Syngerism between dissolved oxygen and cadmium toxicity in five species of aquatic insects.

Continuous-flow bioassays were employed to determine the relationship between dissolved oxygen and cadmium upon five species of aquatic insects, as measured by survival and the amount of cadmium found within the insect. Results indicate the toxicity of cadmium increases as the dissolved oxygen concentration increases. This may be explained by an observed increase in the amount of cadmium found in the insect as the dissolved oxygen concentration increases. Oxygen consumption has been reported to increase as the dissolved oxygen concentration increases (Petty, 1967; Ericksen, 1963; Fox et al., 1937). In this study, using a fixed cadmium concentration, the amount of cadmium found in the insect also increased with an increase in the dissolved oxygen. Therefore, cadmium absorption may be coupled to metabolism.     

Successful cryopreservation of Wuchereria bancrofti microfilariae

A fast freezing technique developed by James (1981) significantly improved the yield of schistosome larvae that could be stored in liquid nitrogen. This was adapted by Ham et al. (1981) to the freezing of microfilariae of Onchocerca spp. with excellent results. They found 70 to 80% of the cryopreserved larvae remained viable using this method and since then Ham (personal communication) has successfully applied the same technique to Brugia malayi microfilariae. The further application to Wuchereria bancrofti is described.     

Cadmium in soil and terrestrial biota,with emphasis on the danish situation

The cadmium load on the soil and terrestrial biota in the industrialized countries appears to be on the increase. Due to a relatively high mobility of this metal in the soil-plant system, the likely gradual increase in soil concentrations will influence the cadmium load on organisms in the terrestrial biota. It might be too early to predict the actual rate of increase in the cadmium load on specific organisms but some attempts to do so have suggested an annual increase rate of 0.5–2% in the human food intake of the metal. Although the present cadmium pollution of the environment at large is not yet crucial, the most sensitive species, man and other long-lived mammals, might soon need introduction of countermeasures to seriously reduce the load of this toxic metal. The most feasible countermeasures to be taken are reductions in emission to air directly or indirectly via reduction of the indiscriminate use of the metal for common consumer goods. A decrease of the inflow to soils in phosphatic fertilizer may be more difficult to curb, but a reduced fertilization rate on most areas might be possible without loss of fertility. Sludge may not be a major source of cadmium nationally, but may locally significantly increase the inflows to agriculture (Statens Naturvårdsverk, 1978; Miljøstyrelsen, 1980; Umweltbundesamt, 1981; Department of the Environment, 1980.     

Leptospirosis in Nepal

We present here a case report of a suspected leptospiral infection in a Nepali soldier, and the results of a serological survey of 188 residents of Eastern Nepal that indicate the infection may be common there. This is the first report of leptospirosis in Nepal although it is known to affect man and animals in most of the temperate and tropical regions of the world, and apparently occurs widely in India (Das Gupta, 1938; Khanna & Iyer, 1971).     

Application of enzyme-linked immunosorbent assay (ELISA) to identification of Anopheles mosquito bloodmeals

The microplate method of the ELISA described by Volleret al. (1974) was manipulated for identification of Anopheles bloodmeals. Blood samples collected from man and from laboratory animals were put in small amounts (1 to 2 μl) on filter paper.Also bloodmeals from A. stephensi fed on human volunteers and guinea-pig were smeared on filter paper one, six 12, 24 and 48 hours after ingestion. The samples were tested by a modified microplate ELISA, using alkaline phosphatase anti-human IgG conjugate.Results showed that ELISA is a quite specific and sensitive technique for the detection of a small amount of human blood, even 24 hours after ingestion by anopheline mosquitoes. The ELISA seems to be a more practical and reproducible method than the precipitin test for identification of arthropod blood-meals, and could also be used for identification of blood spots in forensic laboratories.The anthropophilic index of anopheline mosquitoes is an important factor in the role of different Anopheles mosquitoes in malaria transmission. The technique which has been most commonly used for determination of the source of Anopheles bloodmeals is the precipitin test which was first employed by Uhlenhuthet al. (1908) as a medicolegal procedure for the identification of human blood stains. Later it was used and modified for determining the sources of bloodmeals in mosquitoes and other insects (King & Bull, 1923; Rice & Barber, 1935).Although the precipitin test is quite a specific and reliable test, the microplate indirect method of enzyme-linked immunosorbent assay (ELISA) developed by Volleret al. (1974) may be more practical for the identification of human blood in engorged anopheline mosquitoes. The ELISA test has, therefore, been modified for mosquito bloodmeal identification in this study.     

