Provider perceptions on the management of lupus during pregnancy: barriers to improved care.

BACKGROUND: More than half of pregnancies in women with systemic lupus erythematosus (lupus) result in adverse outcomes for the mother or the fetus. We sought to identify aspects of current rheumatologic care that could be improved to decrease the frequency of poor outcomes. METHODS: Focus groups with clinical rheumatologists, based on the PRECEDE/PROCEED framework, identified factors that influenced care. A group of women with lupus on their reproductive journey contributed to our understanding of the dilemmas and care provided. RESULTS: Medically ill-timed pregnancies and medication non-adherence during pregnancy were identified by rheumatologists as the two key dilemmas in care. We identified several communication gaps as key modifiable barriers to optimal management. The approach to physician-patient communication was often unsuitable to sensitive discussions about pregnancy planning. The communication of treatment plans was frequently hampered by gaps in knowledge and both physician and patient confidence in the data, encouraging non-adherence among nervous patients. Finally, local rheumatologists and obstetricians/gynecologists providers frequently did not communicate, leading to varying treatment plans and confusion for patients. CONCLUSIONS: To decrease the frequency of ill-timed pregnancy and medication non-adherence it will be essential to empower rheumatologists, and women with lupus to have open and accurate conversations about pregnancy planning and management.

A randomized trial of computer-based reminders and audit and feedback to improve HIV screening in a primary care setting.

Despite recommendations for voluntary HIV screening, few medical centres have implemented screening programmes. The objective of the study was to determine whether an intervention with computer-based reminders and feedback would increase screening for HIV in a Department of Veterans Affairs (VA) health-care system. The design of the study was a randomized controlled trial at five primary care clinics at the VA Palo Alto Health Care System. All primary care providers were eligible to participate in the study. The study intervention was computer-based reminders to either assess HIV risk behaviours or to offer HIV testing; feedback on adherence to reminders was provided. The main outcome measure was the difference in HIV testing rates between intervention and control group providers. The control group providers tested 1.0% (n = 67) and 1.4% (n = 106) of patients in the preintervention and intervention period, respectively; intervention providers tested 1.8% (n = 98) and 1.9% (n = 114), respectively (P = 0.75). In our random sample of 753 untested patients, 204 (27%) had documented risk behaviours. Providers were more likely to adhere to reminders to test rather than with reminders to perform risk assessment (11% versus 5%, P < 0.01). Sixty-one percent of providers felt that lack of time prevented risk assessment. In conclusion, in primary care clinics in our setting, HIV testing rates were low. Providers were unaware of the high rates of risky behaviour in their patient population and perceived important barriers to testing. Low-intensity clinical reminders and feedback did not increase rates of screening.

Cost-effectiveness of voluntary HIV screening in Russia.

Russia has one of the world's fastest growing HIV epidemics, and HIV screening has been widespread. Whether such screening is an effective use of resources is unclear. We used epidemiologic and economic data from Russia to develop a Markov model to estimate costs, quality of life and survival associated with a voluntary HIV screening programme compared with no screening in Russia. We measured discounted lifetime health-care costs and quality-adjusted life years (QALYs) gained. We varied our inputs in sensitivity analysis. Early identification of HIV through screening provided a substantial benefit to persons with HIV, increasing life expectancy by 2.1 years and 1.7 QALYs. At a base-case prevalence of 1.2%, once-per-lifetime screening cost $13,396 per QALY gained, exclusive of benefit from reduced transmission. Cost-effectiveness of screening remained favourable until prevalence dropped below 0.04%. When HIV-transmission-related costs and benefits were included, once-per-lifetime screening cost $6910 per QALY gained and screening every two years cost $27,696 per QALY gained. An important determinant of the cost-effectiveness of screening was effectiveness of counselling about risk reduction. Early identification of HIV infection through screening in Russia is effective and cost-effective in all but the lowest prevalence groups.

Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules.

