Superior functional outcome following reverse shoulder arthroplasty compared to hemiarthroplasty for displaced three and four-part fractures in patients 65 and older: Results from a prospective multicentre randomised controlled trial - The Shoulder Hemiarthroplasty or Reverse Polarity Arthoplasty (SHeRPA) trial.

BACKGROUND: Acute unreconstructible 3- or 4-part proximal humerus fractures can be treated with hemiarthroplasty or reverse polarity shoulder arthroplasty. Randomized trials using implants from multiple different companies or uncemented implants have found superior results with reverse polarity arthroplasty. AIMS: This study aims to determine whether cemented reverse polarity arthroplasty produces a superior outcome compared to cemented hemiarthroplasty using one implant system in patients aged 65 years and over at 12 months follow-up as measured with the Constant score. METHODS: A prospective patient and assessor blinded multicenter randomized controlled trial was conducted of shoulder hemiarthroplasty or reverse polarity arthroplasty in patients aged 65 years and older with acute 3- and 4-part proximal humerus fracture not amenable to osteosynthesis. The primary outcome was the Constant score at 12 months with total follow-up to 24 months. Block randomization by site was undertaken using random number generation and sealed envelopes. Power analysis indicated that 17 patients were required in each arm to achieve 80% power with an alpha-value of 5%. Secondary outcome measures were the difference in the mean Constant Score, Quick Disabilities of the Arm Shoulder and Hand Questionnaire (QuickDASH), Oxford Shoulder Score (OSS), American Shoulder and Elbow Surgeons (ASES) Score and EQ5D-5L up to two years; differences in complication rate at one and two years; differences in revision and implant failure at one and two years. RESULTS: 18 patients were randomized to hemiarthroplasty and 18 to reverse polarity arthroplasty across 4 sites. The primary outcome as measured by the Constant score at 12 months was better in the reverse polarity shoulder arthroplasty (RSA) group (Mean 51.1, s.d. 14.9) compared to the hemiarthroplasty (HA) group (mean 35.0, s.d. 13.5) (p=0.004). No significant difference was reported at 24 months but this may be due to high rates of attrition (22%). The mean EQ-5D-5L patient rated health status score was significantly higher in the RSA group compared to the HA group at 12 months. One hemiarthroplasty was revised due to implant uncoupling and one reverse polarity shoulder replacement was revised due to instability. No other complications were recorded. DISCUSSION: Treatment of unreconstructible 3- or 4-part proximal humerus fractures with reverse polarity shoulder arthroplasty results in a superior outcome compared to shoulder hemiarthroplasty at 12 months measured with the Constant score with no increased risk of failure up to 24 months in patients age 65 years and over. High attrition rates are observed in this older population due to cognitive decline and death from other causes.

EXAMINING VARIABILITY IN THE DIAGNOSIS AND MANAGEMENT OF PEOPLE WITH BLEEDING DISORDERS OF UNKNOWN CAUSE: COMMUNICATION FROM THE ISTH SSC SUBCOMMITTEE ON VON WILLEBRAND FACTOR.

BACKGROUND: Bleeding disorder of unknown cause (BDUC) is characterised by a bleeding phenotype in the setting of normal haemostatic testing. No standardised diagnostic criteria or treatment algorithms exist for people with BDUC. To address the unmet need, the International Society on Thrombosis and Haemostasis von Willebrand Factor Scientific Subcommittee (ISTH VWF SCC) performed a real-world survey, aimed at addressing knowledge gaps, developing consensus pathways and ultimately improving care. OBJECTIVES AND METHODS: We sought to determine current international clinical practices in the investigation, registration, and treatment of people with BDUC through an online structured survey of health care providers (HCPs) who managed patient with bleeding disorders. RESULTS: Two hundred and sixteen respondents from 39 countries were included in the final analysis. The clinical assessment of those with a possible bleeding disorder varied, with only 55% excluding hypermobility but high levels (80%) of bleeding assessment tools (BAT) usage. In haemostatic testing only the prothrombin time (PT) and activated partial thromboplastin time (APTT) tests gained universal support. Tranexamic acid (TXA) was favoured for prophylaxis for minor (71%)/major (59%) surgeries and pregnancy (58%) but advice on the treatment advised if bleeding occurred was heterogeneous. The management of heavy menstrual bleeding (HMB) in women despite combined oral contraceptive pill (COCP) use also proved challenging with HCPs selecting multiple alternative strategies. CONCLUSION: Significant variation exists in the recognition, registration and management of people with BDUC worldwide. This survey emphasises the need for consensus pathways to diagnose and treat BDUC to standardise and improve care for patients internationally.

