Graft coronary vasculopathy in cardiac transplantation--evaluation of risk factors by multivariate analysis

The development of coronary vasculopathy is the main determinant of long-term survival in cardiac transplantation. The identification of risk factors, therefore, seems necessary in order to identify possible treatment strategies. Ninety-five out of 397 patients, undergoing orthotopic cardiac transplantation from 10/1985 to 10/1992 were evaluated retrospectively on the basis of perioperative and postoperative variables including age, sex, diagnosis, previous operations, renal function, cholesterol levels, dosage of immunosuppressive drugs (cyclosporin A, azathioprine, steroids), incidence of rejection, treatment with calcium channel blockers at 3, 6, 12, and 18 months postoperatively. Coronary vasculopathy was assessed by annual angiography at 1 and 2 years postoperatively. After univariate analysis, data were evaluated by stepwise multiple logistic regression analysis. Coronary vasculopathy was assessed in 15 patients at 1 (16%), and in 23 patients (24%) at 2, years. On multivariate analysis, previous operations and the incidence of rejections were identified as significant risk factors (P < 0.05), whereas the underlying diagnosis had borderline significance (P = 0.058) for the development of graft coronary vasculopathy. In contrast, all other variables were not significant in our subset of patients investigated. We therefore conclude that the development of coronary vasculopathy in cardiac transplant patients mainly depends on the rejection process itself, aside from patient-dependent factors. Therapeutic measures, such as the administration of calcium channel blockers and regulation of lipid disorders, may therefore only reduce the progress of native atherosclerotic disease in the posttransplant setting.

Multivariate modelling of responses to conditional items: New possibilities for latent class analysis

Questionnaire data may contain missing values because certain questions do not apply to all respondents. For instance, questions addressing particular attributes of a symptom, such as frequency, triggers or seasonality, are only applicable to those who have experienced the symptom, while for those who have not, responses to these items will be missing. This missing information does not fall into the category 'missing by design', rather the features of interest do not exist and cannot be measured regardless of survey design. Analysis of responses to such conditional items is therefore typically restricted to the subpopulation in which they apply. This article is concerned with joint multivariate modelling of responses to both unconditional and conditional items without restricting the analysis to this subpopulation. Such an approach is of interest when the distributions of both types of responses are thought to be determined by common parameters affecting the whole population. By integrating the conditional item structure into the model, inference can be based both on unconditional data from the entire population and on conditional data from subjects for whom they exist. This approach opens new possibilities for multivariate analysis of such data. We apply this approach to latent class modelling and provide an example using data on respiratory symptoms (wheeze and cough) in children. Conditional data structures such as that considered here are common in medical research settings and, although our focus is on latent class models, the approach can be applied to other multivariate models.

Clinical outcome of patients with and without diabetes mellitus after percutaneous coronary intervention with the resolute zotarolimus-eluting stent: 2-year results from the prospectively pooled analysis of the international global RESOLUTE program

OBJECTIVES The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes. BACKGROUND The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes. METHODS We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years. RESULTS The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%). CONCLUSIONS The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

Impact of overlapping newer generation drug-eluting stents on clinical and angiographic outcomes: pooled analysis of five trials from the international Global RESOLUTE Program

BACKGROUND Overlapping first generation sirolimus- and paclitaxel-eluting stents are associated with persistent inflammation, fibrin deposition and delayed endothelialisation in preclinical models, and adverse angiographic and clinical outcomes--including death and myocardial infarction (MI)--in clinical studies. OBJECTIVES To establish as to whether there are any safety concerns with newer generation drug-eluting stents (DES). DESIGN Propensity score adjustment of baseline anatomical and clinical characteristics were used to compare clinical outcomes (Kaplan-Meier estimates) between patients implanted with overlapping DES (Resolute zotarolimus-eluting stent (R-ZES) or R-ZES/other DES) against no overlapping DES. Additionally, angiographic outcomes for overlapping R-ZES and everolimus-eluting stents were evaluated in the randomised RESOLUTE All-Comers Trial. SETTING Patient level data from five controlled studies of the RESOLUTE Global Clinical Program evaluating the R-ZES were pooled. Enrollment criteria were generally unrestrictive. PATIENTS 5130 patients. MAIN OUTCOME MEASURES 2-year clinical outcomes and 13-month angiographic outcomes. RESULTS 644 of 5130 patients (12.6%) in the RESOLUTE Global Clinical Program underwent overlapping DES implantation. Implantation of overlapping DES was associated with an increased frequency of MI and more complex/calcified lesion types at baseline. Adjusted in-hospital, 30-day and 2-year clinical outcomes indicated comparable cardiac death (2-year overlap vs non-overlap: 3.0% vs 2.1%, p=0.36), major adverse cardiac events (13.3% vs 10.7%, p=0.19), target-vessel MI (3.9% vs 3.4%, p=0.40), clinically driven target vessel revascularisation (7.7% vs 6.5%, p=0.32), and definite/probable stent thrombosis (1.4% vs 0.9%, p=0.28). 13-month adjusted angiographic outcomes were comparable between overlapping and non-overlapping DES. CONCLUSIONS Overlapping newer generation DES are safe and effective, with comparable angiographic and clinical outcomes--including repeat revascularisation--to non-overlapping DES.