BACKGROUND: Effective strategies for managing patients with solitary pulmonary nodules (SPN) depend critically on the pre-test probability of malignancy. OBJECTIVE: To validate two previously developed models that estimate the probability that an indeterminate SPN is malignant, based on clinical characteristics and radiographic findings. METHODS: Data on age, smoking and cancer history, nodule size, location and spiculation were collected retrospectively from the medical records of 151 veterans (145 men, 6 women; age range 39-87 years) with an SPN measuring 7-30 mm (inclusive) and a final diagnosis established by histopathology or 2-year follow-up. Each patient's final diagnosis was compared with the probability of malignancy predicted by two models: one developed by investigators at the Mayo Clinic and the other developed from patients enrolled in a VA Cooperative Study. The accuracy of each model was assessed by calculating areas under the receiver operating characteristic (ROC) curve and the models were calibrated by comparing predicted and observed rates of malignancy. RESULTS: The area under the ROC curve for the Mayo Clinic model (0.80; 95% CI 0.72 to 0.88) was higher than that of the VA model (0.73; 95% CI 0.64 to 0.82), but this difference was not statistically significant (Delta = 0.07; 95% CI -0.03 to 0.16). Calibration curves showed that the probability of malignancy was underestimated by the Mayo Clinic model and overestimated by the VA model. CONCLUSIONS: Two existing prediction models are sufficiently accurate to guide decisions about the selection and interpretation of subsequent diagnostic tests in patients with SPNs, although clinicians should also consider the prevalence of malignancy in their practice setting when choosing a model.

Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C.

BACKGROUND: Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha-foetoprotein levels is widely practiced. AIM: To evaluate its cost-effectiveness using a Markov decision model. METHODS: Several screening strategies with abdominal ultrasonography or computerized tomography and serum alpha-foetoprotein at 6-12-month intervals in 40-year-old patients with chronic hepatitis C and compensated cirrhosis were simulated from a societal perspective, resulting in discounted costs per quality-adjusted life-year saved. Extensive sensitivity analysis was performed. RESULTS: For the least efficacious strategy, annual alpha-foetoprotein/ultrasonography, the incremental cost-effectiveness ratio (vs. no screening) was $23 043/quality-adjusted life-year. Biannual alpha-foetoprotein/annual ultrasonography, the most commonly used strategy in the United States, was more efficacious, with a cost-effectiveness ratio of $33 083/quality-adjusted life-year vs. annual alpha-foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha-foetoprotein/ultrasonography, resulted in a cost-effectiveness ratio of $73 789/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography. Biannual alpha-foetoprotein/annual computerized tomography screening resulted in a cost-effectiveness ratio of $51 750/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography screening. CONCLUSIONS: Screening for hepatocellular carcinoma is as cost-effective as other accepted screening protocols. Of the strategies evaluated, biannual alpha-foetoprotein/annual ultrasonography gives the most quality-adjusted life-year gain while still maintaining a cost-effectiveness ratio <$50 000/quality-adjusted life-year. Biannual alpha-foetoprotein/annual computerized tomography screening may be cost-effective.

Design and pilot evaluation of a system to develop computer-based site-specific practice guidelines from decision models.

