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Home medication review (HMR) programs could minimise patients' health-related costs and burdens, thereby enhancing the quality of life and well-being. The aim of this economic evaluation is to determine if home medication review by community pharmacists (HMR-CP) for patients with type 2 diabetes mellitus (T2DM) is a cost-effective intervention from the Malaysian healthcare provider perspective.The economic evaluation was conducted alongside the randomised controlled trial (RCT) to estimate the intermediate cost-effectiveness of HMR-CP for patients with T2DM. A Markov model was then constructed to project the lifetime cost-effectiveness data beyond the RCT. The primary outcomes for the economic evaluation were HbAThe intervention and health services costs throughout the 6-month HMR-CP trial were RM121.45 (USD28.64) [95%CI: RM115.89 to 127.08 (USD27.33-29.97)] per participant. At a 6-month follow-up, a significant reduction in HbAHMR-CP was a cost-effective intervention that had significantly reduced the HbA

To assess the correlation between PFS2 and OS among patients with advanced prostate cancer (PC) in a real-world setting for Japan. This was a retrospective analysis using the Japanese MDV database. Patients with nmCRPC (non-metastatic Castration-Resistant PC), mCRPC (metastatic Castration-Resistant PC), and mCNPC (metastatic Castration-Naïve PC) were identified and their medical records were investigated for PFS2 and death. Association between PFS2 and OS was determined using the Pearson’s, Spearman’s, Kendall's Tau, and Fleischers’ correlation coefficients. A total of 386,484 patients with PC were identified from the database, of which, 1,783 patients with nmCRPC, 630 with mCRPC, and 454 with mCNPC met the predefined eligibility criteria. Significant correlation between PFS2 and OS was observed in patients with nmCRPC (Pearson’s r = 0.873; 95% CI: 0.849 – 0.897, Spearman’s r = 0.909; 95% CI: 0.893 – 0.925; Kendall’s Tau r = 0.831; 95% CI: 0.812 – 0.850, Fleischers’ r = 0.682; 95% CI: 0.601 – 0.764), mCRPC (Pearson’s r = 0.812; 95% CI: 0.758 – 0.865, Spearman’s r = 0.895; 95% CI: 0.868 – 0.923, Kendall’s Tau r = 0.789; 95% CI: 0.755 – 0.823, Fleischers’ r= 0.439; 95% CI: 0.334 – 0.544), and mCNPC (Pearson’s r = 0.931; 95% CI: 0.899 – 0.964, Spearman’s r = 0.943; 95% CI: 0.922 – 0.964, Kendall’s Tau r = 0.866; 95% CI: 0.836 – 0.896, Fleischers’ r = 0.756; 95% CI: 0.624 – 0.888). The results of this study indicate a significant correlation between PFS2 and OS, which adds additional evidence to the existing literature of using PFS2 as a surrogate endpoint for OS in patients with PC.

Ruxu You,1,* Jinyu Liu,2,* David Bin-Chia Wu,3 XinYu Qian,4 Boxiang Lyu,5 Yu Zhang,1 Nan Luo4 1Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3School of Pharmacy, Monash University Malaysia, Kuala Selangor, Malaysia; 4Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 5Machine Learning Department, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA*These authors contributed equally to this workCorrespondence: Nan LuoSaw Swee Hock School of Public Health, National University of Singapore, 16 Medical Drive, Block MD3, Singapore 117597, SingaporeTel +65 6516 4966 Ext 188Fax +65 6779 1489Email ephln@nus.edu.sgObjective: The purpose of this study was to evaluate the cost-effectiveness of the combined use of afatinib and epidermal growth factor receptor (EGFR) testing versus gemcitabine-cisplatin as the first-line treatment for patients with non-small cell lung cancer (NSCLC) in China.Methods: A decision-analytic model, based on clinical phase III trials, was developed to simulate patient transitions. Direct costs were estimated from the perspective of the Chinese healthcare system. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated over a 5-year lifetime horizon. Model robustness was conducted in sensitivity analyses.Results: For the base case, EGFR mutation testing followed by afatinib treatment for advanced NSCLC increased 0.15 QALYs compared with standard chemotherapy at an additional cost of $5069.12. The ICER for afatinib maintenance was $33,416.39 per QALY gained. The utility of PFS and the cost of afatinib had the most important impact on the ICER. Scenario analyses suggested that when a patient assistance program (PAP) was available, ICER decreased to $22,972.52/QALY lower than the willingness-to-pay (WTP) threshold of China ($26,508/QALY).Conclusion: Our results suggest that gene-guided maintenance therapy with afatinib with the PAP might be a cost-effective treatment option compared with gemcitabine – cisplatin in China.Keywords: Economic analysis, incremental cost-effectiveness ratio, NSCLC, EGER mutation testing, Afatinib

