Kendal Williams

Gadolinium-based contrast agents and nephrogenic systemic fibrosis: a systematic review and meta-analysis

BACKGROUND In the past decade, more than 200 cases of nephrogenic systemic fibrosis (NSF) have been identified, primarily among patients with advanced kidney disease. Multiple studies have suggested an association between gadolinium-based contrast agents (GBCAs) and NSF. We performed a systematic review and meta-analysis to examine this potential association. METHODS A systematic review of studies examining the association between any GBCA and NSF was performed. A search for controlled studies was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. If controlled data for a GBCA was not available, we searched for case reports and series. Relevant data were extracted and meta-analyses were performed. RESULTS Seven of 144 identified studies met inclusion criteria; gadodiamide was the sole or predominant GBCA in four of these; one study exclusively examined gadopentetate. Other GBCAs were not specifically examined in controlled or uncontrolled studies. Meta-analysis of controlled trials demonstrated a significant association between GBCA exposure and NSF [odds ratio (OR) 26.7; 95% confidence interval (CI) 10.3-69.4] and gadodiamide and NSF (OR 20.0; 95% CI 3.7-107.8). Examination of the evidence using established criteria suggested that this association was causal. CONCLUSIONS The current state of evidence suggests an association and potentially causal link between the use of GBCAs and the development of NSF among patients with advanced kidney disease. Additional study is warranted to clarify the potential association of GBCAs other than gadodiamide with NSF.

Osteoinductive bone graft substitutes for lumbar fusion: a systematic review

OBJECT Autograft and allograft, the standard approaches for lumbar fusion procedures, have important disadvantages. Bone graft substitutes such as recombinant human bone morphogenetic proteins (rhBMP-2 and rhBMP-7) have emerged as viable alternatives. The authors conducted a systematic review to compare the efficacy and safety of osteoinductive bone graft substitutes using autografts and allografts in lumbar fusion. METHODS A search for prospective controlled trials was conducted on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases. Data were extracted for key outcomes including radiographically demonstrated nonunion, Oswestry Disability Index, operating time, blood loss, and length of hospital stay. The quality of randomized controlled trials was assessed using the Jadad scale. Meta-analyses were performed when feasible, and heterogeneity was assessed using the Q statistic and the I(2) statistic. RESULTS Seventeen of 732 potential studies met the inclusion criteria, with 9 examining rhBMP-2, 3 examining rhBMP-7, 3 examining demineralized bone matrix, and 2 examining autologous growth factor. Recombinant human BMP-2 significantly decreased radiographic nonunion when compared with autologous iliac crest bone graft (AIBG) in a meta-analysis (relative risk 0.27, 95% CI 0.16-0.46). Stratification of meta-analyses by the type of surgical procedure performed yielded similar results. Funnel plots suggested publication bias. Trials of rhBMP-2 suggested reductions in the operating time and surgical blood loss, with less effect on the length of hospital stay. There was no difference in radiographic nonunion with the use of rhBMP-7 when compared with AIBG (relative risk 1.02, 95% CI 0.52-1.98). Neither rhBMP-2 nor rhBMP-7 demonstrated a significant improvement on the Oswestry Disability Index when compared with AIBG. The limited data on demineralized bone matrix and autologous growth factor showed no significant improvement in radiographic outcomes. CONCLUSIONS Recombinant human BMP-2 may be an effective alternative to AIBG in lumbar fusion. Data are limited for other bone graft substitutes.

Hospital-Based Comparative Effectiveness Centers: Translating Research into Practice to Improve the Quality, Safety and Value of Patient Care

Hospital-based comparative effectiveness (CE) centers provide a model that clinical leaders can use to improve evidence-based practice locally. The model is used by integrated health systems outside the US, but is less recognized in the US. Such centers can identify and adapt national evidence-based policies for the local setting, create local evidence-based policies in the absence of national policies, and implement evidence into practice through health information technology (HIT) and quality initiatives. Given the increasing availability of CE evidence and incentives to meaningfully use HIT, the relevance of this model to US practitioners is increasing. This is especially true in the context of healthcare reform, which will likely reduce reimbursements for care deemed unnecessary by published evidence or guidelines. There are challenges to operating hospital-based CE centers, but many of these challenges can be overcome using solutions developed by those currently leading such centers. In conclusion, these centers have the potential to improve the quality, safety and value of care locally, ultimately translating into higher quality and more cost-effective care nationally. To better understand this potential, the current activity and impact of hospital-based CE centers in the US should be rigorously examined.

