Patient Perceptions Regarding Multiple Myeloma and Its Treatment:Qualitative Evidence from Interviews with Patients in the United Kingdom, France, and Germany

BACKGROUND: The current standard of care for multiple myeloma requires several regimens of treatment, with patients experiencing high symptom burden and side effects, which negatively impact health-related quality of life (HRQoL). Thus, it is crucial to understand patient perceptions of multiple myeloma and how patients value different treatment options. OBJECTIVE: The purpose of this study was to conduct an exploratory investigation into concepts that could form attributes that influence treatment choices for patients with multiple myeloma and to identify trade-offs that patients are willing to make between treatment attributes. METHODS: In total, 30 patients with newly diagnosed or relapsed/refractory multiple myeloma from the UK, France, and Germany participated in semistructured interviews talking about their disease experience and symptoms, treatment benefits, treatment burden, perceived side effects, and benefit/risk trade-offs in treatment. The interview audio recordings were transcribed and analyzed using content analysis to identify treatment and disease aspects relevant to patients. RESULTS: Symptoms of fatigue and bone pain and treatment side effects of peripheral neuropathy, diarrhea, and constipation were cited by patients as the most disruptive to their HRQoL. Treatment duration was reported most frequently as a major treatment burden, and patients emphasized the importance of increased life expectancy as a treatment benefit. All patients showed good understanding of benefit/risk trade-offs in treatment, and some patients expressed a preference for more convenient modes of treatment administration. CONCLUSIONS: Qualitative interviews identified key aspects of multiple myeloma treatment that are most important to patients. These findings will inform a wider patient-preferences study, which could improve treatment choice and HRQoL for patients with multiple myeloma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40271-021-00501-7

Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort

BACKGROUND: Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line. METHODS: Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event. RESULTS: In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor-based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively. CONCLUSIONS: High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years

Association Between Raised Blood Pressure and Dysglycemia in Hong Kong Chinese

OBJECTIVE—To investigate the association between raised blood pressure and dysglycemia

Circulating Levels of Adipocyte and Epidermal Fatty Acid–Binding Proteins in Relation to Nephropathy Staging and Macrovascular Complications in Type 2 Diabetic Patients

OBJECTIVE—To investigate the relationships of serum adipocyte fatty acid–binding protein (A-FABP) and epidermal fatty acid–binding protein (E-FABP) with renal dysfunction and macrovascular complications in type 2 diabetic patients

Progression-free survival as a surrogate endpoint for overall survival in patients with relapsed or refractory multiple myeloma

Objectives: The goal of the research was to assess the quantitative relationship between median progression-free survival (PFS) and median overall survival (OS) specifically among patients with relapsed/refractory multiple myeloma (RRMM) based on published randomized controlled trials (RCTs). Methods: Two bibliographic databases (PubMed and Embase, 1970–2017) were systematically searched for RCTs in RRMM that reported OS and PFS, followed by an updated search of studies published between 2010 and 2022 in 3 databases (Embase, MEDLINE, and EBM Reviews, 2010–2022). The association between median PFS and median OS was assessed using the nonparametric Spearman rank and parametric Pearson correlation coefficients. Subsequently, the quantitative relationship between PFS and OS was assessed using weighted least-squares regression adjusted for covariates including age, sex, and publication year. Study arms were weighted by the number of patients in each arm. Results: A total of 31 RCTs (56 treatment arms, 10,450 patients with RRMM) were included in the analysis. The average median PFS and median OS were 7.1 months (SD 5.5) and 28.1 months (SD 11.8), respectively. The Spearman and Pearson correlation coefficients between median PFS and median OS were 0.80 (P &lt; 0.0001) and 0.79 (P &lt; 0.0001), respectively. In individual treatment arms of RRMM trials, each 1-month increase in median PFS was associated with a 1.72-month (95% CI 1.26–2.17) increase in median OS. Conclusion: Analysis of the relationship between PFS and OS incorporating more recent studies in RRMM further substantiates the use of PFS to predict OS in RRMM.</p

Bolaamphiphile analogues of 12-bis-THA Cl2 are potent antimicrobial therapeutics with distinct mechanisms of action against bacterial, mycobacterial, and fungal pathogens.

