Unacceptable Outcomes Research Articles

Comparative Analysis of Osteoarthritis Therapeutics: A Justification for Harnessing Retrospective Strategies via an Inverted Pyramid Model Approach

In this review, we seek to explore two distinct approaches to the clinical management of OA: a prospective approach, addressing primarily one’s genetic predisposition to OA and generating early intervention options, and the retrospective approach, aimed at halting or reversing OA progression post-symptom onset. The clinical management of OA remains challenging, largely due to the limited availability of preventative treatments and failure of existing therapies to modify or reverse the underlying pathophysiology. The prospective approach involves the identification of genetic markers associated with OA and utilizes in vitro and in vivo models to characterize the underlying disease mechanism. Further, this approach focuses on identifying genetic predispositions and unique molecular subtypes of OA to develop individualized treatment plans based on patient genotypes. While the current literature investigating this strategy has been notable, this approach faces substantial challenges, such as extensive time burdens and utilization of extensive genetic testing that may not be economically feasible. Additionally, there is questionable justification for such extensive investigations, given OA’s relatively low mortality rates and burden when contrasted with diseases like specific forms of cancer, which rely heavily on the prospective approach. Alternatively, the retrospective approach primarily focuses on intervention following symptom onset and aims to utilize novel therapeutics to slow or reverse the inflammatory cascade typically seen in disease progression. These treatments, like Hippo pathway inhibitors, have shown initial promise in halting OA progression and alleviating OA symptomology by modulating cellular processes to preserve articular cartilage. In comparison to the prospective approach, the retrospective strategy is likely more cost-effective, more widely applicable, and does not necessitate thorough and invasive genetic screening. However, this approach must still be weighed against the typical natural history of disease progression, which frequently results in total knee arthroplasty and unacceptable outcomes for 15–20% of patients. From a comparative analysis of these two approaches, this review argues that the retrospective strategy, with ideally lower time and economic burden and greater accessibility, offers a more reasonable and effective solution in the context of OA management. Using a similar approach to other management of chronic diseases, we suggest an “Inverted Pyramid” model algorithm, a structured research and development regimen that prioritizes generating widely effective therapies first, with subsequent refinement of treatments based on the development of patient resistance to these therapies. We argue that this strategy may reduce the need for total knee arthroplasty while improving patient outcomes and accessibility.

Working towards more socially acceptable outcomes from airspace modernisation

The UK is currently undertaking a process of airspace modernisation, which has revealed potentially competing objectives for the management of aircraft noise impacts. Communities at some airports are concerned about the fairness of potential outcomes in terms of changes to the pattern of aircraft noise exposure. This research draws upon in-depth community focus groups where the fairness and equity of different airspace change concepts for a fictitious departure route were discussed using a virtual airport scenario. These discussions revealed a preference of minimal change compared to the existing patterns of noise exposure, where the use of a number above metric (N65) was particularly helpful in allowing participants to understand the implications of different airspace change options on the spatial distribution of noise on the ground. The paper demonstrates how N65 data can be used to summarise the consequences of different airspace change options, supporting stakeholders in assessing the relative distributional fairness of each proposal. Such transparency around the consequences of airspace change proposals enhances informational fairness and can help build trust in the procedural fairness of airspace decision-making leading to more socially acceptable outcomes (or the least socially unacceptable outcomes).

Calcar reconstruction in bipolar hemiarthroplasty for unstable intertrochanteric fractures

