Patients undergoing total joint arthroplasty (TJA) have an increased likelihood of having an abnormal coagulation profile compared with the general population. Coagulation abnormalities are often ...screened for before surgery and considered during perioperative planning. This study assesses a preoperative abnormal coagulation profile as a risk factor for postoperative complications after total hip arthroplasty (THA), revision THA (rTHA), total knee arthroplasty (TKA), and revision TKA (rTKA) and then examines specific coagulopathies to determine their influence on complication rates.
Patients who underwent THA, rTHA, TKA, or rTKA from 2011 to 2017 were identified in the American College of Surgeons National Surgical Quality Improvement Program database and then assessed for preoperative abnormal coagulation profiles. Various postoperative complications were analyzed for each cohort, and two separate multivariate regression analyses were used to assess the relationship between abnormal coagulation and postoperative complications.
403,566 THA, rTHA, TKA, or rTKA cases were identified, and 40,466 (10.0%) of patients were found to have an abnormal coagulation profile. Patients with preoperative coagulation abnormalities had higher likelihoods of postoperative complications after primary TJA than in revision TJA. An international normalized ratio>1.2 was associated with the most types of postoperative complications, followed by a bleeding disorder diagnosis. A partial thromboplastin time>35 seconds was associated with only one type of postoperative complication, while a platelet count <150,000 per μL was associated with postoperative complications only after TKA.
TJA in patients with abnormal coagulation profiles may result in adverse outcomes. These patients may benefit from preoperative intervention. Prophylactic care needs to be personalized to the specific coagulation abnormalities present.
T cells expressing chimeric antigen receptors (CAR T cells) have shown impressive therapeutic efficacy against leukemias and lymphomas. However, they have not been as effective against solid tumors ...because they become hyporesponsive (“exhausted” or “dysfunctional”) within the tumor microenvironment, with decreased cytokine production and increased expression of several inhibitory surface receptors. Here we define a transcriptional network that mediates CD8⁺ T cell exhaustion. We show that the high-mobility group (HMG)-box transcription factors TOX and TOX2, as well as members of the NR4A family of nuclear receptors, are targets of the calcium/calcineurin-regulated transcription factor NFAT, even in the absence of its partner AP-1 (FOS-JUN). Using a previously established CAR T cell model, we show that TOX and TOX2 are highly induced in CD8⁺ CAR⁺ PD-1high TIM3high (“exhausted”) tumor-infiltrating lymphocytes (CAR TILs), and CAR TILs deficient in both TOX and TOX2 (Tox DKO) are more effective than wild-type (WT), TOX-deficient, or TOX2-deficient CAR TILs in suppressing tumor growth and prolonging survival of tumor-bearing mice. Like NR4A-deficient CAR TILs, Tox DKO CAR TILs show increased cytokine expression, decreased expression of inhibitory receptors, and increased accessibility of regions enriched for motifs that bind activation- associated nuclear factor κB (NFκB) and basic region-leucine zipper (bZIP) transcription factors. These data indicate that Tox and Nr4a transcription factors are critical for the transcriptional program of CD8⁺ T cell exhaustion downstream of NFAT. We provide evidence for positive regulation of NR4A by TOX and of TOX by NR4A, and suggest that disruption of TOX and NR4A expression or activity could be promising strategies for cancer immunotherapy.
Background
Patients have a unique role in deciding what treatments should be available for them and regulatory agencies should take their preferences into account when making treatment approval ...decisions. This is the first study designed to obtain quantitative patient-preference evidence to inform regulatory approval decisions by the Food and Drug Administration Center for Devices and Radiological Health.
Methods
Five-hundred and forty United States adults with body mass index (BMI) ≥30 kg/m
2
evaluated tradeoffs among effectiveness, safety, and other attributes of weight-loss devices in a scientific survey. Discrete-choice experiments were used to quantify the importance of safety, effectiveness, and other attributes of weight-loss devices to obese respondents. A tool based on these measures is being used to inform benefit-risk assessments for premarket approval of medical devices.
Results
Respondent choices yielded preference scores indicating their relative value for attributes of weight-loss devices in this study. We developed a tool to estimate the minimum weight loss acceptable by a patient to receive a device with a given risk profile and the maximum mortality risk tolerable in exchange for a given weight loss. For example, to accept a device with 0.01 % mortality risk, a risk tolerant patient will require about 10 % total body weight loss lasting 5 years.
Conclusions
Patient preference evidence was used make regulatory decision making more patient-centered. In addition, we captured the heterogeneity of patient preferences allowing market approval of effective devices for risk tolerant patients. CDRH is using the study tool to define minimum clinical effectiveness to evaluate new weight-loss devices. The methods presented can be applied to a wide variety of medical products. This study supports the ongoing development of a guidance document on incorporating patient preferences into medical-device premarket approval decisions.
What's in That Syringe? Gonzalez, Laura S.; Chaney, Mark A.; Wahr, Joyce A. ...
Journal of cardiothoracic and vascular anesthesia,
September 2020, 2020-Sep, 2020-09-00, 20200901, Letnik:
34, Številka:
9
Journal Article
Alcohol misuse is present in over a quarter of trauma patients. Information in the clinical notes of the electronic health record of trauma patients may be used for phenotyping tasks with natural ...language processing (NLP) and supervised machine learning. The objective of this study is to train and validate an NLP classifier for identifying patients with alcohol misuse.
An observational cohort of 1422 adult patients admitted to a trauma center between April 2013 and November 2016. Linguistic processing of clinical notes was performed using the clinical Text Analysis and Knowledge Extraction System. The primary analysis was the binary classification of alcohol misuse. The Alcohol Use Disorders Identification Test served as the reference standard.
