Mechanical thrombectomy (MT) is the standard-of-care treatment for stroke patients with emergent large vessel occlusions. Despite this, little is known about physician decision making regarding MT ...and prognostic accuracy.
A prospective multicenter cohort study of patients undergoing MT was performed at 11 comprehensive stroke centers. The attending neurointerventionalist completed a preprocedure survey prior to arterial access and identified key decision factors and the most likely radiographic and clinical outcome at 90 days. Post hoc review was subsequently performed to document hospital course and outcome.
299 patients were enrolled. Good clinical outcome (modified Rankin Scale (mRS) score of 0-2) was obtained in 38% of patients. The most frequently identified factors influencing the decision to proceed with thrombectomy were site of occlusion (81%), National Institutes of Health Stroke Scale score (74%), and perfusion imaging mismatch (43%). Premorbid mRS score determination in the hyperacute setting accurately matched retrospectively collected data from the hospital admission in only 140 patients (46.8%). Physicians correctly predicted the patient's 90 day mRS tertile (0-2, 3-4, or 5-6) and final modified Thrombolysis in Ischemic Cerebral Infarction score preprocedure in only 44.2% and 44.3% of patients, respectively. Clinicians tended to overestimate the influence of occlusion site and perfusion imaging on outcomes, while underestimating the importance of pre-morbid mRS.
This is the first prospective study to evaluate neurointerventionalists' ability to accurately predict clinical outcome after MT. Overall, neurointerventionalists performed poorly in prognosticating patient 90 day outcomes, raising ethical questions regarding whether MT should be withheld in patients with emergent large vessel occlusions thought to have a poor prognosis.
Many men with prostate cancer will be exposed to androgen deprivation therapy (ADT). While evidence-based ADT use is common, ADT is also used in cases with no or limited evidence resulting in more ...harm than benefit, i.e., overuse. Since there are risks of ADT (e.g., diabetes, osteoporosis), it is important to understand the behaviors facilitating overuse to inform de-implementation strategies. For these reasons, we conducted a theory-informed survey study, including a discrete choice experiment (DCE), to better understand ADT overuse and provider preferences for mitigating overuse.
Our survey used the Action, Actor, Context, Target, Time (AACTT) framework, the Theoretical Domains Framework (TDF), the Capability, Opportunity, Motivation-Behavior (COM-B) Model, and a DCE to elicit provider de-implementation strategy preferences. We surveyed the Society of Government Service Urologists listserv in December 2020. We stratified respondents based on the likelihood of stopping overuse as ADT monotherapy for localized prostate cancer ("yes"/"probably yes," "probably no"/"no"), and characterized corresponding Likert scale responses to seven COM-B statements. We used multivariable regression to identify associations between stopping ADT overuse and COM-B responses.
Our survey was completed by 84 respondents (13% response rate), with 27% indicating "probably no"/"no" to stopping ADT overuse. We found differences across respondents who said they would and would not stop ADT overuse in demographics and COM-B statements. Our model identified 2 COM-B domains (Opportunity-Social, Motivation-Reflective) significantly associated with a lower likelihood of stopping ADT overuse. Our DCE demonstrated in-person communication, multidisciplinary review, and medical record documentation may be effective in reducing ADT overuse.
Our study used a behavioral theory-informed survey, including a DCE, to identify behaviors and context underpinning ADT overuse. Specifying behaviors supporting and gathering provider preferences in addressing ADT overuse requires a stepwise, stakeholder-engaged approach to support evidence-based cancer care. From this work, we are pursuing targeted improvement strategies.
ClinicalTrials.gov, NCT03579680.
Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian ...populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk allelic P = 8.4 × 10−6, odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 allelic P = 7.2 × 10−5, OR = 1.4 (1.2, 1.6) and three non‐synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.
Rabies virus glycoprotein is a type I transmembrane protein exposed on the surface on the mature virus particle that induces virus neutralizing antibodies. In the present study, 60 amino acid ...C-terminal hydrophobic anchor (transmembrane) and cytoplasmic domains of glycoprotein were deleted from full-length glycoprotein and fused with polyhistidine tag. The N-terminal viral signal peptide was also replaced with CD33 signal peptide for efficient secretion in mammalian cells. Following transfection of Madin Darby bovine kidney (MDBK) cells with plasmid encoding this soluble form of glycoprotein, polyclonal populations of stably transfected resistant cells were obtained after G418 selection. The protein was expressed as a glycosylated protein and secreted outside the cells utilizing N-terminal CD33 signal peptide. The secreted soluble glycoprotein was purified from cell culture supernatant by Ni–agarose affinity chromatography utilizing C-terminal polyhistidine tag. Like full-length glycoprotein, the expressed recombinant soluble glycoprotein was found to be immunogenic when injected in rabbits. In this study, we have assessed the potential of recombinant soluble glycoprotein as diagnostic antigen in ELISA and found that this recombinant protein can be used as diagnostic antigen in ELISA for detecting anti-glycoprotein antibodies in immunized host.
The prevalence of maxillary incisor shoveling was studied radiographically in 990 Saudi patients. According to the radiomorphologic characteristics, a new classification was developed and shovel ...teeth were categorized. The findings of this study showed 9% shovel-shaped incisors; among those, 4% were central incisors and 5% were lateral incisors. Frequency of dens invaginatus occurrence with the shovel-shaped incisors was also investigated. Eight percent of shovel-shaped incisors showed presence of dens invaginatus. Prevalence was found to be 4% in central shovel-shaped incisors, whereas that in lateral shovel-shaped incisors was 11%.