Responses to direct-to-consumer advertising in Australia: Comparing experience.

AbsractThis paper examines the potential effect of Direct-to-Consumer (DTC) advertising on consumers' behavioral intentions in relation to a medical issue. Using an online experiment, 1295 people were randomized to two information conditions. One group watched an advertisement for a hypothetical cold sore medicine, while a second (control) group did not view the advertisement, before both groups answered questions on symptoms. The responses were analyzed based on group allocation and the respondents' experience with cold sores. Results indicate that those who viewed the advertisement were more likely to choose the product, and the advertisement had larger effects based on consumer experience.

Discrepancies between proxy estimates and patient reported, health related, quality of life: minding the gap between patient and clinician perceptions in heart failure.

PURPOSE: Health related quality of life (HRQoL) is rarely routinely measured in the clinical setting. In the absence of patient reported data, clinicians rely on proxy and informal estimates to support clinical decisions. This study compares clinician estimates (proxy) with patient reported HRQoL in patients with advanced heart failure and examines factors influencing discrepancies. METHODS: Seventy-five patients with heart failure, (22 females, 53 males) completed the EQ-5D-5L questionnaire. Thirty-nine clinicians (11 medical, 23 nursing, 5 allied health) completed the proxy version (V1) producing 194 dyads. Correlation was assessed using Spearman's rank tests, systematic bias was examined with Bland-Altman analyses. Inter-rater agreement at the domain level, was investigated using linear weighted Kappa statistics while factors influencing the IRG were explored using independent student t-tests, analysis of variance and regression. RESULTS: There was a moderate positive correlation between clinician HRQoL estimates and patient reported utility (r = 0.38; p < .0005). Mean clinician estimates were higher than patient reported utility (0.60 vs 0.54; p = 0.008), with significant underestimation of reported problems apparent in three of the five EQ-5D-5L domains. Patient sex (female), depressed mood and frailty were all associated with an increased inter-rater gap. CONCLUSION: Clinicians in this sample overestimated HRQoL. Factors affecting the inter-rater gap, including sex and depression, support formal HRQoL screening to enhance clinical conversations and decision making. The discrepancy also supports regulatory restriction on the use of expert opinion in the development of QALYs in health economic analysis.

Prevention of postpartum haemorrhage: cost consequences analysis of misoprostol in low-resource settings.

BACKGROUND: While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of Essential Medicines for use in the prevention of postpartum haemorrhage (PPH) in low-resource settings. This study evaluates the costs and health outcomes of use of oral misoprostol to prevent PPH in settings where injectable uterotonics are not available. METHODS: A cost-consequences analysis was conducted from the international health system perspective, using data from a recent Cochrane systematic review and WHO's Mother-Baby Package Costing Spreadsheet in a hypothetical cohort of 1000 births in a mixed hospital (40% births)/community setting (60% births). Costs were estimated based on 2012 US dollars. RESULTS: Using oxytocin in the hospital setting and misoprostol in the community setting in a cohort of 1000 births, instead of oxytocin (hospital setting) and no treatment (community setting), 22 cases of PPH could be prevented. Six fewer women would require additional uterotonics and four fewer women a blood transfusion. An additional 130 women would experience shivering and an extra 42 women fever. Oxytocin/misoprostol was found to be cost saving (US$320) compared to oxytocin/no treatment. If misoprostol is used in both the hospital and community setting compared with no treatment (i.e. oxytocin not available in the hospital setting), 37 cases of PPH could be prevented; ten fewer women would require additional uterotonics; and six fewer women a blood transfusion. An additional 217 women would experience shivering and 70 fever. The cost savings would be US$533. Sensitivity analyses indicate that the results are sensitive to the incidence of PPH-related outcomes, drug costs and the proportion of hospital births. CONCLUSIONS: Our findings confirm that, even though misoprostol is not the optimum choice in the prevention of PPH, misoprostol could be an effective and cost-saving choice where oxytocin is not or cannot be used due to a lack of skilled birth attendants, inadequate transport and storage facilities or where a quality assured oxytocin product is not available. These benefits need to be weighed against the large number of additional side effects such as shivering and fever, which have been described as tolerable and of short duration.

Validation and comparison of EuroQoL-5 dimension (EQ-5D) and Short Form-6 dimension (SF-6D) among stable angina patients.

