Assessment of algorithms for identifying patients with triple-class refractory multiple myeloma using real-world data.

Objective: Patients with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognoses. This high unmet need has prompted the development of new therapies allowing for improved outcomes for these patients. Recently, new targeted therapies for the treatment of patients with relapsed or refractory MM have been approved based on single-arm clinical trial results. Real-world (RW) data enable a better understanding of the effectiveness of new therapies in clinical practice and provide external controls for single-arm studies. However, using RW data to identify patients with TCR MM is challenging and subject to limitations. Methods: In this retrospective cohort study of an analysis of the COTA electronic health record (EHR) database, we used four algorithms to define refractory status and created four groups of patients with TCR MM initiating post-TCR therapy. Each algorithm relied on slightly different criteria to identify TCR patients, but all were based on the International Myeloma Working Group (IMWG)-derived and/or healthcare provider (HCP)-reported progressions within the database. Results: A total of 3815 patients with newly diagnosed MM met the eligibility criteria for this study. The choice of the algorithm did not impact the characteristics of identified patients with TCR MM (Algorithm 1 [n = 404], Algorithm 2 [n = 123], Algorithm 3 [n = 404], and Algorithm 4 [n = 375]), including their demographic and disease characteristics, MM treatment history, or treatment patterns received after becoming TCR. However, identifying TCR MM using a combination of IMWG-derived and HCP-reported progressions allowed up to a 70% increase in the size of the identified group of patients compared with using only IMWG-derived progressions. Conclusion: In RW settings, progressions from both IMWG-derived data and physician reports may be used to identify patients with TCR MM.

COVID-19-related work absenteeism and associated lost productivity cost in Germany: a population-based study.

OBJECTIVE: To estimate COVID-19 absenteeism and indirect costs, by care setting. METHODS: A population-based retrospective cohort study using data from the German Statutory Health Insurance (SHI) database to define outpatient (April 2020-December 2021) and hospitalized (April 2020-October 2022) cohorts of employed working-aged individuals. RESULTS: In the outpatient cohort (n = 369,220) median absenteeism duration and associated cost was 10.0 (IQR: 5.0, 15.0) days and €1,061 (530, 1,591), respectively. In the hospitalized cohort (n = 20,687), median absenteeism and associated cost was 15.0 (7.0, 32.0) days and €1,591 (743, 3,394), respectively. Stratified analyses showed greater absenteeism in older workers, those at risk and those with severe disease. CONCLUSIONS: The hospitalized cohort had longer absenteeism resulting in higher productivity loss. Being older, at risk of severe COVID-19 and higher disease severity during hospitalization were important drivers of higher absenteeism duration.

Elranatamab efficacy in MagnetisMM-3 compared with real-world control arms in triple-class refractory multiple myeloma.

Elranatamab efficacy in the single-arm, registrational MagnetisMM-3 trial (NCT04649359) was compared with that of physician's choice of treatment (PCT) for triple-class refractory multiple myeloma. MagnestisMM-3 eligibility criteria were applied to two USA-based oncology electronic health record databases, COTA and Flatiron Health (FH), to identify cohorts for this study (NCT05932290). Applied statistical techniques accounted for cohort imbalances. MagnetisMM-3 (BCMA-naive; n = 123) outcomes were compared with those from COTA (n = 239) and FH (n = 152). Elranatamab was associated with a significantly higher objective response rate (risk ratios, 1.88-2.25), significantly longer progression-free survival (hazard ratios [HRs], 0.37-0.57), and, across most analyses, significantly longer overall survival (HRs, 0.46-0.66) versus PCT. BCMA-naive patients who were treated with elranatamab exhibited significantly better outcomes than patients treated in real-world clinical practice.

