The Patient-Reported Outcomes Measurement Information System® (PROMIS®) may be used to assess an individual patient's perspective of their physical, mental, and social health through either standard ...or computer adaptive testing (CAT) patient questionnaires. These questionnaires are used across disciplines; however, they have seen considerable application in orthopaedic surgery. Patient characteristics associated with PROMIS CAT completion have not been examined within the context of social determinants of health, such as social deprivation or health literacy, nor has patient understanding of the content of PROMIS CAT been assessed.
(1) What patient demographics, including social deprivation, are associated with completion of PROMIS CAT questionnaires? (2) Is health literacy level associated with completion of PROMIS CAT questionnaires? (3) Do patients with lower health literacy have a higher odds of completing PROMIS CAT without fully understanding the content?
Between June 2022 and August 2022, a cross-sectional study was performed via a paper survey administered to patients at a single, urban, quaternary academic medical center in orthopaedic subspecialty clinics of foot and ankle, trauma, and hand/upper extremity surgeons. We considered all English-speaking patients aged 18 or older, including those with limited reading and/or writing abilities, as eligible provided they received an iPad in clinic to complete the PROMIS CAT questionnaire as part of their routine standard clinical care or they completed the questionnaire via a patient portal before the visit. In all, 946 patients were considered eligible during the study period and a convenience sample of 36% (339 of 946) of patients was approached for inclusion due to clinic time constraints. Fifteen percent (52 of 339) declined to participate, leaving 85% (287 of 339) of patients for analysis here. Median (range) age of study participants was 49 years (35 to 64). Fifty-eight percent (167 of 287) of study participants self-identified as non-Hispanic Black or African American and 26% (75 of 287) as non-Hispanic White. Even proportions were observed across education levels (high school graduate or less, 29% 82 of 287; some college, 25% 73 of 287; college graduate, 25% 71 of 287; advanced degree, 20% 58 of 287). Eighteen percent (52 of 287) of patients reported an annual income bracket of USD 0 to 13,000, and 17% (48 of 287) reported more than USD 120,000. Forty-six percent (132 of 287) of patients worked full-time, 21% (59 of 287) were retired, and 23% (66 of 287) were unemployed or on disability. The primary outcome of interest was self-reported PROMIS CAT questionnaire completion grouped as: fully completed, partially completed, or no part completed. Overall, self-reported PROMIS CAT questionnaire completion proportions were: 80% (229 of 287) full completion, 13% (37 of 287) partial completion, and 7% (21 of 287) no part completed. We collected the National Area Deprivation Index (ADI) score and the Brief Health Literacy Screening Tool (BRIEF) as part of the study survey to associate with level of completion. Additionally, patient understanding of PROMIS CAT was assessed through Likert-scaled responses to a study survey question that directly asked whether the patient understood all of the questions on the PROMIS CAT questionnaire. Responses to this question may have been limited by social desirability bias, and hence may overestimate how many individuals genuinely understood the questionnaire content. However, the benefit of this approach was it efficiently allowed us to estimate the ceiling effect of patient comprehension of PROMIS CAT and likely had a high degree of specificity for detecting lack of comprehension.
ADI score adjusted for age was not associated with PROMIS CAT completion (partial completion OR 1.00 95% CI 0.98 to 1.01; p = 0.72, no part completed OR 1.01 95% CI 0.99 to 1.03; p = 0.45). Patients with lower health literacy scores, however, were more likely to not complete any part of their assigned questionnaires than patients with higher scores (no part completed OR 0.85 95% CI 0.75 to 0.97; p = 0.02). Additionally, 74% (26 of 35) of patients who did not fully understand all of the PROMIS CAT questionnaire questions still fully completed them-hence, 11% (26 of 229) of all patients who fully completed PROMIS CAT did not fully understand the content. Among patients self-reporting full completion of PROMIS CAT with health literacy data (99% 227 of 229), patients with inadequate/marginal health literacy were more likely than patients with adequate health literacy to not fully understand all of the questions (21% 14 of 67 versus 8% 12 of 160, OR 3.26 95% CI 1.42 to 7.49; p = 0.005).
Within an urban, socioeconomically diverse, orthopaedic patient population, health literacy was associated with PROMIS CAT questionnaire completion. Lower health literacy levels increased the likelihood of not completing any part of the assigned PROMIS CAT questionnaires. Additionally, patients completed PROMIS CAT without fully understanding the questions. This indicates that patient completion does not guarantee comprehension of the questions nor validity of their scores, even more so among patients with low health literacy. This is a substantive concern for fidelity of data gathered from PROMIS CAT.