OBJECTIVES: Several preference-based health-related quality of life (HRQoL) instruments have been published and widely used in different populations. However no consensus has emerged regarding the most appropriate instrument in therapeutic area of stable angina. This study compared and validated the psychometric properties of two generic preference-based instruments, the EQ-5D and SF-6D, among Chinese stable angina patients. METHODS: Convergent validity of the EQ-5D and SF-6D was examined with eight a priori hypotheses from stable angina patients in conjunction with Seattle Angina Questionnaire (SAQ). Responsiveness was compared using the effect size (ES), relative efficiency (RE) and receiver operating characteristic (ROC) curves. Agreement between the EQ-5D and SF-6D was tested using intra-class correlation coefficient (ICC) and Bland-Altman plot. Factors affecting utility difference were explored with multiple linear regression analysis. RESULTS: In 411 patients (mean age 68.08 ± 11.35), mean utility scores (SD) were 0.78 (0.15) for the EQ-5D and 0.68 (0.12) for the SF-6D. Validity was demonstrated by the moderate to strong correlation coefficients (Range: 0.368-0.594, P< 0.001) for five of the eight hypotheses in both the EQ-5D and SF-6D. There were no serious floor effects for the EQ-5D and SF-6D, but ceiling effects for the EQ-5D were large. The areas under ROC of them all exceeded 0.5 (0.660-0.814, P< 0.001). The SF-6D showed a better discriminative capacity (ES: 0.573 to 1.179) between groups with different stable-angina-specific health status than the EQ-5D (ES: 0.426 to 1.126). RE suggested that the SF-6D (RE: 44.8 to 177.8%) was more efficient than the EQ-5D except for physical function. Poor agreement between them was observed with ICC (0.448, P< 0.001) and Bland-Altman plot analysis. Multiple liner regression showed that clinical variables significantly (P< 0.05) influenced differences in utility scores between the EQ-5D and SF-6D. CONCLUSIONS: Both EQ-5D and SF-6D are valid and sensitive preference-based HRQoL instruments in Chinese stable angina patients. The SF-6D may be a more effective tool with lower ceiling effect and greater sensitivity. Further study is needed to compare other properties, such as reliability and longitudinal response.

Real-world treatment patterns and outcomes for patients with CLL using the Australian pharmaceutical benefits scheme (PBS) dataset.

This real-world retrospective cohort study using Australian Pharmaceutical Benefits Scheme (PBS) 10% investigated changes in chronic lymphocytic leukemia (CLL) treatment by line of therapy, time-to-next-treatment, treatment duration, and overall survival (OS). Overall, 803 patients received their first PBS-reimbursed CLL medication between 1 January 2011 to 31 July 2021 (median age: 70 years; 64.6% male), 289 post-1 August 2020. In 2011, most first-line (1 L) prescribing was fludarabine, cyclophosphamide, and rituximab (FCR). By 2021, common 1L were chlorambucil ± CD20 (26.1%), Bruton Tyrosine Kinase inhibitor (BTKi) (26.1%), and CD20 monotherapy (23.9%). In 2011, relapsed/refractory (R/R) CLL treatment was CD20 monotherapy or FCR. By 2021, BTKi (57.7%) and venetoclax ± CD20 (26.1%) were most common. Compared to FCR, 1 L treatment duration (Hazard Ratio) was shorter for CD20 monotherapy (1.7) or chlorambucil ± CD20 (2.5). In R/R CLL, median duration was 24 (ibrutinib) and 19 months (venetoclax). Median OS was 127 months. CLLtreatment pattern shave greatly changed in Australia since the introduction of novel therapies.

Patient Access to Orphan Drugs Covered by Medical Insurance in China: Real-World Evidence From Patient Survey.

BACKGROUND: After the inclusion of more high-cost orphan drugs in China's National Reimbursement Drugs List, this study investigated issues relating to patient access to the 7 medicines for 4 rare diseases after listing. METHODS: This study collected data from a national survey conducted in China. Three aspects associated with the accessibility of medicines, namely, approachability, availability, and affordability, were analyzed using descriptive statistics. In addition, multilevel logistic regression models were used to investigate the associations between patient characteristics and the accessibility of surveyed orphan drugs. RESULTS: Of the 999 completed responses included in the study, 15% of the patients (n = 150) did not use the medicines because of non-medicine-related issues. Among the 849 patients using the surveyed medications, 64.4% (n = 547) encountered the problem of unavailability, whereas 51.2% (n = 435) reported affordability as an issue, and 49.6% (n = 320) had health expenditure beyond the catastrophic threshold. The data also indicated that Commercial Medical Insurance helped patients to relieve the cost burden on orphan drugs, but the payout of Commercial Medical Insurance failed to influence patients' decisions to continue the treatments. CONCLUSION: Accessibility of orphan drugs has improved in China after their inclusion in the National Reimbursement Drugs List. Nevertheless, the availability and affordability of medicines remained the barriers for patients to access the desired treatments. It is recommended that further policy refinement in conjunction with the collaboration among healthcare stakeholders is required to deliver better care for patients with rare disease.

