Cost-Effectiveness of Vonoprazan-Based and Rifabutin-Based vs Other Regimens as First-Line Treatment of Helicobacter pylori Infection in the United States.

INTRODUCTION: The economic and clinical implications of eradicating Helicobacter pylori ( H. pylori ) with vonoprazan-based and rifabutin-based regimens vs other existing prepackaged first-line treatment options in the United States are unknown. Therefore, we evaluated the cost-effectiveness of vonoprazan-based and rifabutin-based and other prepackaged regimens for the first-line treatment of H. pylori from the perspective of US healthcare payers. METHODS: We used the state-transition Markov model to conduct a cost-effectiveness analysis of H. pylori eradication with clarithromycin triple, bismuth quadruple, vonoprazan dual, vonoprazan triple, and rifabutin triple regimens. In a cycle length of 2 months, the model estimated the expected costs (expressed in 2022 US$), expected quality-adjusted life-years (QALY), incremental cost-effectiveness ratios, and expected net monetary benefit over 20 years. In addition, we accounted for the present value of future costs and QALY by applying a 3% discounting rate. RESULTS: In this study, rifabutin triple therapy had a lower expected cost but was more effective than clarithromycin triple, bismuth quadruple, and vonoprazan dual regimens; hence, it dominated them. Vonoprazan triple therapy had a higher expected cost (US$ 1,172 vs US$ 1,048) and expected QALY (14.262 vs 14.256) than rifabutin triple therapy, yielding an estimated incremental cost-effectiveness ratio of US$ 22,573/QALY. The study suggested that vonoprazan triple treatment had the highest expected net monetary benefit and was the most cost-effective at willingness-to-pay thresholds between US$50,000 and US$150,000 per QALY, followed by rifabutin triple therapy. DISCUSSION: H. pylori infection eradication with vonoprazan triple therapy would provide the greatest net health and monetary benefit from the perspective of US healthcare payers.

Management of infection among Medicare beneficiaries with HIV/AIDS: risk of diabetes with protease inhibitors and associated racial disparities using big data approach.

Association between protease inhibitors (PI) and Type II diabetes mellitus (T2DM) in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients is largely debated. This study examined the odds of developing T2DM among HIV/AIDS Medicare beneficiaries treated with PI and possible racial disparities in the odds. We performed a nested casecontrol study of Medicare database 2013-2017. We included HIV/AIDS positive beneficiaries who were enrolled continuously in Medicare Part A/B with no previous history of T2DM. PI-users were matched to non-PI users and non-anti-retroviral therapies (ART) users using a1:1 greedy propensity score (PS) matching . Multivariablee logistic regressions were performed to assess the odds of developing T2DM. The analysis included 2,353 HIV/AIDS beneficiaries. Matched samples were generated for PI vs. non-PI groups (n = 484) and PI vs. non-ART groups (n = 490). Compared to the non-PI group, the odds of developing T2DM were higher in PI-users (AOR: 1.76; 95% CI: 1.17-2.64), in Caucasian PI-users (AOR: 1.81; 95% CI: 1.02-3.22) and in African-American PI-users (AOR: 1.86; 95% CI: 1.03-3.36). Compared to the non-ART group, the odds of developing T2DM were higher in PI-users (AOR: 1.87; 95% CI: 1.25-2.81), in Caucasian PI-users (AOR: 1.96; 95% CI: 1.14-3.39) and in African-American PI-users (AOR: 2.05; 95% CI: 1.03-4.09). The use of PI is associated with higher odds of T2DM; odds were higher among African-Americans than Caucasians.

Economic impact of comorbid diabetes and associated racial disparities in managing Medicare beneficiaries with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS).

