Decision Analysis in SHared decision making for Thromboprophylaxis during Pregnancy (DASH-TOP): a sequential explanatory mixed-methods pilot study.

OBJECTIVES: To gain insight into formal methods of integrating patient preferences and clinical evidence to inform treatment decisions, we explored patients' experience with a personalised decision analysis intervention, for prophylactic low-molecular-weight heparin (LMWH) in the antenatal period. DESIGN: Mixed-methods explanatory sequential pilot study. SETTING: Hospitals in Canada (n=1) and Spain (n=4 sites). Due to the COVID-19 pandemic, we conducted part of the study virtually. PARTICIPANTS: 15 individuals with a prior venous thromboembolism who were pregnant or planning pregnancy and had been referred for counselling regarding LMWH. INTERVENTION: A shared decision-making intervention that included three components: (1) direct choice exercise; (2) preference elicitation exercises and (3) personalised decision analysis. MAIN OUTCOME MEASURES: Participants completed a self-administered questionnaire to evaluate decision quality (decisional conflict, self-efficacy and satisfaction). Semistructured interviews were then conducted to explore their experience and perceptions of the decision-making process. RESULTS: Participants in the study appreciated the opportunity to use an evidence-based decision support tool that considered their personal values and preferences and reported feeling more prepared for their consultation. However, there were mixed reactions to the standard gamble and personalised treatment recommendation. Some participants could not understand how to complete the standard gamble exercises, and others highlighted the need for more informative ways of presenting results of the decision analysis. CONCLUSION: Our results highlight the challenges and opportunities for those who wish to incorporate decision analysis to support shared decision-making for clinical decisions.

Methodology for the development of antithrombotic therapy and prevention of thrombosis guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND: To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists. METHODS: Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion. RESULTS: One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance. CONCLUSIONS: AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review.(AU)

Effect of macrolides as part of initial empiric therapy on length of stay in patients hospitalized with community-acquired pneumonia.

BACKGROUND: The choice of antibiotics to treat community-acquired pneumonia (CAP) is primarily empiric, and the effect of this choice on length of stay (LOS) and mortality is largely unknown. OBJECTIVE: To examine the impact of antibiotic choice on these outcomes in general medical patients hospitalized with CAP. METHODS: One hundred patients hospitalized with CAP were prospectively identified. Seventy-six met inclusion criteria and were entered into the study. After hospital discharge, each medical chart was examined by 2 independent physicians who verified the admitting diagnosis and entered the data for antimicrobial regimens, a CAP mortality prediction tool, a social and disposition index, and other health outcomes. Patients were stratified according to the antibiotic received. Simple regression techniques were used to examine the correlation between initial therapy, specifically, ceftriaxone sodium or a macrolide, and LOS and mortality. RESULTS: Patients who received macrolides within the first 24 hours of admission had a markedly shorter LOS (2.8 days) than those not so treated (5.3 days; P = .01). This effect diminished as the interval before administering macrolides increased. Including ceftriaxone as part of the initial therapy did not appear to affect LOS. Patients given a macrolide for initial treatment did not differ significantly from those not treated in terms of mean age, mortality prediction tool score, or Social and Disposition Index score. Eleven of the 12 patients who received macrolides also received a beta-lactam antibiotic. CONCLUSION: Use of macrolides as part of an initial therapeutic regimen appears to be associated with shorter LOS.

Individualizing therapy to prevent long-term consequences of estrogen deficiency in postmenopausal women.

BACKGROUND: Alendronate sodium and raloxifene hydrochloride were recently approved for the prevention of postmenopausal osteoporosis, but data on their clinical efficacy are limited. We compared these drugs with hormone replacement therapy (HRT) to help women and physicians guide postmenopausal treatment decisions. OBJECTIVE: To help physicians understand how they can best help women choose the most beneficial therapy after menopause based on their individual risk profile. METHODS: We developed a decision analytic Markov model to compare the effects of alendronate therapy, raloxifene therapy, and HRT on risks of hip fracture, coronary heart disease (CHD), breast cancer, and life expectancy. Regression models linked individual risk factors to future disease risks and were modified by drug effects on bone density, lipid levels, and associated breast cancer effects. RESULTS: Hormone replacement therapy, alendronate therapy, and raloxifene therapy have similar predicted efficacies in preventing hip fractures (estimated relative risk, 0.57, 0.54, and 0.58, respectively). Hormone replacement therapy should be more than 10 times more effective than raloxifene therapy in preventing CHD, but raloxifene therapy may not induce breast cancer. Women at low risk for hip fracture, CHD, and breast cancer do not benefit significantly from any treatment. Among women at average risk, HRT was preferred unless raloxifene therapy could reduce the risk of breast cancer by at least 66%, compared with a 47% increase for HRT. Women at high risk for CHD benefit most from HRT; women at high risk for breast cancer but low risk for CHD benefit most from raloxifene therapy, but only if it lowers the risk of breast cancer. CONCLUSION: Because of significant differences in the impact of these drugs, treatment choice depends on an individual woman's risk for hip fracture, CHD, and breast cancer.

Cost-effectiveness of therapies for patients with nonvalvular atrial fibrillation.

