Public interest trends for COVID-19 and pandemic trajectory: A time-series analysis of US state-level data.

Google Trends provides spatiotemporal data for user-specific terms scaled from less than 1 (lowest relative popularity) to 100 (highest relative popularity) as a proxy for the public interest. Here we use US state-level data for COVID-19 to examine popularity trends during the pandemic evolution. We used "coronavirus" and "covid" search terms and set the period up from January 1st, 2020, to November 12, 2022. We measured the agreement on web rankings between states using the nonparametric Kendall's W (0 for no concordance to 1 for perfect agreement). We compiled state-level weekly data on COVID-19 incidence and mortality and scaled state curves from 0 to 100 through a min-max normalization process. We used a dynamic time-warping algorithm to calculate similarities between the popularity, mortality, and incidence of COVID-19. The methodology is a pattern recognition process between time series by distance optimization. The similarity was mapped from 0 to 1, with 1 indicating perfect similarity and 0 indicating no similarity. The peak in popularity was in March 2020, succeeded by a decline and a prolonged period of fluctuation around 20%. Public interest rose briefly at the end of 2021, to fall to a low activity of around 10%. This pattern was remarkably consistent across states (Kendal's W 0.94, p < 0.001). Web search trends were an impression of contagion growth: Overall, popularity-mortality trajectories yielded higher similarity indices (median 0.78; interquartile range 0.75-0.82) compared to popularity-incidence trajectories (median 0.74; interquartile range 0.72-0.76, Wilcoxon's exact p<0.001). The popularity-mortality trajectories had a very strong similarity (>0.80) in 19/51 (37%) regions, as opposed to only 4/51 (8%) for popularity-incidence trajectories. State-level data show a fading public concern about COVID-19, and web-search popularity patterns may reflect the COVID-19 trajectory in terms of cases and mortality.

Early Fluvoxamine Reduces the Risk for Clinical Deterioration in Symptomatic Outpatients with COVID-19: A Real-World, Retrospective, before-after Analysis.

Fluvoxamine, a selective serotonin reuptake inhibitor with anti-inflammatory properties, has gained attention as a repurposed drug to treat COVID-19. We aimed to explore the potential benefit of fluvoxamine on outpatients with early SARS-CoV-2 infection. We performed a retrospective study of fluvoxamine adult outpatients with symptomatic COVID-19 disease of early onset (<5 days), in the context of an infectious diseases private practice, between September-December 2021, in Greece. Patients with disease duration ≥5 days, dyspnea and/or hypoxemia with oxygen saturation <94% in room air and pregnancy were excluded from the analysis. In total, 103 patients, 54 males/49 females with a median age of 47 years (39-56), were included in this study. Patient characteristics were balanced before and after the introduction of fluvoxamine. Two patients in the fluvoxamine arm (3.8%; 95% CI 0.4-13) had clinical deterioration compared to 8 patients in the standard of care group (16%; 95% CI 7.2-29.1, p < 0.04). After controlling for age, sex, body mass index > 30 and vaccination status, fluvoxamine was independently associated with a lower risk of clinical deterioration (adj. OR 0.12; 95% CI 0.02-0.70, p < 0.02). Adding on fluvoxamine to treatment for early symptomatic COVID-19 patients may protect them from clinical deterioration and hospitalization, and it is an appealing low-cost, low-toxicity option in the community setting and warrants further investigation.

Public interest trends for Covid-19 and alignment with the disease trajectory: A time-series analysis of national-level data.