12-Bis-THA Cl2 [12,12'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride] is a cationic bolalipid adapted from dequalinium chloride (DQC), a bactericidal anti-infective indicated for bacterial vaginosis (BV). Here, we used a structure-activity-relationship study to show that the factors that determine effective killing of bacterial, fungal, and mycobacterial pathogens differ, to generate new analogues with a broader spectrum of activity, and to identify synergistic relationships, most notably with aminoglycosides against Acinetobacter baumannii and Pseudomonas aeruginosa, where the bactericidal killing rate was substantially increased. Like DQC, 12-bis-THA Cl2 and its analogues accumulate within bacteria and fungi. More hydrophobic analogues with larger headgroups show reduced potential for DNA binding but increased and broader spectrum antibacterial activity. In contrast, analogues with less bulky headgroups and stronger DNA binding affinity were more active against Candida spp. Shortening the interconnecting chain, from the most lipophilic twelve-carbon chain to six, improved the selectivity index against Mycobacterium tuberculosis in vitro, but only the longer chain analogue was therapeutic in a Galleria mellonella infection model, with the shorter chain analogue exacerbating the infection. In vivo therapy of Escherichia coli ATCC 25922 and epidemic methicillin-resistant Staphylococcus aureus 15 (EMRSA-15) infections in Galleria mellonella was also achieved with longer-chain analogues, as was therapy for an A. baumannii 17978 burn wound infection with a synergistic combination of bolaamphiphile and gentamicin. The present study shows how this class of bolalipids may be adapted further to enable a wider range of potential applications. IMPORTANCE While we face an acute threat from antibiotic resistant bacteria and a lack of new classes of antibiotic, there are many effective antimicrobials which have limited application due to concerns regarding their toxicity and which could be more useful if such risks are reduced or eliminated. We modified a bolalipid antiseptic used in throat lozenges to see if it could be made more effective against some of the highest-priority bacteria and less toxic. We found that structural modifications that rendered the lipid more toxic against human cells made it less toxic in infection models and we could effectively treat caterpillars infected with either Mycobacterium tuberculosis, methicillin resistant Staphylococcus aureus, or Acinetobacter baumannii. The study provides a rationale for further adaptation toward diversifying the range of indications in which this class of antimicrobial may be used

Bolaamphiphile Analogues of 12-bis-THA Cl2 Are Potent Antimicrobial Therapeutics with Distinct Mechanisms of Action against Bacterial, Mycobacterial, and Fungal Pathogens

12-Bis-THA Cl2 [12,12'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride] is a cationic bolalipid adapted from dequalinium chloride (DQC), a bactericidal anti-infective indicated for bacterial vaginosis (BV). Here, we used a structure-activity-relationship study to show that the factors that determine effective killing of bacterial, fungal, and mycobacterial pathogens differ, to generate new analogues with a broader spectrum of activity, and to identify synergistic relationships, most notably with aminoglycosides against Acinetobacter baumannii and Pseudomonas aeruginosa, where the bactericidal killing rate was substantially increased. Like DQC, 12-bis-THA Cl2 and its analogues accumulate within bacteria and fungi. More hydrophobic analogues with larger headgroups show reduced potential for DNA binding but increased and broader spectrum antibacterial activity. In contrast, analogues with less bulky headgroups and stronger DNA binding affinity were more active against Candida spp. Shortening the interconnecting chain, from the most lipophilic twelve-carbon chain to six, improved the selectivity index against Mycobacterium tuberculosis in vitro, but only the longer chain analogue was therapeutic in a Galleria mellonella infection model, with the shorter chain analogue exacerbating the infection. In vivo therapy of Escherichia coli ATCC 25922 and epidemic methicillin-resistant Staphylococcus aureus 15 (EMRSA-15) infections in Galleria mellonella was also achieved with longer-chain analogues, as was therapy for an A. baumannii 17978 burn wound infection with a synergistic combination of bolaamphiphile and gentamicin. The present study shows how this class of bolalipids may be adapted further to enable a wider range of potential applications. IMPORTANCE While we face an acute threat from antibiotic resistant bacteria and a lack of new classes of antibiotic, there are many effective antimicrobials which have limited application due to concerns regarding their toxicity and which could be more useful if such risks are reduced or eliminated. We modified a bolalipid antiseptic used in throat lozenges to see if it could be made more effective against some of the highest-priority bacteria and less toxic. We found that structural modifications that rendered the lipid more toxic against human cells made it less toxic in infection models and we could effectively treat caterpillars infected with either Mycobacterium tuberculosis, methicillin resistant Staphylococcus aureus, or Acinetobacter baumannii. The study provides a rationale for further adaptation toward diversifying the range of indications in which this class of antimicrobial may be used

Repensar la profundización financiera: estabilidad y crecimiento en los mercados emergentes

This paper uses a new measure of financial development to show that many benefits in terms of growth and stability can still be reaped from further financial development in most emerging markets. First, it defines financial development as a combination of depth, access and efficiency. Second, it highlights that the economic growth weakens at higher levels of financial development. Third, it indicates that the pace of financial development matters. Forth, it provides a new angle related to the tradeoffs of financial regulation. Finally, it finds that there is no “one-size-fits-all” in the sequencing of developing financial institutions versus markets, though as economies evolve the relative benefits from institutions decline and those from markets increase.En este escrito se usa una nueva medida del desarrollo financiero para mostrar que la mayoría de los mercados emergentes aún puede obtener beneficios de crecimiento y estabilidad con un mayor desarrollo financiero. Primero define el desarrollo financiero como una combinación de profundidad, acceso y eficiencia. Luego muestra que el crecimiento económico se debilita a mayores niveles de desarrollo financiero y que el ritmo del desarrollo financiero es importante; además propone una nueva manera de ver los “tradeoffs” de la regulación financiera. Concluye que no hay una secuencia única en el desarrollo de las instituciones y los mercados financieros, aunque se observa cuando las economías se desarrollan los beneficios relativos de las instituciones disminuyen y los de los mercados aumentan