Antifibrinolytic use in adult cardiac surgery.

Purpose of reviewAntifibrinolytics are used to attenuate the coagulopathy associated with cardiopulmonary bypass. However, recent studies suggest that the antifibrinolytic aprotinin is associated with increased renal and vascular events and death compared to its alternatives. To develop a recommendation for antifibrinolytic use in adult cardiac surgery, we performed a systematic review and meta-analysis to determine the association of the antifibrinolytics with efficacy, safety and cost outcomes. Recent findingsAprotinin, when compared to placebo, significantly decreased blood transfusions and reoperations for bleeding, strokes and cognitive dysfunction, and significantly increased renal dysfunction but not renal failure. Tranexamic acid significantly decreased blood transfusions, but was not statistically associated with other outcomes. Aminocaproic acid was not statistically associated with any measured outcome. Although aprotinin costs more than its alternatives, its costs may approximate those of its alternatives when longer time horizons are considered. SummaryWe support the targeted use of aprotinin in adult cardiac surgery patients at high risk for bleeding or stroke, and discourage the use of aprotinin in those at high risk for renal failure. Although fewer data are available for tranexamic and aminocaproic acid, we support their use as alternatives to aprotinin in those at high risk for bleeding.

Assessing preventability in the quest to reduce hospital readmissions

Hospitals devote significant human and capital resources to eliminate hospital readmissions, prompted most recently by the Centers for Medicare and Medicaid Services (CMS) financial penalties for higher-than-expected readmission rates. Implicit in these efforts are assumptions that a significant proportion of readmissions are preventable, and preventable readmissions can be identified. Yet, no consensus exists in the literature regarding methods to determine which readmissions are reasonably preventable. In this article, we examine strengths and limitations of the CMS readmission metric, explore how preventable readmissions have been defined and measured, and discuss implications for readmission reduction efforts. Drawing on our clinical, research and operational experiences, we offer suggestions to address the key challenges in moving forward to measure and reduce preventable readmissions.

Evidence synthesis activities of a hospital evidence‐based practice center and impact on hospital decision making

BACKGROUND Hospital evidence-based practice centers (EPCs) synthesize and disseminate evidence locally, but their impact on institutional decision making is unclear. OBJECTIVE To assess the evidence synthesis activities and impact of a hospital EPC serving a large academic healthcare system. DESIGN, SETTING, AND PARTICIPANTS Descriptive analysis of the EPCs database of rapid systematic reviews since EPC inception (July 2006-June 2014), and survey of report requestors from the EPCs last 4 fiscal years. MEASUREMENTS Descriptive analyses examined requestor and report characteristics; questionnaire examined report usability, impact, and requestor satisfaction (higher scores on 5-point Likert scales reflected greater agreement). RESULTS The EPC completed 249 evidence reviews since inception. The most common requestors were clinical departments (29%, n = 72), chief medical officers (19%, n = 47), and purchasing committees (14%, n = 35). The most common technologies reviewed were drugs (24%, n = 60), devices (19%, n = 48), and care processes (12%, n = 31). Mean report completion time was 70 days. Thirty reports (12%) informed computerized decision support interventions. More than half of reports (56%, n = 139) were completed in the last 4 fiscal years for 65 requestors. Of the 64 eligible participants, 46 responded (72%). Requestors were satisfied with the report (mean = 4.4), and agreed it was delivered promptly (mean = 4.4), answered the questions posed (mean = 4.3), and informed their final decision (mean = 4.1). CONCLUSIONS This is the first examination of evidence synthesis activities by a hospital EPC in the United States. Our findings suggest hospital EPCs can efficiently synthesize and disseminate evidence addressing a range of clinical topics for diverse stakeholders, and can influence local decision making.

When the decision is what to decide: using evidence inventory reports to focus health technology assessments.

