Patients have multiple expectations of THA and TKA. We asked whether preoperative educational classes addressing recovery during the first year could modify patients’ expectations of their 12-month ...postoperative recovery. Participants were enrolled consecutively in two randomized, controlled trials, one for THA (177 patients) and one for TKA (143 patients). Control patients preoperatively received a standard THA or TKA class addressing recovery immediately after surgery. Intervention patients preoperatively received the standard class plus a joint-specific module addressing recovery during the first 12 months. Before and after the class, patients completed either a hip-specific or knee-specific validated expectations survey. The main outcome was the within-patient change in expectation scores (maximum increase, +100; maximum decrease, −100) before and after the class but preoperatively. Mean changes in hip scores were +3.3 ± 8 for intervention patients (range, −22–+32) and +4.9 ± 8 for control patients (range, −13–+29). Mean changes in knee scores were −3.4 ± 10 for intervention patients (range, −26–+33) and +2.4 ± 10 for control patients (range, −30–+30). Patients’ preoperative expectations of their recovery from THA or TKA can be modified by preoperative educational classes.
Level of Evidence:
Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Abstract
Purpose
Cancer diagnosis is known to affect the family; however, administrative claims data are not commonly used to evaluate the broader impact of cancer diagnosis. This study was designed ...to evaluate the feasibility of using claims data to explore the impact of cancer diagnosis on the caregiver.
Methods
IBM Marketscan data were used to identify eligible cancer patients, who were required to have a second adult over the age of 18 (defined as “caregiver” for this study) covered by the same the healthcare policy. Eligible control pairs included any two adults in the same policy with no evidence of cancer; for each pair one adult was randomly assigned to be the “patient control” while their partner was assigned as “caregiver control”. Probabilistic stratified sampling was used select control pairs for analysis by matching the relative frequencies within sex and age group strata to those of patient/caregiver pairs. Eligible control pairs were probabilistically sampled without replacement until the stratum with at least 0.5 % relative frequency had been completely sampled. Caregiver and caregiver control healthcare resource utilization (HCRU), new diagnoses, and healthcare costs were compared during the 12-month post-diagnosis period. Subgroup analyses were conducted by cancer subtypes (breast, colorectal, lung, gastric, sarcoma) and by sex of the patient and caregiver.
Results
A total of 62,893 patient/caregiver pairs and 449,177 control pairs were included. Overall, caregivers used slightly fewer healthcare resources and expended less costs during the 12-month period after the cancer diagnosis than controls (physician visits; 85.8 % vs. 95.7 %; hospitalizations 5.4 % vs. 7.0 %; emergency room visits 15.7 % versus 16.2 %, all
p
≤ 0.001). This finding was consistent in all subgroup analyses. New diagnoses were lower in the caregiver cohort, except for mental disorders, which were higher than controls (14.3 % vs. 9.9 %,
p
< 0.0001). Psychotherapeutic/antidepressant utilization occurred among 21.0 % of caregivers versus 17.2 % of caregiver controls during this period.
Conclusions
It is feasible to use administrative claims data to evaluate the impact of a cancer diagnosis on the caregiver to evaluate outcomes such as HCRU, diagnoses and costs. These findings raise hypotheses about deferment of health care and increased mental distress during the caregiving period.
Significant barriers, such as lack of professional guidelines, specialized training for interpretation of pharmacogenomics (PGx) data, and insufficient evidence to support clinical utility, prevent ...preemptive PGx testing from being widely clinically implemented. The current study, as a pilot project for the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment Protocol, was designed to evaluate the impact of preemptive PGx and to optimize the workflow in the clinic setting. We used an 84-gene next-generation sequencing panel that included SLCO1B1, CYP2C19, CYP2C9, and VKORC1 together with a custom-designed CYP2D6 testing cascade to genotype the 1013 subjects in laboratories approved by the Clinical Laboratory Improvement Act. Actionable PGx variants were placed in patient's electronic medical records where integrated clinical decision support rules alert providers when a relevant medication is ordered. The fraction of this cohort carrying actionable PGx variant(s) in individual genes ranged from 30% (SLCO1B1) to 79% (CYP2D6). When considering all five genes together, 99% of the subjects carried an actionable PGx variant(s) in at least one gene. Our study provides evidence in favor of preemptive PGx testing by identifying the risk of a variant being present in the population we studied.
This study sought to evaluate advanced psychometric properties of the 15-item Economic Strain and Resilience in Cancer (ENRICh) measure of financial toxicity for cancer patients.
We surveyed 515 ...cancer patients in the greater Houston metropolitan area using ENRICh from March 2019 to March 2020. We conducted a series of factor analyses alongside parametric and non-parametric item response theory (IRT) assessments using Mokken analysis and the graded response model (GRM). We utilized parameters derived from the GRM to run a simulated computerized adaptive test (CAT) assessment.
