Real-world total cost of care by line of therapy in relapsed/refractory diffuse large B-cell lymphoma.

AIMS: There are multiple recently approved treatments and a lack of clear standard-of-care therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). While total cost of care (TCC) by the number of lines of therapy (LoTs) has been evaluated, more recent cost estimates using real-world data are needed. This analysis assessed real-world TCC of R/R DLBCL therapies by LoT using the IQVIA PharMetrics Plus database (1 January 2015-31 December 2021), in US patients aged ≥18 years treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or an R-CHOP-like regimen as first-line therapy. METHODS: Treatment costs and resources in the R/R setting were assessed by LoT. A sensitivity analysis identified any potential confounding of the results caused by the impact of the COVID-19 pandemic on healthcare utilization and costs. Overall, 310 patients receiving a second- or later-line treatment were included; baseline characteristics were similar across LoTs. Inpatient costs represented the highest percentage of total costs, followed by outpatient and pharmacy costs. RESULTS: Mean TCC per-patient-per-month generally increased by LoT ($40,604, $48,630, and $59,499 for second-, third- and fourth-line treatments, respectively). Costs were highest for fourth-line treatment for all healthcare resource utilization categories. Sensitivity analysis findings were consistent with the overall analysis, indicating results were not confounded by the COVID-19 pandemic. LIMITATIONS: There was potential misclassification of LoT; claims data were processed through an algorithm, possibly introducing errors. A low number of patients met the inclusion criteria. Patients who switched insurance plans, had insurance terminated, or whose enrollment period met the end of data availability may have had truncated follow-up, potentially resulting in underestimated costs. CONCLUSION: Total healthcare costs increased with each additional LoT in the R/R DLBCL setting. Further improvements of first-line treatments that reduce the need for subsequent LoTs would potentially lessen the economic burden of DLBCL.

Using a theory-informed approach to guide the initial development of a post-tuberculosis care package in British Columbia, Canada.

BACKGROUND: The importance of addressing the long-term needs of tuberculosis (TB) survivors is gaining increasing attention. One promising approach to improving post-TB care is implementing a post-TB care package. With a specific focus on the perspectives of healthcare providers in British Columbia, Canada, this study aimed to (1) determine a set of components to be included in a post-TB care package, (2) explore barriers and facilitators influencing their implementation, and (3) propose potential solutions to overcome identified challenges. METHODS: Employing a multi-method approach guided by the Theoretical Domains Framework, we first conducted virtual workshops with TB care providers and utilized a modified Delphi process to establish a preliminary list of care package components. Then, we surveyed healthcare providers using closed-ended, Likert-scale questions to identify implementation barriers and enablers. Lastly, we mapped the identified barriers and enablers to establish behaviour change techniques to identify possible solutions to overcome the challenges identified. RESULTS: Eleven participants attended virtual workshops, and 23 of 51 (45.1%) healthcare providers completed questionnaires. Identified components of the post-TB care package included: 1. Linking people with TB to a primary care provider if they do not have one. 2. Referring people with pulmonary TB for an end-of-treatment chest x-ray and pulmonary function testing. 3. Referring people with TB who smoke to a smoking cessation specialist. 4. Sharing a one-page post-TB information sheet with the patient's primary care provider, including a summary of post-TB health concerns, complications, and recommendations to prioritize age-appropriate screening for cardiovascular disease, lung cancer, and depression. Survey results indicated that domain scores for 'environment, context, and resources' were the lowest, suggesting potential implementation barriers. Care navigation services to help individuals overcome health system barriers while transitioning from TB care, information leaflets, and checklists summarizing key post-TB health concerns for patients and healthcare providers to help facilitate discussions may help overcome the identified barriers. CONCLUSION: Healthcare providers in British Columbia acknowledge that post-TB care is integral to comprehensive health care but are limited by time and resources. Care navigation services, a post-TB checklist, and patient information leaflets may help resolve some of these barriers.

Risk factors for SARS-CoV-2 seroprevalence following the first pandemic wave in UK healthcare workers in a large NHS Foundation Trust.

