Distinct kratom user populations across the United States: A regional analysis based on an online survey.

OBJECTIVE: Kratom preparations have raised concerns of public health and safety in the United States. This paper analyzed the patterns and predictors of kratom use by four U.S. regions according to the U.S. Census. METHOD: An anonymous cross-sectional online survey yielded 8,049 valid responses. The data were categorised by regions (Northeast, South, Midwest, and West) and analyzed for the following predictors: age, gender, marital status, ethnicity, employment status, insurance coverage, education, and household income. RESULTS: After adjusting for state population, the survey response rates were highest from Oregon, Idaho, and Florida. Kratom use was significantly lower for both prescription drug dependency and acute or chronic pain in the Northeast region than the rest of the country. Multiple logistic regression models found that gender, employment, and education were significant on the regional level. Higher education was associated with lower kratom use for an illicit drug dependency (p = .002) independent of region whereas men were less likely to use kratom for acute or chronic pain in the Northeast (p < .001) but more likely in the Midwest (p = .041). CONCLUSIONS: The regional pattern of kratom use differed from opioid use data in both demographics and trend direction warranting further investigation.

MAF protein mediates innate resistance to proteasome inhibition therapy in multiple myeloma.

Multiple myeloma (MM) patients with the t(14;16) translocation have a poor prognosis, and unlike other molecular subgroups, their outcome has not improved with the introduction of bortezomib (Bzb). The mechanism underlying innate resistance of MM to Bzb is unknown. In the present study, we have investigated how MAF overexpression impacts resistance to proteasome inhibitor (PI) therapy (Bzb and carfilzomib). High levels of MAF protein were found in t(14;16) cell lines; cell lines from the t(4;14) subgroup had intermediate levels, whereas cell lines from the other subgroups had low levels. High expression of MAF protein in t(14;16) was associated with significantly higher PI half-maximum inhibitory concentration values compared with other molecular subgroups. PI exposure abrogated glycogen synthase kinase 3ß (GSK3ß)-mediated degradation of MAF protein, resulting in increased MAF protein stability and PI resistance. Subsequent studies using loss-of-function and gain-of-function models showed that silencing MAF led to increased sensitivity to PIs, enhanced apoptosis, and activation of caspase-3, -7, -8, -9, poly (ADP-ribose) polymerase, and lamin A/C. In contrast, overexpression of MAF resulted in increased resistance to PIs and reduced apoptosis. These results define the role of MAF and GSK3 in the resistance of t(14;16) MM to PIs and identifies a novel mechanism by which MAF protein levels are regulated by PIs, which in turn confers resistance to PIs.

Efficacy of Intravenous Acetaminophen for Postoperative Analgesia in Primary Total Knee Arthroplasty.

BACKGROUND: The use of intravenous acetaminophen has seen recent enthusiasm as one component of a multimodal approach to pain management. However, there is a lack of literature examining the efficacy of intravenous acetaminophen for pain control in total joint arthroplasty. The purpose of this study was to evaluate the efficacy of intravenous acetaminophen following primary total knee arthroplasty. METHODS: This is a retrospective review of 38 patients undergoing primary total knee arthroplasty by a single surgeon at one institution. Twenty-five patients received 1 gram of intravenous acetaminophen every 6 hours for 24 hours postoperatively. Thirteen patients received no additional intervention. Exclusion criteria were bilateral or concomitant procedures, allergy to medications included in the standard postoperative protocol, neuropathy or sensory disturbances, history of opioid dependence or abuse, deviations from protocol, revision procedures, and incomplete data. Primary outcomes were change in patient-reported visual analog scale (VAS) pain score, overall opioid consumption measured in morphine milligram equivalents, and hospital length of stay. RESULTS: We found no difference in length of stay, at 3.3 days in the control group and 2.9 days in the intervention group. There was a significant difference in VAS score between 16 and 24 hours. There was a statistically significant decrease in overall opioid consumption in the intravenous acetaminophen group 37.6 vs 18.6 morphine milligram equivalents. CONCLUSION: Intravenous acetaminophen is effective in significantly reducing opioid requirements in the first 24 hours following primary total knee arthroplasty. Additionally, there is a clinically significant decrease in VAS pain scores in patients receiving this intervention.

