial valve. Tissue characteristics of bovine pericardium and the possible mechanism of failure are discussed.

A 70-year-old man, who had undergone a radical nephrectomy for localized renal cell carcinoma (RCC) three years ago, was recently evaluated for shortness of breath. During his work-up, a transesophageal echocardiogram and magnetic resonance imaging indicated an extensive vena caval thrombus originating from the renal vein stump. Successful vena caval thrombectomy with cardiopulmonary bypass confirmed that the thrombus was comprised of RCC. This is a rare type of RCC recurrence with an unusual timing (3 years after a nephrectomy), alerting the importance of strict follow-up on all patients even after complete surgical excision of all suspected tumors.