BACKGROUND: Local tailoring of clinical practice guidelines (CPGs) requires experts in medicine and evidence synthesis unavailable in many practice settings. The authors' computer-based system enables developers and users to create, disseminate, and tailor CPGs, using normative decision models (DMs). METHODS: ALCHEMIST, a web-based system, analyzes a DM, creates a CPG in the form of an annotated algorithm, and displays for the guideline user the optimal strategy. ALCHEMIST'S interface enables remote users to tailor the guideline by changing underlying input variables and observing the new annotated algorithm that is developed automatically. In a pilot evaluation of the system, a DM was used to evaluate strategies for staging non-small-cell lung cancer. Subjects (n = 15) compared the automatically created CPG with published guidelines for this staging and critiqued both using a previously developed instrument to rate the CPGs' usability, accountability, and accuracy on a scale of 0 (worst) to 2 (best), with higher scores reflecting higher quality. RESULTS: The mean overall score for the ALCHEMIST CPG was 1.502, compared with the published-CPG score of 0.987 (p = 0.002). The ALCHEMIST CPG scores for usability, accountability, and accuracy were 1.683, 1.393, and 1.430, respectively; the published CPG scores were 1.192, 0.941, and 0.830 (each comparison p < 0.05). On a scale of 1 (worst) to 5 (best), users' mean ratings of ALCHEMIST'S ease of use, usefulness of content, and presentation format were 4.76, 3.98, and 4.64, respectively. CONCLUSIONS: The results demonstrate the feasibility of a web-based system that automatically analyzes a DM and creates a CPG as an annotated algorithm, enabling remote users to develop site-specific CPGs. In the pilot evaluation, the ALCHEMIST guidelines met established criteria for quality and compared favorably with national CPGs. The high usability and usefulness ratings suggest that such systems can be a good tool for guideline development.

Distributed decision support using a web-based interface: prevention of sudden cardiac death.

Although decision models can provide a formal foundation for guideline development and clinical decision support, their widespread use is often limited by the lack of platform-independent software that geographically dispersed users can access and use easily without extensive training. To address these limitations the authors developed a World Wide Web-based interface for previously developed decision models. They describe the use and functionality of the interface using a decision model that evaluates the cost-effectiveness of strategies for preventing sudden cardiac death. The system allows an analyst to use a web browser to interact with the decision model and to change the values of input variables within pre-specified ranges, to specify sensitivity or threshold analyses, to evaluate the decision model, and to view the results generated dynamically. The web site also provides linkages to an explanation of the model, and evidence tables for input variables. The system demonstrates a method for providing distributed decision support to remote users such as guideline developers, decision analysts, and potentially practicing physicians. The web interface provides platform-independent and almost universal access to a decision model. This approach can make distributed decision support both practical and economical, and has the potential to increase the usefulness of decision models by enabling a broader audience to incorporate systematic analyses into both policy and clinical decisions.

Evaluation of genetic tests: APOE genotyping for the diagnosis of Alzheimer disease.

Many studies have now confirmed the association between inheritance of the epsilon 4 allele of the apolipoprotein E (APOE) gene and Alzheimer disease (AD). However, although the medical community holds the near-unanimous opinion that APOE genotyping should not be used for prediction in asymptomatic individuals, controversy remains about whether it should be used for diagnosis in patients who show signs of dementia. We assessed critically the recent clinical studies, on the basis of four criteria recommended to ensure safety and effectiveness of genetic tests. We also developed a formal framework for evaluating the usefulness of APOE genotyping using decision-theoretic principles. We conclude that neither the presence nor absence of an epsilon 4 allele provides diagnostic certainty, and the proper interpretation of either result in heterogeneous populations requires further investigation. The appropriate role of APOE genotyping among elements of a traditional assessment for AD has not been determined. Whether APOE genotyping provides sufficient information to change patient management decisions has not been determined. APOE genotyping presents foreseeable, significant psychosocial consequences for family members that must be weighed against any psychosocial benefits. Therefore, the diagnostic use of APOE genotyping outside research settings is premature until such testing is shown to be of practical value.

Publishing web-based guidelines using interactive decision models.