Clinical management of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is progressing to include chronic/metabolic complications, which may impose a significant economic burden on beneficiaries and Medicare. We assessed the national economic impact of comorbid Type-II Diabetes Mellitus (T2DM) on HIV/AIDS patients and potential raical disparities. This study was a cross-sectional study of Medicare database 2013-2017. Analytical sample included HIV/AIDS positive beneficiaries continuously enrolled in Part A/B. Total medical costs, prescription costs, inpatient costs, outpatient costs, out-of-pocket (OOP) costs, and Medicare costs were assessed from Medicare claims. Generalized linear models with log-link and gamma distribution were used to examine the impact of T2DM on different costs. A total of 2,509 eligible HIV/AIDS positive beneficiaries were identified of which 19.9% (n=498) had T2DM. After adjusting for covariates, T2DM beneficiaries had higher inpatient costs: 63.34% (95% CI: 42.73%-86.94%), outpatient costs: 50.26% (95% CI: 30.70%-72.75%), Medicare costs: 27.95% (95% CI: 13.81%-43.84%), OOP costs: 59.15% (95% CI: 40.02%-80.92%), and total medical costs: 27.83% (95% CI: 14.27%-43.00%) than non-T2DM beneficiaries. Incremental costs were higher among African Americans than Caucasians. Comorbid T2DM mposes a significant economic burden on HIV/AIDS patients and Medicare, which is higheramong African Americans.

Applying mixture cure survival modeling to medication persistence analysis.

PURPOSE: Standard survival models are often used in a medication persistence analysis. These methods implicitly assume that all patients will experience the event (medication discontinuation), which may bias the estimation of persistence if long-term medication persistent patients rate is expected in the population. We aimed to introduce a mixture cure model in the medication persistence analysis to describe the characteristics of long-term and short-term persistent patients, and demonstrate its application using a real-world data analysis. METHODS: A cohort of new users of statins was used to demonstrate the differences between the standard survival model and the mixture cure model in the medication persistence analysis. The mixture cure model estimated effects of variables, reported as odds ratios (OR) associated with likelihood of being long-term persistent and effects of variables, reported as hazard ratios (HR) associated with time to medication discontinuation among short-term persistent patients. RESULTS: Long-term persistent rate was estimated as 17% for statin users aged between 45 and 55 versus 10% for age less than 45 versus 4% for age greater than 55 via the mixture cure model. The HR of covariates estimated by the standard survival model (HR = 1.41, 95% CI = [1.35, 1.48]) were higher than those estimated by the mixture cure model (HR = 1.32, 95% CI = [1.25, 1.39]) when comparing patients with age greater than 55 to those between 45 and 55. CONCLUSIONS: Compared with standard survival modeling, a mixture cure model can improve the estimation of medication persistence when long-term persistent patients are expected in the population.

Regulatory and Clinical Experiences with Biosimilar Filgrastim in the U.S., the European Union, Japan, and Canada.

Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU countries, Japan, the U.S., and Canada since 2008, 2012, 2015, and 2016, respectively. We reviewed experiences and policies for biosimilar filgrastim markets in EU countries and Japan, where uptake has been rapid, and in the U.S. and Canada, where experience is rapidly emerging. U.S. regulations for designating biosimilar interchangeability are under development, and such regulations have not been developed in most other countries. Pharmaceutical substitution is allowed for new filgrastim starts in some EU countries and in Canada, but not Japan and the U.S. In EU countries, biosimilar adoption is facilitated with favorable hospital tender offers. U.S. adoption is reportedly 24%, while the second filgrastim biosimilar is priced 30% lower than branded filgrastim and 20% lower than the first biosimilar filgrastim approved by the U.S. Food and Drug Administration. Utilization is about 60% in EU countries, where biosimilar filgrastim is marketed at a 30%-40% discount. In Japan, biosimilar filgrastim utilization is 45%, primarily because of 35% discounts negotiated by Central Insurance and hospital-only markets. Overall, biosimilar filgrastim adoption barriers are small in many EU countries and Japan and are diminishing in Canada in the U.S. Policies facilitating improved U.S. adoption of biosimilar filgrastim, based on positive experiences in EU countries and Japan, including favorable insurance coverage; larger price discount relative to reference filgrastim pricing; closing of the "rebate trap" with transparent pricing information; formal educational efforts of patients, physicians, caregivers, and providers; and allowance of pharmaceutical substitution of biosimilar versus reference filgrastim, should be considered. IMPLICATIONS FOR PRACTICE: We reviewed experiences and policies for biosimilar filgrastims in Europe, Japan, Canada, and the U.S. Postmarketing harmonization of regulatory policies for biosimilar filgrastims has not occurred. Acceptance of biosimilar filgrastims for branded filgrastim, increasing in the U.S. and in Canada, is commonplace in Japan and Europe. In the U.S., some factors, accepted in Europe or Japan, could improve uptake, including acceptance of biosimilars as safe and effective; larger cost savings, decreasing "rebate traps" where pharmaceutical benefit managers support branded filgrastim, decreased use of patent litigation/challenges, and allowing pharmacists to routinely substitute biosimilar for branded filgrastim.