The nature of electron diffraction patterns of amphibole asbestos and their use in identification

The reported insensitivity of electron diffraction patterns of single amphibole fibers to tilts of ±20° (Skikne et al., 1971;Chisholm, 1973;Seshan, 1976) does not occur when the fibers are thin enough, and Seshan's explanation of it is incorrect. When sufficiently thin fibers are used the patterns can be readily indexed and very clearly differentiate between the different amphibole species.     

A comparison of the susceptibility to niridazole of Schistosoma mansoni and S. intercalatum in mice

Further investigation on the susceptibility of different species of schistosomes to niridazole has been carried out in mice. S. intercalatum was found to be much less susceptible than S. mansoni. This is the first record of experimental chemotherapy of S. intercalatum but is consistent with the clinical observations of Brumpt et al. (1968). S. intercalatum was markedly more resistant than S. mattheei was in the previous study and thus susceptibility to niridazole can differ markedly between different sibling species of schistosomes as it does between different geographical strains of S. mansoni (Taylor and Nelson, 1971). A shift of drug-affected parasites from the portal system to the lungs was found to occur both with S. mansoni and S. intercalatum but was more pronounced with S. mansoni, especially in infections of longer duration and it was commoner in treated than in untreated mice. The higher propensity of S. mansoni to show a “lung shift”, attributed to the higher fecundity of S. mansoni compared to S. intercalatum with consequent higher levels of liver damage, was not responsible for the higher worm kill in the S. mansoni infections, since this disparity in worm kill was maintained in infections treated at a relatively early stage, when few “lung shifts” occurred.     

The epidemiology of Entamoeba histolytica in Mexico City. A pilot survey I

Stocks of intestinal amoebae isolated from hospital patients in Mexico City and grown in monoxenic culture were compared among themselves and with those already described (Sargeaunt & Williams, 1979), using the electrophoretic patterns of four enzymes: glucose phosphate isomerase (GPI), phosphoglucomutase (PGM), L-malate:NADP⁺ oxido-reductase (oxalacetate-decarboxylating) (ME) and hexokinase (HK). New isoenzyme groups (Sargeaunt & Williams, 1979) of all the amoebae, including Entamoeba histolytica have been demonstrated. Amongst these have been found seven more groups of E. histolytica, two new groups of E. hartmanni, one new group of Dientamoeba fragilis and one new group of E. coli. Of the seven new groups of E. histolytica three are known to originate from patients with clinical amoebiasis whilst the remainder are from asymptomatic subjects. Only 11·2% of the 125 isolations were associated with clinical amoebiasis, and these are clearly distinguished from the isolations from asymptomatic patients by their electrophoretic isoenzyme pattern.     

Pentastomiasis and cancer of the colon

The case is described of a 50-year-old man, admitted to a small mission hospital in Zaire, where a preliminary diagnosis of cancer was made. On referral to a bigger hospital he was found to be infected with Entamoeba histolytica and biopsy of the peritoneal tumour revealed a pentastomid nymph, probably of Armillifer armillatus, the most common pentastomid infecting man in Zaire. X-ray subsequently revealed numerous calcified nymphs. Surgical and anti-parasitic treatment are described and the possible association between pentastomid infection and cancer is discussed.As Self, Hopps & Williams (1975) admit, our knowledge of pentastomiasis in Africa is incomplete and it must be assumed that its occurrence is much more widespread than published reports indicate. It may, therefore, exist throughout much of sub-Saharan Africa, as does liver cancer.Nymphal pentastomiasis in man caused by Armillifer armillatus is generally discovered during surgical intervention or at necropsy. Pathological complications caused by the nymphs are very rare. However, Fain (1975) has drawn attention to the possibility of a carcinogenic action of pentastomids and, although the arguments for this association may be weak, it is an interesting hypothesis bearing in mind the association between clonorchiasis and cancer of the bile-ducts and schistosomiasis and cancer of the urinary bladder. We describe below a case of cancer of the colon accompanied by pentastomiasis.     

Mirex. An overview.