Oligo-barcode illuminates holocentric karyotype evolution in Rhynchospora (Cyperaceae).

Holocentric karyotypes are assumed to rapidly evolve through chromosome fusions and fissions due to the diffuse nature of their centromeres. Here, we took advantage of the recent availability of a chromosome-scale reference genome for Rhynchospora breviuscula, a model species of this holocentric genus, and developed the first set of oligo-based barcode probes for a holocentric plant. These probes were applied to 13 additional species of the genus, aiming to investigate the evolutionary dynamics driving the karyotype evolution in Rhynchospora. The two sets of probes were composed of 27,392 (green) and 23,968 (magenta) oligonucleotides (45-nt long), and generated 15 distinct FISH signals as a unique barcode pattern for the identification of all five chromosome pairs of the R. breviuscula karyotype. Oligo-FISH comparative analyzes revealed different types of rearrangements, such as fusions, fissions, putative inversions and translocations, as well as genomic duplications among the analyzed species. Two rounds of whole genome duplication (WGD) were demonstrated in R. pubera, but both analyzed accessions differed in the complex chain of events that gave rise to its large, structurally diploidized karyotypes with 2n = 10 or 12. Considering the phylogenetic relationships and divergence time of the species, the specificity and synteny of the probes were maintained up to species with a divergence time of ~25 My. However, karyotype divergence in more distant species hindered chromosome mapping and the inference of specific events. This barcoding system is a powerful tool to study chromosomal variations and genomic evolution in holocentric chromosomes of Rhynchospora species.

Transmission and Management of Pathogenic Agrobacterium tumefaciens and Rhodococcus fascians in Select Ornamentals.

Pathogenic Agrobacterium tumefaciens and Rhodococcus fascians are phytobacteria that induce crown gall and leafy gall disease, respectively, resulting in undesirable growth abnormalities. When present in nurseries, plants infected by either bacterium are destroyed, resulting in substantial losses for growers, especially those producing plants valued for their ornamental attributes. There are many unanswered questions regarding pathogen transmission on tools used to take cuttings for propagation and whether products used for bacterial disease control are effective. We investigated the ability to transmit pathogenic A. tumefaciens and R. fascians on secateurs and the efficacy of registered control products against both bacteria in vitro and in vivo. Experimental plants used were Rosa × hybrida, Leucanthemum × superbum, and Chrysanthemum × grandiflorum for A. tumefaciens and Petunia × hybrida and Oenothera 'Siskiyou' with R. fascians. In separate experiments, we found secateurs could convey both bacteria in numbers sufficient to initiate disease in a host-dependent manner and that bacteria could be recovered from secateurs after a single cut through an infected stem. In in vivo assays, none of six products tested against A. tumefaciens prevented crown gall disease, although several products appeared promising in in vitro trials. Likewise, four compounds trialed against R. fascians failed to prevent disease. Sanitation and clean planting material remain the primary means of disease management.

Closed Suction Drainage after Total Knee Arthroplasty with Concomitant Intravenous Tranexamic Acid Administration.

Drain use in total knee arthroplasty (TKA) remains controversial. Use has been associated with increased complications, particularly postoperative transfusion, infection, increased cost, and longer hospital stays. However, studies examining drain use were performed before widespread adoption of tranexamic acid (TXA), which markedly reduces transfusion without increasing venous thromboembolism events. We aim to investigate incidence of postoperative transfusion and 90-day return to the operating room (ROR) for hemarthrosis in TKA with use of drains and concomitant intravenous (IV) TXA. Primary TKAs from a single institution were identified from August 2012 to December 2018. Inclusion criteria were primary TKA, age 18 years and over where use of TXA, drains, anticoagulant, and pre- and postsurgical hemoglobin (Hb) were documented during the patient's admission. Primary outcomes were 90-day ROR specifically for hemarthrosis and rate of postoperative transfusion. A total of 2,008 patients were included. Sixteen patients required ROR, three of which were due to hemarthrosis. Drain output was statistically higher in the ROR group (269.3 vs. 152.4 mL, p = 0.05). Five patients required transfusion within 14 days (0.25%). Patients requiring transfusion had significantly lower presurgical Hb (10.2 g/dL, p = 0.01) and 24-hour postoperative Hb (7.7 g/dL, p < 0.001). Drain output between the transfusion and no transfusion groups varied significantly (p = 0.03), with transfusion patients having higher postoperative day 1 drain output of 362.6 mL and total drain output of 376.6 mL. In this series, postoperative drain use with concomitant weight-based IV TXA is shown to be safe and efficacious. We observed exceedingly low risk of postoperative transfusion compared with prior reports of drain use alone as well as preserved low rate of hemarthrosis that has previously been positively linked to drain use.