: The increasing popularity of primary bipolar hemiarthroplasty for comminuted and osteoporotic intertrochanteric femur fractures is well-documented. However, the absence of posteromedial calcar support due to fracture presents a unique challenge: implant instability and varus collapse. Existing solutions, relying on stem modifications or bone cement void filling, encounter limitations in cost-effectiveness and biomechanical performance.: This study evaluated the efficacy of posteromedial calcar reconstruction using autologous cortical grafts harvested from the extracted femoral head and neck in 30 patients with intertrochanteric femur fractures. Following strict inclusion and exclusion criteria, primary bipolar hemiarthroplasty was performed with meticulous graft implantation. Weight-bearing and range-of-motion exercises commenced on postoperative day 1. Functional and radiological outcomes were assessed at 12 months follow-up. The demographic distribution revealed a 50:50 split between patients above and below 75 years old. 73.33% (n=22) fractures were right-sided, and AO 31-A2.2 emerged as the most prevalent fracture pattern (46.67%, n=14). An acceptable functional and radiological outcome was achieved in 93.33% (n=28) patients. Two complications (superficial infection and implant breakage) resulted in unacceptable outcomes. Notably, the calcar grafts demonstrated robust healing in patients with favorable functional outcomes (Excellent and Good), as evidenced by a mean Harris Hip Score of 93.11 at 1 year follow-up. This study demonstrates the potential of a well-shaped, wedged autologous cortical graft harvested from the femoral head and neck as an effective strategy for calcar reconstruction in intertrochanteric femur fractures. This technique facilitates graft union, prevents implant subsidence, and offers enhanced biomechanical stability with optimal stress distribution. Furthermore, it eliminates the need for allograft or donor site morbidity, leading to reduced costs and patient burden.

Obesity and tobacco smoking are independently associated with poor patient-reported outcomes in SLE: a cross-sectional study

We investigated associations of obesity and tobacco smoking with health-related quality of life (HRQoL), pain, fatigue, and functional impairment in systemic lupus erythematosus (SLE). Furthermore, we explored whether there was an effect modification between these two factors. We included adult SLE patients from the Linköping University Hospital (n = 325) in the present cross-sectional analysis. We further included population-based controls and performed cardinality matching to balance age and sex distributions with cases (n = 224). HRQoL was assessed with the EQ-5D index score; pain, fatigue, and overall SLE-related health state with visual analogue scales (VAS; 0 [best] to 100 [worst]); and functional impairment with the HAQ-DI. Unacceptable outcomes were defined as VAS scores corresponding to the 90th percentile derived from the matched controls. SLE patients reported worse scores than controls in all measures, and approximately 30% experienced unacceptable outcomes. When compared with normal-weight, obese SLE patients reported lower HRQoL, and greater functional impairment and risk of unacceptable pain (OR: 3.2; 95% CI 1.6–6.7) and fatigue (OR: 2.1; 95% CI 1.0–4.3). Similarly, the current smokers reported higher levels of functional impairment and a greater risk of unacceptable pain (OR: 3.8; 95% CI 1.8–8.2) and fatigue (OR: 2.8; 95% CI 1.3–5.9) than never smokers. The associations were independent of age, sex, disease duration, disease activity, and organ damage. There was no evidence of a synergistic effect between increased BMI and smoking on any outcome. In summary, obesity and smoking are risk factors for unacceptable patient-reported outcomes in SLE, regardless of clinical activity.

The Coproduction of Health Framework: Seeking Instructive Management Models and Theories.

At the beginning of the 21st century, multiple and diverse social entities, including the public (consumers), private and nonprofit healthcare institutions, government (public health) and other industry sectors, began to recognize the limitations of the current fragmented healthcare system paradigm. Primary stakeholders, including employers, insurance companies, and healthcare professional organizations, also voiced dissatisfaction with unacceptable health outcomes and rising costs. Grand challenges and wicked problems threatened the viability of the health sector. American health systems responded with innovations and advances in healthcare delivery frameworks that encouraged shifts from intra- and inter-sector arrangements to multi-sector, lasting relationships that emphasized patient centrality along with long-term commitments to sustainability and accountability. This pathway, leading to a population health approach, also generated the need for transformative business models. The coproduction of health framework, with its emphasis on cross-sector alignments, nontraditional partner relationships, sustainable missions, and accountability capable of yielding return on investments, has emerged as a unique strategy for facing disruptive threats and challenges from nonhealth sector corporations. This chapter presents a coproduction of health framework, goals and criteria, examples of boundary spanning network alliance models, and operational (integrator, convener, aggregator) strategies. A comparison of important organizational science theories, including institutional theory, network/network analysis theory, and resource dependency theory, provides suggestions for future research directions necessary to validate the utility of the coproduction of health framework as a precursor for paradigm change.

