Clinical Outcomes of Additional Below-The-Ankle Intervention Compared to Below-The-Knee Intervention Alone: A Post-Hoc Analysis of a Prospective Multicenter Study.

PURPOSE: To investigate the clinical implication of additional below-the-ankle (BTA) intervention in patients with chronic limb-threatening ischemia (CLTI) undergoing below-the-knee (BTK) intervention. MATERIALS AND METHODS: A sub-analysis was performed using data from the LIBERTY trial (ClinicalTrials.gov identifier NCT01855412), a prospective, observational, core-laboratory adjudicated, multicenter study of endovascular intervention in 1204 patients. Patients with CLTI (Rutherford Classification 4-6) who underwent BTK intervention were included in this sub-analysis. Participants were then stratified into 2 treatment groups according to whether at least one lesion intervened on was BTA (n=66) or not (n=273). The decision on whether and where to intervene was made during the procedure. The main outcome measures included major amputation, target vessel revascularization (TVR), major adverse events (MAE), survival, amputation-free survival, major adverse limb events or peri-operative death (MALE-POD), and all-cause death. Other outcome measures included procedural success, procedural complications, and wound healing rate. RESULTS: There were no differences in procedural success or severe angiographic complications between the 2 groups. At 1-year post-procedure, patients in the BTK group had a higher rate of freedom from major amputation (95.0% vs. 86.9%, respectively; HR: 2.87, 95% CI: 1.17-7.03), a higher rate of freedom from TVR (80.1% vs. 66.9%, respectively; HR: 1.94, 95% CI: 1.14-3.32), a higher rate of freedom from MALE-POD (94.6% vs. 86.9%, respectively; HR: 2.65, 95% CI: 1.10-6.41), and a higher rate of freedom from MAE at both 1 (76.0% vs. 60.1%, respectively; HR: 2.00, 95% CI: 1.24-3.22) and 3 years post procedure (67.5% vs. 55.8%, respectively; HR: 1.69, 95% CI: 1.08-2.65). There was a significantly lower rate of survival in the BTK group at 3 years (74.3% vs. 91.1%, respectively; HR: 0.35, 95% CI: 0.14-0.87). After risk adjustment, there was a higher rate of all-cause death in the BTK group at 3 years (19.4% vs. 9.1%, respectively; p=0.023) post-intervention. CONCLUSION: Patients with disease requiring intervention to BTA lesions have a potential increased amputation rate in the short term, but BTA intervention carries a potential survival benefit in the long term when compared to BTK intervention alone.

Prognostic implications of baseline 6-min walk test performance in intermediate risk patients undergoing transcatheter aortic valve replacement.

BACKGROUND: While slow gait speed is known to be associated with poor outcomes in patients at high surgical risk who undergo transcatheter aortic valve replacement (TAVR), the prognostic significance of slow gait speed in intermediate risk TAVR patients is poorly understood. OBJECTIVES: We assessed the association between baseline 6-min walk test (6MWT) performance and both 2-year mortality and health status in intermediate risk patients undergoing TAVR as a part of the PARTNER II/S3i studies. METHODS: The association of baseline 6MWT with mortality over 2-years after TAVR was examined using Cox regression; both unadjusted and adjusted for age, left ventricular ejection fraction, coronary artery disease, pulmonary disease, renal insufficiency, and STS score. Patients were divided into four groups according to baseline 6MWT: unable to walk and in three equal tertiles of slow, medium, and fast walkers. Among surviving patients, improvement in 6MWT and quality of life were compared. RESULTS: Among 2,037 intermediate risk TAVR patients (mean age 81.7 years, STS score 5.6%), 8.2% were unable to walk. Baseline 6MWT was associated with all-cause mortality over 2 years (Hazard ratio (HR) 0.87 per 50 m, 95% confidence interval [CI] 0.83 to 0.92, p < .0001). Among surviving patients, the adjusted absolute change in 6MWT at 2 years improved for patients unable to walk (+134.1 m, 95% CI 102.1 to 166 m, p < .0001) and slow walkers (+60.5 m, 95% CI 42.8 to 78.2 m, p < .0001), but was unchanged for medium walkers (-7.3 m, 95% CI -24.3 to 9.6 m, p = .4), and declined for fast walkers (-41.3 m, 95% CI -58.7 to -23.9 m, p < .0001). CONCLUSION: Poor functional capacity is predictive of 2-year mortality in elderly intermediate risk patients undergoing TAVR. However, surviving patients with poor baseline functional capacity had significant improvement in 6MWT performance and quality of life at 2-years following TAVR.

