Multiplex immunoassay for Lyme disease using VlsE1-IgG and pepC10-IgM antibodies: improving test performance through bioinformatics.

The Centers for Disease Control and Prevention currently recommends a 2-tier serologic approach to Lyme disease laboratory diagnosis, comprised of an initial serum enzyme immunoassay (EIA) for antibody to Borrelia burgdorferi followed by supplementary IgG and IgM Western blotting of EIA-positive or -equivocal samples. Western blot accuracy is limited by subjective interpretation of weakly positive bands, false-positive IgM immunoblots, and low sensitivity for detection of early disease. We developed an objective alternative second-tier immunoassay using a multiplex microsphere system that measures VlsE1-IgG and pepC10-IgM antibodies simultaneously in the same sample. Our study population comprised 79 patients with early acute Lyme disease, 82 patients with early-convalescent-phase disease, 47 patients with stage II and III disease, 34 patients post-antibiotic treatment, and 794 controls. A bioinformatic technique called partial receiver-operator characteristic (ROC) regression was used to combine individual antibody levels into a single diagnostic score with a single cutoff; this technique enhances test performance when a high specificity is required (e.g., ≥ 95%). Compared to Western blotting, the multiplex assay was equally specific (95.6%) but 20.7% more sensitive for early-convalescent-phase disease (89.0% versus 68.3%, respectively; 95% confidence interval [95% CI] for difference, 12.1% to 30.9%) and 12.5% more sensitive overall (75.0% versus 62.5%, respectively; 95% CI for difference, 8.1% to 17.1%). As a second-tier test, a multiplex assay for VlsE1-IgG and pepC10-IgM antibodies performed as well as or better than Western blotting for Lyme disease diagnosis. Prospective validation studies appear to be warranted.

Prediction in annotation based guideline encoding.

The encoding of clinical practice guidelines into machine operable representations poses numerous challenges and will require considerable human intervention for the foreseeable future. To assist and potentially speed up this process, we have developed an incremental approach to guideline encoding which begins with the annotation of the original guideline text using markup techniques. A modular and flexible sequence of subtasks results in increasingly inter-operable representations while maintaining the connections to all prior source representations and supporting knowledge. To reduce the encoding bottleneck we also employ a number of machine-assisted learning and prediction techniques within a knowledge-based software environment. Promising results with a straightforward incremental learning algorithm illustrate the feasibility of such an approach.

Cost-effectiveness and contraceptive effectiveness of the transdermal contraceptive patch.

OBJECTIVE: The purpose of this study was to examine implications of increased perfect use on the cost-effectiveness of the contraceptive patch compared with combination oral contraceptives (COCs). STUDY DESIGN: This study compared the patch with low-estrogen-dose COCs. It assumes that the risks of developing a medical condition during use are the same for both the patch and COCs. Differences in net cost and pregnancies avoided during use were modeled. With the use of a pharmacoeconomic model, both methods were compared with a hypothetical reference case of contraception nonuse. The base-case model considered women, ages 15 to 50, in average health in a long-term, mutually monogamous, heterosexual relationship. RESULTS: The base-case analysis showed that use of the patch resulted in a savings of 249 US dollars and 0.03 pregnancies per woman over 2 years compared with COCs. CONCLUSION: This analysis demonstrated that patch use would be cost saving compared with COC use, resulting in a net avoidance of pregnancy for this population. The cost savings are attributed to reduced costs of pregnancy.

Vocabulary requirements for implementing clinical guidelines in an electronic medical record: a case study.

As part of a larger effort to automate guidelines we determined the number and types of clinical variables required to implement two complex clinical guidelines and the adequacy of the electronic medical record (EMR) to capture them. 178 unique variables were required by both guidelines. Variables were classified as simple (existing observation terms in the EMR), calculated (transformations of simple variables), and complex (requiring multiple simple variables and logical rules for combining them). Many variables are unlikely to be instantiated in an EMR without focused efforts to collect them. In addition, many variables required knowledge that was neither provided in the guideline nor referenced. We conclude that, although the EMR contains the necessary variables to implement these guidelines, successful automated implementation requires unambiguous definition of required terms, incorporation of additional knowledge not provided in the guideline and modification of workflow to collect variables not normally captured in routine clinical care.

Costs and net health effects of contraceptive methods.

BACKGROUND: Pregnancy and contraceptive methods both have important health effects that include risks and benefits. The net impact of contraception on women's health has not been reported previously. STUDY DESIGN: This is a cost-utility analysis using a Markov model evaluated by Monte Carlo simulation using the societal perspective for costs. The analysis compared 13 methods of contraception to nonuse of contraception with respect to healthcare costs and quality-adjusted life years (QALYs). Discounting was applied for future costs and health effects. The base-case analysis applies to women of average health and fertility, ranging from 15 to 50 years of age, who are sexually active in a mutually monogamous relationship; smoking rates observed in women of reproductive age were used. Sensitivity analysis extended the analysis to nonmonogamous status and smoking status. RESULTS: Compared with use of no contraception, contraceptive methods of all types result in substantial cost savings over 2 years, ranging from US$5907 per woman for tubal sterilization to US$9936 for vasectomy and health gains ranging from 0.088 QALYs for diaphragm to 0.147 QALYs for depot medroxyprogesterone acetate. Compared with nonuse, even with a time horizon as short as 1 year, use of any method other than sterilization results in financial savings and health gains. Most of the financial savings and health gains were due to contraceptive effects. In a population of patients, even modest increases in the use of the most effective methods result in financial savings and health gains. CONCLUSIONS: Every method of contraception dominates nonuse in most clinical settings. Increasing the use of more effective methods even modestly at the expense of less effective methods will improve health and reduce costs. Methods that require action by the user less frequently than daily are both less costly and more effective than methods requiring action on a daily basis.