Mirex, a chlorinated insecticide, is the active ingredient in bait used to control the imported fire ant. Prepared in 1946, mirex was first introduced for use in pesticidal formulations in 1959; mirex acts as a stomach poison. Extreme persistence in the natural environment provides an opportunity for accumulation in the food chain. No metabolism of mirex appears to take place in mammalian systems, although mirex causes liver damage and has been reported to produce hepatomas in mice. Mirex readily crosses the rat placental barrier; while no teratogenic effects are apparent, reduced litter size and a high incidence of cataracts in the offspring have been reported. An abstracted literature collection spanning the years 1947 to 1976 of 325 references has been published by Waters and Black (1976).     

The effects of macrophages isolated from the lungs of guinea pigs dusted with silica on collagen biosynthesis by guinea pig fibroblasts in cell culture.

Collagen synthesis was measured by the formation of ¹⁴C-hydroxyproline in the cell layer and medium proteins of guinea pig embryo lung fibroblasts in cell culture.Alveolar macrophages were obtained from normal guinea pigs and from guinea pigs which had been exposed in vivo to silica dust. The macrophages were disrupted and fractionated into high speed supernatant (extract) and a residual fraction.Neither the extract nor the residual fraction of 10⁶ normal or silica-treated macrophages had any effect on collagen biosynthesis by fully confluent fibroblast cultures grown in foetal bovine serum. Fractions from 5 × 10⁶ or more macrophage cells inhibited collagen synthesis.When freshly plated or nonconfluent fibroblasts were used the supernatant from 10⁶ silica-treated macrophages, but not the other fractions, caused a 60% stimulation of hydroxyproline formation without concomitant increase in peptide synthesis.The results suggest that the conflicting findings of Heppleston, A. G., and Styles, J. A. (1967a) (Activity of a macrophage factor in collagen formation by silica. Nature (London)214, 521–522.) and (1967b) (Involvement of the macrophage in silicotic fibrogenesis. Fort-schritte der Staublungenforchung, 2, 123–128), and Harington, J. S., Ritchie, Marianne, King, P. C., and Miller, Klara (1973). (The in vitro effects of silica treated hamster macrophages on collagen production by Hamster fibroblasts. J. Pathol.109, 21–37.) on the stimulation of collagen synthesis by an extract of silica-treated macrophages were due to differences in the state of growth of their fibroblast cultures.     

Tricarboxylic acid cycle enzyme activities in adult Schistosoma mansoni and Schistosoma japonicum

Reduced tricarboxylic acid cycle enzyme activities were found in paired adult Schistosoma mansoni and S. japonicum in comparison to those reported for S. mansoni cercariae (Coles, 1973). Succinate dehydrogenase activity, which has not been previously reported for either adult blood fluke, is more than twice as great in paired adult S. japonicum as in paired adult S. mansoni, but the activity is low in both species of adult worms. The similar low levels of tricarboxylic acid cycle enzyme activities which occur in adult S. mansoni and S. japonicum further substantiate the fact that anaerobic glycolysis is the major energy source in adults of both species.     

A trial of povidone iodine dry powder spray for the prevention of infusion thrombophlebitis

The efficacy of povidone iodine dry powder spray in the prevention of infusion thrombophlebitis was assessed in a prospective controlled study. Thrombophlebitis was evaluated clinically, and in addition all cannulae were cultured to detect any bacterial colonization. The incidence of thrombophlebitis was identical in both test and control groups, while the former showed no reduction in the incidence of cannula colonization. It is concluded that the use of povidone iodine dry powder spray for prophylaxis does not reduce the incidence of infusion thrombophlebitis. There was also a significant association (P = 0·03) between the incidence of thrombophlebitis and cannula colonization as measured by the semi-quantitative technique of Maki, Weise &; Sarafin (1977).     

Experimental cutaneous leishmaniasis with Leishmania tropica in albino hairless mice, Mus musculus.