BACKGROUND: The most appropriate treatment(s) for patients with atrial fibrillation remains uncertain. OBJECTIVE: To examine the cost-effectiveness of anti-thrombotic and antiarrhythmic treatment strategies for atrial fibrillation. METHODS: We performed decision and cost-effectiveness analyses using a Markov state transition model. We gathered data from the English-language literature using MEDLINE searches and bibliographies from selected articles. We obtained financial data from nationwide physician-fee references, a medical center's cost accounting system, and one of New England's larger managed care organizations. We examined strategies that included combinations of cardioversion, antiarrhythmic therapy with quinidine, sotalol hydrochloride, or amiodarone, and anticoagulant or antiplatelet therapy. RESULTS: For a 65-year-old man with nonvalvular atrial fibrillation, any intervention results in a significant gain in quality-adjusted life years (QALYs) compared with no specific therapy. Use of aspirin results in the largest incremental gain (1.2 QALYs). Cardioversion followed by the use of amiodarone and warfarin together is the most effective strategy, yielding a gain of 2.3 QALYs compared with no specific therapy. The marginal cost-effectiveness ratios of cardioversion followed by aspirin, with or without amiodarone, are $33800 per QALY and $10800 per QALY, respectively. Cardioversion followed by amiodarone and warfarin has a marginal cost-effectiveness ratio of $92400 per QALY compared with amiodarone and aspirin. Strategies that include cardioversion followed by either quinidine or sotalol are both more expensive and less effective than competing strategies. CONCLUSIONS: Cardioversion of patients with nonvalvular atrial fibrillation followed by the use of aspirin alone or with amiodarone has a reasonable marginal cost-effectiveness ratio. While cardioversion followed by the use of amiodarone and warfarin results in the greatest gain in quality-adjusted life expectancy, it is expensive (ie, has a high marginal cost-effectiveness ratio) compared with aspirin and amiodarone. Finally, for patients who are bothered little by symptoms of atrial fibrillation, cardioversion followed by either aspirin or warfarin without subsequent antiarrhythmic therapy is the treatment of choice.

Patient-specific decisions about hormone replacement therapy in postmenopausal women.

OBJECTIVE: To examine the effect of hormone replacement therapy on life expectancy in postmenopausal women with different risk profiles for heart disease, breast cancer, and hip fracture. DESIGN: Decision analysis using a Markov model. Published regression models were used to link risk factors to disease incidence and to estimate the lifetime risks of developing coronary heart disease (CHD), breast cancer, hip fracture, and endometrial cancer. The impact of hormone therapy on disease incidence was estimated from published epidemiologic studies. SETTING: Mathematical model applicable to primary care. INTERVENTIONS: Treatment with hormone replacement therapy or no hormone replacement therapy. MAIN OUTCOME MEASURE: Life expectancy. RESULTS: Hormone replacement therapy should increase life expectancy for nearly all postmenopausal women, with some gains exceeding 3 years, depending mainly on an individual's risk factors for CHD and breast cancer. For women with at least 1 risk factor for CHD, hormone therapy should extend life expectancy, even for women having first-degree relatives with breast cancer. Women without any risk factors for CHD or hip fracture, but who have 2 first-degree relatives with breast cancer, however, should not receive hormone therapy. CONCLUSIONS: The benefit of hormone replacement therapy in reducing the likelihood of developing CHD appears to outweigh the risk of breast cancer for nearly all women in whom this treatment might be considered. Our analysis supports the broader use of hormone replacement therapy.

Foot infections in diabetic patients. Decision and cost-effectiveness analyses.

OBJECTIVE: To examine the cost-effectiveness of approaches to the diagnosis and treatment of patients with type II (non-insulin-dependent) diabetes mellitus (NIDDM) who have foot infections and suspected osteomyelitis. DESIGN: Decision and cost-effectiveness analyses were performed using a Markov model. We examined the prevalence of osteomyelitis, the major complications and efficacies of long-term antibiotic therapy and surgery, and the performance characteristics of four diagnostic tests (roentgenography, technetium Tc 99m bone scanning, indium in 111-labeled white blood cell scanning, and magnetic resonance imaging). Data were drawn from the English-language literature using MEDLINE searches and bibliographies from selected articles. SETTING: Primary care. PATIENTS: Patients with NIDDM who had foot infections and suspected osteomyelitis but no signs of systemic toxicity. INTERVENTIONS: Following hospitalization for surgical débridement and intravenous antibiotic therapy: (1) treatment for presumed soft-tissue infection, (2) culture-guided empiric treatment for presumed osteomyelitis, (3) 71 combinations of diagnostic tests preceding antibiotic therapy for osteomyelitis, (4) 71 combinations of tests preceding amputation, and (5) immediate amputation. MAIN OUTCOME MEASURES: Quality-adjusted life expectancy, average costs. RESULTS: Culture-guided empiric treatment for osteomyelitis with 10 weeks of oral antibiotic therapy has similar effectiveness to testing followed by a long course of antibiotic therapy if any test result is positive. However, empiric treatment is the least expensive strategy. CONCLUSIONS: Noninvasive testing adds significant expense to the treatment of patients with NIDDM in whom pedal osteomyelitis is suspected, and such testing may result in little improvement in health outcomes. In patients without systemic toxicity, a 10-week course of culture-guided oral antibiotic therapy following surgical débridement may be as effective as and less costly than other approaches.