Background: Successful diabetes treatment requires commitment and understanding of disease management by the patients. Objective: This trial aimed to evaluate the programme effectiveness of home medication review by community pharmacists (HMR-CP) in optimising diabetes care and reducing medication wastage. Methods: A randomised controlled trial was conducted on 166 patients with Type 2 Diabetes Mellitus (T2DM) who were randomly assigned to the intervention or control groups. The intervention group received HMR-CP at 0-month, 3-month, and 6-month. The primary outcome was haemoglobin A1c (HbA1c) while clinical outcomes, anthropometric data, and humanistic outcomes were the secondary outcomes. For the intervention group, drug-related problems (DRP) were classified according to the Pharmaceutical Care Network Europe Foundation (PCNE). Medication adherence was determined based on the Pill Counting Adherence Ratio (PCAR). The cost of medication wastage was calculated based on the total missed dose by the T2DM patients multiplied by the cost of medication. General linear model and generalised estimating equations were used to compare data across the different time-points within and between the groups, respectively. Results: No significant difference was observed in the demographic and anthropometric data at baseline between the two groups except for fasting blood glucose (FBG). There was a significant reduction in the HbA1c (-0.91%) and FBG (-1.62mmol/L) over the study period (p

Objectives: Baseline presence of nonstructural protein 5A (NS5A) resistance-associated variants can attenuate the efficacy of new direct-acting antivirals. A potential method to attain the higher efficacy would be to screen for NS5A polymorphisms prior to the initiation of therapy and to adjust the treatment length based on the test results. However, baseline testing adds additional costs and it is unclear whether this would represent a high value strategy for chronic hepatitis C in China.Methods: A hybrid model compared 1) standard 12-weeks treatment (no testing), 2) shortened 8-weeks treatment (no testing), and 3) baseline testing with 12-/8-weeks treatment for those with/without NS5A polymorphisms from a lifetime Chinese health care payer perspective. All model inputs were retrieved from clinical trials and publically available literature. And sensitivity analyses were also conducted to assess the impact of uncertainty.Results: Baseline testing was associated with overall increase in total health care cost of USD 13.50 and in QALYs of 0.002 compared with standard 12-weeks treatment (no testing), yielded in an ICER of USD 6750/QALY gained. Scenario analyses suggested that shortened 8-weeks treatment (no testing) was found to be lower costs and great QALYs compared with other two strategies when the sustained virologic response (SVR) rate increased to 95%. Sensitivity analyses indicated that the results were robust.Conclusions: Our results suggest prior assessment of NS5A sensitivity followed by optimizing treatment duration was an economic strategy. In addition, shortened 8-weeks treatment (no testing) was shown to be dominant with the SVR rate increased to 95%.

Background and purpose: Several recent randomized controlled trials (RCTs) in non-metastatic castration resistant prostate cancer (nmCRPC) have demonstrated a significant improvement in metastasis-...

Very few data are available to demonstrate the economic benefit of early paliperidone palmitate once-monthly long-acting injectable (PP1M) treatment in patients with schizophrenia or schizoaffective disorder.This study has retrospectively compared the healthcare utilization and associated costs of pre- and post-PPIM treatment in 413 patients with schizophrenia or schizoaffective disorder recruited from three major public hospitals providing psychiatric services in Hong Kong. Patients were categorized into early treatment (≤3 years since diagnosis) and chronic (3 years) groups, and also whether they were receiving polypharmacy (POP).It was found that patients who were started on early therapy with no POP had the most favourable outcomes. Overall results of the entire cohort, including both early and late treatments, indicate that there was a slight increase in annual in-patient days (IP) per patient and outpatient visit (OP) by 3.18 and 1.87, respectively, and a decrease in emergency room visit (ER) of 0.9 (p 0.05). For non-polypharmacy (NP) patients receiving early PP1M therapy, there was a significant decrease in IP and ER of 21.56 (p 0.05) and 1.15 (p 0.05), respectively, but an increase in OP of 1.88 (p 0.05). For patients with POP, there was an all-across increase in IP and all-across decrease in OP and ER. In monetary terms, a NP patient receiving early therapy may have an overall saving of HKD40,878 (USD5,241, 1USD = 7.8HKD) per year compared to HKD6,224 (USD798) in patients where therapy was given after 3 years. For patients with POP, there was an all-across increase in overall spending despite reductions in OP and ER.From the 413 patients studied, potential annual savings is higher by early administration of PPIM in patients with NP. Analysis using multivariate linear regression based on generalized estimating equations and sensitivity analysis using a linear mixed model supported the findings.