Early Venous Thromboembolism Prophylaxis for Isolated High-Grade Blunt Splenic Injury.

BACKGROUND: Nonoperative management (NOM) has become more common in hemodynamically stable patients with high-grade blunt splenic injury. However, there are no widely accepted guidelines for an optimal and safe timeframe for the initiation of venous thromboembolism (VTE) prophylaxis. The purpose of this study was to explore the association between the timing of VTE prophylaxis initiation and NOM failure rate in isolated high-grade blunt splenic injury. METHODS: We utilized the American College of Surgeons Trauma Quality Improvement Program database (2013-2014) to identify adult patients who underwent NOM for isolated high-grade blunt splenic injuries (grades 3-5). The incidence of NOM failure after the initiation of VTE prophylaxis was compared between two groups: VTE prophylaxis <48 h after admission (early prophylaxis group), and ≥48 h (late prophylaxis group). RESULTS: A total of 816 patients met the inclusion criteria. Of those, VTE prophylaxis was not administered in 525 patients (64.3%), whereas VTE prophylaxis was given <48 h and ≥48 h after admission in 144 and 147 patients, respectively. There was no significant difference in the NOM failure rate after the initiation of VTE prophylaxis between the early and late prophylaxis groups (3.5% versus 3.4%, P = 1.00). In the multiple logistic regression analysis, early initiation of VTE prophylaxis was not significantly associated with NOM failure (OR: 1.32, 95% CI 0.35-4.93, P = 0.68). CONCLUSIONS: The results of our study suggest that early initiation of VTE prophylaxis (<48 h) does not increase the risk of NOM failure in patients with isolated high-grade blunt splenic injury.

Opioid Prescription Patterns for Adults With Longstanding Disability and Inflammatory Conditions Compared to Other Users, Using a Nationally Representative Sample.

OBJECTIVES: To investigate the opioid prescription patterns for adults with longstanding physical disability and inflammatory conditions, compared to a mixed group of other opioid users, after excluding cancer patients. DESIGN: Nationally representative cross-sectional study, 2010-2014. SETTING: Medical Expenditure Panel Survey (MEPS). PARTICIPANTS: The participants (N=7134) were adults who participated in MEPS and had at least 1 opioid prescription, did not have cancer, and were between 18 years and 64 years of age. The participants were grouped as longstanding physical disability (group 1), inflammatory conditions (group 2), and a mixed group with at least 1 opioid prescription during the 2-year study period (comparison group). Participants with both groups of conditions were excluded. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Morphine milligram equivalent (MME) doses for each participant were cumulated over a 2-year panel period. RESULTS: By using quantile regression, cumulative MME in groups 1 and 2 was higher than the comparison group across all the percentiles, and differences between condition groups and comparison group became larger in higher percentiles. Participants in group 1 had the highest cumulative MME in 75th and 90th percentiles after controlling for other covariates. CONCLUSIONS: This study documented the opioid prescription patterns for patients with longstanding physical disability or inflammatory conditions. All indexed groups (groups 1 and 2) had higher MME use compared to the comparison group.

Regulatory and clinical considerations for biosimilar oncology drugs.

Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.

Human microbiome: Impact of newly approved treatments on C. difficile infection.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice. SUMMARY: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies. CONCLUSION: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.