Pulmonary Embolism Response Team utilization during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 (n = 74) compared to the same period in 2019 (n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

After-School Programs and Children's Mental Health: Organizational Social Context, Program Quality, and Children's Social Behavior.

OBJECTIVE: The current study examined associations among organizational social context, after-school program (ASP) quality, and children's social behavior in a large urban park district. METHOD: Thirty-two park-based ASPs are included in the final sample, including 141 staff and 593 children. Staff reported on organizational culture (rigidity, proficiency, resistance) and climate (engagement, functionality, stress), and children's social skills and problem behaviors. Children and their parents reported on program quality indicators (e.g., activities, routines, relationships). Parents also completed a children's mental health screener. RESULTS: A series of Hierarchical Linear Models revealed that proficiency and stress were the only organizational predictors of program quality; associations between stress and program quality were moderated by program enrollment and aggregated children's mental health need. Higher child- and parent-perceived program quality related to fewer staff-reported problem behaviors, while overall higher enrollment and higher aggregated mental health need were associated with fewer staff-reported social skills. CONCLUSIONS: Data are informing ongoing efforts to improve organizational capacity of urban after-school programs to support children's positive social and behavior trajectories.

Acute pulmonary embolism unmasking underlying chronic thromboembolic pulmonary hypertension and iliac vein compression syndrome.

We describe the case of a 72-year-old gentleman who was referred to our institution for management of cardiogenic shock from a massive pulmonary embolism. Right heart catheterization revealed a low cardiac index and markedly elevated pulmonary pressures, suggested long-standing venous thromboembolic (VTE) disease that evolved into chronic thromboembolic pulmonary hypertension (CTEPH). The patient was cannulated to veno-arterial extra-corporeal membrane oxygenation and eventually treated with pulmonary embolectomy and thromboendarterectomy. Subsequently discovered inferior vena cava clot and left iliac deep vein thrombosis were treated with suction and mechanical thrombectomy. Intravascular ultrasound of the left lower extremity venous system identified iliac vein compression syndrome (IVCS) as the culprit of the patient's VTE and CTEPH. A left iliac stent was placed and the patient was discharged on Warfarin for anticoagulation. The case illustrates the rapidly expanding armamentarium for VTE treatment and proposes IVCS as a new, potentially underrecognized risk factor for CTEPH.

Adverse events in patients with high platelet reactivity following successful chronic total occlusion PCI: The Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) study.

BACKGROUND: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) typically requires a greater number of stents and longer stent length than non-CTO PCI, placing these patients at greater risk for adverse ischemic events. We sought to determine whether the association between high platelet reactivity (HPR) and the risk of ischemic events is stronger after CTO than non-CTO PCI. METHODS: Patients undergoing successful PCI in the multicenter ADAPT-DES study were stratified according to whether they underwent PCI of a CTO. HPR was defined as VerifyNow platelet reaction units >208. The study primary endpoint was the 2-year risk target vessel failure ([TVF] defined as cardiac death, myocardial infarction, or target lesion revascularization). RESULTS: CTO PCI was performed in 400 of 8448 patients. HPR was present in 34.5% of CTO PCI patients and 43.1% of non-CTO PCI patients (P = .0007). Patients undergoing CTO PCI with versus without HPR had significantly higher 2-year rates of TVF (15.0% versus 8.3%, P = .04) without significant differences in bleeding. HPR was an independent predictor of 2-year TVF (adjusted HR 1.16, 95% CI 1.02-1.34, P = .03) whereas CTO PCI was not (adjusted HR 0.89, 95% CI 0.65-1.22, P = .48). There was a significant interaction between CTO versus non-CTO PCI and PRU as a continuous variable for 2-year TVF (Pinteraction = 0.02). CONCLUSIONS: In ADAPT-DES, HPR was associated with an increased 2-year risk of TVF after PCI, an association that was at least as strong after CTO PCI compared with non-CTO PCI.