Screening for prostate cancer. A decision analytic view.

OBJECTIVE: To determine the clinical and economic effects of screening for prostate cancer with prostate-specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). DESIGN: Decision analytic cost-utility analysis comparing four screening strategies with a strategy of not screening. We assumed that the cancer detection rate and stage distribution were predicted by each combination of tests and that localized cancer was treated with radical prostatectomy. For each strategy, we calculated life expectancy, quality-adjusted life expectancy (QALE), and cost-utility ratios for unselected and high-prevalence populations. DATA: Probabilities and rates for clinical events were gathered from published data. We assessed utilities by the time-trade-off method using urologists, radiation oncologists, and internists as subjects. The Clinical Cost Manager at the New England Medical Center provided cost data. RESULTS: In unselected men between the ages of 50 and 70 years, screening with PSA or TRUS prolonged unadjusted life expectancy but diminished QALE. Screening with DRE alone yielded no reduction in mortality at any age. All programs increased costs. Results were sensitive only to assumptions about the efficacy of treatment. In high-prevalence populations, screening produced a similar pattern: gains in unadjusted life expectancy, losses in QALE, and increased costs. CONCLUSIONS: Our analysis does not support using PSA, TRUS, or DRE to screen asymptomatic men for prostatic cancer. Screening may result in poorer health outcomes and will increase costs dramatically. Assessment of comorbidity, risk attitude, and valuation of sexual function may identify individuals who will benefit from screening, but selecting high-prevalence populations will not improve the benefit of screening.

Management and prevention of thromboembolic events in patients with cancer-related hypercoagulable states: a risky business.

OBJECTIVE: To determine the optimal strategy for managing and preventing thromboembolic events in malignancy-associated hypercoagulable states. DESIGN: A Markov-based decision and cost-effectiveness analysis was performed. The authors explicitly considered consequences of embolic and bleeding events, filter complications, and cancer-related excess mortality. Data were drawn from the current literature. The main outcome measure for each strategy was the quality-adjusted life expectancy and the total average variable costs. SUBJECTS: Patients with advanced malignancies prone to develop thromboembolic events, patients with acute proximal deep venous thrombosis (DVT), and patients who have survived a first episode of pulmonary embolism (PE). INTERVENTIONS: The authors considered three different interventions: 1) OBSERVATION, in which neither anticoagulant therapy nor filter placement is pursued, 2) ANTICOAGULATION, in which long-term anticoagulant therapy is started immediately, and 3) VENA CAVAL FILTER. MAIN RESULTS: Vena caval filter was the preferred strategy for every malignancy studied, yielding an 11% gain in quality-adjusted life expectancy, compared with observation, for patients with acute DVT, and an 18% gain for patients having survived a PE. Anticoagulant therapy yielded gains of 9% and 16%, respectively. Compared with anticoagulant therapy, filter was less costly due to the avoidance of additional expenses incurred by bleeding events. Prophylactic therapy was the least effective of the three strategies examined. CONCLUSIONS: Vena caval filter placement and long-term anticoagulation therapy yield similar outcomes in the setting of cancer-related hypercoagulable states. However, filter insertion is less expensive than anticoagulation. Given the short life expectancy and morbidity of patients with end-stage malignancy, patient preferences for health states must be considered in the decision-making process. If active treatment is pursued, vena caval filter should be used as a primary therapy. Prophylactic therapy is not warranted in any circumstance.

Effect of laboratory variation in the prothrombin-time ratio on the results of oral anticoagulant therapy.

BACKGROUND: Patients receiving long-term anticoagulant therapy may be subject to unnecessary risks of bleeding or thromboembolism because of variability in the commercial thromboplastins used to determine prothrombin time and consequent uncertainty about the actual intensity of anticoagulation. METHODS: We explored the effect of this uncertainty on the benefits and risks of anticoagulation in patients with prosthetic heart valves, using models of thromboembolic and hemorrhagic complications as a function of the intensity of anticoagulation, with quality-adjusted life expectancy and average variable costs used to describe outcomes. RESULTS: Anticoagulation provides a striking benefit for patients whose treatment is conducted within the recommended range of the international normalized ratio (INR)--i.e., 2.5 to 3.5--but if uncertainty about the laboratory results causes the intensity of anticoagulation to fall outside this range, the gain becomes smaller. Uncertainty about the true intensity of anticoagulation may reduce the potential gain in life expectancy, adjusted for quality of life, by more than half and may increase the ratio of costs to effectiveness to almost five times the optimal value. Variability in the intensity of anticoagulation is even greater if older recommendations advocating a higher level of anticoagulation are followed. CONCLUSIONS: Uncertainty about the sensitivities of the commercially available thromboplastins used in the United States can have important clinical and economic effects. This problem could be eliminated if clinical laboratories uniformly reported the intensity of anticoagulation as the INR, by adjusting prothrombin-time ratios for variability in thromboplastins.