OBJECTIVES Health systems frequently make decisions regarding acquisition and use of new technologies. It is desirable to base these decisions on clinical evidence, but often these technologies are used for multiple indications and evidence of effectiveness for one indication does not prove effectiveness for all. Here, we describe two examples of evidence inventory reports that were performed for the purposes of identifying how much and what type of published clinical evidence was available for a given technology, and the contexts in which those technologies were studied. METHODS The evidence inventory reports included literature searches for systematic reviews and health technology assessment (HTA) reports, and systematic searches of the primary literature intended to count and categorize published clinical studies. The reports did not include analysis of the primary literature. RESULTS The inventory reports were completed in 3 to 4 days each and were approximately ten pages in length, including references. Reports included tables listing the number of reported studies by specific indication for use, and whether or not there were randomized trials. Reports also summarized findings of existing systematic reviews and HTA reports, when available. Committees used the inventory reports to decide for which indications they wanted a full HTA report. CONCLUSIONS Evidence inventory reports are a form of rapid HTA that can give decision makers a timely understanding of the available evidence upon which they can base a decision. They can help HTA providers focus subsequent reports on topics that will have the most influence on healthcare decision making.

The Penn Medicine Center for Evidence-Based Practice: Supporting the Quality, Safety, and Value of Patient Care Through Evidence-Based Practice at the Systems Level (USA)

The University of Pennsylvania Health System Center for Evidence-based Practice (CEP) was established in 2006 by the Office of the Chief Medical Officer to support the quality, safety and value of patient care at Penn through evidence-based practice. To accomplish this mission, CEP performs rapid systematic reviews of the scientific literature to inform local practice and policy, translates evidence into practice through the use of computerized clinical decision support (CDS) interventions and clinical pathways, and offers education in evidence-based decision making to trainees, staff and faculty. The Center includes a physician director, three research analysts, six physician and nurse liaisons, a biostatistician, a health economist and an administrator, and collaborates closely with librarians and staff in informatics and quality improvement. To date, CEP has completed over 300 rapid reviews for clinical and administrative leaders on topics ranging from formulary management to device purchasing to development of best clinical practices. CEP has also created approximately 25 CDS tools to integrate evidence into practice, and is developing a pathways program to support standardization of care throughout our growing healthcare system. Lastly, CEP has enhanced the capacity for evidence-based decision making through a novel EBM curriculum for medical students, as well as courses and workshops for housestaff, fellows, faculty, advance practice providers and nurses. Our experience suggests hospital EPCs can efficiently synthesize and implement evidence addressing a range of clinical topics for diverse stakeholders, influence local decision making, and foster a culture of evidence-based practice, strengthening the quality, safety, and value of care provided.

068 Integrating guidelines into local clinical practice and policy using hospital-based health technology assessment

Background Most existing centres for health technology assessment (HTA) are associated with payers or government agencies, and review and analyse emerging and costly technologies. Yet, such centres can exist within individual medical centres as well, and can use HTA methods locally to synthesise, disseminate and implement best clinical practices to improve the quality, safety and value of patient care. Objectives Describe the structure, processes and outcomes of a model of hospital-based HTA (HB-HTA) in the US, such that it can be applied elsewhere. Methods Our academic medical centre established the centre for Evidence-based Practice (CEP) in 2006. CEP synthesises guidelines and studies for clinical and administrative leaders to inform decision-making, integrates select syntheses into practice through clinical decision support (CDS), and provides education in evidence-based practice. Local utilisation and cost data are incorporated where appropriate. Results Nearly 200 evidence reports have been completed to date, and over 35 reports have been integrated into CDS. The median time from project opening to first draft is 4 weeks. CEP also contracts with external organisations such as the CDC and AHRQ on systematic reviews and guidelines. Discussion To complete reviews rapidly, we work closely with requestors to define the questions up front and limit the scope, use experienced analysts to perform high yield searches with single study reviews and extraction, and use best available evidence and existing guidelines and reviews. Implications for Guideline Developers/Users An HB-HTA centre can develop, adapt and implement guidelines locally to support a culture of evidence-based practice and decision-making.