Purpose To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD. Materials and methods We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo. A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George's Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24. Results Inconsistency models were not statistically significant for all outcomes. LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24. All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1. Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant. LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement. Similar trends were observed for the transition dyspnea index and St George's Respiratory Questionnaire outcomes. There were no significant differences in the incidences of adverse events among all treatment options. Conclusion LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement. There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes.

Background To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan. Methods From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized. Results Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within 1 year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909–31.731]) and antibiotic use within 1 year (aOR 3.89, [95% CI, 1.219–12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or VT, endemic community strains in Taiwan, four isolates as ST 8/SCCmec IV (USA 300) and one isolate as ST 239/SCCmec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). Conclusions Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.

Background: The current lack of an effective cure for dementia would exacerbate its prevalence and incidence globally. Growing evidence has linked mindfulness to cognitive and psychological improvements that could be relevant for mild cognitive impairment (MCI). Objective: To investigate whether mindfulness practice can improve health outcomes of MCI. Methods: The study is the first longitudinal mixed-methods observational study with a one-year follow-up period, that customized an eight-week group-based mindfulness training program for older adults with MCI (n = 14). Measures included cognitive function, psychological health, trait mindfulness, adherence to mindfulness practice, and everyday activities functioning as assessed at pre-intervention, post-intervention, and one-year follow-up. Repeated measures ANOVAs, Pearson’s correlation analyses, and Mann-Whitney U tests were performed. Results: The MCI participants showed significant improvements in cognitive function (p

A systematic review and network-meta analysis (NMA) were performed to test significance of the galactagogue effect of fenugreek administrated to lactating women versus other comparators (i.e., placebo/control/other galactagogues). A pairwise comparison for the treatment effect was carried out to generate the forest plot for the NMA. League tables were generated using treatment effect, weighted mean difference (WMD; 95% confidence interval, CI) for all pairwise comparisons, where WMD > 0 favors the column-defining treatment. Five studies were identified with 122 participants receiving treatment with fenugreek. The NMA results of 4 studies indicated that consumption of fenugreek significantly increased amount of the produced breast milk [11.11, CI 95% 6.77, 15.46] versus placebo. The pairwise comparison revealed that fenugreek was effective as a galactagogue compared to placebo, control, and reference groups WMD 17.79 [CI 11.71, 23.88]. However, the effect of fenugreek was substantially inferior to Coleus amboinicus Lour and palm date. The NMA using pairwise comparison demonstrated the effect of C. amboinicus and palm date in the stimulation of the breast milk production was comparable and superior to all comparators.

BACKGROUND Chronic kidney disease (CKD)-associated pruritus (CKD-aP) contributes to poor quality of life, including reduced sleep quality and poor sleep quality is a source of patient stress and is linked to lower health-related quality of life. This study aimed to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-aP. METHOD A multicenter, prospective, randomized, parallel-design, open label interventional study to estimate the effectiveness of zolpidem (10 mg) oral tablets versus acupressure on sleep quality and quality of life in patients with CKD-aP on hemodialysis. A total of 58 hemodialysis patients having sleep disturbance due to CKD-aP completed the entire 8-week follow-up. The patients were divided into a control (acupressure) group of 28 patients and an intervention (zolpidem) group of 30 patients. RESULTS A total of 58 patients having CKD-aP and sleep disturbance were recruited. In the control group there was a reduction in the PSQI score with a mean ± SD from 12.28 ± 3.59 to 9.25 ± 3.99, while in the intervention group the reduction in PSQI score with a mean ± SD was from 14.73 ± 4.14 to 10.03 ± 4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ± SD was 0.49 ± 0.30 and 50.17 ± 8.65, respectively, while for the intervention group the values were 0.62 ± 0.26 and 47.17 ± 5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ± 0.30 to 0.53 ± 0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ± 0.26 to 0.62 ± 0.27 from baseline to week 8. The EQ 5D improved in both groups and the EQ-VAS score was 2.67 points higher at week 8 as compared to baseline in the control group, while in the intervention group the score was 3.33 points higher at week 8 as compared to baseline. Comparing with baseline, the PSQI scores were significantly reduced after week 4 and week 8 (P =