Abstract WP30: Therapeutic Hypothermia With Thin Liquid Convection is Safe and Feasible in Acute Stroke Patients: The Helping Stroke Patients With ThermoSuit Cooling (SISCO) Pilot Study

Introduction: Animal studies have shown that therapeutic hypothermia of 32-34°C (TH) leads to a drop in infarct size after cerebral artery occlusion. Data suggests that early, rapid TH must be achieved to maximize neuroprotection from ischemic injury. There have been two RCTs of TH in stroke patients, both of which cooled slowly and failed to show the benefit of TH. Objective: The present study assessed the safety and feasibility of the ThermoSuit System (TSS) to induce rapid TH in acute ischemic stroke patients enrolled in the SISCO pivotal phase I trial. The TSS circulates cold water directly over the patient’s skin to achieve TH and has previously demonstrated significantly faster cooling than other methods. Methods: Eligible stroke patients were enrolled with an NIHSS > 5, less than 8 hours from LKW, or who met the extended window thrombectomy criteria. Patients were sedated and intubated according to protocols. Cooling was initiated by circulating ice-cold water (0-8°C) through the TSS. The patients were cooled until the core temperature reached 34-33°C, and the suit was removed. Temperature was maintained at 32°C to 34°C for 24 hours following the cooling induction using a conventional cooling blanket. Criteria for study success were defined as 1) at least 50% of the patients achieving 32-34°C within 1 hour; 2) NIHSS and mRS scores at 90 days post-stroke were not statistically worse than historical controls; 3) no significant increase in adverse event rates in cooled subjects vs. historical controls. RESULTS 14 subjects were enrolled, and 13 were cooled. 2 patients were excluded due to treatment delays and 1 due to missing outcome data, leaving 10 patients available for complete analysis. The average NIHSS on admission was 18, and the average patient age was 65. 7 patients had an LVO in the anterior circulation and 3 had posterior circulation strokes. All study success criteria were met. The median cooling time to 34°C was 40 minutes. The rates of unacceptable outcomes at 90 days (mRS >3) were 45% in 1314 published historical controls but only 10% in cooled subjects. Conclusion: The TSS is a safe and effective tool for rapid TH in ischemic stroke patients. Further studies are warranted to assess whether this cooling method is neuroprotective for these patients.

ANKRD2 expression combined with TNFRSF19 expression for evaluating the prognosis of oral squamous cell carcinoma patients

ObjectiveAs an important chemotherapy drug, cisplatin has been widely used in the treatment of many cancers. However, many patients, including oral squamous cell carcinoma (OSCC) patients, experience unacceptable outcomes from cisplatin treatment. Thus, we devised a risk model for predicting the sensitivity of OSCC patients to cisplatin treatment, to provide a reference for clinical practice. MethodsCAL-27 and SCC-9 cell lines treated or not with cisplatin and data from The Cancer Genome Atlas (TCGA) were screened for simultaneously and significantly differentially expressed genes. Next, we built a risk model for predicting cisplatin sensitivity in OSCC patients. Reverse transcription-polymerase chain reaction (RT-PCR), pathological samples and clinical data were used to examine the reliability of the model. ResultsANKRD2 and TNFRSF19 were differentially expressed between the OSCC metastasis cell line HSC-3 treated and not treated with cisplatin, as well as between the OSCC cell line SCC-25 and the cell line SCC25-DDP, which has cisplatin chemoresistance. We found that the expression of ANKRD2 and TNFRSF19 had a significant influence on the prognosis of OSCC patients. The risk model that combined ANKRD2 and TNFRSF19 to predict sensitivity to cisplatin in OSCC patients was confirmed by analysing the pathological samples and follow-up information of clinical patients. ConclusionsThe expression of ANKRD2 and TNFRSF19 is associated with cisplatin sensitivity and prognosis in patients with OSCC. The survival outcome of patients with oral squamous cell carcinoma (OSCC) was found to be significantly worse in those with high expression of ANKRD2 combined with low expression of TNFRSF19. ANKRD2 and TNFRSF19 may be targets for cisplatin sensitivity prediction in OSCC patients. These findings may provide novel strategies for overcoming cisplatin resistance.