Cost-utility analysis of liraglutide versus glimepiride as add-on to metformin in type 2 diabetes patients in China.

OBJECTIVES: The aim of this study was to evaluate the long-term cost-utility of liraglutide versus glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM), based on the results of clinical trial conducted in Asian population. METHODS: The validated UKPDS Outcomes Model was used to project life expectancy, quality adjusted life-years (QALYs), incidence of diabetes-related complication and cost of complications in patients receiving those regimens. Baseline cohort characteristics and treatment effects were derived from an Asian study. China-specific complication costs and utility score were taken from local studies. Patients' outcomes were modeled for 30 years and incremental cost-effectiveness ratios were calculated for liraglutide compared with glimepiride from the healthcare system perspective. Both future costs and clinical benefits were discounted at 3 percent. Sensitivity analyses were performed. RESULTS: Over a period of 30 years, compared with glimepiride, liraglutide 1.8 mg was associated with improvements in life expectancy (0.1 year) and quality adjusted life-year (0.168 QALY), and a reduced incidence of diabetes-related complications leading to an incremental cost-effectiveness ratio per QALY gained versus glimepiride of CNY 25,6871 (DEC 2010, 1 USD = 6.6227 CNY). CONCLUSIONS: Long-term projections indicated that liraglutide was associated with increased life expectancy, QALYs, and reduced complication incidences comparing with glimepiride. When the UK cost of liraglutide was discounted by 38 percent, liraglutide would be a cost-effective option in China from the healthcare system perspective using the 3X GDP/capita per QALY as the WTP threshold.

Psychometric Evaluation of the Mandarin HeartQoL Health-Related Quality of Life Questionnaire Among Patients With Ischemic Heart Disease in China.

OBJECTIVES: This study evaluated the psychometric properties of the Mandarin version of the HeartQoL questionnaire, a core ischemic heart disease (IHD) health-related quality of life (HRQL) instrument, in patients with angina, myocardial infarction (MI), and ischemic heart failure (IHF). METHODS: The English version of HeartQoL was translated into Mandarin. A cross-sectional study was then conducted in mainland China using the Mandarin HeartQoL, Short Form-12 Health Survey, and Hospital Anxiety and Depression Scale. Factor analysis was used to establish the HeartQoL structure and internal consistency reliability and construct validity were assessed. RESULTS: Patients with IHD (n = 412; angina = 112, MI = 151, and IHF = 149) were enrolled. Significantly higher HeartQoL HRQL scores were reported by patients with either angina or MI than by patients with IHF. The 2-factor structure was confirmed by Mokken scale analysis in the total group with strong H coefficients on the global scale (0.64) and both the physical (0.70) and emotional (0.80) subscales. Internal consistency reliability was strong with Cronbach's α ranging from 0.90 to 0.95. Convergent validity was confirmed with strong correlations between similar physical and mental HeartQoL and Short Form-12 Health Survey subscales ranging from 0.77 to 0.82 with divergent validity confirmed with significantly lower correlations between dissimilar constructs. Discriminative validity was confirmed for 72% of the a priori sociodemographic and clinical hypotheses. CONCLUSIONS: The Mandarin version of the HeartQoL HRQL questionnaire demonstrates acceptable internal consistency reliability and convergent, divergent, and discriminative validity in patients with IHD and in each diagnostic subgroup. The data support the use of the HeartQoL to assess and compare HRQL in Mandarin-speaking patients with IHD.

Willingness to pay per quality-adjusted life year: is one threshold enough for decision-making?: results from a study in patients with chronic prostatitis.