Incremental cost and length of stay associated with postprocedure delirium in transcatheter and surgical aortic valve replacement patients in the United States.

OBJECTIVES: To explore the impact of post-procedure delirium on resource utilization following transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively). BACKGROUND: Postprocedure delirium is associated with worse long-term survival after TAVR and SAVR. However, its effect on resource utilization has been understudied. METHODS: Using the 2015 Medicare Provider Analysis and Review File (MedPAR), we retrospectively analyzed elderly (≥80 years) Medicare beneficiaries receiving either SAVR or endovascular TAVR in the United States. Multivariate regression models estimating hospitalization cost and length of stay (LoS) were adjusted for patient demographics, comorbidities, and nondelirium complications. RESULTS: A total of 21,088 discharges were available for analysis (12,114 TAVR and 8,974 SAVR). TAVR patients were older (87 ± 3.8 vs. 84 ± 2.7 years; P < 0.001) with a higher comorbidity burden (Charlson index 3.0 ± 1.8 vs. 2.1 ± 1.7; P < 0.0001). Despite this, fewer TAVR patients (1.6%) experienced postoperative delirium during the index hospitalization compared to surgical patients (3.6%; P < 0.0001). Delirium was associated with a 4.16 [3.51-4.81] day longer hospital LoS and $15,592 ($12,849-$18,334) higher incremental hospitalization cost. When stratified by treatment approach, the adjusted incremental cost of delirium was +$13,862 ($9,431-$18,292) with TAVR and +$16,656 ($13,177-$20,136) with SAVR with an additional hospital LoS of +3.39 (2.34-4.43) days and +4.63 (3.81-5.45) days for TAVR and SAVR, respectively. CONCLUSIONS: Postprocedure delirium is associated with significantly increased hospitalization costs and LoS following AVR. TAVR was associated with a lower postoperative delirium rate compared to SAVR. Post-TAVR delirium may be associated with less resource consumption than post-SAVR delirium.

Connection between organizational culture and climate and empowerment: The perspective of nurse managers.

Health-care organizations differ from other institutions due to their unique structure and management. Organizational culture and climate are the key constructs that compose the organizational social context, and might have an impact on employees, such as nurse managers, and the organization itself. The aim of this study was to analyze the connections between organizational culture and climate and work-related empowerment, and also to present culture and climate profiles at team and organization levels. The research was carried out in Lithuania among 193 nurse managers in seven hospitals using a questionnaire that measured organizational culture and climate (Organizational Social Context instrument), and work-related empowerment (Conditions for Work Effectiveness Questionnaire-II and Work Empowerment Questionnaire). The findings showed that nurse managers were both structurally and psychologically empowered when the organizational culture was proficient and resistant, and the climate was engaged and functional. These results suggest that nurse managers are more likely to be empowered when there is an appropriate organizational culture and climate in the workplace. Creating an empowering work environment might have a positive impact on individual and organizational outcomes.

Concordance Between Administrator and Clinician Ratings of Organizational Culture and Climate.

Organizational culture and climate are important determinants of behavioral health service delivery for youth. The Organizational Social Context measure is a well validated assessment of organizational culture and climate that has been developed and extensively used in public sector behavioral health service settings. The degree of concordance between administrators and clinicians in their reports of organizational culture and climate may have implications for research design, inferences, and organizational intervention. However, the extent to which administrators' and clinicians' reports demonstrate concordance is just beginning to garner attention in public behavioral health settings in the United States. We investigated the concordance between 73 administrators (i.e., supervisors, clinical directors, and executive directors) and 247 clinicians in 28 child-serving programs in a public behavioral health system. Findings suggest that administrators, compared to clinicians, reported more positive cultures and climates. Organizational size moderated this relationship such that administrators in small programs (<466 youth clients served annually) provided more congruent reports of culture and climate in contrast to administrators in large programs (≥466 youth clients served annually) who reported more positive cultures and climates than clinicians. We propose a research agenda that examines the effect of concordance between administrators and clinicians on organizational outcomes in public behavioral health service settings.