Comparative anatomical analysis between lateral supraorbital and minipterional approaches.

The pterional craniotomy, described by Yasargil and Fox in 1975, constitutes the most traditional and important surgical access in vascular neurosurgery. Minimally invasive alternatives include the minipterional (MP) and lateral supraorbital (LSO) craniotomies, which avoid complications such as injury to the frontal branch of the facial nerve, temporal muscle dysfunction, depression of the craniotomy site, frontal sinus opening, and cosmetically unacceptable outcomes. We evaluated and compared the exposures provided by MP and LSO craniotomies through quantitative measurements of the surgical exposure area around the circle of Willis and parasellar regions, as well as angular and linear exposures of the internal carotid artery (ICA) bifurcation, middle cerebral artery (MCA), midpoint of the anterior communicating artery, and tip of the basilar artery (BA). Seven fresh cadavers were dissected at the São Paulo Medical Examiner's Office, SP, and three at the skull base laboratory of Weill Cornell Medical College, New York, USA. The craniotomies were performed sequentially, initially with the LSO craniotomy followed by the MP. After the craniotomy, the surgical exposure area, craniotomy area, and angular exposures in the horizontal and vertical axes were determined. The MP craniotomy provided better angular exposure for the ipsilateral MCA, while the LSO craniotomy and BA provided better vertical axis exposures. The LSO craniotomy provided better angular exposure in the vertical axis for the midpoint of the anterior communicating artery and contralateral ICA bifurcation. Regarding surgical exposure and craniotomy area, there were no statistically significant differences. The MP craniotomy offers a significantly larger surgical exposure compared to the LSO craniotomy, with specific advantages regarding angular exposure to important neurovascular structures. This study provides important quantitative data to guide the choice between these minimally invasive access techniques in vascular neurosurgery.

Breaking the error chain with SEE: cascade analysis of endodontic errors in clinical training

ABSTRACT The ongoing endeavors to uncover the link between the prevalent errors in clinical endodontic training and undergraduate education are founded on tentative assumptions. This investigation was aimed at determining if cascade analysis can provide an understanding of the origins and causes of errors and if the sensitivity of student reports to the impact of errors on treatment outcomes can be established.In 2021, a group of investigators from the endodontics department concerned with clinical dental education launched the Study of Endodontic Errors (SEE). Sixty-six undergraduate dental students at one dental teaching hospital submitted anonymous narratives of problems they witnessed in their root canal treatment practices. The reports were examined to determine the sequence of events and the major errors. We kept track of the consequences of treatment outcomes, both as reported by students and as deduced by investigators.In 77% of the narratives, a chain of errors was recorded. The majority of the errors that took place were related to the working length or width of root canals. A substantial portion, 86%, of these errors could have been prevented through a deeper comprehension of the concepts that underlie working length and width. 75% of the errors that initiated cascades involved losing the correct working length. When asked whether the treatment outcome was compromised, students answered affirmatively in 16% of cases in which their narratives described compromised outcomes. Unacceptable outcomes necessitating re-treatment accounted for only 3% of student-reported consequences, but when investigator-inferred consequences were considered, the percentage more than doubled (7%).Cascade analysis of student error narratives is useful in understanding the triggering chain of events, but students provide insufficient information about how treatment outcomes are affected. Misconceptions about working length and width appear to play a significant role in the propagation of procedural errors.