Self-reported Health Diagnoses and Demographic Correlates With Kratom Use: Results From an Online Survey.

OBJECTIVES: To determine whether diagnosed pre-existing health conditions correlate with Kratom demographics and use patterns. METHODS: A cross-sectional, anonymous US national online survey was conducted among 8049 Kratom users in October, 2016 to obtain demographic, health, and Kratom use pattern information. RESULTS: People who use Kratom to mitigate illicit drug dependence self-reported less pain and better overall health than individuals who used Kratom for acute/chronic pain. Self-reported improvements in pre-existing mental health symptoms (attention deficit and hyperactivity disorder/attention deficit disorder, anxiety, bipolar disorder, post-traumatic stress disorder, and depression) attributed to Kratom use were greater than those related to somatic symptoms (back pain, rheumatoid arthritis, acute pain, chronic pain, fibromyalgia). Demographic variables, including female sex, older age, employment status, and insurance coverage correlated with increased likelihood of Kratom use. CONCLUSIONS: Kratom use may serve as a self-treatment strategy for a diverse population of patients with pre-existing health diagnoses. Healthcare providers need to be engaging with patients to address safety concerns and potential limitations of its use in clinical practice for specific health conditions.

FRAX is a robust predictor of baseline vertebral fractures in multiple myeloma patients.

FRAX is a commonly used tool to evaluate patient fracture risk based on individual patient models that integrate the risks associated with clinical risk factors with or without bone mineral density (BMD) at the femoral neck. Retrospectively, factors identified by the FRAX scoring algorithm were used to predict the risk for vertebral compression fractures at baseline in newly diagnosed multiple myeloma patients. The data were derived from myeloma patients enrolled in Total Therapy Protocols (TT4 & TT5) between 8/2008 and 9/2017. FRAX scores were calculated and baseline PET and MRI imaging obtained. Univariate and multivariate logistic regression analyses determined the association between FRAX components and the existence of vertebral compression fractures, both pathologic and osteoporotic. The patient population had a median age of 61 years (43-76), 37% female, and 87% white. The median major osteoporotic score (MOS) and Hip fracture scores (HFS) for TT4 patients (low-risk myeloma) were 5.6 and 0.5, respectively, while median MOS and HFS for TT5 (high risk myeloma) patients were 6.2 and 0.7, respectively. The odds ratio for fracture at diagnosis in patients with elevated MOS (>2), and HFS (>4.5) was significant OR (1.48, 95% confidence interval (1.35,1.62)) and OR (1.61, 95% confidence interval (1.42, 1.81)), respectively. In sum, an elevated baseline FRAX score was highly predictive of baseline vertebral fractures in MM patients at presentation. In addition, patients with higher FRAX scores had significantly shorter survival in the low-risk (TT4) group but this survival effect was not seen in the high-risk (TT5) group. These findings suggest that FRAX assessment of baseline fracture risk is beneficial in MM patients to identify an individual patients' risk of vertebral fracture.

Comparison of Postbaccalaureate and Baccalaureate Graduates' Performance in First and Second Years of Dental School.