Elranatamab is a new medicine for the treatment of people with multiple myeloma. In the ongoing clinical trial MagnetisMM-3, most people had fewer myeloma cells when treated with elranatamab. However, MagnetisMM-3 only looks at the effects of elranatamab without comparing it to other myeloma treatments. Therefore, a new study was designed to compare the effectiveness of elranatamab in the MagnetisMM-3 study with other treatments used in real-world clinical practice (not in a clinical trial). Data from people in MagnetisMM-3 was compared with data from two US databases (COTA and Flatiron Health) containing health records of patients treated for multiple myeloma in real-life clinical practice. The same criteria used to select patients for the MagnetisMM-3 trial (123 people) were used to identify people with similar characteristics in COTA (239 people) and Flatiron Health (152 people). More people treated with elranatamab had fewer myeloma cells in their bodies after treatment than people who received their doctor's choice of treatment in clinical practice. In fact, six out of ten people treated with elranatamab had fewer myeloma cells versus about three in ten people from each real-world database. People treated with elranatamab versus physician's choice of treatment lived longer without their disease getting worse and lived longer overall. In conclusion, this study found that more people treated with elranatamab responded to treatment and lived longer than similar people from the COTA and Flatiron Health databases who were given treatments available in a real-world clinical setting. Clinical Trial Registration: NCT05932290 (ClinicalTrials.gov).

Effectiveness of BNT162b2 BA.4/5 Bivalent COVID-19 Vaccine against Long COVID Symptoms: A US Nationwide Study.

BACKGROUND: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. METHODS: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. RESULTS: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36-0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41-0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. CONCLUSIONS: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.

Impact of elranatamab on quality of life: Patient-reported outcomes from MagnetisMM-3.

The physical and emotional burden of relapsed or refractory multiple myeloma (RRMM) has been strongly correlated with declining health-related quality of life (QOL) in the patients it affects. This analysis evaluated patient-reported outcomes (PROs) from B-cell maturation antigen (BCMA)-naive (n = 123) and -exposed (n = 64) patients with RRMM enrolled in the MagnetisMM-3 study (NCT04649359) and treated with the humanized, bispecific BCMA-CD3 antibody elranatamab. Patients received two step-up doses of elranatamab (12 mg on day 1, 32 mg on day 4) before starting the full dose of 76 mg on day 8 (each cycle = 28 days). Global health status, functioning and symptom data were collected electronically using validated and myeloma-specific questionnaires. Improvements in PROs occurred early, with marked reductions in pain and disease symptoms and notable improvements in patients' outlook for their future health. Additionally, 40.2% of BCMA-naive and 52.6% of BCMA-exposed patients perceived their disease as 'a little better' or 'much better' by Cycle 1, Day 15. The results from this analysis demonstrated that elranatamab maintained or improved symptomology and general health status, regardless of prior BCMA-directed therapy. Thus, in addition to its clinical benefits, elranatamab therapy may sustain or improve QOL in heavily pretreated patients with RRMM.

Appropriateness of conducting and reporting random-effects meta-analysis in oncology.

A random-effects model is often applied in meta-analysis when considerable heterogeneity among studies is observed due to the differences in patient characteristics, timeframe, treatment regimens, and other study characteristics. Since 2014, the journals Research Synthesis Methods and the Annals of Internal Medicine have published a few noteworthy papers that explained why the most widely used method for pooling heterogeneous studies-the DerSimonian-Laird (DL) estimator-can produce biased estimates with falsely high precision and recommended to use other several alternative methods. Nevertheless, more than half of studies (55.7%) published in top oncology-specific journals during 2015-2022 did not report any detailed method in the random-effects meta-analysis. Of the studies that did report the methodology used, the DL method was still the dominant one reported. Thus, while the authors recommend that Research Synthesis Methods and the Annals of Internal Medicine continue to increase the publication of its articles that report on specific methods for handling heterogeneity and use random-effects estimates that provide more accurate confidence limits than the DL estimator, other journals that publish meta-analyses in oncology (and presumably in other disease areas) are urged to do the same on a much larger scale than currently documented.