Arthroscopic knots: Suture and knot characterisation of modern polyblend suture materials.

Objective: The primary aim of this study was to explore the relationship between the biophysical structure and function of modern suture materials. Particularly the suture's ability to withstand the stressors of surgery and how the material properties affect knot stability. The secondary aim was to investigate the effect that different knots have on the suture material itself. This study builds on previous research assessing suture and knot characteristics but in modern Ultra High Molecular Weight Polyethylene (UHMWPE) materials currently in widespread clinical use in arthroscopic surgery. Methods: Three common UHMWPE sutures and one polyester suture were tested in both a dry and wet state using the Geelong, Nicky's, Surgeon's and Tautline knots. Tensile strength of knots was tested vertically at a 60 mm/min strain rate and 45 mm gauge length. Sutures were tied through a cannula around two 8 mm diameter circular bollards. Testing was conducted in a controlled environment temperature and humidity environment (20 ± 2 °C, 65 ± 2%). Results: No one knot type was optimal over all suture types. Mean tensile strength in both a dry and wet state and a low coefficient of variation (CV) in tensile strength in a wet state were considered as an indication of suitability. With Ethibond sutures this was the Geelong knot (CV:4.2%). With Orthocord sutures both the Geelong and Tautline knots (CV:4.2% and CV:11.9% respectively). With FiberWire sutures the Nickys and Tautline knots (CV:22.6% and CV:22.5% respectively). With ForceFiber sutures all four knots exhibited similar wet tensile strength with high variability showing that all should perform in a similar way invivo. Conclusions: This study demonstrates a statistically significant three-way interaction between polyblend suture materials, the knot and the environment. This has implications for knot security using the tested sutures in different environments, as one knot may not behave the same under all conditions.

Review of optical reporters of radiation effects in vivo: tools to quantify improvements in radiation delivery technique.

Significance: Radiation damage studies are used to optimize radiotherapy treatment techniques. Although biological indicators of damage are the best assays of effect, they are highly variable due to biological heterogeneity. The free radical radiochemistry can be assayed with optical reporters, allowing for high precision titration of techniques. Aim: We examine the optical reporters of radiochemistry to highlight those with the best potential for translational use in vivo, as surrogates for biological damage assays, to inform on mechanisms. Approach: A survey of the radical chemistry effects from reactive oxygen species (ROS) and oxygen itself was completed to link to DNA or biological damage. Optical reporters of ROS include fluorescent, phosphorescent, and bioluminescent molecules that have a variety of activation pathways, and each was reviewed for its in vivo translation potential. Results: There are molecular reporters of ROS having potential to report within living systems, including derivatives of luminol, 2'7'-dichlorofluorescein diacetate, Amplex Red, and fluorescein. None have unique specificity to singular ROS species. Macromolecular engineered reporters unique to specific ROS are emerging. The ability to directly measure oxygen via reporters, such as Oxyphor and protoporphyrin IX, is an opportunity to quantify the consumption of oxygen during ROS generation, and this translates from in vitro to in vivo use. Emerging techniques, such as ion particle beams, spatial fractionation, and ultra-high dose rate FLASH radiotherapy, provide the motivation for these studies. Conclusions: In vivo optical reporters of radiochemistry are quantitatively useful for comparing radiotherapy techniques, although their use comes at the cost of the unknown connection to the mechanisms of radiobiological damage. Still their lower measurement uncertainty, compared with biological response assay, makes them an invaluable tool. Linkage to DNA damage and biological damage is needed, and measures such as oxygen consumption serve as useful surrogate measures that translate to in vivo use.

Incidence of surgical rib fixation at chest wall injury society collaborative centers and a guide for expected number of cases (CWIS-CC1).