The data corpus comprised 91 045 electronic health record notes and 16 091 features. In the final machine learning classifier, 16 features were selected from the first 24 hours of notes for identifying alcohol misuse. The classifier's performance in the validation cohort had an area under the receiver-operating characteristic curve of 0.78 (95% confidence interval CI, 0.72 to 0.85). Sensitivity and specificity were at 56.0% (95% CI, 44.1% to 68.0%) and 88.9% (95% CI, 84.4% to 92.8%). The Hosmer-Lemeshow goodness-of-fit test demonstrates the classifier fits the data well (P = .17). A simpler rule-based keyword approach had a decrease in sensitivity when compared with the NLP classifier from 56.0% to 18.2%.
The NLP classifier has adequate predictive validity for identifying alcohol misuse in trauma centers. External validation is needed before its application to augment screening.
Dynamic laser speckle (DLS) analysis is a very sensitive technique to measure biological activity within samples. In agriculture, the technique is applied to monitor seed germination, but external ...light, water content, and pigments affect the measurements. DLS systems use visible light sources, typically red lasers, which may exacerbate their influences. The main objective of this work is to assess whether infrared (IR) lasers improve the robustness of DLS measurements in seed germination applications. We develop a system where DLS analysis can be performed simultaneously on visible and IR light. Using the system, we quantify how the DLS signal is affected by pigments and scattering. The results show that the use of IR light reduces the variability of the measurements acquired. DLS systems based on IR light appear to be less sensitive to pigments, and the greater penetration of IR light into samples, which is due to reduced scattering, may contribute to the signal collected being correlated to relevant biological processes within the inner tissue. Additionally, water activity provides less influence on the DLS signal when an IR laser is used. These findings support the wider use of IR lasers in DLS-based instruments for applications in biological samples.
Background/Objectives
Psoriasiform eruptions after initiation of dupilumab have been previously described in adults. This report details the risk of developing or unmasking psoriasiform eruptions ...after initiation of dupilumab in children.
Methods
Records of patients ≤18 years of age with atopic dermatitis who developed psoriasiform dermatitis during treatment with dupilumab were reviewed retrospectively.
Results
Six children, 4–18 years of age, on dupilumab for severe atopic dermatitis developed new‐onset psoriasiform dermatitis at a median duration of 8 months (range, 6‐12 months) after dupilumab initiation. Typical locations of psoriasis were involved (face, scalp, trunk, and extensor extremities). The majority showed clearance or near clearance with the use of medium‐strength to potent topical corticosteroid ointments and 83% continued use of the dupilumab. A 7th patient had psoriasis, in addition to severe atopic dermatitis, and the psoriasis was unmasked by its failure to respond to dupilumab.
Conclusion
Although unusual, psoriasiform lesions can appear during effective treatment with dupilumab for atopic dermatitis, potentially reflecting a shift toward cutaneous IL‐23/TH17 pathway activation with dupilumab‐induced suppression of type 2 immunity.
In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in ...patients with newly diagnosed advanced ovarian cancer and a
and/or
(BRCA) mutation. We report overall survival (OS) after a 7-year follow-up, a clinically relevant time point and the longest follow-up for any poly(ADP-ribose) polymerase inhibitor in the first-line setting.
This double-blind phase III trial randomly assigned patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in clinical response to platinum-based chemotherapy to maintenance olaparib (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of OS, a secondary end point, was conducted after a 7-year follow-up.
The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo, and the median follow-up was 88.9 and 87.4 months, respectively. The hazard ratio for OS was 0.55 (95% CI, 0.40 to 0.76;
= .0004
< .0001 required to declare statistical significance). At 7 years, 67.0% of olaparib patients versus 46.5% of placebo patients were alive, and 45.3% versus 20.6%, respectively, were alive and had not received a first subsequent treatment (Kaplan-Meier estimates). The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low, and new primary malignancies remained balanced between treatment groups.
Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in OS with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up.
To describe the creation and validation process of an instructional, didactic and self-applied support tool for teaching-learning Post-Partum Haemorrhage care in simulated settings.
Students ...frequently face difficulties performing the actions in the proper sequence in Post-Partum Haemorrhage simulated cases. Even in a controlled environment, anxiety, nervousness and fear of making mistakes are evident, which render the simulated experience highly stressful. Having a tool with a guideline can help students perform these actions more assertively.
A methodological study to develop a didactic tool.
The creation process of the didactic tool, called Instructional Disk for the Management of Post-Partum Haemorrhage, was divided into five phases: Analysis, Design, Development, Implementation and Evaluation. Nine experts specialised in Obstetrics and Midwifery validated the tool by answering a questionnaire with nine items; in turn, 32 undergraduate Midwifery program students carried out the evaluation using a questionnaire on applicability, functionality, clarity, coherence and usability of the tool in Post-Partum Haemorrhage simulated stations. The data were analysed descriptively, considering absolute agreement when the answers to all questions in the five-point Likert scale corresponded to 5 (I totally agree). The Content Validity Index was calculated for the experts' questionnaires.
In the validation stage, the experts agreed or totally agreed with all nine items, reaching a Content Validity Index = 1. In the total scores assigned by the experts, there was a variation between 80.0% and 100% absolute agreement, with a mean of 95.6%. In the students' assessment, the variation was between 87.5% and 100% absolute agreement, with a mean of 97.7%, in the eight items evaluated. The agreement level above 90% among experts and students was considered high.
The Instructional Disk for the Management of Post-Partum Haemorrhage was validated by experts with extensive experience in Obstetrics and Midwifery care and teaching, ensuring that the content included in the guidelines for the management of Post-Partum Haemorrhage adopted in Brazil is covered. The students positively evaluated this support tool for learning the care to be provided in Post-Partum Haemorrhage cases in the simulated stations.
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