Regulatory agilities impacting review timelines for Pfizer/BioNTech's BNT162b2 mRNA COVID-19 vaccine: a retrospective study.

The appropriate use of regulatory agilities has the potential to accelerate regulatory review, utilize resources more efficiently and deliver medicines and vaccines more rapidly, all without compromising quality, safety and efficacy. This was clearly demonstrated during the COVID-19 pandemic where regulators and industry rapidly adapted to ensure continued supply of existing critical medicines and review and approve new innovative medicines. In this retrospective study, we analyze the impact of regulatory agilities on the review and approval of Pfizer/BioNTech's BNT162b2 mRNA COVID-19 Vaccine globally using regulatory approval data from 73 country/regional approvals. We report on the critical role of reliance and provide evidence that demonstrates reliance approaches and certain regulatory agilities reduced review times for the COVID-19 vaccine. These findings support the case for more widespread implementation of regulatory agilities and demonstrate the important role of such approaches to improve public health outcomes.

Meaningful within-patient change for clinical outcome assessments: model-based approach versus cumulative distribution functions.

OBJECTIVES: The FDA recommends the use of anchor-based methods and empirical cumulative distribution function (eCDF) curves to establish a meaningful within-patient change (MWPC) for a clinical outcome assessment (COA). In practice, the estimates obtained from model-based methods and eCDF curves may not closely align, although an anchor is used with both. To help interpret their results, we investigated and compared these approaches. METHODS: Both repeated measures model (RMM) and eCDF approaches were used to estimate an MWPC on a target COA. We used both real-life (ClinicalTrials.gov: NCT02697773) and simulated data sets that included 688 patients with up to six visits per patient, target COA (range 0 to 10), and an anchor measure on patient global assessment of osteoarthritis from 1 (very good) to 5 (very poor). Ninety-five percent confidence intervals for the MWPC were calculated by the bootstrap method. RESULTS: The distribution of the COA score changes affected the degree of concordance between RMM and eCDF estimates. The COA score changes from simulated normally distributed data led to greater concordance between the two approaches than did COA score changes from the actual clinical data. The confidence intervals of MWPC estimate based on eCDF methods were much wider than that by RMM methods, and the point estimate of eCDF methods varied noticeably across visits. CONCLUSIONS: Our data explored the differences of model-based methods over eCDF approaches, finding that the former integrates more information across a diverse range of COA and anchor scores and provides more precise estimates for the MWPC.

Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures.

Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit-risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change. This Policy Review presents international stakeholder views on the need for SISAQOL-IMI, the agreed on and prioritised set of PRO objectives, and a roadmap to ensure that international consensus recommendations are achieved.

Comparing g-computation, propensity score-based weighting, and targeted maximum likelihood estimation for analyzing externally controlled trials with both measured and unmeasured confounders: a simulation study.

OBJECTIVES: To have confidence in one's interpretation of treatment effects assessed by comparing trial results to external controls, minimizing bias is a critical step. We sought to investigate different methods for causal inference in simulated data sets with measured and unmeasured confounders. METHODS: The simulated data included three types of outcomes (continuous, binary, and time-to-event), treatment assignment, two measured baseline confounders, and one unmeasured confounding factor. Three scenarios were set to create different intensities of confounding effect (e.g., small and blocked confounding paths, medium and blocked confounding paths, and one large unblocked confounding path for scenario 1 to 3, respectively) caused by the unmeasured confounder. The methods of g-computation (GC), inverse probability of treatment weighting (IPTW), overlap weighting (OW), standardized mortality/morbidity ratio (SMR), and targeted maximum likelihood estimation (TMLE) were used to estimate average treatment effects and reduce potential biases. RESULTS: The results with the greatest extent of biases were from the raw model that ignored all the potential confounders. In scenario 2, the unmeasured factor indirectly influenced the treatment assignment through a measured controlling factor and led to medium confounding. The methods of GC, IPTW, OW, SMR, and TMLE removed most of bias observed in average treatment effects for all three types of outcomes from the raw model. Similar results were found in scenario 1, but the results tended to be biased in scenario 3. GC had the best performance followed by OW. CONCLUSIONS: The aforesaid methods can be used for causal inference in externally controlled studies when there is no large, unblockable confounding path for an unmeasured confounder. GC and OW are the preferable approaches.

