Implementation of a Multidimensional Strategy to Reduce Post-PCI Bleeding Risk.

BACKGROUND: The American College of Cardiology Reduce the Risk: PCI Bleed Campaign was a hospital-based quality improvement campaign designed to reduce post-percutaneous coronary intervention (PCI) bleeding events. The aim of the campaign was to provide actionable evidence-based tools for participants to review, adapt, and adopt, depending upon hospital resources and engagement. METHODS: We used data from 8 757 737 procedures in the National Cardiovascular Data Registry between 2015 and 2021 to compare patient and hospital characteristics and bleeding outcomes among campaign participants (n=195 hospitals) and noncampaign participants (n=1384). Post-PCI bleeding risk was compared before and after campaign participation. Multivariable hierarchical logistic regression was used to determine the adjusted association between campaign participation and post-PCI bleeding events. Prespecified subgroups were examined. RESULTS: Campaign hospitals were more often higher volume teaching facilities located in urban or suburban locations. After adjustment, campaign participation was associated with a significant reduction in the rate of bleeding (bleeding: adjusted odds ratio, 0.61 [95% CI, 0.53-0.71]). Campaign hospitals had a greater decrease in bleeding events than noncampaign hospitals. In a subgroup analysis, the reduction in bleeding was noted in non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction patients, but no significant reduction was seen in patients without acute coronary syndrome. CONCLUSIONS: Participation in the American College of Cardiology Reduce the Risk: PCI Bleed Campaign was associated with a significant reduction in post-PCI bleeding. Our results underscore that national quality improvement efforts can be associated with a significant impact on PCI outcomes.

The bleeding risk treatment paradox at the physician and hospital level: Implications for reducing bleeding in patients undergoing percutaneous coronary intervention.

BACKGROUND: Bleeding is a common and costly complication of percutaneous coronary intervention (PCI). Bleeding avoidance strategies (BAS) are used paradoxically less in patients at high-risk of bleeding: "bleeding risk-treatment paradox" (RTP). We determined whether hospitals and physicians, who do not align BAS to PCI patients' bleeding risk (ie, exhibit a RTP) have higher bleeding rates. METHODS: We examined 28,005 PCIs from the National Cardiovascular Data Registry CathPCI Registry for 7 hospitals comprising BJC HealthCare. BAS included transradial intervention, bivalirudin, and vascular closure devices. Patients' predicted bleeding risk was based on National Cardiovascular Data Registry CathPCI bleeding model and categorized as low (<2.0%), moderate (2.0%-6.4%), or high (≥6.5%) risk tertiles. BAS use was considered risk-concordant if: at least 1 BAS was used for moderate risk; 2 BAS were used for high risk and bivalirudin or vascular closure devices were not used for low risk. Absence of risk-concordant BAS use was defined as RTP. We analyzed inter-hospital and inter-physician variation in RTP, and the association of RTP with post-PCI bleeding. RESULTS: Amongst 28,005 patients undergoing PCI by 103 physicians at 7 hospitals, RTP was observed in 12,035 (43%) patients. RTP was independently associated with a higher likelihood of bleeding even after adjusting for predicted bleeding risk, mortality risk and potential sources of variation (OR 1.66, 95% CI 1.44-1.92, P < .001). A higher prevalence of RTP strongly and independently correlated with worse bleeding rates, both at the physician-level (Wilk's Lambda 0.9502, F-value 17.21, P < .0001) and the hospital-level (Wilk's Lambda 0.9899, F-value 35.68, P < .0001). All the results were similar in a subset of PCIs conducted since 2015 - a period more reflective of the contemporary practice. CONCLUSIONS: Bleeding RTP is a strong, independent predictor of bleeding. It exists at the level of physicians and hospitals: those with a higher rate of RTP had worse bleeding rates. These findings not only underscore the importance of recognizing bleeding risk upfront and using BAS in a risk-aligned manner, but also inform and motivate national efforts to reduce PCI-related bleeding.

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression.

The systematic identification of genetic events driving cellular transformation and tumor progression in the absence of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified both known tumor suppressor genes and novel oncogenic drivers of cuSCC. Functional analysis confirms an oncogenic role for the ZMIZ genes, and tumor suppressive roles for KMT2C, CREBBP and NCOA2, in the initiation or progression of human cuSCC. Taken together, our in vivo screen demonstrates an extremely heterogeneous genetic landscape of cuSCC initiation and progression, which can be harnessed to better understand skin oncogenic etiology and prioritize therapeutic candidates.

Covid-19 and Priorities for Research in Aging.