Evaluation of Round Block Technique in Different Juxta-Areolar Malignant Lesions in Early Breast Cancer

Abstract Introduction Conservative surgery has become a well-established alternative to mastectomy in the treatment of breast cancer. However, in case of larger lesions or small-sized breasts, the removal of adequate volumes of breast tissue to achieve tumor-free margins and reducing the risk of local recurrance may compromise the cosmetic outcome, causing unpleasant results. To address these surgical techniques, the socalled oncoplastic techniques, have been introduced in recent years to optimize the efficacy of conservative surgery in terms of both local control and cosmetic results. Aim of the Work To evaluate round block technique in different juxta areolar malignant lesions up to 50 mm from areola in early breast cancer regarding oncologic, surgical and cosmetic outcome - post-operative complications. Patients and Methods A Clinical Interventional descriptive single arm randomized prospective study, conducted on 20 female patients presenting with juxta areolar malignant lesions up to 50 mm from areola in early breast cancer stages T1 and T2. Ages ranging 20 to 70 years to be treated using the “round block” technique. Results None of the patients had any malignant recurrence during follow up visits through 1 year after the surgical removal of the tumor proving that we had performed both techniques safely from oncological point of view. The cosmotic results were found to be excellent in 4 cases, very good in 11 cases, good in 3 cases, fair in 1 case, and poor in 1 case. Unacceptable outcomes (either fair or poor) were observed in only 2 cases who underwent 25% excision or in whom the resected area was part of the lower portion of the breast. Conclusion The round block technique is useful for performing breast-conserving surgery in the upper portion of the breast. However, if the excision volume is greater than 20% and/or excision of a part of the lower portion of the breast is required, other procedures should be considered.

What is the Meaning of Culture Negative Leukocytosis Immediately After Heart Transplantation?

<h3>Purpose</h3> Leukocytosis following heart transplantation (HTx) is common and most likely is due to high dose corticosteroid therapy immediately post-HTx. However, infection must be excluded with pan cultures. The use of anti-T lymphocyte globulin (ATG) induction may also cause leukocytosis due to an inflammatory reaction. We sought to determine whether culture negative leukocytosis in the first week after HTx has deleterious consequences. <h3>Methods</h3> Between 2010 and 2020, we assessed 114 patients who developed leukocytosis within the first week following HTx. Patients were divided into groups by the severity of leukocytosis (WBC 11-14.9 x 10⁹/L, 15-19.9 x 10⁹/L, ≥20 x 10⁹/L). Patients were asymptomatic, had negative cultures, and were not treated with antibiotics. The study population was compared to patients without leukocytosis following HTx. Development of infections in the ensuing 1-6 weeks postoperatively were assessed. Furthermore, 1-year outcomes including survival, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejection (any treated rejection [ATR], acute cellular rejection [ACR], antibody-mediated rejection [AMR]) were evaluated. <h3>Results</h3> Higher levels of asymptomatic leukocytosis (>15 x 10⁹/L) immediately after HTx appears to signal possible subsequent infection. However, it does not lead to unacceptable 1-year outcomes including survival, or freedom from CAV, NF-MACE, or rejection. Induction therapy with ATG does not contribute to the leukocytosis. (See table.) <h3>Conclusion</h3> Continued monitoring should be pursued for asymptomatic culture negative leukocytosis immediately after heart transplantation.

Long-term quality of life and aesthetic outcomes after breast conserving surgery in patients with breast cancer

IntroductionBreast surgery has become less invasive without compromising survival and aimed at improving quality of life (QoL) in terms of satisfaction with cosmesis. Despite that, short-term patient-perceived aesthetic results after breast-conserving surgery (BCS) can still be displeasing. Long-term analysis regarding contentment with cosmesis are lacking and could be different, considering that over time, patients’ priorities might change and a different thought-out judgment could be given. The goal of this study is to describe long-term results in QoL after BCS and to identify possible predictors for disappointing aesthetic results. MethodsIn this retrospective cohort study, the long-term outcomes of QoL, patient-reported outcome measurements and aesthetic outcomes were investigated 4.5–10.8 years after BCS. In total, 104 patients received standardized questionnaires from the European Organisation of Research and Treatment of Cancer. The aesthetic results after BCS were evaluated subjectively through a diverse panel of healthcare observers. Objective assessment of the aesthetic results was done using the BCCT.core system of evaluating standardised breast photographs. Factors influencing aesthetic outcome were statistically analysed. ResultsQoL was high in around 75% of the patients. Correlation between QoL and aesthetic outcomes was found according to Spearman's correlation (r = 0.262, p = 0.007). Significant factors negatively influencing patient reported aesthetic outcomes were sentinel node procedure (p = 0.016), axillary lymph node dissection (p = 0.004), chemotherapy (p = 0.001), and hormonal therapy (p = 0.001). ConclusionThe majority of the patients have acceptable QoL after BCS during long-term follow-up. Unacceptable aesthetic outcomes after BCS are associated with lower QoL and are influenced by sentinel node procedure, axillary lymph node dissection, chemotherapy, and hormonal therapy.