Impacts of FDA approval and Medicare restriction on antiamyloid therapies for Alzheimer's disease: patient outcomes, healthcare costs, and drug development.

In 2021, the US Food and Drug Administration (FDA) granted approval to aducanumab, an antiamyloid antibody for early-stage Alzheimer's disease, despite a lack of clear clinical evidence demonstrating the drug's cognitive benefits. The manufacturer initially priced the drug at a staggering $56,000 per year, a price that was later reduced to $28,200. Unfortunately, these costs do not include the additional expenses associated with monitoring the treatment. However, the Centers for Medicare and Medicaid Services (CMS) recently announced that they will only cover individuals enrolled in clinical trials and will limit coverage of future antiamyloid antibodies. This discrepancy between the FDA and CMS positions has caused confusion and concerns for patients who could potentially benefit from antiamyloid therapy. It is important to acknowledge the clinical and economic uncertainties surrounding aducanumab and its potential impacts on future antiamyloid drug development and approval processes. The FDA's approval, despite limited clinical evidence, raises questions about the integrity and rigor of the approval process. The drug's high cost also raises accessibility concerns, especially for those without insurance or sufficient financial resources. Given the CMS's limited coverage policy, it's critical to evaluate the long-term implications of this decision on future antiamyloid drug development. Without adequate support and coverage from insurance providers, the development and approval of future Alzheimer's treatments may be hindered. In summary, the approval and pricing of aducanumab, coupled with the CMS's limited coverage policy, has created a confusing and concerning landscape for Alzheimer's patients. It's important that stakeholders, including patients, clinicians, insurers, and regulatory bodies, work together to address these challenges and ensure that individuals with Alzheimer's have access to effective, affordable treatments.

A Case Report of Ruptured Popliteal Aneurysm in the Setting of Blunt Trauma.

INTRODUCTION: Popliteal artery aneurysms are in most cases asymptomatic but cause significant complications if ruptured. An acute popliteal aneurysm rupture is relatively rare, and few cases have been documented secondary to blunt trauma. Common presenting signs and symptoms include distal limb ischemia and absent dorsalis pedis pulses. Timely management and recognition of this rare presentation are crucial as this condition can result in limb loss or death if not treated in a timely manner. CASE REPORT: An 80-year-old man with history of hypertension presented to the emergency department complaining of inability to feel sensation below his left knee after falling from ground level. Physical examination was pertinent for bounding radial and femoral pulses bilaterally, although absent dorsalis pedis and posterior tibial pulses to the left lower extremity. Computed tomography angiography identified occlusion of the left superficial femoral arterial lumen associated with a ruptured popliteal aneurysm, approximately eight centimeters in size. He immediately received unfractionated heparin and was admitted to the hospital for left medial thigh exploration and decompressive dermatofasciotomy. CONCLUSION: After confirmation of popliteal aneurysmal rupture with advanced imaging, heparinization and vascular surgery consultation are critical steps that should be taken to prevent limb loss.

Associations Between Opioid Prescriptions and Use of Hospital-Based Services Among US Adults with Longstanding Physical Disability or Inflammatory Conditions Compared to Other Adults in the Medical Expenditure Panel Survey, 2010-2015.

Purpose: To investigate the association of filling opioid prescriptions with healthcare service utilization among a nationally representative sample of adults with disability. Materials and Methods: The Medical Expenditure Panel Survey (MEPS) for 2010-2015, Panels 15-19, was used to identify adults who were prescribed opioids during each two-year period. We examined the data for associations between opioid prescription filling and the number of emergency department (ED) visits and hospitalizations. The participants were grouped as those with inflammatory conditions or with longstanding physical disability, and a comparison group of those without these conditions. Results and conclusions: Opioid prescription filling differed among adults with inflammatory conditions and longstanding physical disability compared to the comparison group (44.93% and 40.70% vs 18.10%, respectively). For both groups of people with disability, the relative rates for an ED visit or hospitalization were significantly higher for those who filled an opioid prescription, compared to adults with the same conditions who did not fill an opioid prescription. People with a longstanding physical disability who filled an opioid prescription had the highest rate ratio of ED use and hospitalization. Results from this investigation demonstrate that opioid prescription filling among persons with inflammatory conditions and longstanding physical disabilities is associated with higher rates of ED visits and hospitalizations.