The majority of the carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis CBZ-SJS/TEN are associated with HLA-B*15:02 in Asian populations where this allele is common. In contrast, the association with HLA-A*31:01 is only reported in Japanese and Europeans. This study aimed to further investigate the association with HLA-A*31:01 besides HLA-B*15:02 in a multiethnic Malaysian population. Twenty-eight CBZ-SJS/TEN cases and 227 CBZ-tolerant controls were recruited. Association was tested by comparing carrier frequencies of the alleles between cases and controls. Significant associations were detected between HLA-B*15:02 and CBZ-SJS/TEN in independent ethnic groups: Malays [P=2.00×10; odds ratio (OR): 49.0; 95% confidence interval (CI): 9.36-256.81], Chinese (P=0.0047; OR: 14.3; 95% CI: 2.38-86.03) and Indians (P=0.04; OR: 13.8; 95% CI: 1.51-124.99). Combined analysis of all ethnic groups showed a significant association with OR Cochran-Mantel-Haenszel (ORCMH) of 26.6 (95% CI: 12.80-55.25; PCMH=2.31×10). In Indians, HLA-A*31:01 was found to be associated significantly with CBZ-SJS/TEN (P=0.023; OR: 10.4; 95% CI: 1.64-65.79) and combined analyses of both variants, HLA-A*31:01 and HLA-B*15:02, increased the strength of the association (P=0.0068; OR: 14.3; 95% CI: 2.20-92.9). Besides HLA-B*15:02, our study found a new association between HLA-A*31:01 and CBZ-SJS/TEN in Indians.

Aims A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios. Methods The pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration–time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R0), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case. Results Oseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios. Conclusion This methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.

Objective: The value of cochlear implantation (CI) has not been established in Taiwan. The purpose of this study was to evaluate the cost-effectiveness of paediatric CI within the context of Taiwan's national health insurance (NHI) programme.Design: A Markov model-based cost-utility analysis (CUA) was conducted to evaluate the cost-effectiveness of a unilateral CI (UCI) with a contralateral acoustic hearing aid (UCI-HA) compared with a bilateral HA. We performed one-way sensitivity analyses to identify the cost variables that affected the incremental cost-effectiveness ratio (ICER) the most. Monte Carlo simulation was used to explore the simultaneous effect of all uncertain parameters on cost-effectiveness.Study sample: Not applicable.Results: Compared with bilateral HAs, the ICER for UCI-HA was $6487 per quality-adjusted life year (QALY) gained. The ICERs were consistently below $7000 per QALY gained and were most sensitive to the selling price of the external CI device. When this selling price increased by 10%, the ICER of UCI-HA would increase to $6954 per QALY gained. UCI-HA has a probability greater than 50% of being cost-effective if the cost-effectiveness threshold exceeds approximately $10,000 per QALY.Conclusions: Our analysis suggested that within the context of Taiwan's NHI programme, UCI is highly cost-effective for deaf children.

Objectives: To compare and assess the performance of 6 osteoporosis risk assessment tools for screening osteoporosis in Malaysian postmenopausal women. Methods: Six osteoporosis risk assessments tools (the Simple Calculated Osteoporosis Risk Estimation [SCORE], the Osteoporosis Risk Assessment Instrument, the Age Bulk One or Never Estrogen, the body weight, the Malaysian Osteoporosis Screening Tool, and the Osteoporosis Self-Assessment Tool for Asians) were used to screen postmenopausal women who had not been previously diagnosed with osteoporosis/osteopenia. These women also underwent a dual-energy X-ray absorptiometry (DXA) scan to confirm the absence or presence of osteoporosis. Results: A total of 164/224 participants were recruited (response rate, 73.2%), of which only 150/164 (91.5%) completed their DXA scan. Sixteen participants (10.7%) were found to have osteoporosis, whilst 65/150 (43.3%) were found to have osteopenia. Using precision-recall curves, the recall of the tools ranged from 0.50 to 1.00, whilst precision ranged from 0.04 to 0.14. The area under the curve (AUC) ranged from 0.027 to 0.161. The SCORE had the best balance between recall (1.00), precision (0.04–0.12), and AUC (0.072–0.161). Conclusions: We found that the SCORE had the best balance between recall, precision, and AUC among the 6 screening tools that were compared among Malaysian postmenopausal women. Keywords: Osteoporosis, Screening, Osteoporosis self-assessment tool for asians, Risk assessment, Performance comparison