Study protocol of Phase 2 open-label multicenter randomized controlled trial for granulocyte-colony stimulating factor (GCSF) in post-Kasai Type 3 biliary atresia.

Animal studies support RCT findings of improved liver function and short-term benefits using repurposed Granulocyte Colonic Stimulating Factor GCSF in adults with decompensated cirrhosis. We describe the protocol for phase 2 RCT of sequential Kasai-GCSF under an FDA-approved IND to test that GCSF improves early bile flow and post-Kasai biliary atresia BA clinical outcome. Immediate post-Kasai neonates, age 15-180 days, with biopsy-confirmed type 3 BA, without access to early liver transplantation, will be randomized 1:1 to standard of care SOC + GCSF at 10 ug/kg in 3 daily doses within 4 days of Kasai vs SOC + NO-GCSF (ClinicalTrials.gov NCT0437391). They will be recruited from children's hospitals in Vietnam, Pakistan and one US center. The primary objective is to demonstrate that GCSF decreases the proportion of subjects with a 3-month post-Kasai serum Total Bilirubin ≥ 34 umol/L by 20%, (for a = 0.05, b = 0.80, i.e., calculated sample size of 218 subjects). The secondary objectives are to demonstrate that the frequency of post-Kasai cholangitis at 6-month and 24-month transplant-free survival are improved. The benefits are that GCSF is an affordable BA adjunct therapy, especially in developing countries, to improve biliary complications, enhance quality of liver and survival while diminishing costly liver transplantation.Clinical trial registration: A phase 1 for GCSF dose and safety determination under ClinicalTrials.gov identifier NCT03395028 was completed in 2019. The current Phase 2 trial was registered under NCT04373941.

Evaluation of Intraoperative, Local Site Injections of Liposomal Bupivacaine as an Alternative to Standard Local Anesthetics in Patients Undergoing Total Hip Arthroplasty.

Background: Achieving postsurgical pain control after total hip arthroplasty (THA) is a critical factor for successful recovery because inadequately treated pain may lead to a delay in ambulation and hospital discharge and have an adverse impact on a patient's quality of life. Objective: This study compares the effectiveness of immediate-release local anesthetics for pain control in THA vs liposomal bupivacaine (LB) related to patient outcomes and costs of care. Methods: This is a retrospective cohort study of consecutive patients undergoing THA at 3 hospitals from January 2013 to July 2016. The control group received plain bupivacaine or ropivacaine while the study group received LB. Generalized linear models were used controlling for several patient factors. Primary measures included length of stay (LOS), hospitalization costs, pain relief, opioid use, and mobility. Secondary outcomes were discharge disposition and 30-, 60-, and 90-day readmissions. Results: One hundred and ninety-six patients were identified, with 103 as controls, 70 receiving LB, and 23 excluded. The LB group showed a decrease in LOS of 0.5 days (2.5 ± 2.6 vs 3.0 ± 2.1 days, P = .010), increased mobility on the day of surgery (27.6 ± 49.3 vs 12.5 ± 48.5 feet, P = .001) and the first day after surgery (186.8 ± 133.8 vs 155.2 ± 135.6, P = .039), and decreased hospital costs ($10 670 vs $11 351, P = .022). There were no significant differences in pain scores, opioid use, adverse events, discharge disposition, or readmissions. Study limitations include retrospective analysis, unblinded participants, and generalizability of results. Conclusions: LB provides an effective alternative to standard local anesthetics in patients undergoing THA based on improvements of inpatient parameters, LOS, and cost measures.