Commonly used methods for guideline development and dissemination do not enable developers to tailor guidelines systematically to specific patient populations and update guidelines easily. We developed a web-based system, ALCHEMIST, that uses decision models and automatically creates evidence-based guidelines that can be disseminated, tailored and updated over the web. Our objective was to demonstrate the use of this system with clinical scenarios that provide challenges for guideline development. We used the ALCHEMIST system to develop guidelines for three clinical scenarios: (1) Chlamydia screening for adolescent women, (2) antiarrhythmic therapy for the prevention of sudden cardiac death; and (3) genetic testing for the BRCA breast-cancer mutation. ALCHEMIST uses information extracted directly from the decision model, combined with the additional information from the author of the decision model, to generate global guidelines. ALCHEMIST generated electronic web-based guidelines for each of the three scenarios. Using ALCHEMIST, we demonstrate that tailoring a guideline for a population at high-risk for Chlamydia changes the recommended policy for control of Chlamydia from contact tracing of reported cases to a population-based screening programme. We used ALCHEMIST to incorporate new evidence about the effectiveness of implantable cardioverter defibrillators (ICD) and demonstrate that the cost-effectiveness of use of ICDs improves from $74 400 per quality-adjusted life year (QALY) gained to $34 500 per QALY gained. Finally, we demonstrate how a clinician could use ALCHEMIST to incorporate a woman's utilities for relevant health states and thereby develop patient-specific recommendations for BRCA testing; the patient-specific recommendation improved quality-adjusted life expectancy by 37 days. The ALCHEMIST system enables guideline developers to publish both a guideline and an interactive decision model on the web. This web-based tool enables guideline developers to tailor guidelines systematically, to update guidelines easily, and to make the underlying evidence and analysis transparent for users.

Theory of coherent phonons in carbon nanotubes and graphene nanoribbons.

We survey our recent theoretical studies on the generation and detection of coherent radial breathing mode (RBM) phonons in single-walled carbon nanotubes and coherent radial breathing like mode (RBLM) phonons in graphene nanoribbons. We present a microscopic theory for the electronic states, phonon modes, optical matrix elements and electron-phonon interaction matrix elements that allows us to calculate the coherent phonon spectrum. An extended tight-binding (ETB) model has been used for the electronic structure and a valence force field (VFF) model has been used for the phonon modes. The coherent phonon amplitudes satisfy a driven oscillator equation with the driving term depending on the photoexcited carrier density. We discuss the dependence of the coherent phonon spectrum on the nanotube chirality and type, and also on the graphene nanoribbon mod number and class (armchair versus zigzag). We compare these results with a simpler effective mass theory where reasonable agreement with the main features of the coherent phonon spectrum is found. In particular, the effective mass theory helps us to understand the initial phase of the coherent phonon oscillations for a given nanotube chirality and type. We compare these results to two different experiments for nanotubes: (i) micelle suspended tubes and (ii) aligned nanotube films. In the case of graphene nanoribbons, there are no experimental observations to date. We also discuss, based on the evaluation of the electron-phonon interaction matrix elements, the initial phase of the coherent phonon amplitude and its dependence on the chirality and type. Finally, we discuss previously unpublished results for coherent phonon amplitudes in zigzag nanoribbons obtained using an effective mass theory.

Chirality-selective excitation of coherent phonons in carbon nanotubes by femtosecond optical pulses.

Using predesigned trains of femtosecond optical pulses, we have selectively excited coherent phonons of the radial breathing mode of specific-chirality single-walled carbon nanotubes within an ensemble sample. By analyzing the initial phase of the phonon oscillations, we prove that the tube diameter initially increases in response to ultrafast photoexcitation. Furthermore, from excitation profiles, we demonstrate that an excitonic absorption peak of carbon nanotubes periodically oscillates as a function of time when the tube diameter undergoes coherent radial breathing mode oscillations.

The potential use of expert systems to enable physicians to order more cost-effective diagnostic imaging examinations.

Educating physicians to order diagnostic imaging examinations more cost-effectively is a difficult and time consuming task, which may be assisted significantly by the use of an expert system. This report is based on a study undertaken at the Health Sciences Centre in Winnipeg, Manitoba, to determine the feasibility of implementing an expert system to aid physicians in selecting appropriate imaging studies. The report reviews the potential benefits, requirements, and limitations of expert systems under development, and highlights the major issues to be considered in choosing such a system for implementation. An extensive literature search was done and is included to aid the reader interested in pursuing this opportunity for improving the cost-effective utilization of expensive diagnostic imaging resources.