PURPOSE: Surgical stabilization of rib fractures (SSRF) improves outcomes in certain patient populations. The Chest Wall Injury Society (CWIS) began a new initiative to recognize centers who epitomize their mission as CWIS Collaborative Centers (CWIS-CC). We sought to describe incidence and epidemiology of SSRF at our institutions. METHODS: A retrospective registry evaluation of all patients (age > 15 years) treated at international trauma centers from 1/1/20 to 7/30/2021 was performed. Variables included: age, gender, mechanism of injury, injury severity score, abbreviated injury severity score (AIS), emergency department disposition, length of stay, presence of rib/sternal fractures, and surgical stabilization of rib/sternal fractures. Classification and regression tree analysis (CART) was used for analysis. RESULTS: Data were collected from 9 centers, 26,084 patient encounters. Rib fractures were present in 24% (n = 6294). Overall, 2% of all patients underwent SSRF and 8% of patients with rib fractures underwent SSRF. CART analysis of SSRF by AIS-Chest demonstrated a difference in management by age group. AIS-Chest 3 had an SSRF rate of 3.7, 7.3, and 12.9% based on the age ranges (16-19; 80-110), (20-49; 70-79), and (50-69), respectively (p = 0.003). AIS-Chest > 3 demonstrated an SSRF rate of 9.6, 23.3, and 39.3% for age ranges (16-39; 90-99), (40-49; 80-89), and (50-79), respectively (p = 0.001). CONCLUSION: Anticipated rate of SSRF can be calculated based on number of rib fractures, AIS-Chest, and age. The disproportionate rate of SSRF in patients age 50-69 with AIS-Chest 3 and age 50-79 with AIS-Chest > 3 should be further investigated, as lower frequency of SSRF in the other age ranges may lead to care inequalities.

Characterization of a unique polysaccharide monooxygenase from the plant pathogen Magnaporthe oryzae.

Blast disease in cereal plants is caused by the fungus Magnaporthe oryzae and accounts for a significant loss in food crops. At the outset of infection, expression of a putative polysaccharide monooxygenase (MoPMO9A) is increased. MoPMO9A contains a catalytic domain predicted to act on cellulose and a carbohydrate-binding domain that binds chitin. A sequence similarity network of the MoPMO9A family AA9 showed that 220 of the 223 sequences in the MoPMO9A-containing cluster of sequences have a conserved unannotated region with no assigned function. Expression and purification of the full length and two MoPMO9A truncations, one containing the catalytic domain and the domain of unknown function (DUF) and one with only the catalytic domain, were carried out. In contrast to other AA9 polysaccharide monooxygenases (PMOs), MoPMO9A is not active on cellulose but showed activity on cereal-derived mixed (1→3, 1→4)-ß-D-glucans (MBG). Moreover, the DUF is required for activity. MoPMO9A exhibits activity consistent with C4 oxidation of the polysaccharide and can utilize either oxygen or hydrogen peroxide as a cosubstrate. It contains a predicted 3-dimensional fold characteristic of other PMOs. The DUF is predicted to form a coiled-coil with six absolutely conserved cysteines acting as a zipper between the two α-helices. MoPMO9A substrate specificity and domain architecture are different from previously characterized AA9 PMOs. The results, including a gene ontology analysis, support a role for MoPMO9A in MBG degradation during plant infection. Consistent with this analysis, deletion of MoPMO9A results in reduced pathogenicity.

C.acnes in the joint, is it all just a false positive?

BACKGROUND: Cutibacterium Acnes (C.acnes) has been linked to several shoulder pathologies. An alternative hypothesis suggests it only occurs in the joint secondary to previous instrumentation. Our hypothesis was patients with previous instrumentation would have C.acnes in their joint if it was in skin. MATERIALS AND METHODS: Sixty-six patients undergoing arthroscopic shoulder surgery had biopsies taken from the affected joint at the time of surgery, along with control biopsies of subdermal fat. The extended culture results were assessed and correlated to previous intervention. RESULTS: 35% tested positive for C.acnes in their joint. 78% were male. 53% had absence of C.acnes in both skin and joint and 29% had presence in both (p = 0.0001). 15% with previous surgery had C.acnes. 53% with previous injection had C.acnes. 25% of patients with virgin joints had C.acnes. There was no statistical difference in the presence of C.acnes in the joint between those with previous instrumentation and without. CONCLUSION: The significant factors for joint C.acnes were male sex and the presence of the bacteria in the fat. Previous instrumentation was not correlated with C.acnes in the joint. This raises the question of whether the process of biopsy itself may lead to inoculation of the joint.