BACKGROUND: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity. METHODS: HCWs at Sheffield Teaching Hospitals NHS Foundation Trust (STH) were prospectively enrolled and sampled at two time points. SARS-CoV-2 antibodies were tested using an in-house assay for IgG and IgA reactivity against Spike and Nucleoprotein (sensitivity 99·47%, specificity 99·56%). Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model. FINDINGS: As of 12th June 2020, 24·4% (n=311/1275) HCWs were seropositive. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0-52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4-56·5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years. INTERPRETATION: HCWs in acute medical units working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more symptomatic individuals. RESEARCH IN CONTEXT: Evidence before this study: We searched PubMed for studies published up to March 6th 2021, using the terms "COVID", "SARS-CoV-2", "seroprevalence", and "healthcare workers", and in addition for articles of antibody titres in different age groups against coronaviruses using "coronavirus", "SARS-CoV-2, "antibody", "antibody tires", "COVID" and "age". We included studies that used serology to estimate prevalence in healthcare workers. SARS-CoV-2 seroprevalence has been shown to be greater in healthcare workers working on acute medical units or within domestic services. Antibody levels against seasonal coronaviruses, SARS-CoV and SARS-CoV-2 were found to be higher in older adults, and patients who were hospitalised.Added value of this study: In this healthcare worker seroprevalence modelling study at a large NHS foundation trust, we confirm that those working on acute medical units, COVID-19 "Red Zones" and within domestic services are most likely to be seropositive. Furthermore, we show that physiotherapists and occupational therapists have an increased risk of COVID-19 infection. We also confirm that antibody titres are greater in older individuals, even in the context of non-hospitalised cases. Importantly, we demonstrate that this can result in age-specific sensitivity in serological assays, where lower antibody titres in younger individuals results in lower assay sensitivity.Implications of all the available evidence: There are distinct occupational roles and locations in hospitals where the risk of COVID-19 infection to healthcare workers is greatest, and this knowledge should be used to prioritise infection prevention control and other measures to protect healthcare workers. Serological assays may have different sensitivity profiles across different age groups, especially if assay validation was undertaken using samples from older and/or hospitalised patients, who tend to have higher antibody titres. Future seroprevalence studies should consider adjusting for age-specific assay sensitivities to estimate true seroprevalence rates.

Adherence and persistence in patients with rheumatoid arthritis at an integrated health system specialty pharmacy.

BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs) improve symptoms and delay progression of rheumatoid arthritis (RA), but adherence is often sub-optimal and many patients change medication (either "switching" to a medication with a different mechanism of action or "cycling" to a medication with the same mechanism of action) during the first year of therapy. Some integrated health-system specialty pharmacies embed pharmacists in clinics to help patients access and adhere to specialty medication. OBJECTIVE: This study assessed DMARD switching, cycling, adherence, and persistence at an outpatient rheumatology clinic with an integrated health-system specialty pharmacy. METHODS: We conducted a retrospective cohort study of adults with RA, naïve to biologic or targeted synthetic DMARDs, who filled ≥ 2 biologic or targeted synthetic DMARD prescriptions within 12 months. Adherence was measured using proportion of days covered (PDC); persistence was computed at 12 months. Univariate analyses compared adherence and persistence between patients with and without a medication change. Ordinal logistic regression examined whether PDC was associated with patient age, gender, race, insurance type, and medication change. RESULTS: We included 772 patients: 79% female/21% male, 89% White/11% non-White, median age 56 years (interquartile range = 48-63). Most patients (84%) did not change medication during the study period, 5% cycled medication one or more times (but did not switch), 9% switched medication one or more times (but did not cycle), and 2% of patients both switched and cycled during the study period. Median PDC of the sample was 0.94 and 73% of patients were persistent. Patients with a medication change had lower PDC than those without (0.89 vs 0.95, P = 0.004), but rate of persistence did not significantly differ between groups (77 vs 72%, P = 0.300). Odds of higher PDC was more likely for men (Odds ratio [OR] = 1.82, 95% confidence interval [CI]: 1.34-2.48, P < 0.001) and less likely for patients who changed medication (OR = 0.65, CI: 0.47-0.91, P = 0.011); age, race, and insurance type were not significant. CONCLUSIONS: Patients with RA demonstrated high medication adherence and persistence, and low rates of switching and cycling. Findings support evidence that integrated health-system specialty pharmacies with clinical pharmacists embedded in outpatient clinics help patients overcome barriers to medication adherence to persist on therapy. DISCLOSURES: This study was funded by Sanofi, Inc. James and J. Choi were employed by Sanofi, Inc., at the time of this study. Peter, Zuckerman, DeClercq, L. Choi, and Tanner, received research funding from Sanofi, Inc., for work on this study. Tanner has also received advisory board/speaker bureau fees from Pfizer, Regeneron, and Sanofi-Aventis. This study was presented as a poster at AMCP Nexus in October 2019 at National Harbor, MD.