This article describes priority areas for research on the impact of the Covid-19 pandemic on older adults that have been identified by the CIHR Institute of Aging (CIHR-IA). The process used by CIHR-IA consists of several iterative phases and thus far has resulted in identification of three key areas for Covid-19 research needs and four cross-cutting thematic areas. The key research priority areas are as follows: response of older adults to disease, vaccination, and therapeutics; mental health and isolation; and supportive care environments. The four cross-cutting themes are equity, diversity, and inclusion (EDI); ethical/moral considerations; evidence-informed practices; and digital health technologies. The priorities outlined in this article will inform CIHR-IA's responses to Covid-19 research needs.

La COVID-19 et les priorités de recherche sur le vieillissement.

Cet article présente les domaines prioritaires de recherche sur les impacts de la pandémie de COVID-19 chez les personnes âgées telles qu'ils ont été identifiés par l'Institut du vieillissement des IRSC (IV-IRSC). Le processus utilisé par l'IV-IRSC a comporté plusieurs phases itératives qui ont permis d'identifier trois secteurs prioritaires parmi les besoins de la recherche relative à la COVID-19, et quatre axes thématiques transversaux. Les secteurs de recherche prioritaires sont : 1) la réponse des personnes âgées à la maladie, à la vaccination et aux traitements, 2) la santé mentale et l'isolement, et 3) les milieux de soins soutenants. Les quatre thèmes transversaux sont : a) l'Équité, la diversité et l'inclusion (EDI), b) les considérations éthiques et morales, c) les pratiques fondées sur les données probantes, et d) les technologies numériques de la santé. Les priorités décrites dans cet article guideront les réponses de l'IV-IRSC aux besoins de la recherche sur la COVID-19.

Facilitating the identification of patients hospitalized for acute myocardial infarction and heart failure and the assessment of their readmission risk through the Patient Navigator Program.

BACKGROUND: Optimal transition care mitigates early hospital readmission risk. Given limited resources, hospitals need to identify patients with high readmission risk. This article examines whether a coordinated quality improvement campaign can help achieve this objective. METHODS: The American College of Cardiology Patient Navigator Program, a 2-year quality improvement campaign, sought to assess the impact of transition care interventions on 30-day readmission rates for patients with acute myocardial infarction (AMI) or heart failure (HF) at 35 hospitals. This article examines the change in 2 of the 36 performance metrics the campaign tracked: the number of AMI and HF patients identified predischarge and those whose readmission risk was assessed. RESULTS: The number of facilities identifying AMI and HF patients predischarge increased from 24 (68.6%) and 28 (80.0%), respectively, at baseline, to 34 (97.1%) (P = .0016) and 34 (97.1%) (P = .014), respectively, at 2 years. The number of facilities assessing the readmission risk of AMI and HF patients risk increased from 9 (25.7%) and 11 (31.4%), respectively, at baseline, to 32 (91.4%) (P < .0001) and 33 (94.5%) (P < .0001), respectively, at 2 years. Importantly, baseline reporting of performance for both metrics was poor, with >25% of the hospitals missing data. CONCLUSIONS: Implementation of a coordinated quality improvement campaign may increase the number of facilities identifying AMI and HF patients predischarge and assessing their readmission risk. Further research is needed to determine if increased identification reduces 30-day readmission or facilitates improvement in other important clinical outcomes.

Analyzing tumor heterogeneity and driver genes in single myeloid leukemia cells with SBCapSeq.

A central challenge in oncology is how to kill tumors containing heterogeneous cell populations defined by different combinations of mutated genes. Identifying these mutated genes and understanding how they cooperate requires single-cell analysis, but current single-cell analytic methods, such as PCR-based strategies or whole-exome sequencing, are biased, lack sequencing depth or are cost prohibitive. Transposon-based mutagenesis allows the identification of early cancer drivers, but current sequencing methods have limitations that prevent single-cell analysis. We report a liquid-phase, capture-based sequencing and bioinformatics pipeline, Sleeping Beauty (SB) capture hybridization sequencing (SBCapSeq), that facilitates sequencing of transposon insertion sites from single tumor cells in a SB mouse model of myeloid leukemia (ML). SBCapSeq analysis of just 26 cells from one tumor revealed the tumor's major clonal subpopulations, enabled detection of clonal insertion events not detected by other sequencing methods and led to the identification of dominant subclones, each containing a unique pair of interacting gene drivers along with three to six cooperating cancer genes with SB-driven expression changes.

Use of Postexposure Prophylaxis After Occupational Exposure to Zaire ebolavirus.