ObjectivesThis study was conducted to evaluate the cost-effectiveness of sunitinib versus interferon-alfa for the treatment of advanced and/or metastatic renal cell carcinoma (RCC) in Singapore.MethodsA partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from a healthcare payer perspective over a 10-year time horizon. Survival curves from the pivotal trial of sunitinib versus interferon-alfa were extrapolated beyond the trial period to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from local public healthcare institutions. The sunitinib dose in the model reflected local prescribing practices whereby a combination of 50 mg (28 percent) and 37.5 mg (72 percent) strengths are used.ResultsThe base-case analysis comparing sunitinib versus interferon-alfa resulted in an incremental cost effectiveness ratio (ICER) of SGD191,061 (USD139,757) per quality-adjusted life-year gained. Sensitivity analysis demonstrated that the ICER was most sensitive to variations in the utility value assumed for the progression-free health state and the price of sunitinib.ConclusionsIn the absence of any price reduction, sunitinib had an exceedingly high ICER and was not considered a cost-effective use of healthcare resources in Singapore's context for the first-line treatment of advanced RCC. The findings from our evaluation will be useful to inform local healthcare decision making and resource allocations for tyrosine kinase inhibitors when appraised alongside comparative clinical effectiveness data and payer affordability considerations.

A cochlear implant is a small electronic device that provides a sense of sound for the user, which can be used unilaterally or bilaterally. Although there is advocacy for the benefits of binaural hearing, the high cost of cochlear implant raises the question of whether its additional benefits over the use of an acoustic hearing aid in the contralateral ear outweigh its costs. This cost-effectiveness analysis aimed to separately assess the cost-effectiveness of simultaneous and sequential bilateral cochlear implantations compared to bimodal hearing (use of unilateral cochlear implant combined with an acoustic hearing aid in the contralateral ear) in children with severe-to-profound sensorineural hearing loss in both ears from the Singapore healthcare payer perspective. Incremental quality-adjusted life year (QALYs) gained and costs associated with bilateral cochlear implants over the lifetime horizon were estimated based on a four-state Markov model. The analysis results showed that, at the 2017 mean cost, compared to bimodal hearing, patients receiving bilateral cochlear implants experienced more QALYs but incurred higher costs, resulting in an incremental cost-effectiveness ratio (ICER) of USD$60,607 per QALY gained for simultaneous bilateral cochlear implantation, and USD$81,782 per QALY gained for sequential bilateral cochlear implantation. The cost-effectiveness of bilateral cochlear implants is most sensitive to utility gain associated with second cochlear implant, and cost of bilateral cochlear implants. ICERs increased when the utility gain from bilateral cochlear implants decreased; ICERs exceeded USD$120,000 per QALY gained when the utility gain was halved from 0.03 to 0.015 in both simultaneous and sequential bilateral cochlear implantations. The choice of incremental utility gain associated with the second cochlear implant is an area of considerable uncertainty.

Objectives To systematically review and assess the quality of the economic evidence of adjuvant trastuzumab usage in early breast cancer in Asian countries. Methods Literature search was performed using 6 electronic databases (PubMed, Scopus, Ovid MEDLINE, EconLit, National Health Service Economic Evaluation Database, and ISI Web of Knowledge). The final search was performed in October 2018. All potential economic studies were then checked for eligibility. The reporting and methodological qualities of each study were independently assessed by 2 authors of this review, using the Consolidated Health Economic Evaluation Reporting Standards, Drummond, and Philips checklists. To compare the different currencies used in these studies, all costs were converted into US dollars (2016). Results A total of 6 studies were included; most of them were performed from the healthcare provider perspective. The incremental cost-effectiveness ratio for evaluation performed for a lifetime horizon were reported at $8573 and $20 816 per quality-adjusted life-year in 2 studies. The model outcome was generally sensitive to the changes in trastuzumab drug acquisition cost and discount rate, as well as its clinical effectiveness. For the quality assessment, all studies fulfilled more than 50% of the requirements in the Consolidated Health Economic Evaluation Reporting Standards, Drummond, and Philips checklists. Conclusions Adjuvant trastuzumab therapy is considered a cost-effective option for early breast cancer in Asian countries including China, Iran, Japan, Singapore, and Taiwan. All studies were generally well conducted. Economic evaluations from the societal perspective, with inclusion of indirect and informal care costs, are warranted to facilitate informed decision making among policy makers.