Integrated framework for rapid climate stress testing on a monthly timestep

“Bottom-up” methods are increasingly used to assess the vulnerability of water systems to climate change. Central to these methods is the climate “stress test”, where the system is subjected to various climatic changes to test for unacceptable outcomes. We present a framework for climate stress testing on a monthly timestep, suitable for systems whose dominant dynamic is seasonal or longer (eg. water resource systems with carry-over storage). The framework integrates multi-site stochastic climate generation with perturbation methods and in-built rainfall runoff modelling. The stochastic generation includes a low frequency component suitable for representing multi-annual fluctuations. Multiple perturbation options are provided, ranging from simple delta change through to altered seasonality and low frequency dynamics. The framework runs rapidly, supporting comprehensive multi-dimensional stress testing without recourse to supercomputing facilities. We demonstrate the framework on a large water resource system in southern Australia. The Matlab/Octave framework is freely available for download from https://doi.org/10.5281/zenodo.5617008.

Optimized Two-Level Control of Islanded Microgrids to Reduce Fluctuations

The main problem in the operation of micro-grids is controlling the voltage and frequency. The inertia of the whole grid is low, so the operation of the system is interrupted by sudden changes in load or incidence in the absence of a proper control system. In order to solve this issue, various control structures have been proposed. In this paper, an optimal distributed control strategy for coordinating multiple distributed generation instances is presented in an islanded microgrid. A secondary frequency control method is implemented in order to eliminate voltage deviation and reduce the small signal error. In this layer, an optimized PID controller is used. PID controller optimization is carried out via the Honey Badger Algorithm, and results are obtained using the MATLAB software. According to the results, inadequate adjustment of a secondary loop leads to poor and unacceptable outcomes, and the necessary power quality is not achieved. However, by using the proposed method, a proper performance of the microgrid in the face of disturbances is achieved.

Effect of Maternal Methadone Use on Neonatal Outcomes: Results of a Cohort Study

Background: Substance abuse treatment is challenging in pregnancy, and methadone maintenance therapy (MMT) is a therapeutic choice. Methadone can cross the placenta and is poorly secreted in breast milk. Given these inconsistent findings of methadone effect on neonatal outcomes, this study was done to investigate the results in neonates of mothers treated with methadone in Mashhad. Methods: In this retrospective cohort study, mothers referring to two academic hospitals of Mashhad University of Medical Sciences, Mashhad, Iran were studied. Three groups were considered: MMT, other drug abusers, and healthy control. Maternal information, including demographic characteristics, fertility characteristics, and methadone treatment-related characteristics, and neonatal information, including demographic characteristics and neonatal outcomes, were assessed. Results: Overall, 122 pregnant women with a mean age of 29.14 ± 4.44 years were studied in three groups: control (n = 59), MMT (n = 32), and other drug abusers (n = 31). Baseline characteristics (mothers’ age, residence, chronic hypertension, preeclampsia, diabetes, heart disease, thyroid disease, and other diseases) were not different between the three groups. The highest history of miscarriage was seen in other drug abusers (35.5%) (P = 0.023). The mean weight, height, and head circumference of neonates in the control group were significantly higher than the MMT group (P &lt; 0.001), and in the MMT group was higher than in the other drugs abusers (P &lt; 0.001). The highest prevalence of malformations (16.1%) and hospitalization in the NICU (51.6%) was observed in infants of other drug abusers. After adjusting for confounding variables, the odds ratio (OR) of low-birth-weight infants was 13.7 in the MMT group and 1946 in the other drugs group compared to the healthy control group. The OR of neonates less than 50cm in height was 11.4 in the MMT group and 22.5 in the other drugs. Besides, the OR of neonates less than 35cm was 4.7 in the MMT group and 7.3 in other drugs. Conclusions: Although the neonates of mothers who used methadone had a higher rate of inappropriate intrauterine growth indices than control group, methadone consumption compared to other drugs had significantly reduced unacceptable outcomes in neonates. Increased gestational age and reduced preterm delivery risk were observed in methadone-treated mothers.