From September 2014 to April 2015, 6 persons who had occupational exposures to Zaire ebolavirus in West Africa received investigational agent rVSV-ZEBOV or TKM-100802 for postexposure prophylaxis and were monitored in the United States. All patients experienced self-limited symptoms after postexposure prophylaxis; none developed Ebola virus disease.

Emergency postexposure vaccination with vesicular stomatitis virus-vectored Ebola vaccine after needlestick.

IMPORTANCE: Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick. OBJECTIVE: To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus. DESIGN AND SETTING: Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014. INTERVENTIONS: The vaccine used was VSVΔG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa. RESULTS: The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected. CONCLUSIONS AND RELEVANCE: It is unknown if VSVΔG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a needlestick. In this patient, postexposure vaccination with VSVΔG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected.

Gender differences in HIV disclosure, stigma, and perceptions of health.

HIV disclosure is a gateway to HIV prevention - particularly among couples living in regions severely affected by the HIV epidemic. This cross-sectional study utilizes data collected from 862 people living with HIV across three countries (Ethiopia, Mozambique, and Uganda) in 2011 to determine the role of partner disclosure on self-reported health perceptions and changes in sexual risk behavior. The study's secondary aims are to understand whether or not internalized stigma mediates this relationship and if there is a different pattern of results by gender. The multivariate analysis reveals that the three key HIV-related independent variables, belonging to a support group, doing volunteer work, and disclosing to one's spouse or partner, were significantly associated with lower levels of internalized stigma. Internalized stigma was associated with self-perceptions of poorer health for both women and men, with women reporting higher levels of internalized stigma than men. Disclosure to spouse was positively associated with perceptions of better health for women but not for men. For men, doing HIV-related volunteer work and disclosing their status to their spouse were positively associated with self-reported changes in sexual risk behavior, although stigma was not found to mediate this relationship. Findings from this study suggest that disclosure and stigma have gender-specific effects on individual well-being and changes in sexual risk behaviors. As such, programs must address gender inequity in disclosure patterns and stigma to enhance prevention efforts.

Management of hyperphosphataemia: practices and perspectives amongst the renal care community.

BACKGROUND: Protein-rich foods are a major source of dietary phosphorus; therefore, helping patients to increase their dietary protein intake, while simultaneously managing their hyperphosphataemia, poses a significant challenge for renal care professionals. OBJECTIVES: To examine the clinical recommendations and practice perceptions of renal care professionals providing nutrition and phosphate control advice to patients with chronic kidney disease (CKD). METHODS: Renal care professionals from four European countries completed an online survey on the clinical management of hyperphosphataemia. RESULTS: The majority of responders recommended a protein intake of less than 1.0 g/kg/day for pre-dialysis patients, 1.2 g/kg/day for patients undergoing peritoneal dialysis (PD) and 1.1-1.2 g/kg/day for patients undergoing haemodialysis (HD). The most common perception was that maintaining dietary protein intake and reducing dietary phosphorus intake are equally important for hyperphosphataemia management. For patients in the pre-dialysis stage, the majority of responders (59%) reported that their first-line management recommendation would be reduction of dietary phosphorus. For patients undergoing PD and HD, the majority of responders (53% and 59%, respectively) reported a first-line management recommendation of both reduction of dietary phosphorus and phosphate binder therapy. More renal nurses than dietitians perceived reducing dietary phosphorus to be more important than maintaining protein intake (for patients undergoing PD, 23% vs. 0%, respectively; for patients undergoing HD, 34% vs. 0%, respectively). CONCLUSION: This renal care community followed professionally accepted guidelines for patient nutrition and management of hyperphosphataemia. There was disparity in the perceptions and recommendations between nurses and dietitians, highlighting the need to standardise management practices amongst renal care professionals.

The Primary Care Leadership Track at the Duke University School of Medicine: creating change agents to improve population health.

PROBLEM: Physicians need training in community engagement, leadership, and population health to prepare them to work with partners within the community and to adapt medical care to address population health needs. APPROACH: With an overall goal of training primary care practitioners to be change agents for improving population health, the Duke University School of Medicine launched the Primary Care Leadership Track (PCLT) in 2011. The four-year PCLT curriculum requires students to contribute to existing community health initiatives, perform community-engaged research, and participate in leadership training. The clinical curriculum incorporates a longitudinal approach to allow students to follow patient outcomes. In addition, students regularly interact with faculty to explore population health issues, review patient cases, and adjust individual learning opportunities as needed. OUTCOMES: The first cohort of PCLT students will graduate in 2015. Prospective comparisons with traditional track students are planned on performance on standardized tests and career choices. NEXT STEPS: The authors created the PCLT as a laboratory in which students can engage with the community and explore solutions to address the health of the public and the future delivery of health care. To meet the goal of training change agents, PCLT leaders need to expand opportunities for students to learn from providers and organizations that are successfully bridging the gap between medical care and public health.

