Essential Medicines in a High Income Country: Essential to Whom?

Objective

To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an “essential” medicine, and how the Essential Medicines List (EML) concept functions in a high income country context.

Methods

In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach.

Findings

Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain.

Conclusions

This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders considered were essential medicines, challenges whether the EML concept is out-dated or underutilised in high income countries.     

LTA4H Genotype Is Associated with Susceptibility to Bacterial Meningitis but Is Not a Critical Determinant of Outcome

Adjunctive dexamethasone saves lives in the treatment of tuberculous meningitis but this response is influenced by the patient’s LTA4H genotype. Despite less certain benefit, adjunctive dexamethasone is also frequently used in the treatment of pyogenic bacterial meningitis, but the influence of LTA4H genotype on outcomes has not been previously investigated. We genotyped the LTA4H promoter region SNP (rs17525495) in 390 bacterial meningitis patients and 751 population controls. rs17525495 was associated with susceptibility to bacteriologically confirmed bacterial meningitis (P = 0.01, OR 1.27 95% confidence interval [CI] 1.05–1.54) but did not influence clinical presentation, disease severity or survival following dexamethasone treatment.     

Novel K3V2(PO4)3/C Bundled Nanowires as Superior Sodium‐Ion Battery Electrode with Ultrahigh Cycling Stability

Sodium‐ion battery has captured much attention due to the abundant sodium resources and potentially low cost. However, it suffers from poor cycling stability and low diffusion coefficient, which seriously limit its widespread application. Here, K₃V₂(PO₄)₃/C bundled nanowires are fabricated usinga facile organic acid‐assisted method. With a highly stable framework, nanoporous structure, and conductive carbon coating, the K₃V₂(PO₄)₃/C bundled nanowires manifest excellent electrochemical performances in sodium‐ion battery. A stable capacity of 119 mAh g^?1 can be achieved at 100 mA g^?1. Even at a high current density of 2000 mA g^?1, 96.0% of the capacity can be retained after 2000 charge–discharge cycles. Comparing with K₃V₂(PO₄)₃/C blocks, the K₃V₂(PO₄)₃/C bundled nanowires show significantly improved cycling stability. This work provides a facile and effective approach to enhance the electrochemical performance of sodium‐ion batteries.     

Combination of Circulating Tumor Cells with Serum Carcinoembryonic Antigen Enhances Clinical Prediction of Non-Small Cell Lung Cancer

Circulating tumor cells (CTCs) have emerged as a potential biomarker in the diagnosis, prognosis, treatment, and surveillance of lung cancer. However, CTC detection is not only costly, but its sensitivity is also low, thus limiting its usage and the collection of robust data regarding the significance of CTCs in lung cancer. We aimed to seek clinical variables that enhance the prediction of CTCs in patients with non-small cell lung cancer (NSCLC). Clinical samples and pathological data were collected from 169 NSCLC patients. CTCs were detected by CellSearch and tumor markers were detected using the Luminex xMAP assay. Univariate analyses revealed that histology, tumor stage, tumor size, invasiveness, tumor grade and carcinoembryonic antigen (CEA) were associated with the presence of CTCs. However, the level of CTCs was not associated with the degree of nodal involvement (N) or tumor prognostic markers Ki-67, CA125, CA199, Cyfra21-1, and SCCA. Using logistic regression analysis, we found that the combination of CTCs with tumor marker CEA has a better disease prediction. Advanced stage NSCLC patients with elevated CEA had higher numbers of CTCs. These data suggest a useful prediction model by combining CTCs with serum CEA in NSCLC patients.     

Association between Body Mass Index and Health-Related Quality of Life: The "Obesity Paradox" in 21,218 Adults of the Chinese General Population

Background

There was no consistent recognition of the association between high or low body mass index (BMI) and health related quality of life (HRQL). The aim of this research was to study the association between BMI and HRQL in Chinese adults, and to further explore the stability of that association in the subgroup analysis stratified by status of chronic conditions.

Methods

A total of 21,218 adults aged 18 and older were classified as underweight, normal weight, overweight, class I obese, and class II obese based on their BMI. HRQL was measured by the SF-36 Health Survey. The independent impact of each BMI category on HRQL was examined through standard least squares regression by comparing the difference of SF-36 scores and the minimum clinically important differences (MCID), which was defined as 3 points.

Results

Compared to the normal weight, the class I obese was significantly associated with better HRQL scores in the mental component summary (MCS) (75.1 vs. 73.4, P<0.001). The underweight had the lowest score in both the physical components summary (PCS) (75.4 vs. 77.5, P<0.001) and mental components summary (MCS) (71.8 vs. 73.4, P<0.001). For the MCID, the HRQL score was reduced by more than 3 points in the physical functioning for the class II obese (D=-3.43) and the general health for the underweight (D=-3.71). Stratified analyses showed a similar result in the health subjects and chronic conditions, and it was significant in the chronic conditions.

Conclusions

The class I obese showed the best HRQL, especially in the mental domain. The worst HRQL was found in the underweight. The class II obese reduced HRQL in the physical functioning only. “Obesity paradox” was more obvious in the participants with chronic conditions.     