Although pneumococcal conjugate vaccines (PCVs) have been available for prevention of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae (S. pneumoniae) for over a decade, their adoption into national immunization programmes in low- and middle-income countries (LMICs) is still limited. Economic evaluations (EEs) play a crucial role in support of evidence-informed decisions. This systematic review aims to provide a critical summary of EEs of PCVs and identify key drivers of EE findings in LMICs. We searched Scopus, ISI Web of Science, PubMed, Embase and Cochrane Central from their inception to 30 September 2015 and limited the search to LMICs. The search was undertaken using the search strings ‘pneumococc* AND conjugat* AND (vaccin* OR immun*)’ AND ‘economic OR cost-effectiveness OR cost-benefit OR cost-utility OR cost-effectiveness OR cost-benefit OR cost-utility’ in the abstract, title or keyword fields. To be included, each study had to be a full EE of a PCV and conducted for an LMIC. Studies were extracted and reviewed by two authors. The review involved standard extraction of the study overview or the characteristics of the study, key drivers or parameters of the EE, assumptions behind the analyses and major areas of uncertainty. Out of 134 records identified, 22 articles were included. Seven studies used a Markov model for analysis, while 15 studies used a decision-tree analytic model. Eighteen studies performed a cost-utility analysis (CUA), with disability-adjusted life-years, quality-adjusted life-years or life-years gained as a measure of health outcome, while four studies focused only on cost-effectiveness analysis (CEA). Both CEA and CUA findings were provided by eight studies. Herd effects and serotype replacement were considered in 10 and 13 studies, respectively. The current evidence shows that both the 10-valent and 13-valent PCVs are probably cost effective in comparison with the 7-valent PCV or no vaccination. The most influential parameters were vaccine efficacy and coverage (in 16 of 22 studies), vaccine price (in 13 of 22 studies), disease incidence (in 11 of 22 studies), mortality from IPD and pneumonia (in 8 of 22 studies) and herd effects (in 4 of 22 studies). The findings were found to be supportive of the products owned by the manufacturers. Our review demonstrated that an infant PCV programme was a cost-effective intervention in most LMICs (in 20 of 22 studies included). The results were sensitive to vaccine efficacy, price, burden of disease and sponsorship. Decision makers should consider EE findings and affordability before adoption of PCVs.

Intravenous immunoglobulin (IVIG) has been recommended for steroid-resistant chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The treatment, however, is very costly to healthcare system, and there remains no evidence of its economic justifiability. This study aimed to conduct an economic evaluation (EE) of IVIG plus corticosteroids in steroid-resistant CIDP in Thailand.A Markov model was constructed to estimate the lifetime costs and outcomes for IVIG plus corticosteroids in comparison with immunosuppressants plus corticosteroids in steroid-resistant CIDP patients from a societal perspective. Efficacy and utility data were obtained from clinical literature, meta-analyses, medical record reviews, and patient interviews. Cost data were obtained from list prices, an electronic hospital database, published source, and patient interviews. All costs [in 2015 US dollars (US$)] and outcomes were discounted at 3 % annually. One-way and probabilistic sensitivity analyses were conducted.In the base-case, the incremental costs and quality-adjusted life years (QALYs) of IVIG plus corticosteroids versus immunosuppressants plus corticosteroids were US$2112.02 and 1.263 QALYs, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of US$1672.71 per QALY gained. Sensitivity analyses revealed that the utility value of disabled patients was the greatest influence on ICER. At a societal willingness-to-pay threshold in Thailand of US$4672 per QALY gained, IVIG plus corticosteroids had a 92.1 % probability of being cost effective.At a threshold of US$4672 per QALY gained, IVIG plus corticosteroids is considered a cost-effective treatment for steroid-resistant CIDP patients in Thailand.

A cross-sectional study was carried out among HCPs in Northwest General Hospital & Research Centre, Hayatabad Peshawar, Pakistan. The purpose of this study was to investigate knowledge, awareness and attitude of HCPs towards influenza vaccination. A total of N=170 questionnaires were distributed among the staff. There was a 97% response rate to this survey (n=165). The median age of the respondents was 30 years and most of them, 98 (59.0%), were from age group of 24-30 years. The majority of the HCPs that participated in this study were male 106 (64.2%), and by profession, the majority were physicians 77 (46.7%), followed by pharmacists and nurses. A majority 114 (69.1%) believed that it was not compulsory for HCPs to get vaccinated for influenza. Top three identified barriers to vaccination were: not everyone is familiar with the availability of the influenza vaccination at their institution (Relative importance weight factors (RIWF)=0.71), due to needle fear I do not like to get vaccinated (RIWF=0.70) and it is not compulsory for healthcare professionals to get vaccinated for influenza (RIWF=0.64). The logistic regression analysis has revealed association for job experience and profession with the most of the eleven knowledge item. However, when overall sum of eleven items were tested to identify the factors affecting the knowledge score, along with profession (-0.215 [-0.389 to 0.040]; p=0.016) and job experience (0.823 [0.521-1.125]; p