Data from web search engines have become a valuable adjunct in epidemiology and public health, specifically during epidemics. We aimed to explore the concordance of web search popularity for Covid-19 across 6 Western nations (United Kingdom, United States, France, Italy, Spain and Germany) and how timeline changes align with the pandemic waves, Covid-19 mortality, and incident case trajectories. We used the Google Trends tool for web-search popularity, and "Our World in Data" on Covid-19 reported cases, deaths, and administrative responses (measured by stringency index) to analyze country-level data. The Google Trends tool provides spatiotemporal data, scaled to a range of <1 (lowest relative popularity) to 100 (highest relative popularity), for the selected search terms, timeframe, and region. We used "coronavirus" and "covid" as search terms and set the timeframe up to November 12, 2022. We obtained multiple consecutive samples using the same terms to validate against sampling bias. We consolidated national-level incident cases and deaths weekly and transformed them to a range between 0 to 100 through the min-max normalization algorithm. We calculated the concordance of relative popularity rankings between regions, using the non-parametric Kendall's W, which maps concordance between 0 (lack of agreement) to 1 (perfect match). We used a dynamic time-warping algorithm to explore the similarity between Covid-19 relative popularity, mortality, and incident case trajectories. This methodology can recognize the similarity of shapes between time-series through a distance optimization process. The peak popularity was recorded on March 2020, to be followed by a decline below 20% in the subsequent three months and a long-standing period of variation around that level. At the end of 2021, public interest spiked shortly to fade away to a low level of around 10%. This pattern was highly concordant across the six regions (Kendal's W 0.88, p< .001). In dynamic time warping analysis, national-level public interest yielded a high similarity with the Covid-19 mortality trajectory (Similarity indices range 0.60-0.79). Instead, public interest was less similar with incident cases (0.50-0.76) and stringency index trajectories (0.33-0.64). We demonstrated that public interest is better intertwined with population mortality, rather than incident case trajectory and administrative responses. As the public interest in Covid-19 gradually subsides, these observations could help predict future public interest in pandemic events.

Economic Analysis of Infectious Disease Consultation for Staphylococcus aureus Bacteremia Among Hospitalized Patients.

Importance: Staphylococcus aureus bacteremia is associated with a significant burden of mortality, morbidity, and health care costs. Infectious disease consultation may be associated with reduced mortality and bacteremia recurrence rates. Objective: To evaluate the cost-effectiveness of infectious disease consultation for Staphylococcus aureus bacteremia. Design, Setting, and Participants: In this economic evaluation, a decision-analytic model was constructed comparing infectious disease consult with no consult. The population was adult hospital inpatients with Staphylococcus aureus bacteremia diagnosed with at least 1 positive blood culture. Cost-effectiveness was calculated as deaths averted and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Costs and outcomes were calculated for a time horizon of 6 months. The analysis was performed from a societal perspective and included studies that had been published by January 2022. Interventions: Patients received or did not receive formal bedside consultation after positive blood cultures for Staphylococcus aureus bacteremia. Main Outcomes and Measures: The main outcomes were incremental difference in effectiveness (survival probabilities), incremental difference in cost (US dollars) and incremental cost-effectiveness ratios (US dollars/deaths averted). Results: This model included 1708 patients who received consultation and 1273 patients who did not. In the base-case analysis, the cost associated with the infectious disease consult strategy was $54 137.4 and the associated probability of survival was 0.77. For the no consult strategy, the cost was $57 051.2, and the probability of survival was 0.72. The incremental difference in cost between strategies was $2913.8, and the incremental difference in effectiveness was 0.05. Overall, consultation was associated with estimated savings of $55 613.4/death averted (incremental cost-effectiveness ratio, -$55613.4/death averted). In the probabilistic analysis, at a willingness-to-pay threshold of $50 000, infectious disease consult was cost-effective compared with no consult in 54% of 10 000 simulations. In cost-effectiveness acceptability curves, the consult strategy was cost-effective in 58% to 73%) of simulations compared with no consult for a willingness-to-pay threshold ranging from $0 to $150 000. Conclusions and Relevance: These findings suggest that infectious disease consultation may be a cost-effective strategy for management of Staphylococcus aureus bacteremia and that it is associated with health care cost-savings.

Comparative Analysis of Mortality From Coronavirus Disease 2019 Across the European Union Countries and the Effects of Vaccine Coverage.