A 350 ka record of climate change from Lake El'gygytgyn, Far East Russian Arctic: refining the pattern of climate modes by means of cluster analysis

Abstract. Rock magnetic, biochemical and inorganic records of the sediment cores PG1351 and Lz1024 from Lake El���gygytgyn, Chukotka peninsula, Far East Russian Arctic, were subject to a hierarchical agglomerative cluster analysis in order to refine and extend the pattern of climate modes as defined by Melles et al. (2007). Cluster analysis of the data obtained from both cores yielded similar results, differentiating clearly between the four climate modes warm, peak warm, cold and dry, and cold and moist. In addition, two transitional phases were identified, representing the early stages of a cold phase and slightly colder conditions during a warm phase. The statistical approach can thus be used to resolve gradual changes in the sedimentary units as an indicator of available oxygen in the hypolimnion in greater detail. Based upon cluster analyses on core Lz1024, the published succession of climate modes in core PG1351, covering the last 250 ka, was modified and extended back to 350 ka. Comparison to the marine oxygen isotope (���18O) stack LR04 (Lisiecki and Raymo, 2005) and the summer insolation at 67.5��� N, with the extended Lake El���gygytgyn parameter records of magnetic susceptibility (���LF), total organic carbon content (TOC) and the chemical index of alteration (CIA; Minyuk et al., 2007), revealed that all stages back to marine isotope stage (MIS) 10 and most of the substages are clearly reflected in the pattern derived from the cluster analysis.

Adapting to climate change through sustainable land management: experiences of a pilot project in Tajikistan

Tajikistan is particularly exposed to the risks of climate change. Its widely degraded landscapes are badly prepared to cope with changes in precipitation patterns, increased temperatures, droughts, and the spread of pests and disease. Sustainable land management (SLM) provides a ���basket of opportunities��� to address these challenges, particularly for increasing land productivity, improving livelihoods, and protecting ecosystems. Within the Pilot Program for Climate Resilience (PPCR) in Tajikistan 70 SLM technologies and approaches on how to implement SLM were documented with the World Overview of Conservation Approaches and Technologies (WOCAT ) tools in 2011. For this purpose a climate change adaptation module was developed and tested in order to enhance the understanding about climate change resilience of SLM practices and community workshops conducted to on adaptation mechanisms by rural communities in Tajikistan. The analysis came up with four guiding principles for applying SLM for adapting to climate change: 1. Diversification of land use technologies and farm incomes; 2. Intensification of use of natural resources; 3. Expansion of highly productive land use technologies; 4. Protection of land and livelihoods from extreme weather events. Furthermore, SLM must be up-scaled from isolated plots to entire zones or landscapes and the project developed the concept of three concentric villages zones, the in-, near- and off-village zones. Land users, advisors, and decision- and policy makers face the task of finding management practices that best suit site-specific conditions. This task is most efficiently addressed in collaborative effort, and building up and managing a respective knowledge platform.