Hereditary, socio-behavioural, and immuno-hormonal predictors of incident rheumatoid arthritis and therapy response influences on survival versus matched control subjects using a generalised structural equation model.

OBJECTIVES: Incident onset and survival outcomes involve multiple risk factors and complex interactions preferably investigated in a single study. A generalized structural equation model (GSEM) was used to build an integrative framework to analyse multiple risk factors for incident rheumatoid arthritis (RA) and factors affecting long-term survival outcome. METHODS: Incident RA cases (n=54) had onsets between 1977 and 1994, after cohort entry in 1974. Four cohort control (CN) subjects (n=216) were matched on entry to each case in the community-based CLUE cohort and 270 subjects were followed from 1995 through 2017. Baseline variables included demographic, RA family history, behavioural factors and z-score levels of serum immunological, cytokine, isotype rheumatoid factors (RFs), adrenal steroids, luteinising hormone, prolactin and sex steroids. Four numerical integration methods of GSEM were performed in Stata 15. RESULTS: Cohort entry factors predicting RA onset included family history of RA, cigarette smoking and IgM RF. Total survival time from cohort entry was associated with incident RA and baseline variables of age, years of completed education, cigarette smoking, immunoreactive proteins and androgenic-anabolic steroids. Mortality of RA was significantly greater than CN subjects for cases having less than good therapy responses in 1995 and only for RA onset before age 60 years. Androgenic-anabolic steroid z-scores significantly correlated with improved survival only in CN subjects with assigned onset before the age of 60. CONCLUSIONS: Successful use of GSEM is feasible in analyses of prospective incident and subsequent survival data and promises to advance understanding of risk factors, survival, and casual pathways.

Impact of liposomal bupivacaine on opioid use, hospital length of stay, discharge status, and hospitalization costs in patients undergoing total hip arthroplasty.

Aims: Effective postsurgical analgesia hastens recovery, reduces hospital length of stay (LOS), and decreases hospitalization costs for total hip arthroplasty (THA). Improving these outcomes is critical for value-based surgical bundled payment programs such as the Medicare Comprehensive Care for Joint Replacement and similar programs for commercial insurance providers. This study compared clinical outcomes and hospitalization costs for patients undergoing THA with and without liposomal bupivacaine (LB).Materials and methods: This retrospective, comparative cohort study used data from the Premier Healthcare Database from the 10 hospitals with highest use of LB for THA from January 2011 through April 2017. A cohort undergoing THA with LB at those hospitals was compared with a propensity-score matched cohort at those hospitals who had THA without LB. Descriptive, univariate, and multivariable analyses compared post-surgical inpatient opioid consumption, hospital LOS, discharge status, same-hospital readmissions, and total hospitalization costs. Analyses were performed using the Pearson Chi-square test (categorical variables) and Wilcoxon or Student t-test (continuous variables).Results: For patients with Medicare (with LB, n = 3622; without LB, n = 3610) and commercial insurance (with LB, n = 2648; without LB, n = 2709), use of LB was associated with lower post-surgical inpatient opioid consumption (105 and 81 mg, respectively; p < 0.0001), a 0.7-day shorter LOS (p < 0.0001), a 1.6-1.7-fold increased likelihood of home discharge (p < 0.0001), and no increase in readmissions (p ≥ 0.103). Total hospitalization costs were $561 lower with LB in the Medicare population (p < 0.0001) and $41 higher with LB in the commercial population (p = 0.7697).Limitations: Hospitalization costs were estimated from the hospital chargemaster. Findings from these 10 hospitals may not represent other US hospitals.Conclusions: At select hospitals, THA with LB was associated with reduced post-surgical inpatient opioid consumption, shorter hospital LOS, increased likelihood of home discharge, and lower hospitalization costs. Post-surgical pain management with LB may help hospitals in value-based bundled payment programs.