Mechanisms of Change in the ARC Organizational Strategy: Increasing Mental Health Clinicians' EBP Adoption Through Improved Organizational Culture and Capacity.

The development of efficient and scalable implementation strategies in mental health is restricted by poor understanding of the change mechanisms that increase clinicians' evidence-based practice (EBP) adoption. This study tests the cross-level change mechanisms that link an empirically-supported organizational strategy for supporting implementation (labeled ARC for Availability, Responsiveness, and Continuity) to mental health clinicians' EBP adoption and use. Four hundred seventy-five mental health clinicians in 14 children's mental health agencies were randomly assigned to the ARC intervention or a control condition. Measures of organizational culture, clinicians' intentions to adopt EBPs, and job-related EBP barriers were collected before, during, and upon completion of the three-year ARC intervention. EBP adoption and use were assessed at 12-month follow-up. Multilevel mediation analyses tested changes in organizational culture, clinicians' intentions to adopt EBPs, and job-related EBP barriers as linking mechanisms explaining the effects of ARC on clinicians' EBP adoption and use. ARC increased clinicians' EBP adoption (OR = 3.19, p = .003) and use (81 vs. 56 %, d = .79, p = .003) at 12-month follow-up. These effects were mediated by improvement in organizational proficiency culture leading to increased clinician intentions to adopt EBPs and by reduced job-related EBP barriers. A combined mediation analysis indicated the organizational culture-EBP intentions mechanism was the primary carrier of ARC's effects on clinicians' EBP adoption and use. ARC increases clinicians' EBP adoption and use by creating proficient organizational cultures that increase clinicians' intentions to adopt EBPs.

Predictors of poor outcomes after transcatheter aortic valve replacement: results from the PARTNER (Placement of Aortic Transcatheter Valve) trial.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a less invasive option for treatment of high-risk patients with severe aortic stenosis. We sought to identify patients at high risk for poor outcome after TAVR using a novel definition of outcome that integrates quality of life with mortality. METHODS AND RESULTS: Among 2137 patients who underwent TAVR in the PARTNER (Placement of Aortic Transcatheter Valve) trial or its associated continued access registry, quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire-Overall Summary Scale (KCCQ-OS; range 0-100, where a higher score equates to a better quality of life) at baseline and at 1, 6, and 12 months after TAVR. A poor 6-month outcome (defined as death, KCCQ-OS score <45, or ≥10-point decrease in KCCQ-OS score compared with baseline) occurred in 704 patients (33%). Using a split-sample design, we developed a multivariable model to identify a parsimonious set of covariates to identify patients at high risk for poor outcome. The model demonstrated moderate discrimination (c-index=0.66) and good calibration with the observed data, performed similarly in the separate validation cohort (c-index=0.64), and identified 211 patients (10% of the population) with a ≥50% likelihood of a poor outcome after TAVR. A second model that explored predictors of poor outcome at 1 year identified 1102 patients (52%) with ≥50% likelihood and 178 (8%) with ≥70% likelihood of a poor 1-year outcome after TAVR. CONCLUSIONS: Using a large, multicenter cohort, we have developed and validated predictive models that can identify patients at high risk for a poor outcome after TAVR. Although model discrimination was moderate, these models may help guide treatment choices and offer patients realistic expectations of outcomes based on their presenting characteristics. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Impact of preoperative moderate/severe mitral regurgitation on 2-year outcome after transcatheter and surgical aortic valve replacement: insight from the Placement of Aortic Transcatheter Valve (PARTNER) Trial Cohort A.