Cutaneous leishmaniasis was produced in 90 hairless mice, Mus musculus, with cultures of two strains of Leishmania tropica (one isolated from an exogenous human case in Texas, and the other a gerbil strain from the USSR). The mice were inoculated intradermally in five areas of the dorsal side of the body. Most of the inoculated mice developed visible cutaneous leishmaniasis. The early lesions at the sites of inoculation were small red papules appearing within one to two months following inoculation; some of these papules disappeared after a few weeks, others became nodular or pustular. These lesions gradually enlarged and became ulcerated, measuring about 5 to 10 mm in diameter, and some persisted as long as 386 days. The edges of the lesions were usually raised, indurated, and pink; the adjacent skin showed no visible reaction. The centre of the ulcer was either moist or covered with a dry brownish-grey crust. In a few cases the lesions were very extensive and merged with each other, covering nearly two thirds of the dorsal body surface. Smears from the edges of the lesions were positive for the amastigote (aflagellar) form of L. tropica, which produced infections when inoculated into other hairless mice and grew readily in promastigote (flagellar) form on NNP-2 medium (Packchanian, 1959) with suitable antibiotics (Packchanian, 1957). Although mice were inoculated intradermally with L. tropica, several animals with extensive skin lesions of cutaneous leishmaniasis also developed generalized leishmaniasis. This was proved by positive blood culture tests for promastigotes (from 15 mice) and by demonstration of the amastigote form of L. tropica in various organs such as the spleen, liver, kidney, heart and lymph nodes. On the other hand, heart blood from 18 mice with small skin lesions when tested during 62 to 269 days following infection, yielded negative results for promastigotes. The mice were kept under observation (60 to 478 days) before they were killed or died. The results of this study have demonstrated that the hairless mouse, Mus musculus, is a suitable laboratory animal for studying experimental cutaneous leishmaniasis.     

Sex-linked mutations in Drosophila after exposure to various mixtures of gas atmospheres

Drosophila melanogaster males, Canton-Special strain, were exposed to six different gas atmospheres, to determine the sex-linked recessive lethal mutation rate utilizing the Basc technique (Muller and Oster, 1963). All of these gases were significantly mutagenic to Drosophila. One of the gases, perfluorobutene-2 was studied in mixtures with compressed air, carbon dioxide, oxygen, or nitrogen to determine its effects in combination with various components of air. A gas-mixing device for exposing Drosophila was constructed for the monitoring and mixing of the gases studied. Treatment with perfluorobutene-2 produced a recessive mutation rate of 1.78% as compared to 0.25% for compressed air. This was higher than any mutation rate obtained when perfluorobutene-2 was mixed with oxygen, nitrogen, carbon dioxide, or compressed air. The quantity of perfluorobutene-2 present in the mixture was the principal factor in contributing to a high mutation rate.     

Mycetoma in Nigeria

Three cases of mycetoma, in which the causative fungus would seem to be identical, have been described. The fungus is regarded as belonging to the actinomycotic group of mycetomas in accordance with the definitions given by Chalmers and Archibald (1918). A culture was forwarded to Mr. P. TATE, of the Molteno Institute for Research in Parasitology, University of Cambridge, who kindly reported that the fungus most probably was Aspergillus pelletieri (Laveran, 1906), a synonym for which is Nocardia indica (Kanthack, 1893), (Chalmers, and Christopherson, 1916).     

Telephone Care Management's Effectiveness in Coordinating Care for Medicaid Beneficiaries in Managed Care: A Randomized Controlled Study

Objective

To test the effectiveness of a telephone care management intervention to increase the use of primary and preventive care, reduce hospital admissions, and reduce emergency department visits for Medicaid beneficiaries with disabilities in a managed care setting.

Data Source

Four years (2007–2011) of Medicaid claims data on blind and/or disabled beneficiaries, aged 20–64.

Study Design

Randomized control trial with an intervention group (n = 3,540) that was enrolled in managed care with telephone care management and a control group (n = 1,524) who remained in fee-for-service system without care management services. Multi-disciplinary care coordination teams provided telephone services to the intervention group to address patients'' medical and social needs.

Data Collection/Extraction

Medicaid claims and encounter data for all participants were obtained from the state and the managed care organization.

Principal Findings

There was no significant difference in use of primary care, specialist visits, hospital admissions, and emergency department between the intervention and the control group. Care managers experienced challenges in keeping members engaged in the intervention and maintaining contact by telephone.