Navigating our way through a hospital ransomware attack: ethical considerations in delivering acute orthopaedic care.

Ransomware attacks on healthcare systems are becoming more prevalent globally. In May 2021, Waikato District Health Board in New Zealand was devastated by a major attack that crippled its information technology system. The Department of Orthopaedic Surgery faced a number of challenges to the way they delivered care including, patient assessment and investigations, the deferral of elective surgery, and communication and patient confidentiality. These issues are explored through the lens of the four key principles of medical ethics in the hope that they will provide some guidance to future departments who may experience such attacks.

Investigating Media Coverage and Public Perceptions of the HPV Vaccine in China - A Content Analysis of Weibo Posts.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The HPV vaccination has been widely advocated around the world since the vaccine is beneficial in avoiding diseases, including some sexually transmitted diseases, brought on by HPV infections. For most Chinese, the HPV vaccine is still a relatively new concept, having only been made available to the general public in 2016. Despite the vaccine's increased prominence, there is still a lack of investigation about how the public is influencing the conversation about HPV vaccines and the public's perception of this vaccine. With the theoretical construct of the Health Belief Model, this study conducts both quantitative and qualitative content analysis to investigate the existing media narratives around HPV vaccines in China and the changes in public opinion by looking at users' contributions on Weibo, one of China's most popular social networking sites. It was found that different groups of Weibo users had contributed to diverse narratives surrounding HPV vaccination. Though the public awareness of HPV vaccination had been improved along with increasingly active communication practices and enhanced public health services, public knowledge about HPV remains inadequate. Therefore, to facilitate the popularisation of HPV related knowledge, more effort should be invested in tailoring and disseminating messages that communicate responsive and comprehensive HPV related information.

Enterococcus faecalis thrives in dual-species biofilm models under iron-rich conditions.

Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) are pathogenic strains that often coexist in intestinal flora of humans and are prone to cause biofilm-associated infections, such as gastrointestinal tract and urinary tract infections. Earlier studies have demonstrated that E. faecalis biofilm can metabolize ferrous ions in iron-rich environments and promote biofilm growth under in-vivo conditions. However, the influence of iron transporters on dual-species biofilm growth and the nature of molecular-level interactions between iron transporter proteins and Fe2+ remains unknown. Therefore, in this work, co-culture studies were performed and the study indicates that Fe2+ at concentrations of 50-150 µM promotes the colonization of E. coli, and Fe2+ concentrations of 50-200 µM promote the growth of E. faecalis and dual-species colonies. Atomic absorption spectroscopy results reveal that Fe2+ ion augmentation in bacterial cells was increased to 4 folds in the single-species model and 11 folds in the dual-species model under iron-supplemented conditions. Furthermore, Fe2+ augmentation increased the antibiotic resistance of E. faecalis in both single- and dual-species bacterial cultures. In addition, in-silico docking were performed to determine a three-dimensional (3D) structure of ferrous iron-transporter proteins FeoB of E. faecalis and its affinity to extracellular Fe2+. Our model suggests that the FeoB facilitates the Fe2+ uptake in E. faecalis cells in the absence of iron chelator, 2,2-bipyridyl.

Primary cutaneous adenoid cystic carcinoma of the neck presenting as a rapidly growing posterior triangle neck mass.

A woman in her 70s presented to a tertiary otorhinolaryngology outpatient department with a 25-year history of right-sided subcutaneous neck lesion that had steadily grown over the preceding 6 months, now with skin involvement. The patient was asymptomatic except for some mild tenderness. The 3 × 3 cm mass lay fixed to deep tissues adjacent to the sternocleidomastoid muscle, though no associated lymphadenopathy was found on palpation, with imaging confirming no regional or distant metastases. Biopsy confirmed the lesion to be primary cutaneous adenoid cystic carcinoma, a malignancy not previously described as a primary on the neck, which was treated by wide local excision after multidisciplinary team discussion. The lesion was completely excised with negative margins, and after surveillance over 3 years, the patient is still well with no signs of recurrence.

Single-Surgery Co-Implantation of Autologous Primary Articular Chondrocytes with Bone Marrow Cells in the Treatment of Articular Cartilage Lesions: Observations from the Operating Room on Tissue Input and Cell Output.