Cost-effectiveness of a potential vaccine for Coccidioides immitis.

Coccidioidomycosis, a systemic fungal infection, affects Americans living in the Southwest. We evaluated the cost- effectiveness of a potential vaccine against Coccidioides immitis. Using a decision model we developed, we estimate that among children, vaccination would saved 1.9 quality-adjusted life days (QALD) and $33 per person. Among adults, screening followed by vaccination would save 0.5 QALD per person and cost $62,000 per quality adjusted life year gained over no vaccination. If the birth cohort in highly endemic counties of California and Arizona were immunized in 2001, 11 deaths would be averted and $3 million would be saved (in net present value) over the lifetime of these infants. Vaccination of adults to prevent disseminated coccidioidomycosis would provide a modest health benefit similar in magnitude to other vaccines but would increase net expenditures. Vaccination of children in highly endemic regions would provide a larger health benefit and would reduce total health care expenditures.

Prevention of sudden cardiac death: a probabilistic model for decision support.

As part of the Cardiac Arrhythmia and Risk of Death Patient Outcomes Research Team (CARD PORT) study we are developing a comprehensive decision model to help physicians identify preferred strategies for preventing sudden cardiac death. The model integrates three components: a screening model, a treatment model, and a value model. Ultimately this model will use the CARD PORT's collective findings to produce policy recommendations and will support patient-specific clinical decision making. Our initial modeling suggests the importance of patient-specific value models in an analysis of treatment options. Although our model is specific to cardiac sudden death, other medical domains that exhibit similar characteristics--the importance of patient preferences and the uncertainty regarding the benefits of strategies for risk stratification and treatment--can use a conceptual framework similar to the approach we used to represent strategies to prevent sudden cardiac death.

Monitored isoniazid prophylaxis for low-risk tuberculin reactors older than 35 years of age: a risk-benefit and cost-effectiveness analysis.

BACKGROUND: Isoniazid chemoprophylaxis effectively prevents the development of active infectious tuberculosis. Current guidelines recommend withholding this prophylaxis for low-risk tuberculin reactors older than 35 years of age because of the risk for fatal isoniazid-induced hepatitis. However, recent studies have shown that monitoring for hepatotoxicity can significantly reduce the risk for isoniazid-related death. OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of monitored isoniazid prophylaxis for low-risk tuberculin reactors older than 35 years of age. DESIGN: A Markov model was used to compare the health and economic outcomes of prescribing or withholding a course of prophylaxis for low-risk reactors 35, 50, or 70 years of age. Subsequent analyses evaluated costs and benefits when the effect of transmission of Mycobacterium tuberculosis to contacts was included. MEASUREMENTS: Probability of survival at 1 year, number needed to treat, life expectancy, and cost per year of life gained for individual persons and total population. RESULTS: Isoniazid prophylaxis increased the probability of survival at 1 year and for all subsequent years. For 35-year old, 50-year-old, and 70-year-old tuberculin reactors, life expectancy increased by 4.9 days, 4.7 days, and 3.1 days, respectively, and costs per person decreased by $101, $69, and $11, respectively. When the effect of secondary transmission to contacts was included, the gains in life expectancy per person receiving prophylaxis were 10.0 days for 35-year-old reactors, 9.0 days for 50-year-old reactors, and 6.0 days for 70-year-old reactors. Costs per person for these cohorts decreased by $259, $203, and $100, respectively. The magnitude of the benefit of isoniazid prophylaxis is moderately sensitive to the effect of isoniazid on quality of life. The hypothetical provision of isoniazid prophylaxis for all low-risk reactors older than 35 years of age in the U.S. population could prevent 35,176 deaths and save $2.11 billion. CONCLUSIONS: Monitored isoniazid prophylaxis reduces mortality rates and health care costs for low-risk tuberculin reactors older than 35 years of age, although reductions for individual patients are small. For the U.S. population, however, the potential health benefits and economic savings resulting from wider use of monitored isoniazid prophylaxis are substantial. We should consider expanding current recommendations to include prophylaxis for tuberculin reactors of all ages with no contraindications.

Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A cost-effectiveness analysis.

BACKGROUND: Low-molecular-weight heparins are effective for treating venous thrombosis, but their cost-effectiveness has not been rigorously assessed. OBJECTIVE: To evaluate the cost-effectiveness of low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. DESIGN: Decision model. DATA SOURCES: Probabilities for clinical outcomes were obtained from a meta-analysis of randomized trials. Cost estimates were derived from Medicare reimbursement and other sources. TARGET POPULATION: Two hypothetical cohorts of 60-year-old men with acute deep venous thrombosis. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTION: Fixed-dose low-molecular-weight heparin or adjusted-dose unfractionated heparin. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. An in-patient hospital setting was used for the base-case analysis. Secondary analyses examined outpatient treatment with low-molecular-weight heparin. RESULTS OF BASE-CASE ANALYSIS: Total costs for inpatient treatment were $26,516 for low-molecular-weight heparin and $26,361 for unfractionated heparin. The cost of initial care was higher in patients who received low-molecular-weight heparin, but this was partly offset by reduced costs for early complications. Low-molecular-weight heparin treatment increased quality-adjusted life expectancy by approximately 0.02 years. The incremental cost-effectiveness of inpatient low-molecular-weight heparin treatment was $7820 per QALY gained. Treatment with low-molecular-weight heparin was cost saving when as few as 8% of patients were treated at home. RESULTS OF SENSITIVITY ANALYSIS: When late complications were assumed to occur 25% less frequently in patients who received unfractionated heparin, the incremental cost-effectiveness ratio increased to almost $75,000 per QALY gained. When late complications were assumed to occur 25% less frequently in patients who received low-molecular-weight heparin, this treatment resulted in a net cost savings. Inpatient low-molecular-weight heparin treatment became cost saving when its pharmacy cost was reduced by 31% or more, when it reduced the yearly incidence of late complications by at least 7%, when as few as 8% of patients were treated entirely as outpatients, or when at least 13% of patients were eligible for early discharge. CONCLUSIONS: Low-molecular-weight heparins are highly cost-effective for inpatient management of venous thrombosis. This treatment reduces costs when small numbers of patients are eligible for outpatient management.

Presentation and explanation of medical decision models using the World Wide Web.

We demonstrated the use of the World Wide Web for the presentation and explanation of a medical decision model. We put on the web a treatment model developed as part of the Cardiac Arrhythmia and Risk of Death Patient Outcomes Research Team (CARD PORT). To demonstrate the advantages of our web-based presentation, we critiqued both the conventional paper-based and the web-based formats of this decision-model presentation with reference to an accepted published guide to understanding clinical decision models. A web-based presentation provides a useful supplement to paper-based publications by allowing authors to present their model in greater detail, to link model inputs to the primary evidence, and to disseminate the model to peer investigators for critique and collaborative modeling.

Design of a modular, extensible decision support system for arrhythmia therapy.

We developed a decision-support system for evaluation of treatment alternatives for supraventricular and ventricular arrhythmias. The system uses independent decision models that evaluate the costs and benefits of treatment for recurrent atrioventricular-node reentrant tachycardia (AVNRT), and of therapies to prevent sudden cardiac death (SCD) in patients at risk for life-threatening ventricular arrhythmias. Each of the decision models is accessible through a web-based interface that enables remote users to browse the model's underlying evidence and to perform analyses of effectiveness, cost effectiveness, and sensitivity to input variables. Because the web-based interface is independent of the models, we can extend the functionality of the system by adding decision models. This system illustrates that the use of a library of web-accessible decision models provides decision support economically to widely dispersed users.