Conclusions

The lack of success for Medicaid beneficiaries, along with other recent studies, suggests that more intensive and more targeted interventions may be more effective for the high-needs population.Only about 7 percent of Medicaid beneficiaries are blind and/or disabled, but they account for 40 percent of Medicaid spending (Vladeck 2003). Because they are low income as well, they are likely to be a vulnerable and hard-to-reach group that experiences greater difficulty navigating the health care system (Agency for Healthcare Research and Quality 2008; Kaiser Family Foundation 2010). Many states are looking for cost-effective strategies to provide medical services to this population. One such strategy is care management.Care management describes programs that are intended to increase appropriate use of medical care while reducing unnecessary services, such as emergency department (ED) visits and hospitalizations (Wagner et al. 2001; Mattke, Seid, and Ma 2007). In care management programs, to meet patients'' needs, care managers (who are usually nurses or Master''s level clinicians) encourage patients to seek appropriate treatment, help them find and make appointments with health care professionals, make sure they are keeping appointments and taking prescribed medications, educate them about treatment effectiveness, and identify other needs that patients might have (Wagner et al. 2001; Rittenhouse and Robinson 2006). Care managers also often work with primary care physicians (PCPs), providing them with information designed to help them monitor a patient''s overall health care use and communicate with other health care providers.Care management programs have traditionally focused on patients with chronic conditions such as diabetes mellitus, asthma, depression, coronary artery disease, and congestive heart failure (Wagner et al. 2001; Mattke, Seid, and Ma 2007). Studies have shown that care management can improve health outcomes for patients with particular chronic health conditions, such as diabetes (Sidorov et al. 2002; Dorr et al. 2005; Glazier et al. 2006; Chin et al. 2007), cardiovascular disease (Harris et al. 2003; Sequist et al. 2006), and congestive heart failure (Gorski and Johnson 2003; DeWalt et al. 2006). For patients with depression, care management has encouraged patients to talk to mental health specialists, increased their use of antidepressants, reduced their depression, improved their health, and improved their work performance and job retention (Wang et al. 2007; Mohr et al. 2008; Kroenke et al. 2010). In addition, care management has been found to reduce the costs of care in some settings (Handley, Shumway, and Schillinger 2008), although this might not be the norm (Peikes et al. 2009).Despite the success of care management in some settings, there has not been a rigorous evaluation of this approach in a diverse set of Medicaid beneficiaries with multiple chronic conditions. For example, studies of Medicaid care management in Florida (Afifi et al. 2007; Kominski et al. 2008) and Virginia (Zhang et al. 2008) have found improvements such as fewer hospital stays and ED visits. However, those studies used nonrandomly chosen comparison groups, and the results may have confounded the effects of the programs with other unobserved differences between the groups (Rosenbaum and Rubin 1983; Bell et al. 1995; Michalopoulos, Bloom, and Hill 2004). This is an important gap in the research as more than 20 states operate some form of care management for this population (Rosenman et al. 2006; Arora et al. 2008). This article begins to fill this gap in knowledge by presenting results from a randomized study of a telephone care management program for blind and/or disabled Medicaid beneficiaries in Colorado, many of whom often have multiple chronic conditions.     

The environmental model segment approach for estimating potential environmental concentrations: II. Application of the model to p-dichlorobenzene and trichloroethene

The Environmental Model Segment Approach introduced in Part I (R. Frische, W. Klöpffer, G. Rippen, and K. O. Günther, 1984,Ecotoxicol. Environ. Safety8, 352–362) is applied to estimate potential environmental concentrations of p-dichlorobenzene and trichloroethene. Environmental concentrations of these chemicals can be estimated only with difficulty by other models because of many diffuse emission sources emitting mainly into the air. By comparison of the estimated with the measured environmental concentrations it is found that the claim of the model to yield values which apply to reasonable unfavorable environmental boundary conditions is satisfied for the medium air and for the biota (fish). Soil concentrations calculated by means of the model, assuming equilibrium with high air concentrations, are higher than the measured ones, while the calculated water concentrations are lower than the values often measured for river waters. The latter fact may be attributed to direct input of the substances into water which is not being taken into account.     

Cost‐Effectiveness of an Electronic Medical Record Based Clinical Decision Support System

Background and Objective

Medical groups have invested billions of dollars in electronic medical records (EMRs), but few studies have examined the cost-effectiveness of EMR-based clinical decision support (CDS). This study examined the cost-effectiveness of EMR-based CDS for adults with diabetes from the perspective of the health care system.

Data Sources/Setting

Clinical outcome and cost data from a randomized clinical trial of EMR-based CDS were used as inputs into a diabetes simulation model. The simulation cohort included 1,092 patients with diabetes with A1c above goal at baseline.

Study Design

The United Kingdom Prospective Diabetes Study Outcomes Model, a validated simulation model of diabetes, was used to evaluate remaining life years, quality-adjusted life years (QALYs), and health care costs over patient lifetimes (40-year time horizon) from the health system perspective.