Relationship of Nonsteroidal Anti-Inflammatory Drug Use During Pregnancy with Autism Spectrum Disorder and Intellectual Disability Among Offspring.

Objective: This study aimed to examine the association of nonsteroidal anti-inflammatory drug (NSAID) use by pregnant women during pregnancy with autism spectrum disorder (ASD) and intellectual disability (ID) in their children among Medicaid-insured mother-child dyads. Materials and Methods: We conducted a retrospective cohort study linking multiple datasets of South Carolina for the years between 2010 and 2017, in which the main exposure variable was NSAID use during pregnancy and outcome variables were ASD only, ID only, and ASD with ID. We conducted a multinomial logistic regression analysis, controlling for identified risk factors for ASD (mother's age, race, body-mass index, preeclampsia, and gestational diabetes). Results: NSAID use during pregnancy was found to be associated with ID only in both unadjusted and adjusted analyses. Children with mothers who had NSAID prescriptions were 26% more likely to have ID in comparison with children whose mothers did not have NSAID prescriptions (odds ratio: 1.26 [1.10-1.46]). The other risk factors identified for ASD were maternal age, race, preeclampsia, smoking, low birth weight, and obesity. For ID, the risk factors were maternal age, race, smoking, birth weight, overweight, and obesity, all of which were also associated with ASD with ID, except for overweight. Conclusions: NSAID usage during pregnancy was found to be associated with ID only and not with ASD. However, more research is needed to validate the effect of NSAIDs during pregnancy on ASD and ID among children.

Extended-release mesalamine granules for ulcerative colitis.

OBJECTIVE: To evaluate the efficacy and safety of extended-release mesalamine granules in the maintenance of remission in ulcerative colitis (UC). DATA SOURCES: Literature was obtained through searches of MEDLINE (1990-June 2012) using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk. Bibliographies from retrieved articles were searched for additional citations. STUDY SELECTION AND DATA EXTRACTION: All English-language articles reporting on use of extended-release mesalamine granules in humans identified through the search were evaluated and included. DATA SYNTHESIS: The preferred initial treatment for induction and maintenance of remission in mild to moderate UC is agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine, sulfasalazine). Mesalamine granules are available as an encapsulated product in the US and as a nonencapsulated formulation in Europe. Data evaluating encapsulated mesalamine granules for induction of remission are lacking; however, the European mesalamine granule formulation has been evaluated for induction of remission. Patients receiving mesalamine granules for induction achieved clinical and endoscopic remission more frequently than those receiving placebo. Two pivotal, randomized, double-blind, placebo-controlled, multicenter studies have evaluated encapsulated mesalamine granules for maintenance in 562 adults in remission from UC. In both studies, the proportion of patients who remained relapse-free at 6 months was higher for those receiving encapsulated mesalamine granules than placebo. Mesalamine granules are well tolerated, with headache, nausea, and upper respiratory infections being the most frequently reported adverse effects. CONCLUSIONS: Current evidence supports the use of extended-release mesalamine granules for maintenance of remission in mild to moderate UC. Further studies are necessary to examine the ideal dose and regimen of encapsulated mesalamine granules for induction of remission in UC.

Are pregnant women with disability prescribed opioids more and at higher dosages than those without disability?: A retrospective cohort study of South Carolina Medicaid beneficiaries.