Gender-based screening for chlamydial infection and divergent infection trends in men and women.

OBJECTIVES: To assess the potential impact of chlamydial screening policy that recommends routine screening of women but not men. METHODS: Population surveys of probability samples of Baltimore adults aged 18 to 35 years in 1997-1998 and 2006-2009 collected biospecimens to estimate trends in undiagnosed chlamydial infection. Survey estimates are compared to surveillance data on diagnosed chlamydial infections reported to the Health Department. RESULTS: Prevalence of undiagnosed chlamydial infection among men increased from 1.6% to 4.0%, but it declined from 4.3% to 3.1% among women (p = 0.028 for test of interaction). The annual (average) number of diagnosed infections was substantially higher among women than men in both time periods and increased among both men and women. Undiagnosed infection prevalence was substantially higher among black than non-black adults (4.0% vs 1.2%, p = 0.042 in 1997-98 and 5.5% vs 0.7%, p<0.001 in 2006-09). CONCLUSION: Divergent trends in undiagnosed chlamydial infection by gender parallel divergent screening recommendations that encourage chlamydial testing for women but not for men.

Epidemiology of undiagnosed trichomoniasis in a probability sample of urban young adults.

T. vaginalis infection (trichomoniasis) is the most common curable sexually transmitted infection (STI) in the U.S. It is associated with increased HIV risk and adverse pregnancy outcomes. Trichomoniasis surveillance data do not exist for either national or local populations. The Monitoring STIs Survey Program (MSSP) collected survey data and specimens which were tested using nucleic acid amplification tests to monitor trichomoniasis and other STIs in 2006-09 among a probability sample of young adults (N = 2,936) in Baltimore, Maryland--an urban area with high rates of reported STIs. The estimated prevalence of trichomoniasis was 7.5% (95% CI 6.3, 9.1) in the overall population and 16.1% (95% CI 13.0, 19.8) among Black women. The overwhelming majority of infected men (98.5%) and women (73.3%) were asymptomatic. Infections were more common in both women (OR = 3.6, 95% CI 1.6, 8.2) and men (OR = 9.0, 95% CI 1.8, 44.3) with concurrent chlamydial infection. Trichomoniasis did not vary significantly by age for either men or women. Women with two or more partners in the past year and women with a history of personal or partner incarceration were more likely to have an infection. Overall, these results suggest that routine T vaginalis screening in populations at elevated risk of infection should be considered.

Ensuring good quality RNA for quantitative real-time PCR isolated from renal proximal tubular cells using laser capture microdissection.

BACKGROUND: In order to provide gene expression profiles of different cell types, the primary step is to isolate the specific cells of interest via laser capture microdissection (LCM), followed by extraction of good quality total RNA sufficient for quantitative real-time polymerase chain reaction (qPCR) analysis. This LCM-qPCR strategy has allowed numerous gene expression studies on specific cell populations, providing valuable insights into specific cellular changes in diseases. However, such strategy imposed challenges as cells of interests are often available in limited quantities and quality of RNA may be compromised during long periods of time spent on collection of cells and extraction of total RNA; therefore, it is crucial that protocols for sample preparation should be optimised according to different cell populations. FINDINGS: We made several modifications to existing protocols to improve the total RNA yield and integrity for downstream qPCR analyses. A modified condensed hematoxylin and eosin (H&E) staining protocol was developed for the identification of rat renal proximal tubular cells (PTCs). It was then determined that a minimal of eight thousands renal PTCs were required to meet the minimal total RNA yield required for downstream qPCR. RNA integrity was assessed using at every progressive step of sample preparation. Therefore, we decided that the shortened H&E staining, together with microdissection should be performed consecutively within twenty minutes for good quality for gene expression analysis. These modified protocols were later applied on six individual rat samples. A panel of twenty rat renal drug transporters and five housekeeping genes showed Ct values below thirty-five, confirming the expression levels of these drug transporters can be detected. CONCLUSIONS: We had successfully optimized the protocols to achieve sufficient good quality total RNA from microdissected rat renal PTCs for gene expression profiling via qPCR. This protocol may be suitable for researchers who are interested in employing similar applications for gene expression studies.

Dietary trends and management of hyperphosphatemia among patients with chronic kidney disease: an international survey of renal care professionals.