Outcomes Associated With Osteochondral Allograft Transplantation in Dogs.

The purpose of this study was to retrospectively characterize outcomes and complications associated with osteochondral allograft transplantation for treating chondral and osteochondral lesions in a group of client-owned dogs with naturally-occurring disease. Records were reviewed for information on signalment, treated joint, underlying pathology (e.g., osteochondritis dissecans; OCD), and type, size, and number of grafts used. Complications were classified as “trivial” if no treatment was provided, “non-surgical” if non-surgical treatment were needed, “minor surgical” if a minor surgical procedure such as pin removal were needed but the graft survived and function was acceptable, or “major” if the graft failed and revision surgery were needed. Outcomes were classified as unacceptable, acceptable, or full function. Thirty-five joints in 33 dogs were treated including nine stifles with lateral femoral condyle (LFC) OCD and 10 stifles with medial femoral condyle (MFC) OCD treated with osteochondral cylinders or “plugs.” There were 16 “complex” procedures of the shoulder, elbow, hip, stifle, and tarsus using custom-cut grafts. In total there were eight trivial complications, one non-surgical complication, two minor surgical complications, and five major complications for a total of 16/35 cases with complications. Accordingly, there were five cases with unacceptable outcomes, all of whom had major complications while the other 30 cases had successful outcomes. Of the 30 cases with successful outcomes, 15 had full function and 15 had acceptable function. Based on these subjective outcome assessments, it appears osteochondral allograft transplantation is a viable treatment option in dogs with focal or complex cartilage defects. However, no conclusions can be made regarding the inferiority or superiority of allograft transplantation in comparison to other treatment options based upon these data.

Abstract 14266: Outcomes of Chest Pain Patients Following Application of a Validated High Sensitivity Troponin Algorithm: Comparison of 30 Day Death/ MI of Algorithm Concordant vs Discordant Discharges

Introduction: High sensitivity troponin (hsTn) assays effectively risk stratify patients with chest pain when a validated serial algorithm is utilized. Most of these algorithms require multiple draws for initial values in an intermediate range below a cutoff considered unequivocally consistent with MI. Little is known regarding outcomes of patients who are discharged following deviation from these algorithms. Hypothesis: Minor deviation from a validated hsTn algorithm may yield unacceptable outcomes in chest pain patients. Methods: Retrospective review of outcomes in patients presenting with chest pain to Geisinger Health System emergency departments and discharged based on application of a validated 0/1/3 hour hsTroponinT (hsTnT) algorithm over a 2-year period. We compared 30-day death/MI in patients who had hsTnT results that were consistent with “ruling out” (algorithm concordant) vs those who were discharged despite either equivocal hsTnT results or incomplete application of the algorithm (algorithm discordant). Patients who were admitted or met criteria for MI based on a peak hsTnT &gt; 52ng/L were excluded. Results: Out of 10,342 patients discharged after hsTnT algorithm, 1,166 (11.3%) were algorithm-discordant. Thirty-day death/MI occurred in 13 (0.14%) of patients managed protocol concordant and 16 (1.37%)of patients managed protocol discordant (p&lt;0.001). The 16 discordant pts with death/MI were algorithm-discordant due to either having only a single hsTnT draw (12) or a 0-1hr delta &gt; 5ng/L (4). Comparing all patients with vs without 30day death/MI, univariate predictors included median age (66 vs 50yr, p&lt;0.0001), prior CAD history (41.4 vs 17.5%, p=0.002), hyperlipidemia (44.8 vs 21.8%, p=0.006) and hsTnT algorithm discordance (55.2 vs 11.1%, p&lt;0.001). A multivariable logistic regression model found that among univariate predictors only algorithm discordance was an independent predictor of 30-day death/MI (OR 6.42, p&lt;0.001). Conclusions: Deviation from an hsTnT algorithm was associated significantly with increased 30 day cardiac events. This study highlights the importance of maintaining concordance with algorithm details when using hsTnT assays to triage chest pain patients.