Principal Findings

Patients in the intervention group had significantly lowered A1c (0.26 percent, p = .014) relative to patients in the control arm. Intervention costs were $120 (SE = 45) per patient in the first year and $76 (SE = 45) per patient in the following years. In the base case analysis, EMR-based CDS increased lifetime QALYs by 0.04 (SE = 0.01) and increased lifetime costs by $112 (SE = 660), resulting in an incremental cost-effectiveness ratio of $3,017 per QALY. The cost-effectiveness of EMR-based CDS persisted in one-way, two-way, and probabilistic sensitivity analyses.

Conclusions

Widespread adoption of sophisticated EMR-based CDS has the potential to modestly improve the quality of care for patients with chronic conditions without substantially increasing costs to the health care system.Diabetes is a common and costly chronic disease. In 2007, 17.9 million U.S. residents were diagnosed with diabetes at a cost to the economy of $174 billion (American Diabetes Association 2008).¹ The Centers for Disease Control has estimated the lifetime risk of developing diabetes for individuals born in the United States in 2000 to be 32.8 percent for men and 38.5 percent for women (Narayan et al. 2003). Despite recent improvement trends, in 2008, less than 20 percent of diabetes patients reached evidence-based goals for glycated hemoglobin (A1c), blood pressure (BP), and low-density lipoprotein (LDL) cholesterol (Saydah, Fradkin, and Cowie 2004; Hoerger et al. 2008). Appropriate control of these risk factors would substantially reduce the rate of major microvascular or macrovascular diabetes-related complications and their associated costs (Patel et al. 2007; Dluhy and McMahon 2008; Gaede et al. 2008; Gerstein et al. 2008; Holman et al. 2008).One of the major barriers to improved diabetes care is the lack of timely intensification of pharmacotherapy in patients who have not achieved recommended clinical goals. Many factors contribute to this problem, including competing demands at the time of the visit (Parchman et al. 2007) and medication nonadherence (Karter et al. 2009). Rates of treatment intensification when patient are not at goal hover around 70–80 percent (Bolen et al. 2009). Studies have linked higher rates of treatment intensification by a primary care provider (PCP) to improved A1c, BP, and LDL control (McEwen et al. 2009).Interventions to improve the rates of appropriate treatment intensification include team-based case management, telephone-based management, and information technology-based interventions (Piette et al. 2001; Norris et al. 2002b; Bu et al. 2007). Integrated clinical decision support (CDS) systems have the potential to improve clinical care for millions of persons who are enrolled in health plans that have deployed electronic medical records (EMRs). EMRs can be programmed to include sophisticated algorithms that take advantage of current and past clinical information to provide detailed recommendations at the time of a clinical encounter (Von Korff et al. 1997; Wagner 1998; de Jaegher and Jegers 2001).Initial efforts at EMR-based CDS for diabetes typically improved processes of care (such as rate of A1c or LDL testing or eye exams) but failed to improve A1c, BP, or LDL control (Montori et al. 2002; Meigs et al. 2003;Crosson et al. 2005; O''Connor et al. 2005; Ziemer et al. 2006; Grant et al. 2008; Peterson et al. 2008). EMR-based CDS for other chronic conditions such as hypertension, congestive heart failure (CHF), and asthma similarly failed to improve key intermediate clinical outcomes (Montgomery and Fahey 1998; Tierney et al. 2003; Balas et al. 2004; Murray et al. 2004). A careful reading of these studies identified several possible reasons why these efforts failed: first, most CDS was limited to general prompts and reminders and did not include more detailed drug-specific advice; second, introduction of CDS was usually not accompanied by changes in staff responsibilities and clinic workflow to maximize the impact on clinical care; third, rather than being used for visit planning, CDS displays were usually provided late in the encounter and were often skipped over or not viewed by PCPs.A new generation of EMR-based CDS addressed these concerns by providing treatment recommendations including personalized and detailed drug-specific advice, and by reorganizing the workflow to incorporate recommendations into visits-planning activities. As a result, these system-wide interventions are beginning to have an impact on intermediate outcomes including A1c, BP, and LDL. However, concerns remain regarding the potential costs of these interventions, and evidence on both their costs and cost-effectiveness is limited. This study examines the cost-effectiveness of an EMR-based CDS that was implemented in a large Midwestern health plan.