Real-World Data (RWD) on the 3-Year Follow-Up Outcomes of Different CNS Prophylaxis Strategies Across CNS-IPI Risk Groups in Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma

PURPOSE CNS relapse in patients with diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis with a median survival of about 2.5 months. Data demonstrating best prophylactic strategy remain controversial and need further definition. PATIENTS AND METHODS We present data of 110 patients with DLBCL treated with standard systemic therapy divided into four groups based on primary CNS prophylaxis strategy and CNS International Prognostic Index (IPI) risk categories. We compared their 3-year CNS relapse rate and overall survival in each group. RESULTS The CNS prophylaxis strategy consisted of intrathecal (IT) methotrexate (MTX) in group 1, high-dose (HD) MTX in group 2, combination IT and HD MTX in group 3, and IT and/or HD MTX with intensive chemotherapy in group 4. At 3 years, CNS relapse rate was 8.6% (4/46), 8.3% (1/12), 4.8% (2/42), and 18% (2/11) in groups 1-4 ( P = .64), respectively. According to CNS IPI, the CNS relapse rate was 16.6%, 10.1%, and 0% in high-, intermediate-, and low-risk groups, respectively. The 3-year overall survival rate was 69%, 75%, 80%, and 45% in groups 1-4 ( P = .71), respectively. CONCLUSION Our study while did not find statistical significance did indicate a lower incidence of CNS relapse with the addition of systemic HD MTX to IT MTX in the high-risk DLBCL population.

Waiting for Godot: A cross sectional survey based analysis of the hydroxychloroquine prophylaxis strategy against COVID-19 in India

Background: India currently has the second largest burden of infections due to COVID-19. Health Care Worker (HCW) shortages are endemic to Indian healthcare. It should therefore be a huge priority to protect this precious resource as a critical component of the systemic response to this pandemic. Advisories from the Indian Council of Medical Research (ICMR) have focused on using hydroxychloroquine prophylaxis against COVID-19 in at risk HCW. This prophylaxis strategy has no evidence. In further jeopardy there appear to insubstantial attempts to build this evidence as well. In this connection, we commissioned a survey within our Institution to estimate the penetration of hydroxychloroquine (HCQ) use and use this to statistically model the impact of current ongoing studies in India. We also briefly review the literature on HCQ prophylaxis for COVID-19. Design and methods: A structured survey designed using RedCAP application was disseminated among healthcare professionals employed at an academic referral tertiary care centre via online social media platforms. The survey was kept open for the entire month of June 2020. The survey was additionally used to statistically model the size of studies required to comprehensively address the efficacy of HCQ in this setting.Results: 522 responses were received, of which 4 were incomplete. The ICMR strategy of 4 or more doses of HCQ was complete only in 15% of HCW in our survey. The majority of respondents were doctors (238, 46%). Amongst all category of responders, only 12% (n=63) received the full course. A majority of those who initiated the chemoprophylaxis with HCQ turned out to be medical professionals (59/63) with neither nurse nor other categories of healthcare workers accessing the medication. The respondents of our institutional survey did not report any life-threatening side effects. Presuming efficacy as per ICMR modelling for new registry trial on the lines of the published case control study, equal allocation between cases and controls and assuming a RR of 1.3.6, the power of such a study would be very low for n=2000 for event rates from 2.5-12.5%. Conclusion: We report the low penetration of HCQ chemoprophylaxis among the healthcare workers of our institution. We highlight the inherent drawbacks in the study design of current national COVID related trial based on the statistical modelling of our survey results and published literature, and thereby emphasis the need of evidence-based strategies contributing to research policy at national level.

Is Routine Prophylaxis Against Pneumocystis jirovecii Needed in Liver Transplantation? A Retrospective Single-Centre Experience and Current Prophylaxis Strategies in Spain

In liver transplant (LT) recipients, Pneumocystis jirovecii pneumonia (PJP) is most frequently reported before 1992 when immunosuppressive regimens were more intense. It is uncertain whether universal PJP prophylaxis is still applicable in the contemporary LT setting. We aimed to examine the incidence of PJP in LT recipients followed at our institution where routine prophylaxis has never been practiced and to define the prophylaxis strategies currently employed among LT units in Spain. All LT performed from 1990 to October 2019 were retrospectively reviewed and Spanish LT units were queried via email to specify their current prophylaxis strategy. During the study period, 662 LT procedures were carried out on 610 patients. Five cases of PJP were identified, with only one occurring within the first 6 months. The cumulative incidence and incidence rate were 0.82% and 0.99 cases per 1000 person transplant years. All LT units responded, the majority of which provide prophylaxis (80%). Duration of prophylaxis, however, varied significantly. The low incidence of PJP in our unprophylaxed cohort, with most cases occurring beyond the usual recommended period of prophylaxis, questions a one-size-fits-all approach to PJP prophylaxis. A significant heterogeneity in prophylaxis strategies exists among Spanish LT centres.