BACKGROUND: The effect of preoperative mitral regurgitation (MR) on clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) is controversial. This study sought to examine the impact of moderate and severe MR on outcomes after TAVR and surgical aortic valve replacement (SAVR). METHODS AND RESULTS: Data were drawn from the randomized Placement of Aortic Transcatheter Valve (PARTNER) Trial cohort A patients with severe, symptomatic aortic stenosis undergoing either TAVR (n=331) or SAVR (n=299). Both TAVR and SAVR patients were dichotomized according to the degree of preoperative MR (moderate/severe versus none/mild). At baseline, moderate or severe MR was reported in 65 TAVR patients (19.6%) and 63 SAVR patients (21.2%). At 30 days, among survivors who had isolated SAVR/TAVR, moderate/severe MR had improved in 25 SAVR patients (69.4%) and 30 TAVR patients (57.7%), was unchanged in 10 SAVR patients (27.8%) and 19 TAVR patients (36.5%), and worsened in 1 SAVR patient (2.8%) and 4 TAVR patients (5.8%; all P=NS). Mortality at 2 years was higher in SAVR patients with moderate or severe MR than in those with mild or less MR (49.8% versus 28.1%; adjusted hazard ratio, 1.73; 95% confidence interval, 1.01-2.96; P=0.04). In contrast, MR severity at baseline did not affect mortality in TAVR patients (37.0% versus 32.7%, moderate/severe versus none/mild; hazard ratio, 1.14; 95% confidence interval, 0.72-1.78; P=0.58; P for interaction=0.05). CONCLUSIONS: Both TAVR and SAVR were associated with a significant early improvement in MR in survivors. However, moderate or severe MR at baseline was associated with increased 2-year mortality after SAVR but not after TAVR. TAVR may be a reasonable option in selected patients with combined aortic and mitral valve disease. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

The organizational social context of mental health medicaid waiver programs with family support services: implications for research and practice.

Peer family support specialists (FSS) are parents with practical experience in navigating children's mental health care systems who provide support, advocacy, and guidance to the families of children who need mental health services. Their experience and training differ from those of formally trained mental health clinicians, creating potential conflicts in priorities and values between FSS and clinicians. We hypothesized that these differences could negatively affect the organizational cultures and climates of mental health clinics that employ both FSS and mental health clinicians, and lower the job satisfaction and organizational commitment of FSS. The Organizational Social Context measure was administered on site to 209 FSS and clinicians in 21 mental health programs in New York State. The study compared the organizational-level culture and climate profiles of mental health clinics that employ both FSS and formally trained clinicians to national norms for child mental health clinics, assessed individual-level job satisfaction and organizational commitment as a function of job (FSS vs. clinician) and other individual-level and organizational-level characteristics, and tested whether FSS and clinicians job attitudes were differentially associated with organizational culture and climate. The programs organizational culture and climate profiles were not significantly different from national norms. Individual-level job satisfaction and organizational commitment were unrelated to position (FSS vs. clinician) or other individual-level and organizational-level characteristics except for culture and climate. Both FSS' and clinicians' individual-level work attitudes were associated similarly with organizational culture and climate.

Diagnosis of Peripheral Artery Disease Using Backflow Abnormalities in Proximal Recordings of Accelerometer Contact Microphone (ACM).

OBJECTIVE: The development of an accurate, non-invasive method for the diagnosis of peripheral artery disease (PAD) from accelerometer contact microphone (ACM) recordings of the cardiac system. METHODS: Mel frequency cepstral coefficients (MFCCs) are initially extracted from ACM recordings. The extracted MFCCs are then used to fine-tune a pre-trained ResNet50 network whose middle layers provide streams of high-level-of-abstraction coefficients (HLACs) which could provide information on blood pressure backflow caused by arterial obstructions in PAD patients. A vision transformer is finally integrated with the feature extraction layer to detect PAD, and stratify the severity level. This architecture is coined multi-stream-powered vision transformer (MSPViT). The performance of MSPViT is evaluated on 74 PAD and 21 healthy subjects. RESULTS: Sensitivity, specificity, F1 score, and area under the curve (AUC) of 99.45%, 98.21%, 99.37%, and 0.99, respectively, are reported for the binary classification which ensures accurate detection of PAD. Furthermore, MSPViT suggests average sensitivity, specificity, F1 score, and AUC of 96.66%, 97.34%, 96.29%, and 0.96, respectively, for the classification of subjects into healthy, mild-PAD, and severe-PAD classes. The silhouette score is calculated to assess the separability of clusters formed for classes in the penultimate layer of MSPViT. An average silhouette score of 0.66 and 0.81 demonstrate excellent cluster separability in PAD detection and severity classification, respectively. CONCLUSION: The achieved performance suggests that the proximal ACM-driven framework can replace state-of-the-art techniques for PAD detection. SIGNIFICANCE: This study presents a fundamental step towards prompt and accurate diagnosis of PAD and stratification of its severity level.