Association Between Exposure of Ipratropium and Salmeterol and Diagnosis of Multiple Sclerosis: A Matched Case-control Study.

PURPOSE: Ipratropium and salmeterol were found to stimulate oligodendrocyte differentiation in a high-throughput drug screening assay; thus, they may play a role in the risk reduction of multiple sclerosis (MS). So far, they have not been examined in any clinical data. This study aims at investigating the association between ipratropium and salmeterol and reduced diagnosis of MS with the use of real-world clinical data. METHODS: We conducted a 1:10 matched case-control study that compared the exposure of ipratropium and salmeterol between patients with MS and control patients over the past 2 years, using the MS Flowsheet Registry of OSF HealthCare Saint Francis Medical Center. Cases were matched to control patients, based on service year/quarter, age, sex, race, and payer type. The relationship was examined with a Poisson regression model and a generalized structural equation model. FINDINGS: The sample in our analysis included 217 patients with MS and 2164 matched control patients. The mean (SD) age for both patients with MS and control patients was 41 (11.8) years with a range of 18 to 75 years. The MS group had consistently less prescriptions of ipratropium and salmeterol than the control group in the past 1, 2, and 3 years before the index date. Our multivariable analysis found that the control group had 3.2 more prescriptions (95% CI, 1.4-7.1; P = 0.006) of either ipratropium or salmeterol in the past 2 years than the MS group, even if controlling for other confounders. In the generalized structural equation model, we found that use of ipratropium and salmeterol was significantly associated with reduced diagnosis of MS (P = 0.036), whereas smokers and people with family history of MS were more likely to have a diagnosis of MS (P < 0.001). IMPLICATIONS: The observed association between ipratropium and salmeterol use and reduced diagnosis of MS indicates that they might potentially serve as agents in the treatment of MS.

Uncomplicated Urinary Tract Infection in Ambulatory Primary Care Pediatrics: Are We Using Antibiotics Appropriately?

OBJECTIVES: Antimicrobial stewardship programs target antimicrobial use within the inpatient care setting. However, most antimicrobials are prescribed at ambulatory sites. We aim to determine the appropriateness of the diagnosis and treatment of uncomplicated urinary tract infection (UTI) in children within the outpatient setting at our institution, and to evaluate the cost of antibiotic treatment in our patient cohort. METHODS: This retrospective study was conducted by reviewing electronic records of patients aged 2 to 18 years diagnosed with uncomplicated UTI and treated with antibiotics in the outpatient setting from January 1, 2016, to April 30, 2016. Appropriate diagnosis was defined as confirmed UTI that included: pyuria (>5 white blood cells per high-power field or positive for leukocyte esterase), a positive urine culture (≥50,000 colony units/mL of a single uropathogen for a catheterized sample or ≥100,000 colony units/mL for a clean catch urine sample), and lower urinary tract symptoms. Treatment was considered appropriate if the patient was prescribed first-line antibiotic for the susceptible isolate (trimethoprim sulfamethoxazole, amoxicillinclavulanate, nitrofurantoin, and cephalexin), and if the appropriate dose was used. RESULTS: We included 178 patients receiving a diagnosis of uncomplicated UTI and treated with antibiotics. Of these, 70% received an inappropriate diagnosis (n = 125). 58% (n= 72) of improperly diagnosed patients had polymicrobial growth in their urine cultures. Antibiotics prescribed mostly in this group were trimethoprim-sulfamethoxazole (53%, n = 66) and cephalexin (22%, n = 27). Only 30% of all included patients received an appropriate diagnosis (n = 53). Of all appropriate diagnosis patients (n = 53), 26% were treated inappropriately (n = 14) with either wide-spectrum antibiotics (n = 8) or with low calculated dose (n = 6). The estimated cost of antibiotic treatment for the inappropriate diagnosis group (n = 125) was $10,755.87. CONCLUSION: Antimicrobial stewardship programs should target the pediatric outpatient setting and antibiograms should be developed. Education of providers about the appropriate diagnosis and treatment of uncomplicated UTI in children is essential for reducing the cost of inappropriate therapy.