Carbon dioxide and climate impulse response functions for the computation of greenhouse gas metrics: a multi-model analysis

The responses of carbon dioxide (CO2) and other climate variables to an emission pulse of CO2 into the atmosphere are often used to compute the Global Warming Potential (GWP) and Global Temperature change Potential (GTP), to characterize the response timescales of Earth System models, and to build reduced-form models. In this carbon cycle-climate model intercomparison project, which spans the full model hierarchy, we quantify responses to emission pulses of different magnitudes injected under different conditions. The CO2 response shows the known rapid decline in the first few decades followed by a millennium-scale tail. For a 100 Gt-C emission pulse added to a constant CO2 concentration of 389 ppm, 25 �� 9% is still found in the atmosphere after 1000 yr; the ocean has absorbed 59 �� 12% and the land the remainder (16 �� 14%). The response in global mean surface air temperature is an increase by 0.20 �� 0.12 ��C within the first twenty years; thereafter and until year 1000, temperature decreases only slightly, whereas ocean heat content and sea level continue to rise. Our best estimate for the Absolute Global Warming Potential, given by the time-integrated response in CO2 at year 100 multiplied by its radiative efficiency, is 92.5 �� 10���15 yr W m���2 per kg-CO2. This value very likely (5 to 95% confidence) lies within the range of (68 to 117) �� 10���15 yr W m���2 per kg-CO2. Estimates for time-integrated response in CO2 published in the IPCC First, Second, and Fourth Assessment and our multi-model best estimate all agree within 15% during the first 100 yr. The integrated CO2 response, normalized by the pulse size, is lower for pre-industrial conditions, compared to present day, and lower for smaller pulses than larger pulses. In contrast, the response in temperature, sea level and ocean heat content is less sensitive to these choices. Although, choices in pulse size, background concentration, and model lead to uncertainties, the most important and subjective choice to determine AGWP of CO2 and GWP is the time horizon.

An Innovative Family Preservation Program in an African American Community: Longitudinal Analysis

This paper presents a secondary analysis of data from a longitudinal evaluation of a community-based family preservation program in Portland, Oregon, designed for and by African Americans. Families served by the Family Enhancement Program (FEP) resemble chronically neglecting families in terms of numbers of children and length of contact with child protective services. Six- and twelve-month follow-ups for FEP clients were compared to data on families served by the Oregon State Office of Services to Children and Families (SOSCF). The author found that FEP families are more likely than SOSCFfamilies to show greater improvement between the pretest scores and the posttest scores for number of days in placement, number of placements, and number of founded maltreatment reports.

Implementation analysis of the Texas Vendor Drug Program

An agency is accountable to a legislative body in the implementation of public policy. It has a responsibility to ensure that the implementation of that policy is consistent with its statutory objectives.^ The analysis of the effectiveness of implementation of the Vendor Drug Program proceeded in the following manner. The federal and state roles and statutes pursuant to the formulation of the Vendor Drug Program were reviewed to determine statutory intent and formal provisions. The translation of these into programmatic details was examined focusing on the factors impacting the implementation process. Lastly, the six conditions outlined by Mazmanian and Sabatier as criteria for effective implementation, were applied to the implementation of the Vendor Drug Program to determine if the implementation was effective in relation to consistency with statutory objectives.^ The implementation of the statutes clearly met four of the six conditions for effective implementation: (1) clear and consistent objectives; (2) a valid causal theory; (3) structured the process to maximize agency and target compliance with the objectives; and (4) had continued support of constituency groups and sovereigns.^ The implementation was basically consistent with the statutory objectives, although the determination of vendor reimbursement has had and continues to have problems. ^

Survey of safety climate in public hospitals in Costa Rica in 1997

In response to growing concern for occupational health and safety in the public hospital system in Costa Rica, a research program was initiated in 1995 to evaluate and improve the safety climate in the national healthcare system through regional training programs, and to develop the capacity of the occupational health commissions in these settings to improve the identification and mitigation of workplace risks. A cross-sectional survey of 1000 hospital-based healthcare workers was conducted in 1997 to collect baseline data that will be used to develop appropriate worker training programs in occupational health. The objectives of this survey were to: (1) describe the safety climate within the national hospital system, (2) identify factors associated with safety climate focusing on individual and organizational variables, and (3) to evaluate the relationship between safety climate and workplace injuries and safety practices of employees. Individual factors evaluated included the demographic variables of age, gender, education and profession. Organizational factors evaluated included training, psychosocial work environment, job-task demands, availability of protective equipment and administrative controls. Work-related injuries and safety practices of employees included the type and frequency of injuries experienced and reported, and compliance with established safety practices. Multivariate regression analyses demonstrated that training and administrative controls were the two most significant predictors of safety climate. None of the demographic variables were significant predictors of safety climate. Safety climate was inversely and significantly associated with workplace injuries and positively and significantly associated with safety practices. These results suggest that training and administrative controls should be included in future training efforts and that improving safety climate will decrease workplace injuries and increase safety practices. ^