Cost-Effectiveness of Long-Term Prophylaxis Versus on-Demand Treatment with Von Willebrand Factor Concentrate in Severe Inherited Von Willebrand Disease

Introduction: von Willebrand Disease (VWD) is the most common inherited bleeding disorder with significant variability in clinical phenotype. Patients with the most severe forms of VWD suffer from frequent bleeding complications including mucosal bleeding, gastrointestinal hemorrhage, hemarthrosis, and muscle hematomas. Long-term prophylaxis with von Willebrand factor (VWF) concentrate has been shown to reduce the frequency of bleeding episodes, but higher costs associated with regular VWF concentrate administration remains a barrier to access. Methods: We constructed a Markov state transition model to compare the cost-effectiveness of on-demand treatment (ODT) with long-term prophylaxis (PRO) from a United States (US) societal perspective with costs inflated to 2020 US dollars using the Consumer Price Index. Cycle-length was one month with a one-year time horizon and during each cycle, patients could experience either major (hemarthrosis, gastrointestinal bleeding, muscle hematoma), minor (epistaxis, other mucosal bleeding), or no bleeding. Model inputs for event probabilities, costs, and utility were obtained from previously published literature; while there are no specific utility data for these treatment strategies in VWD patients, we assumed they would be similar to published age-specific utilities used in hemophilia analyses and performed sensitivity analyses to assess these assumptions. The base case scenario was modeled on a 70 kg patient with severe VWD receiving plasma-derived VWF concentrate. In the PRO strategy, patients received 60 units/kg every 3 days. ODT patients were only treated for specific bleeding events (minor bleeding: 60 units/kg every 12 hours for 3 days in the outpatient setting; major bleeding: VWF concentrate 60 units/kg every 12 hours for 5 days in the hospital). Microsimulation of 1000 trials was performed using to calculate mean quality-adjusted life-years (QALYs) and costs associated with the two treatment strategies. TreeAge Pro 2017 (TreeAge Software, Williamstown, MA) was used to construct the model and perform analyses. Results: In the base-case scenario using plasma-derived VWF concentrate, on-demand treatment resulted in a mean cost of US$1,140,586 (± $65,215) generating 0.52 QALYs (±0.01) while the prophylaxis strategy resulted in a mean cost of US$918,329 (± $94,983) generating 0.8 QALYs (±0.04). The microsimulation was repeated to reflect the cost of recombinant VWF concentrate for prophylaxis and a single dose of recombinant factor VIII. Using recombinant VWF, on-demand treatment resulted in a mean cost of US$1,568,005 (± $94206) and generated 0.52 QALYs (±0.01) while the prophylaxis strategy resulted in a mean cost of US$1,343,715 (± $124,974) and generated 0.8 QALYs (±0.04). One-way sensitivity analysis of model inputs showed this result to be robust, as prophylaxis remained the preferred strategy at a willingness to pay (WTP) threshold of US$150,000/QALY for both plasma-derived and recombinant therapies (Figure). Conclusions: With greater effectiveness and lower total societal health care costs, the prophylaxis strategy dominated the on-demand treatment strategy. While the cost of long-term prophylaxis is primarily due to the high cost of VWF concentrate every 3 days, this strategy results in significantly fewer bleeding episodes per year resulting in more QALYs. Our findings suggest that when compared to on-demand treatment, long-term prophylaxis with VWF concentrate is a cost-effective strategy in patients with severe forms of VWD, which helps to avoid expensive hospitalizations and decreased quality of life due to bleeding episodes and their complications. Figure 1 Disclosures No relevant conflicts of interest to declare.

Change in the Dominant Side of Chewing as a Serious Factor for Adjusting the Prophylaxis Strategy for Implant-Supported Fixed Dental Prosthesis of Bounded Lateral Defects

Objective The main purpose of this article is to study the effect of a change in the dominant side of chewing after prosthetics with fixed structures on implants on the main indicators of osseointegration, adaptation to dentures, and the clinical dental status of patients. Materials and Methods In a clinical trial, an analysis was made of the adaptation of 64 patients to intraosseous implant-supported fixed dentures and 56 apparently healthy volunteers. The examination complex included determination of the functionally dominant side of chewing, gnathodynamometry and electromyography indicators of masticatory muscles, and radiological osseointegration criteria. The overall treatment outcomes were evaluated using a visual analogue scale and an objective medical questionnaire, “Prognosis of Adaptation to Orthopedic Structures.” Results Patients were divided into two subgroups: with a change in the dominant side of chewing after completion of orthopaedic treatment (40 cases) and without a change in the dominant side of chewing (24 cases). In the second subgroup of patients, in contrast to the first subgroup, relatively better indicators of gnathodynamometer and electromyography were observed. So, in the first group, gnathodynamometry indicators on the dominant side were 255.7 N and in the second group 225 N after 9 to 12 months. Electromyography indices amounted to (198.5 μV s) to (166.3 μV s) after 9 to 12 months. Bone density remained at the required level, and overall treatment outcomes were higher. Namely, the compact plate of the alveolar ridge was preserved, and the condition of the bone tissue around the implants testified to stable osseointegration. The participation of surface masticatory muscles in adaptation of patients to intraosseous implant-supported fixed orthopaedic structures and the necessity and importance of changing the dominant chewing side for the general outcomes of orthopaedic treatment have been discussed. Conclusions It has been established that a change in the functionally dominant chewing side is accompanied by relatively unstable indicators of chewing function, which is combined with increased loads on the installed prostheses during 3 to 6 months of adaptation. This must be taken into account when planning an individual patient adaptation complex for dental orthopaedic structures.