Diagnosis of Coexisting Valvular Heart Diseases Using Image-to-Sequence Translation of Contact Microphone Recordings.

OBJECTIVE: Development of a contact microphone-driven screening framework for the diagnosis of coexisting valvular heart diseases (VHDs). METHODS: A sensitive accelerometer contact microphone (ACM) is employed to capture heart-induced acoustic components on the chest wall. Inspired by the human auditory system, ACM recordings are initially transformed into Mel-frequency cepstral coefficients (MFCCs) and their first and second derivatives, resulting in 3-channel images. An image-to-sequence translation network based on the convolution-meets-transformer (CMT) architecture is then applied to each image to find local and global dependencies in images, and predict a 5-digit binary sequence, where each digit corresponds to the presence of a specific type of VHD. The performance of the proposed framework is evaluated on 58 VHD patients and 52 healthy individuals using a 10-fold leave-subject-out cross-validation (10-LSOCV) approach. RESULTS: Statistical analyses suggest an average sensitivity, specificity, accuracy, positive predictive value, and F1 score of 93.28%, 98.07%, 96.87%, 92.97%, and 92.4% respectively, for the detection of coexisting VHDs. Furthermore, areas under the curve (AUC) of 0.99 and 0.98 are respectively reported for the validation and test sets. CONCLUSION: The high performances achieved prove that local and global features of ACM recordings effectively characterize heart murmurs associated with valvular abnormalities. SIGNIFICANCE: Limited access of primary care physicians to echocardiography machines has resulted in a low sensitivity of 44% when using a stethoscope for the identification of heart murmurs. The proposed framework provides accurate decision-making on the presence of VHDs, thus reducing the number of undetected VHD patients in primary care settings.

Determination and control of low-level amino acid misincorporation in human thioredoxin protein produced in a recombinant Escherichia coli production system.

Escherichia coli is used extensively in the production of proteins within biotechnology for a number of therapeutic applications. Here, we discuss the production and overexpression of the potential biopharmaceutical human thioredoxin protein (rhTRX) within E. coli. Overexpression of foreign molecules within the cell can put an enormous amount of stress on the translation machinery. This can lead to a misfiring in the construction of a protein resulting in populations differing slightly in amino acid composition. Whilst this may still result in a population of active molecules being expressed, it does present significant problems with molecules that are destined for clinical applications. Amino acid misincorporation of this subset could potentially result in antibodies being raised to these unnatural proteins. Cross-reaction with a patient's endogenous thioredoxin could then lead to an autoimmune phenomena and serious health implications. Generally, the issue of misincorporation appears not to be a routine regulatory concern (see ICH Q6B guidelines). Therefore, amino acid misincorporation may not have been detected, much less explored in the clinic as the occurrence or absence of these random errors is not routinely reported. Using current technologies based on proteomics, the ability to find misincorporation critically depends upon the criteria for matching theoretical and experimental mass spectrometry data. Additionally, isolation and extraction of these mistranslated proteins from the production process is both difficult and expensive. Therefore, it is advantageous to find routes for removing their production during the upstream phase. In this study, we show how modern proteomic technology can be used to identify and quantify amino acid misincorporation. Using these techniques we have shown how manipulation of gene sequence and scoping of fermentation media composition can lead to the reduction and elimination of these misincorporations in rhTRX.

Reliability and validity of a treatment adherence measure for child psychiatric rehabilitation.

OBJECTIVE: Treatment adherence, defined as the degree to which practitioners implemented prescribed program principles and activities and avoided proscribed activities, has been an area of growing interest in mental health services for children with severe emotional and behavioral disorders. This study evaluated the reliability and validity of a treatment adherence measure for child psychiatric rehabilitation (CPSR). METHODS: Parents of children receiving CPSR (n = 79) or psychotherapy (n = 27) completed the Children's Psychosocial Rehabilitation Treatment Adherence Measure (CTAM) and a measure of 2-week session impact. Psychiatric rehabilitation (PSR) supervisors identified PSR practitioners with reputations for high or low adherence to the model. The CTAM's discriminant validity was assessed by using known-groups procedures and predictive validity by examining its relationship to 2-week session impact. RESULTS: The CTAM demonstrated excellent internal consistency (α = .92), discriminant validity (p = .002, d = .72; p = .021, d = .59), and predictive validity (B = 2.24, SE = .31, p < .001), accounting for 28% of the child-level variance in 2-week session impact. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings suggest the CTAM is a reliable and valid measure of treatment adherence for CPSR programs with a skill-teaching focus. Providers and agencies should take steps to enhance treatment adherence because it may be an important predictor of children's short-term response to CPSR.