BACKGROUND: Mortality is a critical measure of disease impact. The European Union (EU) countries share the same regulatory framework but different implementation policies. METHODS: We extracted cumulative COVID-19 mortality data across the EU countries. We evaluated the 27 member states using the location quotient (LQ) to adjust for the expected mortality in the whole EU region, where an LQ <1 signifies a more and an LQ >1 a less favorable outcome. We categorized EU members into 3 distinct profiles based on their LQ estimates: favorable profile, LQ ≤0.9; unfavorable profile, LQ >1.10; and average profile, LQ between 0.9 and 1.10. We compared LQ estimates and profiles with the prevaccination era that ended in December 2020 with the COVID-19 vaccine rollout. RESULTS: Twelve member states had a favorable profile, 4 had an average profile, and 11 had an unfavorable profile. In quantitative analysis, an improvement (negative LQ difference) was noted across countries with higher vaccination coverage (median, 71% fully vaccinated vs 57% for countries with positive LQ differences). There was a significant negative association between the share of fully vaccinated and LQ changes (ρ = -0.62, P < .001) and a significant 4-month lag effect. After COVID-19 vaccines became available, 4 countries improved their profile and 5 moved to a worse profile. CONCLUSIONS: There is significant variability in mortality and impact of COVID-19 between countries, even if they share the same regulatory framework. Extending immunization coverage may lead the transition to a more favorable profile, and alter the trajectory of COVID-19 mortality.

The Cost-effectiveness of Cefazolin Compared With Antistaphylococcal Penicillins for the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia.

BACKGROUND: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is associated with significant morbidity, mortality, and hospitalization costs. Cefazolin and antistaphylococcal penicillins (ASPs), such as nafcillin, are the preferred treatments for MSSA bacteremia. The aim of this study was to compare the cost-effectiveness of each approach. METHODS: We constructed a decision-analytic model comparing the use of cefazolin with ASPs for the treatment of MSSA bacteremia. Cost-effectiveness was determined by calculating deaths averted and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. RESULTS: In the base-case analysis, the cost associated with the cefazolin strategy was $38 863.1, and the associated probability of survival was 0.91. For the ASP strategy, the cost was $48 578.8, and the probability of survival was 0.81. The incremental difference in cost between the 2 strategies was $9715.7, with hospital length of stay being the main driver of cost, and the incremental difference in effectiveness was 0.10. Overall, cefazolin results in savings of $97 156.8 per death averted (ICER, $-97 156.8/death averted). In the probabilistic analysis, at a willingness-to-pay of $50 000, cefazolin had a 68% chance of being cost-effective compared with ASPs. In cost-effectiveness acceptability curves, the cefazolin strategy was cost-effective in 73.5%-81.8% of simulations compared with ASP for a willingness-to-pay ranging up to $50 000. CONCLUSIONS: The use of cefazolin is a cost-effective strategy for the treatment of MSSA bacteremia and, when clinically appropriate, this strategy results in considerable health care cost-savings.

How Should Economic Analyses Inform Nosocomial Infection Control?

Nosocomial infections are public health threats with often grave human costs. Because implementing screening and best outbreak response practices is costly for health care organizations, allocating resources for interventions requires consensus among stakeholders with a plurality of perspectives about how to weigh prospective interventions' risks and benefits. Economic analysis can facilitate decision making but is relatively new in nosocomial infection prevention and control. This article describes features of and reasons for economic analysis in this specific area and focuses on emerging challenges in antimicrobial stewardship.

Medicare Part D Spending on Drugs Prescribed by Oncologists: Temporal Trends and Regional Variation.

PURPOSE: Drug cost is a significant factor in the ever-increasing expenditures for cancer health care. METHODS: We used Medicare Part D administrative data to explore prescribing patterns and attributed drug costs of oncologists from 2013 to 2017. We highlighted regional variation in spending and potential associations. We used the location quotient (LQ) to measure the relative concentration of oncologists compared with the national average by hospital referral regions. Costs were reported in 2017 US dollars (inflation adjusted) for cross-year comparisons. RESULTS: Oncology's share in Part D spending showed an uninterrupted increasing trend. In 2017, oncologists prescribed medicines with $12.8 billion in Part D costs (8.3% of all Part D payments), which exceeded 2013 costs by $7.3 billion, when their claim payments were $5.5 billion (5.0% of all Part D payments). Oncology contributed a higher annual growth in Part D drug costs compared with all other providers (15.1% and 3.1%, respectively, for 2017). The top 3 drugs increased cost by approximately $3.5 billion from 2013 to 2017. Across hospital referral regions, the oncologists' Part D share varied (median in 2017, 7.7%; interquartile range, 6.2%-9.3%) and was higher across regions where oncologists had an LQ significantly > 1 (mostly in areas with centers that excel in cancer care) and lower for an LQ significantly < 1 (median, 9.7% v 6.2%, respectively; P < .001). CONCLUSION: Oncology increased its share in Part D drug spending, disproportionately to all other providers, with regional differences partially moderated by the oncology workforce and quality of cancer care.