Venous thromboembolism prophylaxis in ambulatory cancer patients initiating chemotherapy: A cost-effectiveness analysis.

7074 Background: Venous thromboembolism (VTE) is a major cause of morbidity and mortality among cancer patients. The Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) randomized controlled trial concluded that apixaban is a safe and effective option for VTE prophylaxis in high-risk ambulatory cancer patients initiating a new chemotherapy regimen. We performed a cost-effectiveness analysis from a health system perspective to determine if apixaban is a feasible prophylactic strategy for this population. Methods: A decision model was created from a third party payer perspective with a time horizon of 6 months, based on the treatment arms of the AVERT trial: (1) apixaban 2.5 mg twice daily for 6 months during active chemotherapy versus (2) placebo. Rates of VTE (4.2% apixaban vs 10.2% placebo), major bleeding (3.5% vs 1.8%) and clinically relevant nonmajor bleeding (CRNMB) (7.3% vs 5.5%) were modeled from the results of the AVERT trial. Cost estimates for treatments and events were obtained from wholesale drug costs, previously published studies and Medicare reimbursement data, and adjusted for inflation to 2018 dollars. Quality adjusted life years were calculated based on previously published utility values for the health states of advanced cancer, DVT, PE, and major bleeding events. An exploratory analysis was performed comparing prophylactic aspirin to no prophylaxis assuming a VTE rate of 7.2%, major bleeding rate of 3.5%, and CRNMB rate of 7.3%, based on the conservative assumptions that while aspirin may not be as effective at preventing VTE, the rate of clinically significant bleeding events would be similar or greater than that of apixaban. Results: In the base case model, apixaban is more costly and more effective than placebo (ICER = $5,013,190/QALY), and the cost per VTE prevented in the apixaban arm is $33,000. In one-way sensitivity analysis, if the cost of apixaban were reduced by 40% from $3,197 to $1,250 for a 6 month course, this could potentially be a cost-effective prophylaxis strategy with an ICER less than $100,000/QALY. In the alternative analysis, aspirin dominates placebo as it is both more effective and less expensive, and remains cost-effective even when the rate of clinically recognized bleeding with aspirin exceeds 15%. Conclusions: Further investigation into less costly prophylactic options such as generic direct oral anticoagulants (once available) and aspirin is warranted prior to broader implementation of a VTE prophylaxis strategy in this population.

Pre-Exposure Prophylaxis for COVID-19 Disease.

As we approach June 2020, more than five million people worldwide have been infected with the SARS-CoV-2 coronavirus and more than 300,000 have died of COVID-19 disease. International economies remain at a standstill, and social isolation based on palpable fear of death remains the order of the day. The United States and other countries are moving toward resuming work activities and social interaction to boost economic recovery. While this makes financial sense, from a medical perspective our population may suffer severe losses in the absence of a viable prophylaxis strategy for SARS-CoV-2. Herein we present a plan to address this problem.

Efficacy and safety of the combination of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease in lung transplant recipients (CYTOCOR STUDY): an open-label, randomised, non-inferiority clinical trial

IntroductionProlonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought to reduce their use. The monitoring of cell immunity against CMV could be an alternative as it has shown to be useful in identifying transplant patients at low risk of infection, who could benefit from shorter prophylaxis. Theaimof the CYTOCOR study is to demonstrate that the combination of a reduced prophylaxis strategy with subsequent CMV-specific immunological monitoring would allow CMV infection to be controlled in lung transplant patients as effectively as the usual strategy (prophylaxis followed by pre-emptive therapy), while reducing the side effects of antivirals due to the shorter duration of prophylaxis.Methods and analysisPhase III randomised, open, multicentre, parallel, non-inferiority clinical trial to study the efficacy and safety of the combination of a prophylaxis strategy up to month +3 post-transplant followed by immuno-guided prophylaxis using the QuantiFERON-CMV technique up to month +12 post-transplant to prevent CMV disease in CMV-seropositive lung transplant recipients. This strategy will be compared with a combination of a usual prophylaxis strategy up to month +6 post-transplant followed by pre-emptive therapy up to month +12. To study the incidence of CMV disease, patients will be followed up to 18 months post-transplantation. A total of 150 patients are expected to be recruited for the study.Ethics and public disseminationThe clinical trial has been approved by the Research Ethics Committees and authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS).If the hypothesis of this clinical trial is verified, the dissemination of the results could change clinical practice by increasing knowledge about the safety and efficacy of discontinuing valganciclovir prophylaxis in lung transplant recipients.Trial registration numberNCT03699254.