Exploring behaviors, treatment beliefs, and barriers to oral chemotherapy adherence among adult leukemia patients in a rural outpatient setting

Objective: Adherence to oral chemotherapy is essential for patients with chronic myeloid leukemia (CML) and multiple myeloma (MM) to remain in remission. Few studies have used a Likert-type scale to measure medication adherence in CML and MM patients. We applied a validated treatment adherence tool, the ASK-12 (Adherence Starts with Knowledge®) survey, which assessed inconvenience and forgetfulness, treatment beliefs, and medication-taking behaviors recorded on a five-point Likert-type scale at two visits. Results: A medication adherence survey was administered to 42 newly diagnosed or pre-existing CML or MM patients at two outpatient oncology clinics affiliated with an academic medical center in rural eastern North Carolina. Thirty-one patients completed surveys at visit 1 and visit 2 (median 4.5 months apart). Most patients were treated for MM (65%), were non-Hispanic black (68%) and female (58%). Within subscales, mean adherence scores decreased between visits, signaling better adherence. Overall, visit scores were correlated (0.63, p = 0.001). Forgetting to take medication sometimes was the most common reason for non-adherence. Medication costs were not a barrier for MM patients. Greater patient–provider informed decision-making was identified as an opportunity for quality improvement among CML patients. The ASK-12 survey provided a strategy to obtain robust information on medication adherence

Photometric and spectroscopic analysis of the Type II SN 2020jfo with a short plateau

We present high-cadence photometric and spectroscopic observations of SN~2020jfo in ultraviolet and optical/near-infrared bands starting from $\sim 3$ to $\sim 434$ days after the explosion, including the earliest data with the 10.4\,m GTC. SN~2020jfo is a hydrogen-rich Type II SN with a relatively short plateau duration ($67.0 \pm 0.6$ days). When compared to other Type II supernovae (SNe) of similar or shorter plateau lengths, SN~2020jfo exhibits a fainter peak absolute $V$-band magnitude ($M_V = -16.90 \pm 0.34$ mag). SN~2020jfo shows significant H$\alpha$ absorption in the plateau phase similar to that of typical SNe~II. The emission line of stable [Ni~II] $\lambda$7378, mostly seen in low-luminosity SNe~II, is very prominent in the nebular-phase spectra of SN~2020jfo. Using the relative strengths of [Ni~II] $\lambda$7378 and [Fe~II] $\lambda$7155, we derive the Ni/Fe production (abundance) ratio of 0.08--0.10, which is $\sim 1.5$ times the solar value. The progenitor mass of SN~2020jfo from nebular-phase spectral modelling and semi-analytical modelling falls in the range of 12--15\,$M_\odot$. Furthermore, semi-analytical modelling suggests a massive H envelope in the progenitor of SN~2020jfo, which is unlikely for SNe~II having short plateaus.Comment: 20 pages (plus 5 pages appendix), 19 figures, Accepted for publication in MNRA

Deletion of chromosomal region 8p21 confers resistance to Bortezomib and is associated with upregulated Decoy trail receptor expression in patients with multiple myeloma

Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21)

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM)

A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs ofMMin 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better captureMMrisk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA

Effect of prednisolone on lung function and bronchodilator responses in stable COPD

Background : The effect of a short course of prednisolone on lung function and bronchodilator responsiveness in COPD is debatable. Methodology : After baseline spirometry and measurement of response to inhaled salbutamol, 31 patients with COPD were randomized to the steroid group (given 40 mg/day prednisolone for 7 days) while 29 patients were assigned to the control group. All the patients continued on their usual medication based on published management guidelines. The lung function and response to salbutamol were reassessed on day 8. Results : Both FEV 1 and FVC increased after salbutamol to the same extent in both the groups on the two test days. The proportions of FEV 1 and FVC responders were also similar in the two groups. The bronchodilator response was not reproducible and several responders of day I became non-responders on day 8 and vice versa in both the groups. At the end of 1 week, the prebronchodilator lung function showed similar improvement in FEV 1 and FVC in the two groups. A multiple logistic regression procedure failed to identify factors that could predict a steroid response. Conclusions : A short course of prednisolone does not favourably affect lung function and bronchodilator responsiveness in stable COPD

Nuances in the Management of Older People With Multiple Myeloma.

Multiple myeloma is a disease of the elderly, with about a third of patients at diagnosis older than 75 years of age. Yet, the population of elderly patients is heterogeneous: older patients are more likely to have comorbidities and frailties complicating both their initial diagnosis and subsequent management, but these are not consistent across the group. Furthermore, patients with comorbidities and frailty are generally underrepresented in clinical trials. Despite the survival of myeloma patients increasing following the introduction of novel agents, older patients continue to have worse outcomes with increased treatment-related toxicity. Treatment tolerability is not defined by age alone, rather a combination of age, physical function, cognitive function, and comorbidities. These factors all influence patients' tolerability of treatment and therefore treatment efficacy and should also be considered when reviewing the results of clinical trials. It is the nuances of determining how these factors interact that should influence initial treatment and ongoing management decisions and these will be discussed here