Spatial association patterns between post-acute care services and acute care facilities in the United States.

BACKGROUND: There is increasing demand for post-acute care services, which is amplified by the COVID-19 pandemic. AIMS: We studied the pattern of spatial association between post-acute care services and acute care facilities and evaluated how geographic variability could influence their use. METHODS: We compiled data on CMS-certified acute care and critical access hospitals and post-acute health care services (nursing homes, home health care services, inpatient rehabilitation facilities, long-term care hospitals, and hospice facilities). We used the colocation quotient (CLQ) to measure the magnitude and direction of association (clustering or segregation) between post-acute care providers and hospitals. This metric allows pairwise comparison of categorical data; a value <1 indicates spatial segregation and a value >1 spatial clustering. Unity marks the lack of spatial dependence (random distribution). RESULTS: With the exception of nursing homes (CLQ 1.26), all other types of post-acute care providers are spatially segregated from rural critical access hospitals. Long-term care facilities ranked first (had the lowest global CLQ, 0.06), hospice facilities ranked last (had the highest global CLQ estimate, 0.54). Instead, post-acute care services either clustered with (inpatient rehabilitation 2.76, long-term care 2.10, nursing homes 1.37) or were only weakly segregated (home health care 0.86) from acute care hospitals. Home health care (1.44), hospice services (1.46), and nursing homes (1.08) spatially clustered with the same category of services. Results were robust in the sensitivity analysis and we provided illustrative examples of local variation for the states of MA and IA. CONCLUSION: Post-acute care services are isolated from critical access hospitals, and have a clustering pattern with the same category services and acute care hospitals. Such misdistribution of resources may result in both underuse and a substitution effect on the type of post-acute care between rural and urban areas and undermine public health during increasing demand, such as the COVID-19 pandemic.

Web search popularity, publicity, and utilization of direct oral anticoagulants in the United States, 2008-2018: A STROBE-compliant study.

We aimed to study the changing popularity of oral anticoagulants and the potential association between media coverage and real-world utilization practice, using time series analysis.In this STROBE-compliant study, we used Google Trends data to study public interest for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, and edoxaban) and warfarin in the United States (10-year coverage, beginning July 1st, 2008 ending June 30th, 2018). We validated our findings on a sample of 50 consecutive datasets (accumulated between July 6th, 2018 and October 19th, 2018), using the same search criteria. We used the LexisNexis Academic database to quantify monthly media coverage for DOACs and explored its association with interest by the public, using the cross-correlation coefficient function. Finally, we studied the association between public interest and real-world utilization data, including published US-wide data on ambulatory anticoagulation visits.The approval of dabigatran in 2010 marked an increasing public interest for DOACs. Dabigatran exhibited a steep rise early after Food and Drug Administration approval that peaks in 2011, to be surpassed sequentially by rivaroxaban (2012) and apixaban (2014). Apixaban has outperformed its competitors in popularity since mid-2017, and, by the end of the observation period, was close to warfarin that is on first place. Media coverage was low before approval of the first oral DOAC (dabigatran), increased thereafter (median 13 news articles per month vs 64, P < .001), with peaks on the approval dates (81 vs 48, P = .003). Media coverage had a weak immediate impact on DOACs public interest and public interest patterns preceded changes in ambulatory anticoagulation visits by up to 5 months.For a long-run observation period, a single Google Trends search will suffice to produce robust estimations of the relative popularity between treatment options, such as oral anticoagulants. Media coverage has limited immediate impact and relative public interest is a potential lead indicator of changes in actual utilization.

The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients: A decision analytic model.

PURPOSE: Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. METHODS: A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. RESULTS: The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. DISCUSSION: Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

The Cost-Effectiveness of Corticosteroids for the Treatment of Community-Acquired Pneumonia.