The transcriptional landscape of the cultured murine middle ear epithelium in vitro.

Otitis media (OM) is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology, it is clear that epithelial abnormalities underpin the disease. The mechanisms underpinning epithelial remodelling in OM remain unclear. We recently described a novel in vitro model of mouse middle ear epithelial cells (mMEECs) that undergoes mucociliary differentiation into the varied epithelial cell populations seen in the middle ear cavity. We now describe genome wide gene expression profiles of mMEECs as they undergo differentiation. We compared the gene expression profiles of original (uncultured) middle ear cells, confluent cultures of undifferentiated cells and cells that had been differentiated for 7 days at an air liquid interface (ALI). >5000 genes were differentially expressed among the three groups of cells. Approximately 4000 genes were differentially expressed between the original cells and day 0 of ALI culture. The original cell population was shown to contain a mix of cell types, including contaminating inflammatory cells that were lost on culture. Approximately 500 genes were upregulated during ALI induced differentiation. These included some secretory genes and some enzymes but most were associated with the process of ciliogenesis. The data suggest that the in vitro model of differentiated murine middle ear epithelium exhibits a transcriptional profile consistent with the mucociliary epithelium seen within the middle ear. Knowledge of the transcriptional landscape of this epithelium will provide a basis for understanding the phenotypic changes seen in murine models of OM.

Risk factors for SARS-CoV-2 seroprevalence following the first pandemic wave in UK healthcare workers in a large NHS Foundation Trust.

Background: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity. Methods: HCWs at Sheffield Teaching Hospitals NHS Foundation Trust were prospectively enrolled and sampled at two time points. We developed an in-house ELISA for testing participant serum for SARS-CoV-2 IgG and IgA reactivity against Spike and Nucleoprotein. Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model. Results: Our in-house assay had a sensitivity of 99·47% and specificity of 99·56%. We found that 24·4% (n=311/1275) of HCWs were seropositive as of 12th June 2020. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0-52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4-56·5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years. Conclusions:  HCWs in acute medical units and those working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more severe COVID-19 cases.

Estimated Sp02/Fio2 ratio to predict mortality in patients with suspected COVID-19 in the Emergency Department: a prospective cohort study

BackgroundThis study examined whether the presence and severity of Type 1 Respiratory Failure (T1RF), as measured by the ratio of pulse oximetry to estimated fraction of inspired oxygen (SpO2/eFiO2 ratio), is a predictor of in-hospital mortality in patients presenting to the ED with suspected COVID-19 infection. MethodsWe undertook a prospective observational cohort study of patients admitted to hospital with suspected COVID-19 in a single ED in England. We used univariate and multiple logistic regression to examine whether the presence and severity of T1RF in the ED was independently associated with inhospital mortality. Results180 patients with suspected COVID-19 infection met the inclusion criteria for this study, of which 39 (22%) died. Severity of T1RF was associated with increased mortality with odds ratios (OR) and 95% confidence intervals of 1.58 (0.49 - 5.14), 3.60 (1.23 - 10.6) and 18.5 (5.65 - 60.8) for mild, moderate and severe T1RF, respectively. After adjusting for age, gender, pre-existing cardiovascular disease, neutrophil-lymphocyte ration (NLR) and estimated glomerular filtration rate (eGFR), the association remained, with ORs of 0.63 (0.13 - 3.03), 3.95 (0.94 - 16.6) and 45.8 (7.25 - 290). The results were consistent across a number of sensitivity analyses. ConclusionsSeverity of T1RF in the ED is an important prognostic factor of mortality in patients admitted with suspected COVID-19 infection. Current prediction models frequently do not include this factor and should be applied with caution. Further large scale research on predictors of mortality in COVID-19 infection should include SpO2/eFiO2 ratios or a similar measure of respiratory dysfunction. KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSA number of studies have identified potential variables to predict mortality in patients with COVID-19 but have mainly focused on laboratory measures. The primary pathophysiology and cause of death seems to be lung injury leading to an acute respiratory distress syndrome (ARDS) like illness, clinically presenting as type 1 respiratory failure (T1RF). Despite this, only a very small number of studies have included measurements of respiratory dysfunction as predictor of mortality. What this study addsTo our knowledge, this is the first study to examine the association between T1RF as measured by the ratio of pulse oximetry (SpO2) and estimated fraction of inspired oxygen (FiO2) and mortality in patients admitted with suspected COVID-19. The presence and severity of T1RF are strongly associated with mortality. At the same time, other factors previously shown to be associated with mortality are potentially less important than currently assumed, once adjusted for the severity of T1RF.