OBJECTIVE: The objective of this study was to review the opinions and experiences of renal care professionals to examine dietary trends among patients with chronic kidney disease (CKD) and problems associated with the clinical management of hyperphosphatemia. DESIGN: This was an online survey comprising open and closed questions requesting information on patient dietary trends and the clinical management of hyperphosphatemia. The study was conducted in 4 European countries (the Netherlands, Spain, Sweden, and the United Kingdom). SUBJECTS: Participants were 84 renal care professionals. INTERVENTION: This was an online survey. MAIN OUTCOME MEASURE: Responder-reported experiences and perceptions of patient dietary trends and hyperphosphatemia management were assessed. RESULTS: Most survey responders (56%) observed an increase in the consumption of processed convenience food, 48% noticed an increase in the consumption of foods rich in phosphorus-containing additives, and 60% believed that there has been a trend of increasing patient awareness of the phosphorus content of food. Patients undergoing hemodialysis (HD) were most likely to experience difficulties in following advice on dietary phosphorus restriction (38% of responders estimated that 25-50% of their patients experienced difficulties, and 29% estimated that 51-75% experienced difficulties). Maintaining protein intake and restricting dietary phosphorus were perceived as being equally important by at least half of responders for predialysis patients (56%) and for those undergoing peritoneal dialysis and HD (54% and 50%, respectively). There were international variations in dietary trends and hyperphosphatemia management. CONCLUSION: Although most responders have observed a trend of increasing awareness of the phosphorus content of food among patients with CKD, the survey results indicate that many patients continue to experience difficulties when attempting to restrict dietary phosphorus. The survey responses reflect the global trend of increasing consumption of processed convenience foods and phosphorus-containing additives, which has implications for the management of hyperphosphatemia in patients with CKD.

'What's in the NIDDK CDR?'--public query tools for the NIDDK central data repository.

The National Institute of Diabetes and Digestive Disease (NIDDK) Central Data Repository (CDR) is a web-enabled resource available to researchers and the general public. The CDR warehouses clinical data and study documentation from NIDDK funded research, including such landmark studies as The Diabetes Control and Complications Trial (DCCT, 1983-93) and the Epidemiology of Diabetes Interventions and Complications (EDIC, 1994-present) follow-up study which has been ongoing for more than 20 years. The CDR also houses data from over 7 million biospecimens representing 2 million subjects. To help users explore the vast amount of data stored in the NIDDK CDR, we developed a suite of search mechanisms called the public query tools (PQTs). Five individual tools are available to search data from multiple perspectives: study search, basic search, ontology search, variable summary and sample by condition. PQT enables users to search for information across studies. Users can search for data such as number of subjects, types of biospecimens and disease outcome variables without prior knowledge of the individual studies. This suite of tools will increase the use and maximize the value of the NIDDK data and biospecimen repositories as important resources for the research community. Database URL: https://www.niddkrepository.org/niddk/home.do.

Tools to optimize the functionality of a leukemia clinical trial team.

A multidisciplinary approach offers efficiency and quality care by delegating tasks according to individuals' expertise. However, increasingly stringent regulatory requirements, albeit essential for successful conduct of clinical trials, have magnified the workload of research teams. We describe tools that have efficiently addressed regulatory requirements and facilitated the conduct of clinical trials. The research team consisted of a merge of healthcare providers and research staff. Each individual team consisted of a hematologist, a physician assistant and a nurse coordinator, supported by a shared group of clinical research coordinators, an investigational drug pharmacist, a regulatory associate and a data manager. Technology tools, complemented by operational reorganization, optimized knowledge, documentation and communication, and allowed high volume enrollment with consistent regulatory compliance. We conclude that technology combined with a coordinated team care approach can facilitate the integration of trials in clinical practice.

Testing a service integration model: results from the HIV/AIDS initiative, ConnectHIV.

Staff of 20 AIDS Service Organizations (ASOs), grantees of the initiative ConnectHIV in the United States, developed a theoretical model of five categories of factors - external, community, organizational, staff, and client - that lead to effective service integration (SI) and took part in a self-assessment related to the model. The model was tested empirically using GEE analysis to assess the effect of ASO SI scores on client outcomes from participation in HIV/AIDS interventions involving case management with persons living with HIV/AIDS. Results showed that clients served by ASOs with more effective SI were more knowledgeable of HIV disease, healthier (higher CD4, lower viral load) and perceived themselves as healthier than clients in ASOs with less effective SI. In addition, clients at ASOs with more effective SI more often showed stronger gains in CD4 count over their time in the HIV/AIDS intervention than those at ASOs with less effective SI. Further research is needed on models and measurement of SI in order to effectively investigate the impact of HIV SI on client health outcomes.