Cost-Effectiveness of Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Older Patients With High-Risk Myelodysplastic Syndrome: Analysis of BMT CTN 1102.

PURPOSE: BMT CTN 1102 was a phase III trial comparing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT) to standard of care for persons with intermediate- or high-risk myelodysplastic syndrome (MDS). We report results of a cost-effectiveness analysis conducted alongside the clinical trial. METHODS: Three hundred eighty-four patients received HCT (n = 260) or standard of care (n = 124) according to availability of a human leukocyte antigen-matched donor. Cost-effectiveness was calculated from US commercial and Medicare perspectives over a 20-year time horizon. Health care utilization and costs were estimated using propensity score-matched cohorts of HCT recipients in the OptumLabs Data Warehouse (age 50-64 years) and Medicare (age 65 years and older). EuroQol 5 Dimension (EQ-5D) surveys of trial participants were used to derive health state utilities. RESULTS: Extrapolated 20-year overall survival for those age 50-64 years was 29% for HCT (n = 105) versus 13% for usual care (n = 44) and 31% for HCT (n = 155) versus 12% for non-HCT (n = 80) for those age 65 years and older. HCT was more effective (+2.36 quality-adjusted life-years [QALYs] for age 50-64 years and +2.92 QALYs for age 65 years and older) and more costly (+$452,242 in US dollars (USD) for age 50-64 years and +$233,214 USD for age 65 years and older) than usual care, with incremental cost-effectiveness ratios of $191,487 (USD)/QALY and $79,834 (USD)/QALY, respectively. For persons age 50-64 years, there was a 29% chance that HCT was cost-effective using a willingness-to-pay (WTP) threshold of $150K (USD)/QALY and 51% at a $200K (USD)/QALY. For persons age 65 years and older, the probability was 100% at a WTP >$150K (USD)/QALY. CONCLUSION: Among patients age 65 years and older with high-risk MDS, RIC HCT is a high-value strategy. For those age 50-64 years, HCT is a lower-value strategy but has similar cost-effectiveness to other therapies commonly used in oncology.

Cost-Effectiveness of Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Bone Marrow Transplantation: Evidence from BMT CTN 1101.

BMT CTN 1101 was a Phase III randomized controlled trial comparing reduced-intensity conditioning followed by double unrelated umbilical cord blood transplantation (UCBT) versus HLA-haploidentical related donor bone marrow transplantation (haplo-BMT) for patients with high-risk hematologic malignancies. Here we report the results of a parallel cost-effectiveness analysis of these 2 hematopoietic stem cell transplantation (HCT) techniques. In this study, 368 patients were randomized to unrelated UCBT (n = 186) or haplo-BMT (n = 182). We estimated healthcare utilization and costs using propensity score-matched haplo-BMT recipients from the OptumLabs Data Warehouse for trial participants age <65 years and Medicare claims for participants age ≥65 years. Weibull models were used to estimate 20-year survival. EQ-5D surveys by trial participants were used to estimate quality-adjusted life-years (QALYs). At a 5-year follow-up, survival was 42% for haplo-BMT recipients versus 36% for UCBT recipients (P = .06). Over a 20-year time horizon, haplo-BMT is expected to be more effective (+.63 QALY) and more costly (+$118,953) for persons age <65 years. For those age ≥65 years, haplo-BMT is expected to be more effective and less costly. In one-way uncertainty analyses, for persons age <65, the cost per QALY result was most sensitive to life-years and health state utilities, whereas for those age ≥65, life- years were more influential than costs and health state utilities. Compared to UCBT, haplo-BMT was moderately more cost-effective for patients age <65 years and less costly and more effective for persons age ≥65 years. Haplo-BMT is a fair value choice for commercially insured patients with high-risk leukemia and lymphoma who require HCT. For Medicare enrollees, haplo-BMT is a preferred choice when considering costs and outcomes.

Impact of the COVID-19 pandemic on paediatric orthopaedic trauma workload in central London: a multi-centre longitudinal observational study over the "golden weeks".

