Cost-effectiveness of molecular diagnostic assays for the therapy of severe sepsis and septic shock in the emergency department.

OBJECTIVES: Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED. METHODS: We developed a decision analysis model with primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients' length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described. Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed. RESULTS: Under baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER -$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity≥52%, panel efficiency≥39%, and assay cost≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained≤$20,000/death averted for every studied sensitivity (i.e. 0.5-0.95), panel efficiency≥34%, and assay cost≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was≤$135 and the panel efficiency was≥77%. CONCLUSIONS: The incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios.

Cost-effectiveness of rapid diagnostic assays that perform directly on blood samples for the diagnosis of septic shock.

Molecular diagnostic assays that test directly whole blood provide the ability to decrease inappropriate antimicrobial therapy and improve survival in patients with septic shock. We developed a decision analysis model to evaluate the cost-effectiveness of the addition of molecular assays to blood cultures in adults admitted to medical ICUs with septic shock. Under baseline assumptions, the use of molecular diagnostic methods was cost-saving in all cases that the length of hospital stay differed by 2 and 4 days between patients receiving appropriate and inappropriate antimicrobial therapy. In the case that the length of stay was the same, the use of molecular methods was cost-effective with an estimated incremental cost-effectiveness ratio (ICER) < $3000 per death averted. In the extreme that the length of stay between the 2 groups was the same, the highest cost reached was when the cost of the assay was $1000, with the estimated ICER being < $20,000 per death averted.

Use of T2MR in invasive candidiasis with and without candidemia.

The mortality associated with invasive candidiasis remains unacceptably high. The T2 magnetic resonance (T2MR) assay is a novel US FDA-approved molecular diagnostic assay for the diagnosis of candidemia that can rapidly detect the five most commonly isolated Candida spp. In clinical trials, T2MR has exhibited good clinical sensitivity and specificity. Potential benefits from the adoption of T2MR technology in the diagnostic and therapeutic algorithms for invasive candidiasis can arise from timely diagnosis of disease, increased case detection, tailored therapy and decrease in empiric antifungal treatment. As everyday clinical experience with the assay is evolving, we discuss the utility of T2MR in invasive candidiasis with and without candidemia based on the currently available evidence regarding its performance.

Discrepancy between financial disclosures of authors of clinical practice guidelines and reports by industry.

There is a substantial effort to increase the accuracy of conflicts of interest (COI) reporting, and reduce the influence of COI between physicians and industry, especially as it relates to clinical practice guidelines.We used the newly implemented Open Payments dataset to evaluate the accuracy of COI disclosures of authors of clinical practice guidelines that were either newly published or revised within 2014 and were included in the National Guideline Clearinghouse (NGC) website (maintained by the U.S. Department of Health and Human Services). Authors were considered as having inaccurate COI disclosure if they had not reported all companies from which they had received funds >$5000 in the 12 months preceding the guideline's publication.We identified 223 guidelines that were either newly published (109/223; 48.9%) or revised (114/223; 51.1%) within 2014 and were included in the NGC website. Among the 1329 guideline authors with available Open Payments data, 523 received >$5000 from at least 1 healthcare-associated entity. However, only 56 out of the 523 authors (10.7%) were found to have accurate COI disclosure. The percentage of authors with accurate COI disclosure in revised guidelines was significantly lower than in newly published guidelines (6.8% vs 14.3%; P < 0.01) and was also found to differ between specialties. Furthermore, authors were less likely to inaccurately disclose "research payments" (37/49, 75.5%) compared to "general payments" (488/559, 87.3%, P = 0.02) as well as "other/associated research funding" (430/506, 85.0%, P = 0.08). No statistically significant association was detected between funding amount and disclosure accuracy.The majority of guideline authors lacked significant COIs, but among authors that received significant funds from at least 1 healthcare-associated entity the frequency of accurate disclosure was low. These findings indicate that the current process of disclosing COIs may be suboptimal and a proactive approach should be adopted in order to minimize COI reporting discrepancies. Furthermore, every effort should be undertaken to ensure the completeness and accuracy of the data recorded in the Open Payments database.

Prevalence and impact of Clostridium difficile infection in elderly residents of long-term care facilities, 2011: A nationwide study.

The elderly population is particularly vulnerable to Clostridium difficile infection (CDI), but the epidemiology of CDI in long-term care facilities (LTCFs) is unknown.We performed a retrospective cohort study and used US 2011 LTCF resident data from the Minimum Data Set 3.0 linked to Medicare claims. We extracted CDI cases based on International Classification of Diseases-9 coding, and compared residents with the diagnosis of CDI to those who did not have a CDI diagnosis during their LTCF stay. We estimated CDI prevalence rates and calculated 3-month mortality rates.The study population consisted of 2,190,613 admissions (median age 82 years; interquartile range 76-88; female to male ratio 2:1; >80% whites), 45,500 of whom had a CDI diagnosis. The nationwide CDI prevalence rate was 1.85 per 100 LTCF admissions (95% confidence interval [CI] 1.83-1.87). The CDI rate was lower in the South (1.54%; 95% CI 1.51-1.57) and higher in the Northeast (2.29%; 95% CI 2.25-2.33). Older age, white race, presence of a feeding tube, unhealed pressure ulcers, end-stage renal disease, cirrhosis, bowel incontinence, prior tracheostomy, chemotherapy, and chronic obstructive pulmonary disease were independently related to "high risk" for CDI. Residents with a CDI diagnosis were more likely to be admitted to an acute care hospital (40% vs 31%, P < 0.001) and less likely to be discharged to the community (46% vs 54%, P < 0.001) than those not reported with CDI during stay. Importantly, CDI was associated with higher mortality (24.7% vs 18.1%, P = 0.001).CDI is common among the elderly residents of LTCFs and is associated with significant increase in 3-month mortality. The prevalence is higher in the Northeast and risk stratification can be used in CDI prevention policies.