BACKGROUND: Nationally, individuals with disability have higher rates of opioid use and misuse and are prescribed higher doses than those without disability. Opioid prescriptions during pregnancy are associated with adverse birth outcomes. OBJECTIVE: To understand the difference in opioid prescribing during pregnancy over time by disability status among Medicaid beneficiaries who gave birth from 2008 to 2017 in South Carolina. METHODS: Data from hospital discharges, vital records, and pharmacy were linked to determine the mother's disability status, opioid prescriptions filled during pregnancy, and other maternal characteristics. Disability status was characterized into physical disability, inflammatory conditions, intellectual and developmental disabilities (IDD), and psychiatric conditions. Bivariate analyses and negative binomial regression were utilized to obtain adjusted rate ratios for total opioid prescriptions and total morphine milligram equivalents (MME) during pregnancy per live birth. Models were adjusted for chronic pain status. The final analytic sample included 319,752 births to 224,838 mothers. RESULTS: Almost 7% of the births were to mothers with at least one type of disability. Overall, those with disability had a significantly higher adjusted rate ratio of total opioid prescriptions (aRR: 2.36; 95% CI: 2.21-2.52) and total MME (aRR: 2.29; 95% CI: 2.07-2.52) during pregnancy per live birth than those without disability. These findings were seen across all the diagnostic groups, except IDD, where there were no significant differences. CONCLUSIONS: The current study found that women with physical, inflammatory, and psychiatric disability were prescribed more opioids and at higher dosages during pregnancy than their counterparts without disability, after adjusting for chronic pain status.

Effectiveness of Conjugate and Polysaccharide Pneumococcal Vaccines for Prevention of Severe Pneumococcal Disease Among Inflammatory Bowel Disease Patients.

BACKGROUND: Streptococcus pneumoniae is an important pathogen responsible for severe pneumococcal diseases, including pneumonia, bacteraemia/sepsis, and meningitis. Inflammatory bowel disease [IBD] patients have an increased risk for infections due to an altered immune system and treatment with immunosuppressive medications. The aim of this study was to assess the prevalence of severe pneumococcal disease [SPD] and evaluate the impact of pneumococcal vaccination on the risk of SPD in Veterans with IBD. METHODS: Subjects with IBD and SPD were identified from the VA Health Administration database using ICD9/10 codes. Pneumococcal vaccination and use of immunosuppressant medications were collected. Risk of SPD was evaluated using an adjusted Cox proportional hazards model controlling for demographics, medications, vaccination, and comorbidities. RESULTS: A total of 1798 cases of SPD were identified [283 pneumonia, 1513 bacteraemia, and two meningitis]. SPD patients were older [60.9 years vs 59.4 years; p <0.001], had more comorbidities [Charlson Comorbidity Index of 2.11 vs 0.96; p <0.001], and had increased mortality [4.6% vs 1.5%, p <0.001]. The risk of SPD was increased in Crohn's disease (hazard ratio [HR] 1.15; 95% confidence interval [CI] 1.05-1.27) and with more comorbidities [HR 1.45; 95% CI 1.42-1.48]. Use of immunosuppressive medications increased the risk of SPD. Receipt of PCV13 either alone or in combination with PPSV23 predicted a 5-fold decreased risk of SPD compared with no vaccination. CONCLUSIONS: Risk factors for severe pneumococcal disease include having Crohn's disease, more comorbidities, and exposure to combination immunosuppression. Vaccination with PCV13 alone or in combination with PPSV23 and revaccination with PPSV23, was protective against SPD. All IBD patients should be evaluated for pneumococcal vaccination, particularly those receiving or expected to receive immunosuppressive therapies.

The impact of statin use prior to intensive care unit admission on critically ill patients with sepsis.