OBJECTIVE: To estimate the willingness to pay (WTP) per quality-adjusted life year (QALY) ratio with the stated preference data and compare the results obtained between chronic prostatitis (CP) patients and general population (GP). METHODS: WTP per QALY was calculated with the subjects' own health-related utility and the WTP value. Two widely used preference-based health-related quality of life instruments, EuroQol (EQ-5D) and Short Form 6D (SF-6D), were used to elicit utility for participants' own health. The monthly WTP values for moving from participants' current health to a perfect health were elicited using closed-ended iterative bidding contingent valuation method. RESULTS: A total of 268 CP patients and 364 participants from GP completed the questionnaire. We obtained 4 WTP/QALY ratios ranging from $4700 to $7400, which is close to the lower bound of local gross domestic product per capita, a threshold proposed by World Health Organization. Nevertheless, these values were lower than other proposed thresholds and published empirical researches on diseases with mortality risk. Furthermore, the WTP/QALY ratios from the GP were significantly lower than those from the CP patients, and different determinants were associated with the within group variation identified by multiple linear regression. CONCLUSIONS: Preference elicitation methods are acceptable and feasible in the socio-cultural context of an Asian environment and the calculation of WTP/QALY ratio produced meaningful answers. The necessity of considering the QALY type or disease-specific QALY in estimating WTP/QALY ratio was highlighted and 1 to 3 times of gross domestic product/capita recommended by World Health Organization could potentially serve as a benchmark for threshold in this Asian context.

Validation and comparison of EuroQol and short form 6D in chronic prostatitis patients.

OBJECTIVE: Generic, preference-based health-related quality of life (HRQoL) instruments is increasingly used in health-care decision-making process. However, to our knowledge, no such HRQoL instrument has been validated or used in chronic prostatitis. We therefore aimed to assess and compare the psychometric properties of EuroQol (EQ-5D) and Short Form 6D (SF-6D) among chronic prostatitis patients in China. METHODS: Consenting patients were interviewed using EQ-5D and SF-6D. Convergent and discriminative construct validities were examined with five and two a priori hypotheses, respectively. Sensitivity was compared using receiver operating characteristic (ROC) curves and relative efficiency (RE) statistics. Agreement between instruments was assessed with intra-class correlation coefficients and Bland-Altman plot, while factors affecting utility difference were explored with multiple liner regression models. RESULTS: In 268 subjects, mean (SD) EQ-5D and SF-6D utility scores were comparable at 0.73 (0.15) and 0.75 (0.10), respectively. Five of the seven hypotheses for construct validity were fulfilled in both instruments. The areas under ROC of them all exceeded 0.5 (P < 0.001). SF-6D had 9.7-19.9% higher efficiency than EQ-5D at detecting the difference in chronic prostatitis symptom severity. Despite no significant difference in utility scores between two instruments, lack of agreement was observed with low intraclass correlation coefficient (0.218-0.630) and Bland-Altman plot analysis. Chronic prostatitis symptom severity significantly (P < 0.05) influenced differences in utility scores between EQ-5D and SF-6D. CONCLUSIONS: Both EQ-5D and SF-6D are demonstrated to be valid and sensitive HRQoL measures in Chinese chronic prostatitis patients, with SF-6D showing better HRQoL dimension coverage, greater sensitivity, lower ceiling effect, and more rational distribution. Further research is needed to determine longitudinal response and reliability.

Health-related quality of life in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE: To examine the health-related quality of life (HRQoL) and factors associated with HRQoL in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using two generic preference-based HRQoL instruments, EQ-5D (plus EQ-VAS) and SF-6D, with the results compared with general population. METHOD: CP/CPPS patients were recruited from two tertiary referral hospitals, and the general populations were randomly approached. After informed consent, subjects were interviewed using EQ-5D, EQ-VAS and SF-6D, and their socio-demographic and medical information was solicited. RESULTS: Compared to the general population (n = 364), CP/CPPS patients (n = 268) reported significantly worse HRQoL with median score of the EQ-5D utility index (0.73 vs. 0.85), SF-6D utility index (0.76 vs. 0.81), and EQ-VAS (70.0 vs. 85.0). Multiple linear regression analyses showed pain symptom had the strongest predictive power for HRQoL, compared to symptom duration and urinary symptom. Socio-demographic factors and comorbidities did not significantly contribute to poorer HRQoL. CONCLUSION: CP/CPPS patients experienced deteriorated HRQoL with lower health-related utility scores compared to general population, and pain severity was the main physical symptom predicting decreased health-related utility. Further studies are needed to provide the reference utility index for the comparison and better characterizing the influence of geographic and cultural factors on variation of health-related utility of CP/CPPS patients.