Among participants, mean age was 58.49 years and 278 (54%) were female. The initial round factor analysis results suggested a one-factor scale structure. Negligible levels of differential item functioning (DIF) were evident between eight items. Three items were removed due to local interdependence (Q3>+0.4). The original 11-point numerical rating scale did not function well, and a new 3-point scoring system was implemented. The final 12-item ENRICh had acceptable fit to the GRM (p<0.001; TLI = 0.94; CFI = 0.95; RMSEA = 0.09; RMSR = 0.06) as well as good scalability and dimensionality. We observed high correlation between CAT version scores and the 12-item measure (r = 0.98). During CAT, items 2 (money you owe) and 4 (stress level about finances) were most frequently administered, followed by items 1 (money in savings) and 5 (ability to pay bills). Scores from these four items alone were strongly correlated with that of the 12-item ENRICh (r = 0.96).
These CAT and 4-item versions provide options for quick screening in clinical practice and low-burden assessment in research.
Forest managers in the United States must respond to the need for climate-adaptive strategies in the face of observed and projected climatic changes. However, there is a lack of on-the-ground forest ...adaptation research to indicate what adaptation measures or tactics might be effective in preparing forest ecosystems to deal with climate change. Natural resource managers in many areas are also challenged by scant locally or regionally relevant information on climate projections and potential impacts. The Adaptive Silviculture for Climate Change (ASCC) project was designed to respond to these barriers to operationalizing climate adaptation strategies by providing a multiregion network of replicated operational-scale research sites testing ecosystem-specific climate change adaptation treatments across a gradient of adaptive approaches, and introducing conceptual tools and processes to integrate climate change considerations into management and silvicultural decisionmaking. Here we present the framework of the ASCC project, highlight the implementation process at two of the study sites, and discuss the contributions of this collaborative science-management partnership.
Objective: The current study examined predictors and moderators of two interventions for binge-eating disorder (BED). Method: Participants were 112 adults with BED (Mage = 39.7 ± 13.4 years; MBMI = ...35.1 ± 13.4 kg/m2; 82% female; 91% Caucasian) randomly assigned to integrative cognitive-affective therapy for BED (ICAT-BED) or guided self-help cognitive-behavioral therapy (CBTgsh). Generalized linear models examined predictors and moderators of objective binge-eating episode (OBE) frequency and OBE abstinence at end-of-treatment (EOT) and 6-month follow-up (FU). Results: Lower levels of baseline dietary restraint and emotion regulation difficulties predicted greater reductions in OBE frequency at EOT and FU, respectively. At EOT, greater pretreatment self-control predicted greater reductions in OBE frequency in ICAT-BED than CBTgsh (ps < .05). In addition, low shape/weight overvaluation predicted greater reductions in OBE frequency in ICAT-BED than CBTgsh, whereas high shape/weight overvaluation predicted comparable reductions in OBE frequency across treatments at EOT (ps < .02). At EOT and FU, greater baseline actual-ideal self-discrepancy predicted significantly greater reductions in OBE frequency in ICAT-BED, than CBTgsh (ps < .02). No significant predictor or moderator effects were observed for models examining OBE abstinence. Conclusion: This study identified two general predictors and four moderators of BED treatment response. However, only one predictor (actual-ideal self-discrepancy) interacted with treatment type to differentially predict OBE frequencies at both EOT and FU. Altogether, findings suggest that ICAT-BED may confer specific and durable improvements in OBE frequencies among individuals with high actual-ideal self-discrepancy. Therefore, patients demonstrating these characteristics may be more likely to benefit from ICAT-BED.
What is the public health significance of this article?
This study suggests that ICAT-BED is an efficacious treatment for BED and may be particularly effective for reducing binge-eating frequency among individuals with certain symptom presentations. This study highlights the potential importance of assessing pretreatment patient characteristics, particularly actual-ideal self-discrepancy, to inform treatment plans and selection of targeted intervention approaches.
The Ebola virus (EBOV) genome only encodes a single viral polypeptide with enzymatic activity, the viral large (L) RNA-dependent RNA polymerase protein. However, currently, there is limited ...information about the L protein, which has hampered the development of antivirals. Therefore, antifiloviral therapeutic efforts must include additional targets such as protein–protein interfaces. Viral protein 35 (VP35) is multifunctional and plays important roles in viral pathogenesis, including viral mRNA synthesis and replication of the negative-sense RNA viral genome. Previous studies revealed that mutation of key basic residues within the VP35 interferon inhibitory domain (IID) results in significant EBOV attenuation, both in vitro and in vivo. In the current study, we use an experimental pipeline that includes structure-based in silico screening and biochemical and structural characterization, along with medicinal chemistry, to identify and characterize small molecules that target a binding pocket within VP35. NMR mapping experiments and high-resolution x-ray crystal structures show that select small molecules bind to a region of VP35 IID that is important for replication complex formation through interactions with the viral nucleoprotein (NP). We also tested select compounds for their ability to inhibit VP35 IID–NP interactions in vitro as well as VP35 function in a minigenome assay and EBOV replication. These results confirm the ability of compounds identified in this study to inhibit VP35–NP interactions in vitro and to impair viral replication in cell-based assays. These studies provide an initial framework to guide development of antifiloviral compounds against filoviral VP35 proteins.
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•Ebola VP35 is a multifunctional viral protein critical for viral replication.•VP35 IID structure revealed several drugable pockets.•In silico screen identified potential binders near functionally important patches.•Binding was validated by NMR and complex x-ray crystal structures.•Select small molecules inhibit VP35 functions in vitro and in cell-based studies.
The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In ...this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials.
To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can ...deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR).
We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR.
The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance.
This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.
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