OBJECTIVE: To evaluate the impact of pre-intensive care unit admission (pre-ICU) statin use on all-cause in-hospital mortality and ICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Adult ICUs at tertiary hospitals. PATIENTS: Adult critically ill patients diagnosed with sepsis admitted to the ICUs. INTERVENTION: The exposure was pre-ICU statin prescription (statin users); unexposed represented absence of pre-ICU prescription (non-users). MEASUREMENT AND MAIN RESULTS: We used the 2001-2012 Medical Information Mart for Intensive Care-III (MIMIC-III) database to determine average treatment effect (ATE) of pre-ICU statin use on 30-day ICU mortality, ICU LOS, and 30-day in-hospital mortality using the Augmented Inverse Propensity Weighted technique (AIPW), after adjusting for confounding factors (age, race, health insurance, corticosteroids use, vital signs, laboratory tests, and Sequential Organ Failure Assessment score (SOFA). We measured 30-day ICU mortality as deaths within 30 days of admission to the ICU, and ICU LOS was measured in fractional days. A 30-day in-hospital mortality was measured as death within 30 days of hospital admission. A total of 8200 patients with sepsis were identified; 19.8% (1623) were statin users, and 80.2% (6577) were non-users. Most were Caucasian, aged 80 years and above, and male. After adjusting for confounding factors, pre-ICU statin use decreased 30-day ICU mortality (ATE, -0.026; 95% confidence interval [CI], -0.048 to -0.009); ICU LOS (ATE, -0.369; 95% Cl, -0.849 to -0.096); and 30-day in-hospital mortality (ATE, -0.039; 95% CI, -0.084 to -0.026) on average compared with non-statin use, respectively. In a stratified analysis, the result for ICU LOS (ATE, -0.526; 95% CI, -0.879 to -0.241) and 30-day in-hospital mortality (ATE, -0.023; 95% CI, -0.048 to -0.002) was consistent among patients admitted to the medical ICU. CONCLUSIONS: Among patients with sepsis admitted to the medical ICU, pre-ICU statin use is causally associated with a decrease in 30-day ICU mortality, ICU LOS, and 30-day in-hospital mortality compared to non-use. This study adds to the totality of evidence on the pleiotropic effect of statin use in patients with sepsis.

Changes in Cost-Effectiveness for Chronic Hepatitis C Virus Pharmacotherapy: The Case for Continuous Cost-Effectiveness Analyses.

BACKGROUND: Cost-effectiveness evaluations for hepatitis C virus (HCV) treatments have been published frequently, but new products with significant cost and effectiveness differences make these analyses obsolete. How valuable are economic models for a fixed time period in a dynamic market? OBJECTIVE: To estimate the cost-effectiveness of the best available HCV treatment at different points in time, using the same comparator to demonstrate how rapid innovation in a disease area influences economic outcomes. METHODS: A Markov model was used to calculate the cost-effectiveness of treatment in 2010, 2012, 2014, 2016, and 2018 compared with a standard comparator (no treatment) from the payer perspective. Expected drug costs and treatment effectiveness estimates for sustained virologic response (SVR) were calculated using recommended regimens for each of the 6 HCV genotypes at each time point and distribution of genotypes in the United States. Patients entered the model with different stages of fibrosis. Utility estimates for each health state were used to calculate quality-adjusted life-years (QALYs) earned at each cycle. Incremental cost-effectiveness ratios were reported for each year to compare the "treatment versus no treatment" decision at that time. RESULTS: No HCV treatment resulted in a gain of 11.54 QALYs over a 20-year time horizon at a cost of $42,938. Costs for treated groups were $69,075, $123,267, $125,431, $86,782, and $56,470 for the 2010, 2012, 2014, 2016, and 2018 scenarios, respectively. QALYs gained for treated groups were 12.90, 12.97, 13.34, 13.39, and 13.46 for the 2010, 2012, 2014, 2016, and 2018 scenarios, respectively. The incremental cost-effectiveness ratios in each year compared with no treatment were $19,218 per QALY, $56,104 per QALY, $45,829 per QALY, $23,699 per QALY, and $7,048 per QALY. CONCLUSIONS: Treatment effectiveness for HCV has increased steadily, while treatment costs increased substantially from 2010-2014 before decreasing to its lowest point in 2018. Thus, the dynamic nature of innovation creates the need for iterative cost-effectiveness analyses. DISCLOSURES: No outside funding supported this study. Mattingly reports unrelated consulting from the National Health Council, Bristol Myers Squibb, G&W Laboratories, Allergy and Asthma Foundation of American, and the Massachusetts Health Policy Commission. Love reports an unrelated research grant from the American Cancer Society.