Elevated High-Sensitivity C-Reactive Protein Levels Predict Decreased Survival for Nasopharyngeal Carcinoma Patients in the Intensity-Modulated Radiotherapy Era

Purpose

This study aimed to clarify the prognostic utility of high-sensitivity C-reactive protein (hs-CRP) in nasopharyngeal carcinoma (NPC) patients in the Intensity-Modulated Radiotherapy (IMRT) era.

Patients and Methods

In this observational study, 1,589 non-metastatic NPC patients treated with IMRT were recruited. Blood samples were collected before treatment for examination of hs-CRP levels. We evaluated the association of pretreatment hs-CRP levels with overall survival rate (OS), progression free survival rate (PFS), locoregional relapse free survival rate (LRFS) and distant metastasis free survival rate (DMFS).

Results

Baseline hs-CRP levels were correlated with sex, clinical stage, body mass index, smoking status, and EBV DNA level. Multivariate analysis showed that hs-CRP had significant association with OS (HR:1.723; 95%CI:1.238–2.398; p = 0.001), PFS (HR:1.621; 95%CI:1.273–2.064; p<0.001) and DMFS (HR:1.879; 95%CI:1.394–2.531; p<0.001). In subgroups such as advanced-stage group, low EBV DNA group and high EBV DNA group, elevated hs-CRP levels still predicted poor clinical outcomes. Furthermore, in patients with chronic HBV infection, decreased 4-year survival was observed in the cohort of high hs-CRP levels, with 87.4% vs. 94.9% (p = 0.023) for OS, 65.2% vs. 90.8% (p<0.001) for PFS, and 67.6% vs. 95.0% (p<0.001) for DMFS. A similar finding was observed for patients with cardiovascular disease, with 79.1% vs. 90.2% (p = 0.020) for PFS, and 71.4% vs. 97.6% (p = 0.002) for DMFS.

Conclusion

Elevated serum hs-CRP levels were correlated with poor survival for NPC patients in the IMRT era, playing a complementary role to TNM stage and EBV DNA. In addition, elevated hs-CRP level was still an effective indicator for patients with chronic HBV infection and cardiovascular disease.     

Effects of dietary beta-1, 3 glucan on innate immune response of large yellow croaker, Pseudosciaena crocea

The present study was conducted to investigate the effects of dietary beta-1, 3 glucan on the innate immune response and protection against Vibrio harveyi infection in large yellow croaker, Pseudosciaena crocea. A basal diet was supplemented with 0% (control), 0.09% (low) and 0.18% (high) beta-1, 3 glucan to formulate three experimental diets. Each diet was randomly allocated to triplicate groups of fish in floating sea cages (1.5 x 1.5 x 2.0m), and each cage was stocked with 100 fish (initial average weight 9.75+/-0.35 g). Fish were fed twice daily (05:00 and 17:00) to apparent satiation for 8 weeks. The results of 8 weeks feeding trial showed that low glucan supplementation (0.09%) significantly enhanced fish growth, whereas high supplementation (0.18%) did not. The serum lysozyme activity was significantly increased with the increase of dietary glucan (P < 0.05), and fish fed the diet with high glucan had significantly higher lysozyme activity compared with low glucan. There were no significant differences in alternative complement pathway (ACP) activity between fish fed diets with and without supplementation of glucan. The phagocytosis percentage (PP) and respiratory burst activity in fish fed the diet with 0.09% glucan were significantly higher than those in fish fed with the control diet (P < 0.05), but both immunological parameters significantly decreased in fish fed the diet with high supplementation compared with low supplementation and no significant difference was observed between the control and high supplementation groups. The challenge experiment showed that fish fed the diet with low glucan had significantly lower cumulative mortality compared with the control and high glucan groups (P < 0.05), but no significant difference was observed between the control and high supplementation groups. These results suggested that low glucan could enhance growth and innate immunity of large yellow croaker with an 8-week oral administration, but higher supplementation did not influence growth, or further improve immunity of large yellow croaker.     

Anti-hyperglycemic activity of an aqueous extract from flower buds of Cleistocalyx operculatus (Roxb.) Merr and Perry

A screening of 5 plants used for making drinks in Vietnam revealed a Cleistocalyx operculatus (Roxb.) Merr and Perry flower bud extract to have the highest inhibitory activity against the alpha-glucosidase enzyme. The anti-hyperglycemic effects of an aqueous extract from flower buds of Cleistocalyx operculatus (CO), a commonly used material for drink preparation in Vietnam, were therefore investigated in vitro and in vivo. In vitro, the CO extract inhibited the rat-intestinal maltase and sucrase activities, with IC50 values of 0.70 and 0.47 mg/ml, respectively. These values are lower than those for a guava leaf extract (GE; IC50 0.97 and 1.28 mg/ml, respectively). Postprandial blood glucose testing of normal mice and STZ-induced diabetic rats by maltose loading (2 g/kg body weight (bw)) showed that the blood glucose reduction with CO (500 mg/kg bw) was slightly less than that with acarbose (25 mg/kg bw) but was more potent than that with GE (500 mg/kg bw). In an 8-week experiment, the blood glucose level of STZ diabetic rats treated with 500 mg of CO/kg bw/day was markedly decreased in comparison with that of non-treated diabetic rats. Consequently, CO is considered to be a promising material for preventing and treating diabetes.