BACKGROUND: The use of corticosteroids as adjunct treatment for community-acquired pneumonia (CAP) is associated with potential clinical benefits. The aim of this study was to evaluate the cost-effectiveness of this approach. METHODS: We constructed a decision-analytic model comparing the use of corticosteroids + antibiotics with that of placebo + antibiotics for the treatment of CAP. Cost-effectiveness was determined by calculating deaths averted and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. RESULTS: In the base-case analysis, corticosteroids + antibiotics resulted in savings of $142,795 per death averted. In the probabilistic analysis, at a willingness to pay of $50,000, corticosteroids + antibiotics had a 86.4% chance of being cost-effective compared with placebo + antibiotics. In cost-effectiveness acceptability curves, the corticosteroids + antibiotics strategy was cost-effective in 87.6% to 94.3% of simulations compared with the placebo + antibiotics strategy for a willingness to pay ranging from $0 to $50,000. In patients with severe CAP (Pneumonia Severity Index classes IV/V) the corticosteroids + antibiotics strategy resulted in savings of $70,587 and had a 82.6% chance of being cost-effective compared with the placebo + antibiotics strategy. CONCLUSIONS: The use of corticosteroids + antibiotics is a cost-effective strategy and results in considerable health care cost-savings, especially among patients with severe CAP (Pneumonia Severity Index classes IV/V).

The Cost-effectiveness of Antimicrobial Lock Solutions for the Prevention of Central Line-Associated Bloodstream Infections.

Background: Antimicrobial lock solutions are a low-cost strategy that can reduce the incidence of central line-associated bloodstream infection (CLABSI). The aim of this study was to evaluate the cost-effectiveness of antimicrobial locks for the prevention of CLABSI. Methods: We constructed a decision-analytic model comparing antimicrobial lock solutions to heparin locks for the prevention of CLABSI in 3 settings: hemodialysis, cancer treatment, and home parenteral nutrition. Cost-effectiveness was determined by calculating CLABSIs prevented and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Results: In probabilistic analysis, at a willingness to pay of $50000, antimicrobial lock solutions had a 96.24% chance of being cost-effective, compared with heparin locks in the hemodialysis setting, an 88.00% chance in the cancer treatment setting, and a 92.73% chance in the home parenteral nutrition setting. In base-case analysis, antimicrobial lock solutions resulted in savings of $68721.03 for the hemodialysis setting, $85061.41 for the cancer setting, and $78513.83 for the home parenteral nutrition setting per CLABSI episode prevented. Conclusions: In 3 distinct and clinically important settings (hemodialysis, cancer treatment, and home parenteral nutrition), antimicrobial lock solutions are an effective strategy for the prevention of CLABSI, and their use can result in significant healthcare savings.

The Cost-Effectiveness of Rapid Diagnostic Testing for the Diagnosis of Bloodstream Infections with or without Antimicrobial Stewardship.