Adaptation of Cost Analysis Studies in Practice Guidelines.

Clinical guidelines play a central role in day-to-day practice. We assessed the degree of incorporation of cost analyses to guidelines and identified modifiable characteristics that could affect the level of incorporation.We selected the 100 most cited guidelines listed on the National Guideline Clearinghouse (http://www.guideline.gov) and determined the number of guidelines that used cost analyses in their reasoning and the overall percentage of incorporation of relevant cost analyses available in PubMed. Differences between medical specialties were also studied. Then, we performed a case-control study using incorporated and not incorporated cost analyses after 1:1 matching by study subject and compared them by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement requirements and other criteria.We found that 57% of guidelines do not use any cost justification. Guidelines incorporate a weighted average of 6.0% (95% confidence interval [CI] 4.3-7.9) among 3396 available cost analyses, with cardiology and infectious diseases guidelines incorporating 10.8% (95% CI 5.3-18.1) and 9.9% (95% CI 3.9- 18.2), respectively, and hematology/oncology and urology guidelines incorporating 4.5% (95% CI 1.6-8.6) and 1.6% (95% CI 0.4-3.5), respectively. Based on the CHEERS requirements, the mean number of items reported by the 148 incorporated cost analyses was 18.6 (SD = 3.7), a small but significant difference over controls (17.8 items; P = 0.02). Included analyses were also more likely to directly relate cost reductions to healthcare outcomes (92.6% vs 81.1%, P = 0.004) and declare the funding source (72.3% vs 53.4%, P < 0.001), while similar number of cases and controls reported a noncommercial funding source (71% vs 72.7%; P = 0.8).Guidelines remain an underused mechanism for the cost-effective allocation of available resources and a minority of practice guidelines incorporates cost analyses utilizing only 6% of the available cost analyses. Fulfilling the CHEERS requirements, directly relating costs with healthcare outcomes and transparently declaring the funding source seem to be valued by guideline-writing committees.

Methicillin-resistant Staphylococcus aureus prevention strategies in the ICU: a clinical decision analysis*.

OBJECTIVES: ICUs are a major reservoir of methicillin-resistant Staphylococcus aureus. Our aim was to estimate costs and effectiveness of methicillin-resistant Staphylococcus aureus prevention policies. DESIGN AND INTERVENTIONS: We evaluated three up-to-date methicillin-resistant Staphylococcus aureus prevention policies, namely, 1) nasal screening and contact precautions of methicillin-resistant Staphylococcus aureus-positive patients; 2) nasal screening, contact precautions, and decolonization (targeted decolonization) of methicillin-resistant Staphylococcus aureus carriers; and 3) universal decolonization without screening. We implemented a decision-analytic model with deterministic and probabilistic analyses. Methicillin-resistant Staphylococcus aureus infections averted, quality-adjusted life years gained, and incremental cost-effectiveness ratios were calculated. Cost-effectiveness planes and acceptability curves were plotted for various willingness-to-pay thresholds to address uncertainty. MEASUREMENTS AND MAIN RESULTS: At base-case scenario, universal decolonization was the dominant strategy; it averted 1.31% and 1.59% of methicillin-resistant Staphylococcus aureus infections over targeted decolonization and screening and contact precautions, respectively, and saved $16,203/quality-adjusted life year over targeted decolonization and 14,562/quality-adjusted life year over screening and contact precautions. Results were robust in sensitivity analysis for a wide range of input variables. In probabilistic analysis, universal decolonization increased quality-adjusted life years by 1.06% (95% CI, 1.02-1.09) over targeted decolonization and by 1.29% (95% CI, 1.24-1.33) over screening and contact precautions; universal decolonization resulted in average savings of $172 (95% CI, $168-$175) and $189 (95% CI, $185-$193) over targeted decolonization and screening and contact precautions, respectively. With willingness-to-pay threshold per quality-adjusted life year gained ranging from $0 to $50,000, universal decolonization was dominant over targeted decolonization in 67.5-75.4% and dominant over screening and contact precautions in 66.0-75.4%. CONCLUSIONS: In the ICU setting, universal decolonization outperforms the other two strategies and is likely to be cost-effective even at low willingness-to-pay thresholds. Assuming 700 annual ICU admissions in an average 12-bed ICU, the projected annual savings reach $129,500 to $135,100.