Influenza-associated mortality has not been quantified in the Philippines. Here, we constructed multiple negative binomial regression models to estimate the overall and age-specific excess mortality rates (EMRs) associated with influenza in the Philippines from 2006 to 2015. The regression analyses used all-cause mortality as the dependent variable and meteorological controls, time, influenza A and B positivity rates (lagged for up to two time periods), and annual and semiannual cyclical seasonality controls as independent variables. The regression models closely matched observed all-cause mortality. Influenza was estimated to account for a mean of 5,347 excess deaths per year (1.1% of annual all-cause deaths) in the Philippines, most of which (67.1%) occurred in adults aged ≥60 years. Influenza A accounted for 85.7% of all estimated excess influenza deaths. The annual estimated influenza-attributable EMR was 5.09 (95% CI: 2.20-5.09) per 100,000 individuals. The EMR was highest for individuals aged ≥60 years (44.63 [95% CI: 4.51-44.69] per 100,000), second highest for children aged less than 5 years (2.14 [95% CI: 0.44-2.19] per 100,000), and lowest for individuals aged 10 to 19 years (0.48 [95% CI: 0.10-0.50] per 100,000). Estimated numbers of excess influenza-associated deaths were considerably higher than the numbers of influenza deaths registered nationally. Our results suggest that influenza causes considerable mortality in the Philippines-to an extent far greater than observed from national statistics-especially among older adults and young children.

This study aimed to evaluate the long-term cost-effectiveness of ticagrelor plus aspirin versus generic clopidogrel plus aspirin in acute coronary syndrome patients in Hong Kong (HK) from a public hospital’s perspective. The study has adapted a previously developed two-component prediction model. The first component is a simple decision tree corresponding to the first year. Afterwards events in the second year onwards were estimated using a state-transition Markov model incorporating the potential of recurrent events such as myocardial infarction and strokes that could lead to death for estimating the long-term economic and health outcomes measured as cost per quality-adjusted life year (QALYs). Kaplan Meier survival analysis was employed to determine the risk of events. Probabilistic sensitivity analysis was used to estimate the probability of ticagrelor being cost-effective. A cost-effectiveness acceptability curve was used to estimate the willingness-to-pay of patients. The use of ticagrelor led to improved clinical outcomes by gaining additional life-years and QALYS over 5-year and lifetime time horizons. The incremental cost-effectiveness ratio was above 1 Gross Domestic Product (GDP) per capita only for the 1-year results. By replacing clopidogrel with ticagrelor for life-time, the incremental drug costs were offset by the substantial reduction in other direct costs, leading to an overall cost-savings of HK 2,878 per patient. The probabilistic sensitivity analysis showed that ticagrelor has 53.5% chance of being dominant and 34.7% being cost-effective at a threshold of 1 GDP per capita for Hong Kong. A cost-effectiveness acceptability curve also showed that the willingness-to-pay for ticagrelor was 90% at 1 GDP per capita. Ticagrelor plus aspirin appeared to be cost-effective over 5-year and life-time projection periods compared to clopidogrel plus aspirin.

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

Reply to: https://www.tandfonline.com/doi/full/10.1080/13696998.2018.1503597 Original Article: https://www.tandfonline.com/doi/full/10.1080/13696998.2017.1387119 Cost-effectiveness analyses (CEAs) ...

Aim. The present study was conducted to determine the glycaemic effects of sitagliptin in type 2 diabetes patients.Methods. Data was collected from patient medical records of a major teaching hospital in Malaysia, from 2009 to 2012. Glycated hemoglobin (HbA1c) values prior to and up to 12 months after the initiation of sitagliptin were analysed. The change inHbA1cvalues was accounted for based on a generalized linear model generated using the Generalized Estimating Equations (GEE) method.Results and Discussion. Of the 457 patients, 53.6% were elderly and 81.4% were overweight. The meanHbA1c(standard deviation) before initiation of sitagliptin was 8.5 (1.4)%. This dropped to 7.7 (1.4)%, 3 to 6 months after initiation of sitagliptin, with a mean difference of 0.8% (95% confidence interval (CI): 0.7–1.0; P<0.001). However, this value increased to 8.0 (1.7)% after 7 to 12 months on sitagliptin (P=0.002) with a mean difference from baseline of 0.6% (95% CI: 0.4–0.7;P < 0.001).Conclusion. In routine clinical practice, sitagliptin produces a significant reduction in meanHbA1c(0.8%) within the first 6 months of use which corresponds to efficacy data obtained in controlled clinical trials. However, this reduction was lesser, 7 to 12 month later.

Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care.To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective.A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I-IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalapril Results: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively.At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.

Introduction Several tools have been developed to assess the severity of pruritus. In Malaysia, no tool has been validated to assess pruritus in patients with chronic kidney disease (CKD). Therefore, the aim of our study was to validate the Malay 5D itching scale (M5D-IS) among patients with CKD in Malaysia. Method The English version of the 5D-IS was translated into Malay according to International Guidelines. Face and content validity was determined by an expert panel and pilot tested in patients with end-stage renal disease (ESRD). The M5D-IS was then validated in a tertiary hospital in Malaysia from May to June 2016. We recruited patients with (i.e., patients with ESRD) and without pruritus (i.e., patients with stage 1–3 CKD) (to determine if the M5D-IS could discriminate between the two groups), and administered the M5D-IS at baseline and 2 weeks later. Exploratory factor analysis was used to examine the construct validity. Internal consistency was assessed using Cronbach’s alpha and intraclass correlation coefficient was calculated to assess the reliability of the instrument. Results A total of 70 participants were recruited (response rate = 100%). The majority were males (51.4%) and Malay (67.1%). Exploratory factor analysis revealed that the 5D-IS had 2-factor loadings: “daily routine activity” and “pattern of itching,” which explained 77.7% of the variance. The overall score of the M5D-IS, as well as for each domain, was significantly worse in participants with pruritus (9.83 ± 0.35), compared to those without pruritus (5.51 ± 0.93, p

Purpose To develop and validate the English version of the Satisfaction Questionnaire for Osteoporosis Prevention (SQOP) in Malaysia. Methods The SQOP was modified from the Osteoporosis Patient Satisfaction Questionnaire and developed based on literature review and patient interviews. Face and content validity were established via an expert panel. The SQOP consists of two sections: clinical services and types of counseling. There were 23 items in total, each with a five-point Likert-type response. Satisfaction score was calculated by converting the total score to a percentage. A higher score indicates higher satisfaction. English speaking, non-osteoporotic, postmenopausal women aged ≥50 years were included in the study. Participants were randomized to either the control or intervention group. Intervention participants were provided counseling, whereas control participants received none. Participants answered the SQOP at baseline and 2 weeks later. Results A total of 140 participants were recruited (control group: n=70; intervention group: n=70). No significant differences were found in any demographic aspects. Exploratory factor analysis extracted seven domains. Cronbach’s α for the domains ranged from 0.531–0.812. All 23 items were highly correlated using Spearman’s correlation coefficient 0.469–0.996 (P, Video abstract

The accumulation of autophagosomes in the terminal step of the autophagic process has recently emerged as a potentially maladaptive process in the septic heart and lung. However, the role of autophagy in the septic liver has not been ascertained. This study was investigated by first examining the entire sequence of the autophagic process in the liver of septic mice. Second, a novel pharmacotherapeutic approach was utilized to treat sepsis with autophagy enhancer/inhibitor. Sepsis was induced by cecal ligation and puncture (CLP). C57BL/6 mice received autophagy enhancer carbamazepine (CBZ), autophagy inhibitor 3-methyladenine (inhibition of autophagosomal formation), or chloroquine (impairment of autophagosomal clearance). We found that the whole autophagic process was activated at 4 h after CLP; however, it did not proceed to completion during the 4- to 24-h time period, as indicated by accumulated autophagosomes and decreased autophagic flux. Carbamazepine, which induced complete activation of the autophagic process, improved CLP survival. This protective effect was also associated with decreased cell death, inflammatory responses, and hepatic injury. However, disruption of autophagosomal clearance with chloroquine abolished the above protective effects in CBZ-treated CLP mice. 3-Methyladenine, which resulted in inhibition of the autophagosomal formation, did not show any above beneficial effects in CLP mice. Impaired autophagosome-lysome fusion resulting in incomplete activation of autophagy may contribute to sepsis-induced liver injury. Treatment with CBZ may serve a protective role in the septic liver, possibly through the effect of complete activation of autophagic process.