The impact of racial and ethnic disparities in inhaled corticosteroid adherence on healthcare expenditures in adults with asthma.

Purpose: The purpose of this study is to determine racial and ethnic disparities with the adherence to inhaled corticosteroids (ICSs) in adults with persistent asthma, and their association with healthcare expenditures. Methods: A retrospective, cross-sectional study using the Medical Expenditure Panel Survey (MEPS) 2013-2014 data included patients ≥18 years with persistent asthma. Median medication possession ratio (MPR) was used to dichotomize adherence levels. Multivariate regression analysis was conducted to ascertain the association between adherence and race/ethnicity. Total expenditures and association with adherence were analyzed using a generalized linear model with a log link function and gamma distribution. Unadjusted expenditures were compared after bootstrapping. Results: The average MPR of ICSs for the sample of 277 patients was 0.34. The average MPR level was 0.33 among whites, 0.37 among African-Americans and 0.35 among other minorities. The average MPR was 0.30 among Hispanics, and 0.35 among non-Hispanics. African-Americans were less likely to be adherent than whites (OR 0.95). Hispanics were less likely to be adherent (OR 0.4; CI 0.206-0.777). Higher adherence was associated with significantly higher total health expenditure than lower adherence ($19,223 vs. $12,840 respectively, p < .0001). African-Americans had slightly higher total expenditure compared to whites; however, other minorities had significantly lower health expenditures compared to whites (p = .01). Non-Hispanics spent significantly less on healthcare compared to Hispanics (p = .04). Conclusions: Valuable insight into the economic cost of the disparities as they relate to persistent asthma provides further evidence of possible ethnic inequities that warrant addressing.

The impact of patient education and shared decision making on hospital readmissions for COPD.

PURPOSE: Education on the self-management of COPD has been shown to improve patients' quality of life and reduce hospital admissions. This study aimed to assess the feasibility of a pilot, pragmatic COPD Chronic Care (CCC) education program led by registered respiratory therapists and determine the CCC's impact on hospital readmissions, patient activation, and health status. PATIENTS AND METHODS: This was a prospective, randomized, pilot study of inpatients with COPD admitted to a US community hospital between August 2014 and February 2016. In total, 308 patients were randomized 1:1 to receive standard care with or without the CCC program. Outcomes included the number of patients completing the program, frequency and time to first all-cause and COPD-related hospital readmissions, and changes in the Patient Activation Measure (PAM) and COPD Assessment Test (CAT). RESULTS: Overall, 37% (n=52) of patients in the CCC group and 29% (n=48) of patients in the control group remained in the study for 6 months and completed all follow-up phone calls. In total, 74% (n=105) of patients in the CCC group and 69% (n=115) of patients in the control group had at least one readmission (P=0.316). The time to first all-cause and COPD-related readmission appeared shorter for patients in the CCC group compared with the control group (mean [standard deviation]: 50.2 [54.5] vs 59.9 [63.1] days and 95.1 [80.2] vs 113.7 [82.4] days, respectively; both P=0.231). Patients experienced significant improvement from baseline in mean PAM (both groups) and CAT (CCC group) scores. CONCLUSION: Utilizing respiratory therapists to lead a chronic care education program for COPD in a community hospital was feasible. Although CCC patients showed improvements in perceived symptom severity, they were readmitted sooner than control group patients. However, the program did not impact the frequency of hospital readmissions. A more comprehensive disease management program may be needed to improve outcomes.

Comorbidities and treatment outcomes in multidrug resistant tuberculosis: a systematic review and meta-analysis.

Little is known about the impact of comorbidities on multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) treatment outcomes. We aimed to examine the effect of human immunodeficiency virus (HIV), diabetes, chronic kidney disease (CKD), alcohol misuse, and smoking on MDR/XDRTB treatment outcomes. We searched MEDLINE, EMBASE, Cochrane Central Registrar and Cochrane Database of Systematic Reviews as per PRISMA guidelines. Eligible studies were identified and treatment outcome data were extracted. We performed a meta-analysis to generate a pooled relative risk (RR) for unsuccessful outcome in MDR/XDRTB treatment by co-morbidity. From 2457 studies identified, 48 reported on 18,257 participants, which were included in the final analysis. Median study population was 235 (range 60-1768). Pooled RR of unsuccessful outcome was higher in people living with HIV (RR = 1.41 [95%CI: 1.15-1.73]) and in people with alcohol misuse (RR = 1.45 [95%CI: 1.21-1.74]). Outcomes were similar in people with diabetes or in people that smoked. Data was insufficient to examine outcomes in exclusive XDRTB or CKD cohorts. In this systematic review and meta-analysis, alcohol misuse and HIV were associated with higher pooled OR of an unsuccessful outcome in MDR/XDRTB treatment. Further research is required to understand the role of comorbidities in driving unsuccessful treatment outcomes.