Economic burden and treatment patterns for patients with diffuse large B-cell lymphoma and follicular lymphoma in the USA.

AIM: Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are common types of non-Hodgkin's lymphoma, and real-world evidence continues to be lacking for healthcare costs and utilization among DLBCL and FL patients. Our study aims to describe medical and pharmacy costs and health resource utilization and to characterize longitudinal treatment patterns among these patients. METHODS: A retrospective observational study was performed among adult patients with DLBCL or FL using the US MarketScan (Truven) administrative claims data from 1 January 2007 to 31 December 2015. Diagnoses of DLBCL and FL were based upon ICD-9 codes. Identifications of treatment lines involved 30 lymphoma-specific anticancer systemic agents. Direct healthcare costs and utilizations were computed in the 1-year postdiagnosis period. Generalized linear models with a gamma link were used to compare healthcare costs between therapies with and without rituximab. RESULTS: A total of 2767 DLBCL and 5989 FL patients received frontline therapy. The majority received treatment within 3 months after initial diagnosis (DLBCL 79.9% and FL 62.4%) and were treated with rituximab or bendamustine either alone or in combination (DLBCL 67.4% and FL 84.7%). The total healthcare costs were US $15,555 and $10,192 per patient per month within 1 year following their initial diagnosis for DLBCL and FL, respectively. The medical costs were nearly twice as much as the drug costs for DLBCL patients. Both DLBCL and FL patients receiving rituximab had higher pharmacy costs but lower medical costs (p < 0.001). During the first year following initial diagnosis, the resource utilization (per patient per month) of DLBCL patients included 0.21 inpatient admissions, 0.26 radiation therapy, 2.63 outpatient or office visits, 0.18 emergency room visits, 0.06 intensive care unit admissions and 0.10 stem cell transplantation. FL patients occupied less health resources than DLBCL patients. CONCLUSION: The healthcare costs and health resources utilized were considerable in non-Hodgkin's lymphoma, especially DLBCL patients.

Long-term effectiveness of a gambling intervention program among children in central Illinois.

Youth gambling is an increasing concern. As a response, the "Don't Gamble Away our Future (DGAOF)" program has been implemented among children in central Illinois. We aim to assess the long-term effectiveness of this school-based youth gambling prevention program in Illinois using the data from 2005 to 2009. The intervention included interactive PowerPoint presentations and prevention materials in parent packets. Students aged 8 to 18 years were eligible to participate in the intervention and the questionnaire pre-post knowledge tests (total score 0-9). Students in 5th grade and above also received a gambling behavior screen test using the Modified South Oaks Gambling Screening for Teens (MSOGST) for identifying probable gamblers. Multivariable generalized mixed models were conducted to detect the effects of a 5-year youth gambling prevention program as controlling potential confounders. A total of 16,262 and 16,421 students completed pre-post tests and MSOGST tests, respectively. Of 16,262, half were female, the majority (76.1%) were from senior high school, and 21.3% received the intervention at least twice. The median gap between interventions was 368 days. Students receiving multiple interventions had higher scores on the pre-test as compared to those receiving a single intervention (P<0.001 for all comparisons among groups), and they demonstrated an increasing trend of awareness about gambling over time (P<0.001 for multiple interventions; P = 0.538 for single intervention). The prevalence of problem gambling had decreased among students receiving the intervention twice as compared to receiving the intervention once (7.9% versus 9.4%; OR = 0.89, 95% CL: 0.82-0.97). However, this effect was not confirmed among students receiving the intervention three or more times. In conclusion, the DGAOF program has demonstrated a positive long-term impact on increasing gambling knowledge and partially reducing pathological gamblers through direct training. It suggests that multiple repeated interventions are important for youth gambling prevention.