Background and purpose - The COVID-19 pandemic has been recognised as an unprecedented global health crisis. This study assesses the impact on a large acute paediatric hospital service in London, evaluating the trends in the acute paediatric orthopaedic trauma referral caseload and operative casemix before (2019) and during (2020) COVID-19 lockdown. Patients and methods - A longitudinal retrospective observational prevalence study of both acute paediatric orthopaedic trauma referrals and operative caseload was performed for the first 6 "golden weeks" of lockdown. These data were compared with the same period in 2019. Statistical analyses included median (± median absolute deviation), risk and odds ratios as well as Fisher's exact test to calculate the statistical significance, set at p ≤ 0.05. Results - Acute paediatric trauma referrals in 2020 were reduced by two-thirds compared with 2019 (n = 302 vs. 97) with a halving risk (RR 0.55) and odds ratios (OR 0.43) of sporting-related mechanism of injuries (p = 0.002). There was a greater use of outpatient telemedicine in the COVID-19 period with more Virtual Fracture Clinic use (OR 97, RR 84, p < 0.001), and fewer patients being seen for consultation and followed up face to face (OR 0.55, RR 0.05, p < 0.001). Interpretation - The impact of the COVID-19 pandemic has led to a decline in the number of acute paediatric trauma referrals, admissions, and operations during the COVID period. There has also been a significant change in the patient pathway with more being reviewed via the means of telemedicine to reduce the risk of COVID-19 transmission and exposure. More work is required to observe for similar trends nationwide and globally as the pandemic has permanently affected the entire healthcare infrastructure.

The impact of COVID-19 on the future of orthopaedic training in the UK.

The COVID-19 pandemic has had a major impact on global healthcare systems, has drastically affected patient care, and has had widespread effects upon medical education. As plans are being devised to reinstate elective surgical services, it is important to consider the impact that the pandemic has had and will continue to have on surgical training. We describe the effect COVID-19 has had at all levels of training in the UK within trauma and orthopaedics and evaluate how training might change in the future. We found that the COVID-19 pandemic has significantly impacted trainees within trauma and orthopaedics at all levels of training. It had led to reduced operative exposure, cancellations of examinations and courses, and modifications to speciality recruitment and annual appraisals. This cohort of trainees is witnessing novel methods of delivering orthopaedic services, which will continue to develop and become part of routine practice even once the pandemic has resolved. It will be important to observe the extent to which the rapid changes currently being introduced will impact the personal health, safety, and career progression of current trainees.

Disparities in United States hospitalizations for serious infections in patients with and without opioid use disorder: A nationwide observational study.

BACKGROUND: Patients with opioid use disorder (OUD) who are hospitalized for serious infections requiring prolonged intravenous antibiotics may face barriers to discharge, which could prolong hospital length of stay (LOS) and increase financial burden. We investigated differences in LOS, discharge disposition, and charges between hospitalizations for serious infections in patients with and without OUD. METHODS AND FINDINGS: We utilized the 2016 National Inpatient Sample-a nationally representative database of all discharges from US acute care hospitals. The population of interest was all hospitalizations for infective endocarditis, epidural abscess, septic arthritis, or osteomyelitis. The exposure was OUD, and the primary outcome was LOS until discharge, assessed by using a competing risks analysis to estimate adjusted hazard ratios (aHRs). Adjusted odds ratio (aOR) of discharge disposition and adjusted differences in hospital charges were also reported. Of 95,470 estimated hospitalizations for serious infections (infective endocarditis, epidural abscess, septic arthritis, and osteomyelitis), the mean age was 49 years and 35% were female. 46% had Medicare (government-based insurance coverage for people age 65+ years), and 70% were non-Hispanic white. After adjustment for potential confounders, OUD was associated with a lower probability of discharge at any given LOS (aHR 0.61; 95% CI 0.59-0.63; p < 0.001). OUD was also associated with lower odds of discharge to home (aOR 0.38; 95% CI 0.33-0.43; p < 0.001) and higher odds of discharge to a post-acute care facility (aOR 1.85; 95% CI 1.57-2.17; p < 0.001) or patient-directed discharge (also referred to as "discharge against medical advice") (aOR 3.47; 95% CI 2.80-4.29; p < 0.001). There was no significant difference in average total hospital charges, though daily hospital charges were significantly lower for patients with OUD. Limitations include the potential for unmeasured confounders and the use of billing codes to identify cohorts. CONCLUSIONS: Our findings suggest that among hospitalizations for some serious infections, those involving patients with OUD were associated with longer LOS, higher odds of discharge to post-acute care facilities or patient-directed discharge, and similar total hospital charges, despite lower daily charges. These findings highlight opportunities to improve care for patients with OUD hospitalized with serious infections, and to reduce the growing associated costs.