Fourth-Generation Total Wrist Arthroplasty: A Systematic Review of Clinical Outcomes.

Background The purpose of total wrist arthroplasty is to reduce pain and maintain mobility in a painful destructed wrist. First-, second-, and third-generation total wrist arthroplasties have shown unacceptable outcomes with high failure rates. In 2004, the fourth-generation total wrist implants were introduced to address the clinical problems encountered in the previous generations of total wrist implants. Methods Outcomes and complications of fourth-generation total wrist implants were systematically reviewed in the literature (2004-present), including the Universal 2, ReMotion, Freedom, Motec, and Maestro total wrist implants. Results The literature search yielded 114 papers, of which 18 (990 implants) were included in this systematic review. The quality of evidence was low. All implants effectively reduced pain and improved functionality of the wrist. The Motec wrist implant demonstrated the highest survival rate at 10 year follow-up (86%). Conclusion This systematic review suggests a substantial improvement of quality in fourth-generation total wrist arthroplasty.

A Framework for Validation of Synthesized MicroElectrode Dot Array Actuations for Digital Microfluidic Biochips

Digital Microfluidics is an emerging technology for automating laboratory procedures in biochemistry. With more and more complex biochemical protocols getting mapped to biochip devices and microfluidics receiving a wide adoption, it is becoming indispensable to develop automated tools and synthesis platforms that can enable a smooth transformation from complex cumbersome benchtop laboratory procedures to biochip execution. Given an informal/semi-formal assay description and a target microfluidic grid architecture on which the assay has to be implemented, a synthesis tool typically translates the high-level assay operations to low-level actuation sequences that can drive the assay realization on the grid. With more and more complex biochemical assay protocols being taken up for synthesis and biochips supporting a wider variety of operations (e.g., MicroElectrode Dot Arrays (MEDAs)), the task of assay synthesis is getting intricately complex. Errors in the synthesized assay descriptions may have undesirable consequences in assay operations, leading to unacceptable outcomes after execution on the biochips. In this work, we focus on the challenge of examining the correctness of synthesized protocol descriptions, before they are taken up for realization on a microfluidic biochip. In particular, we take up a protocol description synthesized for a MEDA biochip and adopt a formal analysis method to derive correctness proofs or a violation thereof, pointing to the exact operation in the erroneous translation. We present experimental results on a few bioassay protocols and show the utility of our framework for verifiable protocol synthesis.

When Ethics is a Technical Matter: Engineers' Strategic Appeal to Ethical Considerations in Advocating for System Integrity.

Situated in critiques of the “moral muteness” of technical rationality, we examine concepts of ethics and the avoidance of ethical language among Australian gas pipeline engineers. We identify the domains in which they saw ethics as operating, including public safety, environmental protection, sustainability, commercial probity, and modern slavery. Particularly with respect to ethical matters that bear on public safety, in the course of design and operational activities, engineers principally advocated for action using technical language, avoiding reference to potential consequences such as death or destruction of property. Within their organizations, they saw themselves as occupying a technical “line of defense”. We argue that this focus on technical language is action-oriented. Ethics tells practitioners of unacceptable outcomes, but it does not guide them in what they need to do to avoid that outcome in practice. We observed some cases where engineers had not made the connection between their role and ethics in the sense of public safety. We argue that muteness on ethical matters can obscure the nature of the risk where technical advice is being taken on by non-technical actors, and where technical actors themselves do not have a clear sense of their public safety obligations.