Postbaccalaureate programs help predental students strengthen their basic science knowledge and improve their study skills before applying or reapplying for dental school admission. A high percentage of postbac students are admitted to and graduate from dental schools, but gaining greater understanding of how well these students perform in key areas of the first two years' curriculum would be useful for the design of those programs. The aim of this study was to evaluate postbac dental students' performance in the D1 and D2 years at one U.S. dental school compared to dental students with a four-year baccalaureate degree only. Performance assessed was the students' dental school grades in basic science courses, in all D1 and D2 didactic courses, and on preclinical simulation lab practical exams. Didactic and practical scores were gathered anonymously for the Classes of 2013-18 at the College of Dental Medicine-Arizona (CDMA) at Midwestern University, where postbac students with master's degrees from the affiliated College of Health Sciences made up 6-19% of each class. The two cohorts chosen for comparison were students with baccalaureate degrees only and students with one-year Master of Arts degrees from the College of Health Sciences. The scores of these postbac dental students and their non-postbac peers were found to be comparable in the basic science courses. However, for all the didactic courses combined, the non-postbac cohort had significantly higher mean scores than the postbac cohort for the fall quarter 2 and winter quarter 2 in 2013-15 and all years combined. The practical scores for the two cohorts were not significantly different for any year. Overall, this study demonstrated that the MA program in the College of Health Sciences prepared the postbac students to compete on an equal level with the non-postbac students in the CDMA D1 and D2 curriculum.

Extensive Remineralization of Large Pelvic Lytic Lesions Following Total Therapy Treatment in Patients With Multiple Myeloma.

Osteolytic bone lesions are a hallmark of multiple myeloma (MM) bone disease. Bone destruction is associated with severely imbalanced bone remodeling, secondary to increased osteoclastogenesis and significant osteoblast suppression. Lytic lesions of the pelvis are relatively common in MM patients and are known to contribute to the increased morbidity because of the high risk of fracture, which frequently demands extensive surgical intervention. After observing unexpected radiological improvement in serial large pelvic CT assessment in a patient treated in a total therapy protocol, the radiographic changes of pelvic osteolytic lesions by PET/CT scanning in patients who received Total Therapy 4 (TT4) treatment for myeloma were retrospectively analyzed. Sixty-two (62) patients with lytic pelvic lesions >1 cm in diameter were identified at baseline PET/CT scanning. Follow-up CT studies showed that 27 of 62 patients (43%) with large baseline pelvic lesions achieved significant reaccumulation of radiodense mineralization at the lytic cortical site. The average size of lytic lesions in which remineralization occurred was 4 cm (range, 1.3 to 10 cm). This study clearly demonstrates that mineral deposition in large pelvic lesions occurs in a significant proportion of MM patients treated with TT4, potentially affecting patient outcomes, quality of life, and future treatment strategies. © 2017 American Society for Bone and Mineral Research.

Assessment of Total Lesion Glycolysis by 18F FDG PET/CT Significantly Improves Prognostic Value of GEP and ISS in Myeloma.

Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography with CT attenuation correction (18F-FDG PET/CT) is useful in the detection and enumeration of focal lesions and in semiquantitative characterization of metabolic activity (glycolytic phenotype) by calculation of glucose uptake. Total lesion glycolysis (TLG) and metabolic tumor volume (MTV) have the potential to improve the value of this approach and enhance the prognostic value of disease burden measures. This study aims to determine whether TLG and MTV are associated with progression-free survival (PFS) and overall survival (OS), and whether they improve risk assessments such as International Staging System (ISS) stage and GEP70 risk.Experimental Design: 192 patients underwent whole body PET/CT in the Total Therapy 3A (TT3A) trial and were evaluated using three-dimensional region-of-interest analysis with TLG, MTV, and standard measurement parameters derived for all focal lesions with peak SUV above the background red marrow signal.Results: In multivariate analysis, baseline TLG > 620 g and MTV > 210 cm3 remained a significant factor of poor PFS and OS after adjusting for baseline myeloma variables. Combined with the GEP70 risk score, TLG > 205 g identifies a high-risk-behaving subgroup with poor expected survival. In addition, TLG > 205 g accurately divides ISS stage II patients into two subgroups with similar outcomes to ISS stage I and ISS stage III, respectively.Conclusions: TLG and MTV have significant survival implications at baseline and offer a more precise quantitation of the glycolytic phenotype of active disease. These measures can be assessed more readily than before using FDA-approved software and should be standardized and incorporated into clinical trials moving forward. Clin Cancer Res; 23(8); 1981-7. ©2016 AACR.