OBJECTIVE: Single-surgery variants of autologous chondrocyte implantation to repair cartilage are emerging, but practical data on such procedures are scarce. We set out to describe a 1-stage autologous chondrocyte co-implantation procedure and include quantitative characteristics of the biopsy tissues collected and of the cells obtained from those tissues in the operating room. DESIGN: Data concerning patient age, articular cartilage lesion size and location, as well as measurements of cartilage biopsy mass, bone marrow aspirate volume, and the cell yields harvested from those biopsies were intraoperatively collected for 141 patients. RESULTS: The mean patient age was 35.7 ± 9.8 years, and the mean total lesion size was 4.0 ± 3.1 cm2. Cartilage biopsy mass ranged from 0.19 to 2.0 gram and provided a mean yield of 1.23 × 106 chondrocytes/gram. Bone marrow aspirate volume ranged from 7.2 to 62 milliliters and provided a mean yield of 7.18 × 106 mononuclear cells/mL. The cell yields did not correlate with patient age, which ranged from 12 to 57 years. The mean primary chondrocyte supply was 272 thousand per cm2 of lesion, ranging from 10.4 thousand to 1.07 million per cm2. The total cell supply was kept at 9 million cells per cm2 of lesion by adding mononuclear cells to the chondrocytes. The mean tissue processing time was 100 ± 19 minutes, which was frequently used to perform concurrent interventions. CONCLUSION: Single-surgery co-implantation of clinically relevant numbers of autologous primary articular chondrocytes and bone marrow cells is feasible for a wide range of ages and lesion sizes.

Costs per patient achieving remission with venetoclax-based combinations in newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemotherapy.

BACKGROUND: Venetoclax, in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC), received confirmatory approval in 2020 by the US Food and Drug Administration for the treatment of newly diagnosed acute myeloid leukemia (AML) in patients aged 75 years or older or who are ineligible for intensive induction chemotherapy. The economic value associated with response to venetoclax combinations compared with other treatments for this patient population has not been comprehensively evaluated. OBJECTIVE: To assess the cost per patient achieving remission with venetoclax combination therapies, compared with other therapies for newly diagnosed patients with AML who are ineligible for intensive induction chemotherapy, from a US third-party payer perspective. METHODS: The analysis used treatment effect estimates (ie, complete remission [CR] + CR with incomplete blood count recovery [CRi]) from a network meta-analysis and annual cost estimates from a prior budget impact model. The model considered the total cost of care including the costs of drug and administration, adverse events, hospitalization, disease monitoring, blood transfusions, and subsequent AML management when patients discontinued active treatment. Costs per patient achieving CR + CRi associated with venetoclax + azacitidine, venetoclax + LDAC, azacitidine, decitabine, LDAC, and best supportive care (ie, treatment given with the intent to maximize quality of life without specific antileukemic intent, such as blood transfusion products and antibiotics) were calculated as the annual total cost of care per patient divided by the CR + CRi rate. All costs were adjusted to 2020 US dollars. RESULTS: Venetoclax combination therapies were estimated to have substantially lower costs per patient achieving CR + CRi (venetoclax + azacitidine: $473,960; venetoclax + LDAC: $428,071) than alternative treatments. Azacitidine was estimated to have the the highest cost per patient achieving CR + CRi ($1,197,438), followed by best supportive care ($869,849), LDAC ($689,101), and decitabine ($594,074). A pair-wise matrix of the difference between therapies estimated that both venetoclax + azacitidine and venetoclax + LDAC were associated with significantly lower costs per patient achieving CR + CRi than azacitidine (by $723,477 and $769,367, respectively) and LDAC (by $215,141 and $261,030; all P < 0.05). CONCLUSIONS: From a US third-party payer perspective, venetoclax in combination with azacitidine or LDAC was estimated to be associated with a significantly lower cost per patient achieving CR + CRi than azacitidine or LDAC among newly diagnosed patients with AML ineligible for intensive chemotherapy. DISCLOSURES: This research was supported by AbbVie Inc. and Genentech. The sponsors helped design the study, interpret the data, and draft the manuscript. Drs Bui and Kapustyan are employees of and have equity ownership in AbbVie; Dr Choi was an employee of AbbVie during the study's conduct and has equity ownership. Ms Ma and Dr Montez are employees of and have equity ownership in Genentech. Drs Song and Chai, Ms Yin, and Dr Betts are employees of Analysis Group, Inc., which has received funding from AbbVie and Genentech for the conduct of this research. Dr LeBlanc reports personal fees for consulting or advisory boards from AbbVie, Agios/Servier, AstraZeneca, Amgen, Astellas, BlueNote, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Genentech, GSK, Pfizer, and Seattle Genetics; royalties from UpToDate; speakers bureau fees from Agios/Servier, AbbVie, and BMS/Celgene; and grants and/or research contracts from the American Cancer Society, AstraZeneca, BMS, Jazz Pharmaceuticals, and Seattle Genetics.