Impact of treatment with liposomal bupivacaine on hospital costs, length of stay, and discharge status in patients undergoing total knee arthroplasty at high-use institutions.

Aims: Post-surgical pain experienced by patients undergoing total knee arthroplasty (TKA) can be severe. Enhanced recovery after surgery programs incorporating multimodal analgesic regimens have evolved in an attempt to improve patient care while lowering overall costs. This study examined clinical and economic outcomes in hospitals using liposomal bupivacaine (LB) for pain control following TKA.Methods: This retrospective observational study utilized hospital chargemaster data from the Premier Healthcare Database from January 2011 through April 2017 for the 10 hospitals with the highest number of primary TKA procedures using LB. Within these hospitals, patients undergoing TKA who received LB were propensity-score matched in a 1:1 ratio to a control group not receiving LB. Outcomes included hospital length of stay (LOS), discharge status, 30-day same-hospital readmissions, total hospitalization costs, and opioid consumption; only patients with Medicare or commercial insurance as the primary payer for TKA were considered.Results: The study population included 20,907 Medicare-insured patients (LB = 10,411; control =10,496) and 12,505 patients with commercial insurance (LB = 6,242; control = 6,263). Overall, LOS was 0.6 days shorter with LB (p < 0.0001), and patients who received LB were 1.6-times more likely to be discharged home (p < 0.0001). Total hospitalization costs for the TKA procedure were lower with LB for patients with both Medicare (-$616; P < 0.0001) and commercial insurance (-$775; p < 0.0001). Opioid consumption was lower with LB in both payer populations (p < 0.0001). No significant differences for 30-day readmissions were found.Limitations: Costs were estimated using Premier charge-to-cost ratios and limited to goods and services recorded in the chargemaster. Findings from these 10 hospitals may not be representative of other US hospitals.Conclusions: In a sub-set of 10 US hospitals with the highest use of LB for TKA, LB use was associated with shorter hospital LOS, increased home discharge, lower total hospitalization costs, and decreased opioid use after TKA.

Comparison of cost and outcomes in patients receiving thoracic epidural versus liposomal bupivacaine for video-assisted thoracoscopic pulmonary resection.

BACKGROUND: Thoracic Epidural has long been the most recommended treatment for postoperative pain management in general thoracic surgery. This study compares liposomal bupivacaine (LB) as an alternative method for pain control and compares it to the standard. METHODS: LB was compared to thoracic epidural bupivacaine hydrochloride (TE BH) in 387 patients who underwent video-assisted thoracoscopic pulmonary resection (VATS-R) at our institution. Patients received either continuous TE BH or intraoperative LB at a predetermined dose. A total of 237 patients received TE BH from April 2010 to March 2014 and 143 patients received LB from April 2014 to March 2016. After propensity matching, 95 patients in each group had similar demographics and clinical characteristics including gender, age, race, American Society of Anesthesia (ASA) classification, Zubrod scores, and FEV1 and DLCO percent predicted measurements. Outcome measures included hospital costs, length of stay (LOS), adverse events, postoperative opioid medication use, and pain scores. RESULTS: Compared to the TE BH group, the LB group had significantly lower pain scores (average visual analogue scale the day of surgery: 3.9 versus 4.5, p < 0.05), decreased postoperative opioid medication (morphine equivalent dose during the first 3 days: 344.5 versus 269.5, p < 0.05), and lower total and direct hospital costs ($2906 and $1865 respectively, p < 0.05). Although a shorter LOS in the LB group was not statistically significant (4.3 versus 5.1 days, p = 0.156), more patients in the LB group were discharged directly home than the control group (44.2% versus 28.4%, p < 0.05). There was no difference noted in overall adverse events including 30-day readmissions between the two groups. CONCLUSION: LB is a viable alternative for pain management in patients undergoing VATS-R. With recent scrutiny on healthcare costs and the opioid epidemic, these results are encouraging and should be further investigated.