Bloodstream infections are associated with considerable morbidity and health care costs. Molecular rapid diagnostic tests (mRDTs) are a promising complement to conventional laboratory methods for the diagnosis of bloodstream infections and may reduce the time to effective therapy among patients with bloodstream infections. The concurrent implementation of antimicrobial stewardship programs (ASPs) may reinforce these benefits. The aim of this study was to evaluate the cost-effectivenesses of competing strategies for the diagnosis of bloodstream infection alone or combined with an ASP. To this effect, we constructed a decision-analytic model comparing 12 strategies for the diagnosis of bloodstream infection. The main arms compared the use of mRDT and conventional laboratory methods with or without an ASP. The baseline strategy used as the standard was the use of conventional laboratory methods without an ASP, and our decision-analytic model assessed the cost-effectivenesses of 5 principal strategies: mRDT (with and without an ASP), mRDT with an ASP, mRDT without an ASP, conventional laboratory methods with an ASP, and conventional laboratory methods without an ASP. Furthermore, based on the availability of data in the literature, we assessed the cost-effectivenesses of 7 mRDT subcategories, as follows: PCR with an ASP, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis with an ASP, peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with an ASP, a blood culture nanotechnology microarray system for Gram-negative bacteria (BC-GP) with an ASP, a blood culture nanotechnology microarray system for Gram-positive bacteria (BC-GN) with an ASP, PCR without an ASP, and PNA-FISH without an ASP. Our patient population consisted of adult inpatients in U.S. hospitals with suspected bloodstream infection. The time horizon of the model was the projected life expectancy of the patients. In a base-case analysis, cost-effectiveness was determined by calculating the numbers of bloodstream infection deaths averted, the numbers of quality-adjusted life years gained, and incremental cost-effectiveness ratios (ICERs). In a probabilistic analysis, uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. In the base-case analysis, MALDI-TOF analysis with an ASP was the most cost-effective strategy, resulting in savings of $29,205 per quality-adjusted life year and preventing 1 death per 14 patients with suspected bloodstream infection tested compared to conventional laboratory methods without an ASP (ICER, -$29,205/quality-adjusted life year). BC-GN with an ASP (ICER, -$23,587/quality-adjusted life year), PCR with an ASP (ICER, -$19,833/quality-adjusted life year), and PCR without an ASP (ICER, -$21,039/quality-adjusted life year) were other cost-effective options. In the probabilistic analysis, mRDT was dominant and cost-effective in 85.1% of simulations. Importantly, mRDT with an ASP had an 80.0% chance of being cost-effective, while mRDT without an ASP had only a 41.1% chance. In conclusion, our findings suggest that mRDTs are cost-effective for the diagnosis of patients with suspected bloodstream infection and can reduce health care expenditures. Notably, the combination of mRDT and an ASP can result in substantial health care savings.

Medicare part D prescribing for direct oral anticoagulants in the United States: Cost, use and the "rubber effect".

INTRODUCTION: Direct oral anticoagulants (DOAC) have gained an increased share over warfarin for prevention and treatment of thromboembolic disease. We studied DOAC adoption across providers and medical specialties. METHODS: Retrospective, cross-sectional analysis of Medicare Part D public use files (PUF), 2013 to 2015. We summarized prescription data for claims and drug payment, stratified by drug class, specialty and calendar year. We treated DOAC claims as a count outcome and explored patterns of expansion across prescribers via a truncated negative binomial regression. We described dispersion and spread in DOAC prescribing, across hospital referral regions (HRRs), including the p90/p10 ratios, and the median absolute deviation from the median. RESULTS: In 2015 part D PUF, oral anticoagulant claims have climbed to approximately 24.4 million with a payment cost of approximately $3.3 billion. DOAC claims comprised 31.0% of oral anticoagulant claims, showing a relative increase of approximately 127% compared to 2013. The upper decile of prescribers accounted for half of the oral anticoagulant prescriptions and the resulting cost. The median cost per DOAC claim in 2015 was $367.4 (interquartile range 323.9 to 445.9), as opposed to $12.3 (interquartile range 9.2 to 16.5) for warfarin. The median cost per standardized (30-day supply) prescription was $317.0 (interquartile range 303.8 to 324.3) and $8.0 (6.7 to 9.8) for DOACs and warfarin, respectively. DOAC adoption differs by specialty. Cardiologists, cardiac electrophysiologists and orthopedics had the highest predicted DOAC share per 100 claims (53.8, 72.9 and 71.5, respectively in 2015); nephrologists, family practitioners and geriatricians the lowest (22.3, 21.5 and 20.7, respectively in 2015). The p90/p10 ratio and the median absolute deviation from the median varied across HRRs and correlated positively with the prevalence of stroke and atrial fibrillation in the Medicare population. CONCLUSIONS: DOACs have been increasing their share year-over-year, but adoption varies across specialties. In prevalent areas for stroke and atrial fibrillation, prescription dispersion magnifies, and this may signify a rapid adoption by top providers.

Systemic activation of NLRP3 inflammasome in patients with severe primary Sjögren's syndrome fueled by inflammagenic DNA accumulations.