Estimates of conditional survival in gastric cancer reveal a reduction of racial disparities with long-term follow-up.

INTRODUCTION: In prior analyses, conditional survival (CS) estimates for gastric cancer have weighed clinical and pathologic factors to predict prognosis at time intervals after surgery. Since racial disparities in gastric cancer outcomes were not considered, our objective was to determine whether race influences CS estimates. METHODS: Data from the Surveillance, Epidemiology, and End Results cancer registry were used to identify gastric adenocarcinoma patients who underwent curative surgical intervention between 1988 and 2005. Five-year relative conditional survival (RCS) was computed for patients who survived at least 1 to 5 years after surgery. RCS was calculated by assessing observed and expected survival in an age- and race-matched standard population. Results were compared across time and racial groups (white, black, and Asian) using z test statistics. RESULTS: Of 14,067 patients, 63.8 % were white, 15.5 % black, and 20.7 % Asian. Racial disparities among groups were observed with improved survival of Asians at time point zero and improved RCS at 1 year. At 5 years following curative surgery, each racial group had increased RCS and the greatest magnitude of relative increase was observed in white and black patients (121 and 118 %, respectively). Comparison of RCS at the 5-year time point revealed a reduction of racial disparities in survival among the three groups. CONCLUSIONS: Our investigation shows that racial disparities in gastric cancer outcomes are pronounced at the time of curative surgery but diminish after years of survival, thus suggesting race has less influence over outcomes the longer patients survive. The reasons for reduction of racial disparities remain unclear and warrant future study.

Racial and ethnic disparities in gastric cancer outcomes: more important than surgical technique?

Racial and ethnic disparities in cancer care are major public health concerns and their identification is necessary to develop interventions to eliminate these disparities. We and others have previously observed marked disparities in gastric cancer outcomes between Eastern and Western patients. These disparities have long been attributed to surgical technique and extent of lymphadenectomy. However, more recent evidence suggests that other factors such as tumor biology, environmental factors such as Helicobacter pylori infection and stage migration may also significantly contribute to these observed disparities. We review the literature surrounding disparities in gastric cancer and provide data pertaining to potential contributing factors.

Exponential error reduction in pretransfusion testing with automation.

BACKGROUND: Protecting the safety of blood transfusion is the top priority of transfusion service laboratories. Pretransfusion testing is a critical element of the entire transfusion process to enhance vein-to-vein safety. Human error associated with manual pretransfusion testing is a cause of transfusion-related mortality and morbidity and most human errors can be eliminated by automated systems. However, the uptake of automation in transfusion services has been slow and many transfusion service laboratories around the world still use manual blood group and antibody screen (G&S) methods. STUDY DESIGN AND METHODS: The goal of this study was to compare error potentials of commonly used manual (e.g., tiles and tubes) versus automated (e.g., ID-GelStation and AutoVue Innova) G&S methods. Routine G&S processes in seven transfusion service laboratories (four with manual and three with automated G&S methods) were analyzed using failure modes and effects analysis to evaluate the corresponding error potentials of each method. RESULTS: Manual methods contained a higher number of process steps ranging from 22 to 39, while automated G&S methods only contained six to eight steps. Corresponding to the number of the process steps that required human interactions, the risk priority number (RPN) of the manual methods ranged from 5304 to 10,976. In contrast, the RPN of the automated methods was between 129 and 436 and also demonstrated a 90% to 98% reduction of the defect opportunities in routine G&S testing. CONCLUSION: This study provided quantitative evidence on how automation could transform pretransfusion testing processes by dramatically reducing error potentials and thus would improve the safety of blood transfusion.

Yield increases in intact influenza vaccine virus from chicken allantoic fluid through isolation from insoluble allantoic debris.

A yield enhancement technology for use in influenza vaccine manufacturing has been developed to maximize the recovery of influenza virus from allantoic fluid of virus-infected chick embryos; the standard raw material for influenza vaccine. Virus associated with amorphous debris in the allantoic fluid can be dissociated from the debris and recovered, thereby increasing viral yield. Dissociation can be achieved by subjecting the virus-debris complex to conditions of increased ionic strength at defined pH. Multifold increases in viral yield per ml of allantoic fluid were observed. The degree of yield enhancement is strain-specific, however, increases were observed in all type A and type B influenza strains tested. The heightened influenza virus recoveries can facilitate rapid vaccine manufacture, with increased numbers of doses produced, and may become essential at a time of influenza pandemic.