Can the Direct Medical Cost of Chronic Disease Be Transferred across Different Countries? Using Cost-of-Illness Studies on Type 2 Diabetes, Epilepsy and Schizophrenia as Examples.

OBJECTIVES: To systematically review cost of illness studies for schizophrenia (SC), epilepsy (EP) and type 2 diabetes mellitus (T2DM) and explore the transferability of direct medical cost across countries. METHODS: A comprehensive literature search was performed to yield studies that estimated direct medical costs. A generalized linear model (GLM) with gamma distribution and log link was utilized to explore the variation in costs that accounted by the included factors. Both parametric (Random-effects model) and non-parametric (Boot-strapping) meta-analyses were performed to pool the converted raw cost data (expressed as percentage of GDP/capita of the country where the study was conducted). RESULTS: In total, 93 articles were included (40 studies were for T2DM, 34 studies for EP and 19 studies for SC). Significant variances were detected inter- and intra-disease classes for the direct medical costs. Multivariate analysis identified that GDP/capita (p<0.05) was a significant factor contributing to the large variance in the cost results. Bootstrapping meta-analysis generated more conservative estimations with slightly wider 95% confidence intervals (CI) than the parametric meta-analysis, yielding a mean (95%CI) of 16.43% (11.32, 21.54) for T2DM, 36.17% (22.34, 50.00) for SC and 10.49% (7.86, 13.41) for EP. CONCLUSIONS: Converting the raw cost data into percentage of GDP/capita of individual country was demonstrated to be a feasible approach to transfer the direct medical cost across countries. The approach from our study to obtain an estimated direct cost value along with the size of specific disease population from each jurisdiction could be used for a quick check on the economic burden of particular disease for countries without such data.

Efficacy and Safety of Thrombin-Receptor Antagonist (Atopaxar and Vorapaxar) in Patients with Acute Coronary Syndrome or Coronary Artery Disease-A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Meta-analysis for the efficacy and safety data of thrombin-receptor antagonist (TRA) based on patients with acute coronary syndrome (ACS) or coronary artery disease (CAD) and indirect comparisons between TRAs were not available. OBJECTIVES: We intended to synthesize the primary end points based on different patient populations (ACS or CAD) as well as perform indirect comparison between two newly invented antiplatelet agents atopaxar and vorapaxar. METHODS: A literature search was performed in MEDLINE, Embase, and Cochrane Library. Incidences of major adverse cardiovascular events (MACEs) and bleeding events according to thrombolysis in myocardial infarction were selected as primary outcomes, whereas adverse effects were considered as secondary outcomes. Corresponding results were synthesized using Revman 5.1 according to ACS or CAD cohorts. RESULTS: Among the seven included randomized controlled trials, the efficacy end points in the TRA treatment group were favorable compared with placebo. Specifically, the odds ratio (OR) of MACEs was 0.80 (95% confidence interval [CI] 0.52-1.22) for patients with ACS and 0.74 (95% CI 0.53-1.05) for the cohort with CAD. The events of bleeding were unanimously superior in the placebo arm for both cohorts. The indirect comparison showed a superior trend in favor of atopaxar over vorapaxar in occurrences of MACEs (OR 0.93; 95% CI 0.38-1.32), myocardial infarction (OR 0.52; 95% CI 0.13- 0.95), and cardiovascular death (OR 0.82; 95% CI 0.12-4.24) and caused less incidence of bleeding. CONCLUSIONS: Besides being more effective than placebo in improving the incidence of MACEs but with a higher risk of bleeding, TRAs may exert different effects in patients with ACS and CAD. Indirect comparisons also suggested that atopaxar might be better than vorapaxar in lowering the incidence of MACEs, myocardial infarction, and cardiovascular death and at the same time with lower risks of bleeding.

Transferability of indirect cost of chronic disease: a systematic review and meta-analysis.