Sjögren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes. For this purpose, we evaluated sera, PBMC, circulating monocytes and salivary glands (SG) from different SS patient subgroups and controls. We found that SS patients at high risk for lymphoma and those with established lymphoma display high serum cf-DNA levels, substantial extranuclear DNA accumulations in PBMC and SG tissues, a unique NLRP3 inflammasome gene signature in PBMC, and significantly increased serum IL-18 and ASC levels. In these patients, the circulating monocytes manifested NLRP3 inflammasome activation and increased response to NLRP3 stimuli, whereas SG-infiltrating macrophages exhibited signs of NLRP3 activation and pyroptosis. Cell-free nucleic acids isolated from patients' sera competently primed the activation of both NLRP3 and AIM2 inflammasomes in healthy monocytes. SS patients also manifested diminished DNaseI activity in serum and DNaseII expression in PBMC, which inversely correlated with indices of inflammasome activation. DNaseII gene-silencing in healthy monocytes led to cytoplasmic DNA deposition and activation of inflammasome-related genes and of caspase1. Our data reveal the occurrence of systemic NLRP3 inflammasome activation in severe SS, which is associated with widespread extranuclear accumulations of inflammagenic DNA and impaired DNA degradation. These findings can provide novel biomarkers and new therapeutic targets for the management of SS patients with adverse outcomes.

Thermal ablation may improve outcomes in patients with colorectal liver metastasis: a case-control study.

PURPOSE: Local thermal ablation may extend the scope of palliative therapy in patients with colorectal liver metastasis. We performed a retrospective, case-controlled study to compare patients with colorectal liver metastases that were treated with percutaneous radiofrequency (RF) or microwave (MW) thermal ablation, against the control group of chemotherapy alone. METHODS: We described baseline demographics, ablation sessions, procedure duration and related complications. We compared outcomes of percutaneous thermal ablation versus chemotherapy alone (controls) in patients with colorectal liver metastasis. The control group assigned (non-ablated patients) had similar demographics and prior treatment profile when compared to ablated patients. Progression-free survival (PFS) and overall survival (OS) were estimated for the two groups. RESULTS: Twenty-eight cases with 57 baseline hepatic lesions (median age 68 years; male to female ratio 2:1) were evaluated and compared with 48 controls. A total of 55 sessions (52 RF, 3 MW) were performed among the cases, with minimal procedural time (median 8 min), zero mortality and no severe complications (3 cases of local hepatic hematoma not requiring hospitalization). Ablated patients had prolonged median PFS (19.4 months) and OS (27.5 months) when compared against controls (14.0 and 21.4 months, respectively). After adjusting for hepatic involvement, PFS estimates were comparable and OS was better for the ablated group. One and 2-year survival estimates were 0.96 and 0.79 for thermal ablation patients compared with 0.82 and 0.52 for controls (p=0.05 and p=0.07, respectively). CONCLUSION: Percutaneous thermal ablation may delay progression and death in colorectal cancer patients with metastatic liver disease.

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.

FcγRIIa-H131R variant is associated with inferior response in diffuse large B cell lymphoma: A meta-analysis of genetic risk.

PURPOSE: Low-affinity variants FcγRIIIa-V158F and FcγRIIa- H131R may alter response to rituximab-based chemotherapy in diffuse large B-cell lymphoma (DLBCL) but available clinical evidence is inconclusive. Our purpose was to explore their association in terms of treatment response. METHODS: We performed a meta-analysis of published literature to associate these variants with complete remission after upfront immunochemotherapy in DLBCL, and summarized the genetic risk using the model-free approach of generalized odds ratio (ORG). PubMed and EMBASE search (up to July 2014) yielded five pertinent studies. RESULTS: FcγRIIa-H131R was associated with an inferior response to treatment (ORG 0.67; 95%CI 0.46-0.97) and an additive mode of inheritance, with the genetic risk of heterozygotes assigned in the middle between high affinity (H/H) and lower affinity (R/R) genotypes. This effect was unrelated to risk stratification, as no association was documented for FcγRIIa-H131R variant with the international prognostic index (IPI) (ORG 1.02; 95%CI 0.79-1.31 for IPI 3-5 over 0-2). FcγRIIIa-V158F had no impact on treatment response but linkage disequilibrium and defective antibody-dependent cell-mediated cytotoxicity may have affected the outcome. CONCLUSION: FcγRIIa-H131R but not FcγRIIIa-V158F may modify treatment response in DLBCL.

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.