Barriers and Benefits to the Use of Patient-Reported Outcome Measures in Routine Clinical Care: A Qualitative Study.

Patient-reported outcomes (PROs) provide information on how health care affects patient health and well-being and represent a patient-centered approach. Despite this potential, PROs are not widely used in clinical settings. Semi-structured focus groups were conducted with 3 stakeholder groups (patients, providers, and health care administrators) to determine the top 5 perceived barriers and benefits of PRO implementation. The Delphi technique was employed to obtain consensus and rank order responses. Patients perceived survey length to be important, whereas providers and administrators perceived time to collect data and patient health literacy, respectively, as the greatest barriers to PRO implementation. The greatest perceived benefits were the ability to track changes in clinical symptoms over time, improved quality of care, and better disease control among patients, providers, and administrators, respectively. These results may guide the development of novel frameworks for PRO implementation by addressing perceived barriers and building on the perceived benefits to encourage adoption of PROs.

The Assessment of Total Energy Expenditure During a 14-Day In-Season Period of Professional Rugby League Players Using the Doubly Labelled Water Method.

Rugby League is a high-intensity collision sport competed over 80 min. Training loads are monitored to maximize recovery and assist in the design of nutritional strategies although no data are available on the total energy expenditure (TEE) of players. We therefore assessed resting metabolic rate (RMR) and TEE in six Super League players over 2 consecutive weeks in-season including one game per week. Fasted RMR was assessed followed by a baseline urine sample before oral administration of a bolus dose of hydrogen (deuterium 2H) and oxygen (18O) stable isotopes in the form of water (2H218O). Every 24 hr thereafter, players provided urine for analysis of TEE via DLW method. Individual training load was quantified using session rating of perceived exertion (sRPE) and data were analyzed using magnitude-based inferences. There were unclear differences in RMR between forwards and backs (7.7 ± 0.5 cf. 8.0 ± 0.3 MJ, respectively). Indirect calorimetry produced RMR values most likely lower than predictive equations (7.9 ± 0.4 cf. 9.2 ± 0.4 MJ, respectively). A most likely increase in TEE from Week 1 to 2 was observed (17.9 ± 2.1 cf. 24.2 ± 3.4 MJ) explained by a most likelyincrease in weekly sRPE (432 ± 19 cf. 555 ± 22 AU), respectively. The difference in TEE between forward and backs was unclear (21.6 ± 4.2 cf. 20.5 ± 4.9 MJ, respectively). We report greater TEE than previously reported in rugby that could be explained by the ability of DLW to account for all match and training-related activities that contributes to TEE.

Evaluation of the performance improvement CME paradigm for pain management in the long-term care setting.

OBJECTIVE: A performance improvement continuing medical education (PI CME) activity was designed to assist clinicians with accurately identifying and appropriately managing persistent pain in long-term care facility (LTCF) residents. DESIGN: Volunteer LTCFs participated in a three-stage PI CME model consisting of: 1) baseline assessment, 2) implementation of practice improvement interventions, and 3) reassessment. Expert faculty chose performance measures and interventions for the activity. A champion was designated ateach LTCF to collect resident charts and enter data into an online database. SETTING: Eight LTCFs located across the United States participated in the activity. PATIENTS: Fifty resident charts were randomly selected by each LTCF champion (25 for stage 1 and 25 for stage 3); a total of 350 charts were reviewed. INTERVENTIONS: In addition to a toolkit containing numerous performance improvement resources, an in-service meeting led by an expert faculty member was conducted at each LTCF. OUTCOME MEASURES: Stage 3 data were collected 6 weeks after implementation of interventions and compared with stage 1 baseline data to measure change in performance. RESULTS: Aggregate data collected from seven LTCFs completing the PI CME activity through stage 3 revealed improvements from baseline in four of five performance measures. CONCLUSIONS: This CME activity allowed for collection of data demonstrating performance improvement in persistent pain management. The tools used as part of the intervention (available at http://www.achlpicme.org/LTC/toolkit) may help other clinicians enhance their management of LTCF residents with persistent pain.