Clinical implementation of the PROMIS CAT in orthopaedic populations will benefit from further research into health literacy to increase questionnaire completion and to ensure that patients understand the content of the questions they are answering, which will increase the internal validity of the outcome measure.
A survey incorporating qualitative measures of student self‐efficacy beliefs was administered to 1,387 first‐year engineering students enrolled in ENGR 106, Engineering Problem‐Solving and Computer ...Tools, at Purdue University. The survey was designed to identify factors related to students' self‐efficacy beliefs, their beliefs about their capabilities to perform the tasks necessary to achieve a desired outcome. Open‐ended questions prompted students to list factors affecting their confidence in their ability to succeed in the course. Students were then asked to rank these factors based on the degree to which their self‐efficacy beliefs were influenced. Gender trends emerged in student responses to factors that affect confidence in success. These trends are discussed in light of the categories identified by efficacy theorists as sources of self‐efficacy beliefs. The results presented here provide a useful look at the first‐year engineering experiences that influence students' efficacy beliefs, an important consideration in explaining student achievement, persistence, and interest.
This qualitative study explored the engineering self‐efficacy beliefs held by students enrolled in their first engineering course at Purdue University. Findings from the thematic analysis of ...one‐on‐one interviews with 12 students enrolled in the course are presented. Results demonstrate the susceptibility of first‐year engineering students' self‐efficacy beliefs to the influence of performance comparisons based on the speed with which students were able to perform various tasks, the degree of contribution they were able to achieve when working with others, how much material they had mastered, and their grades. Gender differences were also identified in the way in which men and women were influenced by these experiences. Descriptions of how students made performance comparisons, including the logical progression from a specific experience through the modification of confidence in success, are offered.
Background
Belantamab mafodotin (belamaf) has demonstrated clinically meaningful antimyeloma activity in patients with heavily pretreated multiple myeloma. However, it is highly active against ...dividing cells, contributing to off-target adverse events, particularly ocular toxicity. Changes in best corrected visual acuity (BCVA) and corneal examination findings are routinely monitored to determine Keratopathy Visual Acuity (KVA) grade to inform belamaf dose modification.
Objective
We aimed to develop a semiautomated mobile app to facilitate the grading of ocular events in clinical trials involving belamaf.
Methods
The paper process was semiautomated by creating a library of finite-state automaton (FSA) models to represent all permutations of KVA grade changes from baseline BCVA readings. The transition states in the FSA models operated independently of eye measurement units (e.g., Snellen, logMAR, decimal) and provided a uniform approach to determining KVA grade changes. Together with the FSA, the complex decision tree for determining the grade change based on corneal examination findings was converted into logical statements for accurate and efficient overall KVA grade computation. First, a web-based user interface, conforming to clinical practice settings, was developed to simplify the input of key KVA grading criteria. Subsequently, a mobile app was developed that included additional guided steps to assist in clinical decision-making.
Results
The app underwent a robust Good Clinical Practice validation process. Outcomes were reviewed by key stakeholders, our belamaf medical lead, and the systems integration team. The time to compute a patient's overall KVA grade using the Belamaf Eye Exam (BEE) app was reduced from a 20- to 30-min process to <1–2 min. The BEE app was well received, with most investigators surveyed selecting “satisfied” or “highly satisfied” for its accuracy and time efficiency.
Conclusions
Our semiautomated approach provides for an accurate, simplified method of assessment of patients’ corneal status that reduces errors and quickly delivers information critical for potential belamaf dose modifications. The app is currently available on the Apple iOS and Android platforms for use by investigators of the DREAMM clinical trials, and its use could easily be extended to the clinic to support healthcare providers who need to make informed belamaf treatment decisions.
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome ...Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection.
We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects.
ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = - 0.28, p = 0.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of -0.26 (p = 0.033) and - 0.40, (p = 0.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES. Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E-06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively).
This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.
•Clostridium difficile CD2718 is an active sortase.•CD2718 recognizes a (S/P)PXTG- instead of a LPXTG-motif.•CD2718 can ligate to the side-chain amino group of diaminopimelic acid.•CD2718 has four ...potential protein substrates, CD0386, CD2831, CD3246 and CD3392.