BACKGROUND: Indirect cost is an important component in economic evaluations. The variation in the magnitude of indirect costs across studies and countries is substantial and affects the transferability of results across jurisdictions. OBJECTIVE: This study explored the factors involved in the variation of reported indirect cost and investigated the feasibility of transferring indirect costs across settings. METHODS: A systematic literature review was conducted to identify studies estimating indirect costs for four selected chronic diseases, namely, asthma (AS), diabetes (DI), rheumatoid arthritis (RA) and schizophrenia (SC). A multiple linear regression analysis was run to identify the factors that potentially explain the variation in reported indirect costs. Parametric (fixed- and random-effect models) and non-parametric (bootstrapping method) meta-analyses were applied to local gross domestic product (GDP)/capita-adjusted indirect costs for each disease. Results from the three different analytical methods were compared to ascertain the robustness of estimation. RESULTS: The systematic literature review identified 77 articles that reported indirect costs of AS (n = 18), DI (n = 20), RA (n = 25) and SC (n = 14) for literature synthesis. Substantial inter- and intra-disease variations among the indirect cost studies were observed with respect to geographic distribution, methodology and magnitude of cost estimation. Regression analysis showed that disease categories and local GDP/capita significantly (p < 0.001) contributed to the variance of indirect cost. The range of intra-disease variation in indirect costs was substantially reduced after adjusting by and expressing values as local GDP/capita. The GDP-adjusted indirect cost in terms of percentage of local GDP/capita of AS was the lowest and that of SC was the highest. Bootstrapping estimation was relatively conservative, with slightly wider confidence intervals (CIs) than the parametric method, with a mean (95 % CI) of 2.12 % (1.4089-2.9332) for AS, 10.65 % (7.215-14.7438) for DI, 21.98 % (17.4360-27.0631) for RA, and 79.19 % (52.4243-117.833) for SC. CONCLUSION: It would be convenient and feasible to construct a universal reference range of indirect cost for a specific disease based on existing data and present this as a percentage of local GDP to assist local decision making in jurisdictions where indirect cost data are not available.

Clinical efficacy and safety of the newer antiepileptic drugs as adjunctive treatment in adults with refractory partial-onset epilepsy: a meta-analysis of randomized placebo-controlled trials.

OBJECTIVE: To evaluate the clinical efficacy and safety of the newer antiepileptic drugs (AEDs), namely, Eslicarbazepine (ESL), Retigabine/Ezogabine (RTG), Carisbamate (CAR), Lacosamide (LAC), Brivaracetam (BRI) or Perampanel (PER) as adjunctive therapy for adults with partial-onset seizures (POS). METHODS: A systematic review of Randomized placebo-controlled Trials (RCTs) of newer AEDs was conducted. Electronic databases and identified bibliographies were searched to retrieve RCTs. The primary outcomes were responder rates and withdrawal rates, adverse effects. Pooled effects of odds ratio (OR), risk ratio (RR) and risk differences (RD) were derived from meta-analysis implemented in Revmen 5.1. RESULTS: In total, 15 RCTs were included. All the studies contained a baseline and treatment phase. The pooled OR of all newer AEDs vs placebo was 2.16 (95% CI: 1.82, 2.57) for responder rates, 1.54 (1.12, 2.10) for withdrawal rates, 1.67 (1.34, 2.08) for adverse effects. The indirect comparisons between individual newer AED and all other newer AEDs suggested the similar results in responder rates (ORs, BRI 1.79 [-1.50, 5.08], RTG 1.41 [0.49, 2.33]). CONCLUSIONS: The pooled ORs suggested newer AEDs might be more effective than placebo while with higher incidence of adverse effects. The indirect comparisons suggested BRI, followed by RTG, might be more effective than all other newer AEDs, which could be confirmed by future clinical studies.

Burden of Disease Studies in the Asia-Pacific Region: Are There Enough being Performed to Provide Information for Evidence-Based Health Policy?

OBJECTIVE: To review published studies of Burden of Disease (BOD) performed in the Asia-Pacific (AP) region. METHOD: Overlapping strategy of searching four electronic databases was used to identify studies of BOD published during 1993-2009. The quality of identified studies was assessed according to the categories of burden reflected and scope of BOD information included. Chronological and regional distributions of research output were analyzed. RESULTS: Among 524 articles identified for review, 27.7% (n=145) were classified as complete summary measures as being most informative BOD studies from health policy maker's perspective and 72.3% (n=379) as using only partial measures. Although an increasing trend of publication of BOD articles was observed, the quantity of publication was not commensurate with the number of diseases, especially for researches using summary measures. Unbalance of research output of BOD among different diseases areas and selected countries/regions was observed. CONCLUSION: The paucity of specific studies in AP region needs to be addressed. Furthermore, in order to improve the quality of research, a clear definition of BOD study and a uniform template for the research method from health policy-makers' perspective would be necessary.