Endovascular Treatment of a Popliteal Artery Aneurysm Via Transpedal Approach: A Case Report.

Popliteal artery aneurysm (PAA) has been increasingly treated with endovascular intervention in recent years. However, whether transpedal access can be utilized to treat PAA has not been widely reported. We report a case of successful treatment of a PAA with a covered stent via retrograde transpedal approach in an 80-year male with prohibitive surgical risk who initially failed antegrade approach. This case demonstrates the feasibility of treating PAA via a retrograde transpedal access in selected patients.

Transradial Endovascular Intervention: Results From the Radial accEss for nAvigation to Your CHosen Lesion for Peripheral Vascular Intervention (REACH PVI) Study.

BACKGROUND/PURPOSE: The transradial approach has been proposed as an alternative to traditional transfemoral access for diagnostic and therapeutic purposes in several catheterization procedures. Historically, extended length devices for lower limb endovascular interventions have been limited. The aim of this study was to investigate the acute clinical outcomes of orbital atherectomy (OA) via transradial access (TRA) for the treatment of lower extremity peripheral artery disease (PAD). METHODS/MATERIALS: REACH PVI was a multicenter, prospective, observational study (NCT03943160) including subjects with PAD and target lesion morphology appropriate for OA. All patients were followed post-procedure through the first standard of care follow-up visit. RESULTS: A total of 50 patients were enrolled. In most cases the indication for intervention was disabling claudication (74.0%). Overall, 50 target lesions were treated, 92.0% of lesions were femoropopliteal and 8.0% were infrapopliteal. The average lesion length was 98.3 ± 87.5 mm and 78.0% of the lesions were severely calcified. Balloon angioplasty was performed in 98.0% of target lesions, while a stent was deployed in 16.0%. Treatment success was 98.0%; in only one case the result was sub-optimal (>30% stenosis with stent placement) and a significant dissection was reported. No serious distal embolization, serious thrombus formation or serious acute vessel closure were observed intra- or post-procedurally. CONCLUSIONS: Transradial OA followed by percutaneous transluminal angioplasty for lower extremity PAD is feasible and demonstrates a favorable safety profile. Extended length devices such as the Extended Length Orbital Atherectomy System could further facilitate transradial endovascular procedures by increasing its spectrum of application.

Efficient detection of aortic stenosis using morphological characteristics of cardiomechanical signals and heart rate variability parameters.

Recent research has shown promising results for the detection of aortic stenosis (AS) using cardio-mechanical signals. However, they are limited by two main factors: lacking physical explanations for decision-making on the existence of AS, and the need for auxiliary signals. The main goal of this paper is to address these shortcomings through a wearable inertial measurement unit (IMU), where the physical causes of AS are determined from IMU readings. To this end, we develop a framework based on seismo-cardiogram (SCG) and gyro-cardiogram (GCG) morphologies, where highly-optimized algorithms are designed to extract features deemed potentially relevant to AS. Extracted features are then analyzed through machine learning techniques for AS diagnosis. It is demonstrated that AS could be detected with 95.49-100.00% confidence. Based on the ablation study on the feature space, the GCG time-domain feature space holds higher consistency, i.e., 95.19-100.00%, with the presence of AS than HRV parameters with a low contribution of 66.00-80.00%. Furthermore, the robustness of the proposed method is evaluated by conducting analyses on the classification of the AS severity level. These analyses are resulted in a high confidence of 92.29%, demonstrating the reliability of the proposed framework. Additionally, game theory-based approaches are employed to rank the top features, among which GCG time-domain features are found to be highly consistent with both the occurrence and severity level of AS. The proposed framework contributes to reliable, low-cost wearable cardiac monitoring due to accurate performance and usage of solitary inertial sensors.