Covalent attachment of surface proteins to the cell wall of Gram-positive bacteria requires a sortase-mediated transpeptidation reaction. In almost all Gram-positive bacteria, the housekeeping sortase, sortase A, recognizes the canonical recognition sequence LPXTG (X=any amino acid). The human pathogen Clostridium difficile carries a single putative sortase gene (cd2718) but neither transpeptidation activity nor specificity of CD2718 has been investigated. We produced recombinant CD2718 and examined its transpeptidation activity in vitro using synthetic peptides and MALDI-ToF(-ToF) MS analysis. We demonstrate that CD2718 has sortase activity with specificity for a (S/P)PXTG motif and can accommodate diaminopimelic acid as a substrate for transpeptidation.
C. difficile sortase B (CD2718)cleavesCD2831 by enzymatic study (View interaction)
C. difficile sortase B (CD2718)cleavesCD3246 by enzymatic study (View interaction)
Social networks describe the pattern of intraspecific interactions within a population. An individual’s position in a social network often is expected to influence its fitness, but only a few studies ...have examined this relationship in natural populations. We investigated the fitness consequences of network position in a wild beetle population. Copulation success of male beetles positively covaried with strength (a measure of network centrality) and negatively covaried with clustering coefficient (CC) (a measure of cliquishness). Further analysis using mediation path models suggested that the activity level of individuals drove the relationships between strength and fitness almost entirely. In contrast, selection on CC was not explained by individual behaviours. Although our data suggest that social network position can experience strong sexual selection, it is also clear that the relationships between fitness and some network metrics merely reflect variation in individual‐level behaviours.
The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to ...estimate the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success.
A multicenter, prospective study was conducted in biologic-naïve patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively.
From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval CI, 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%-79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio HR, 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104.
Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess.
gov, Number: NCT02856763.
Opioid prescribing after orthopedic surgeries varies widely, and there is little consensus establishing proper standards of care. This retrospective cohort study examines opioid prescribing trends ...following total hip (THA) and knee (TKA) arthroplasty and evaluates preoperative opioid use as a predictor of duration and magnitude of postoperative opioid use.
Patients who underwent THA or TKA in a nationwide insurance database were stratified by preoperative opioid use. Naive, sporadic, and chronic users were defined as 0, 1, or 2+ prescriptions filled 6 months before surgery. Patients were excluded for readmission or subsequent surgery. Duration of opioid use was defined as time between the procedure and the last opioid prescription record, and magnitude of opioid use was defined as quantity of pills filled by 30 days postop.
Naive patients were less likely than chronic users to fill any opioid prescription after surgery (THA: 61.5% naive vs 90.4% chronic, TKA: 72.0% naive vs 95.9% chronic), and they obtained fewer pills (THA: 73 pills naive vs 126 pills chronic, TKA: 86 pills naive vs 126 pills chronic, 5-mg oxycodone equivalent). Between 10% (THA) and 13% (TKA) of naive and between 47% (THA) and 62% (TKA) of chronic users continued opioid use at 1 year postop.
Chronic users obtain more opioids postoperatively and continue filling prescriptions for longer than naive patients. This work benchmarks norms regarding opioid use and furthermore these data highlight the powerful effect of opioid exposure during surgery as 10%-13% of naive patients continued opioids at 1 year postop.
Abstract CD1d-restricted invariant natural killer T (iNKT) cells constitute an important immunoregulatory T cell subset that can be activated by the synthetic glycolipid α-galactosylceramide ...(α-GalCer) and initiate antitumor immune responses. As cancer patients are frequently treated with aminobisphosphonates (NBP), it is relevant to determine possible effects of NBP on CD1d-restricted glycolipid Ag-presentation to iNKT cells. We report a striking reduction of α-GalCer-induced iNKT cell activation by monocyte derived dendritic cells (moDC) upon their exposure to NBP during maturation. We found that production of apolipoprotein E (apoE), which is a known facilitator of trans-membrane transport of exogenously derived glycolipids, was significantly diminished in moDC exposed to NBP. As the inhibitory effect of NBP on iNKT cell activation was alleviated by exogenous apoE, our data indicate that reduced apoE production by antigen presenting cells (APC) through NBP limits glycolipid-induced iNKT cell activation. This should be taken into account in the design of iNKT cell-based anti-cancer therapies.
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