Monocyte-mediated rotenone neurotoxicity towards human neuroblastoma SH-SY5Y: role of mitogen-activated protein kinases.

Increasing evidence has suggested an important role for rotenone in the pathogenesis of Parkinson's disease (PD). In this report, sequential linking of two culture systems, monocytic THP-1 cell line and SH-SY5Y neuroblastoma, was utilized. The supernatant from rotenone-stimulated THP-1 cells was used as the incubating medium for the second culture which adopted cells of the SH-SY5Y neuroblastoma. At 6.25-50 nM, concentrations that were nontoxic to SH-SY5Y directly, rotenone induced dose-dependent cell death on SH-SY5Y through stimulating monocyte THP-1 within a period of 48 h. Cytotoxicity was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Hoechst 33258 staining revealed that the treatment of SH-SY5Y with rotenone-stimulated THP-1 supernatant resulted in condensed nuclei and a decrease in cell size. Apoptotic rate measured by flow cytometric analysis indicated that at 25 and 50 nM, the percentage of apoptotic SH-SY5Y cells accumulated to 31.5% and 37.0% respectively. We further investigated whether rotenone (50 nM) activated mitogen-activated protein kinase (MAPK) cascades, and found it had effect on p38 MAPK and ERK in THP-1 cells, but not JNK. Pretreatment of THP-1 cells with the MAPK kinase inhibitor, PD98059, inhibited THP-1 cell-mediated rotenone neurotoxicity towards SH-SY5Y, whereas the p38 MEK inhibitor, SB203580, had no effect. These results suggested that activation of microglia intracellular signaling pathway may also involve in microglia-enhanced rotenone neurotoxicity.

Potentiation of adenosine A1 receptor agonist CPA-induced antinociception by paeoniflorin in mice.

The effect of paeoniflorin (PF), a major constituent isolated from Paeony radix, on N6-Cyclopentyladenosine (CPA), a selective adenosine A1 receptor (A1 receptor) agonist, induced antinociception was examined in mice. In the tail-pressure test, CPA (0.05, 0.1, 0.2 mg/kg, s.c.) could induce antinociception in a dose-dependent manner. PF (5, 10, 20 mg/kg, s.c.) alone failed to exhibit any antinociceptive effect in mice; however, pretreatment of PF (20 mg/kg, s.c.) could significantly enhance CPA-induced antinociception. Additionally, pretreatment of 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.25 mg/kg, s.c.), a selective A1 receptor antagonist, could antagonize the antinociceptive effect of combining CPA with PF. Furthermore, in the competitive binding experiments, PF did not displace the binding of [3H]-8-Cyclopentyl-1,3-dipropylxanthine ([3H]-DPCPX) but displaced that of [3H]-2-Chloro-N6-cyclopentyladenosine ([3H]-CCPA, a selective A1 receptor agonist) to the membrane preparation of rat cerebral cortex. These results suggested that PF might selectively increase the binding and antinociceptive effect of CPA by binding with A1 receptor.

Down regulation of cyclooxygenase-2 is involved in delayed neuroprotection by ischemic preconditioning in rats.

AIM: To examine whether the prostaglandins (PGs) pathway is involved in triggering delayed neuroprotection by ischemic preconditioning (IPC) and evaluate the effects of IPC on cyclooxygenase-2 (COX-2) expression following focal cerebral ischemia and reperfusion in rats. METHODS: IPC was induced by 10 min of saline infusion into the left internal carotid artery with the right common carotid artery clamped at the same time. Middle cerebral artery occlusion (MCAO) and reperfusion model was produced using intraluminal filament method. RESULTS: IPC 48 h prior to MCAO significantly reduced infarct area as compared with MCAO alone. A nonselective inhibitor of COX indomethacin (3 mg/kg, ip) applied 1 h prior to or 1 h after IPC failed to affect its protective effects. IPC had no direct effect on the cortex COX-2 mRNA and protein expression 72 h later, but decreased the expression of COX-2 mRNA and protein following ischemia and reperfusion insult. CONCLUSION: PGs pathways was not involved in triggering delayed neuroprotection by IPC, and IPC induced down-regulation of COX-2 following focal cerebral ischemia and reperfusion in rats in vivo.