The impact of remission duration on the long-term economic burden of acute myeloid leukemia among patients without hematopoietic stem cell transplant in the United States.

BACKGROUND AND AIMS: Acute myeloid leukemia (AML) prognosis is poor, with sustained remission occurring in <35% of young adults and <15% of older adults. This descriptive study examined the potential benefit of prolonged remission on the economic burden of AML. METHODS: Using the IBM MarketScan Commercial and Medicare Supplemental databases, we identified newly diagnosed patients with AML without hematopoietic stem cell transplantation from January 1, 2012 to December 31, 2018; AML diagnosis was the index date. Patients had 6 months of pre-index eligibility and were followed until the end of continuous eligibility, study data, or death. Active treatment and supportive care cohorts were defined; duration-of-remission subgroups (0 to <3, 3 to <6, 6 to <12, and ≥12 months) were established among active treatment patients with remission. Healthcare service utilization and costs were reported over follow-up and mutually exclusive treatment, remission, and post-relapse periods. RESULTS: This study included 1,558 active treatment and 1,127 supportive care patients who were followed for a median of 232 and 62 days, respectively. Over follow-up, active treatment and supportive care patients incurred mean ± standard deviation all-cause healthcare costs of $55,723 ± $61,994 and $68,596 ± $100,375 per-patient-per-month (PPPM), respectively. Decreasing PPPM costs were observed with increased remission duration (0 to <3 months: $71,823 ± $62,635; 3 to <6 months: $54,262 ± $44,734; 6 to <12 months: $35,287 ± $23,699; and ≥12 months: $15,615 ± $10,560). Although median follow-up varied by up to 5-fold, total costs were largely similar across duration-of-remission subgroups (0 to <3 months: $438,569 ± $332,675; 3 to <6 months: $590,411 ± $598,245; 6 to <12 months: $482,902 ± $369,115; and ≥12 months: $448,867 ± $316,133). CONCLUSIONS: The economic burden of AML is substantial, even among untreated patients. Further, among patients with remission, longer durations in remission are associated with reduced PPPM healthcare costs, suggesting that remission-prolonging treatments could help mitigate healthcare costs.

Clinical and cost-effectiveness of Knee Arthroplasty versus Joint Distraction for Osteoarthritis (KARDS): protocol for a multicentre, phase III, randomised control trial.

INTRODUCTION: Knee replacement (KR) is a clinically proven procedure typically offered to patients with severe knee osteoarthritis (OA) to relieve pain and improve quality of life. However, artificial joints fail over time, requiring revision associated with higher mortality and inferior outcomes. With more young people presenting with knee OA and increasing life expectancy, there is an unmet need to postpone time to first KR. Knee joint distraction (KJD), the practice of using external fixators to open up knee joint space, is proposed as potentially effective to preserve the joint following initial studies in the Netherlands, however, has not been researched within an NHS setting. The KARDS trial will investigate whether KJD is non-inferior to KR in terms of patient-reported postoperative pain 12 months post-surgery. METHODS AND ANALYSIS: KARDS is a phase III, multicentre, pragmatic, open-label, individually randomised controlled non-inferiority trial comparing KJD with KR in patients with severe knee OA, employing a hybrid-expertise design, with internal pilot phase and process evaluation. 344 participants will be randomised (1:1) to KJD or KR. The primary outcome measure is the Knee Injury and Osteoarthritis Outcomes Score (KOOS) pain domain score at 12 months post-operation. Secondary outcome measures include patient-reported overall KOOS, Pain Visual Analogue Scale and Oxford Knee Scores, knee function assessments, joint space width, complications and further interventions over 24 months post-operation. Per patient cost difference between KR and KJD and cost per quality-adjusted life year (QALY) gained over 24 months will be estimated within trial, and incremental cost per QALY gained over 20 years by KJD relative to KR predicted using decision analytic modelling. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Research Ethics Committee (REC) and Health Research Authority (HRA). Trial results will be disseminated at clinical conferences, through relevant patient groups and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN14879004; recruitment opened April 2021.