Cost-utility analysis of antiviral use under pandemic influenza using a novel approach - linking pharmacology, epidemiology and heath economics.

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.

Estimating emollient usage in patients with eczema.

BACKGROUND: Atopic eczema (AE) is characterized by reduced skin hydration (SH) and impaired integrity of the skin. Proper emollient usage is an important facet of AE management and patients are encouraged to use emollients liberally. AIM: To evaluate whether the amount of emollient and skin cleanser used correlates with eczema severity, SH or transepidermal water loss (TEWL), and whether liberal usage alters disease severity, SH and TEWL. METHODS: We studied SH and TEWL at three common measurement sites on the forearm (antecubital flexure, 20 mm below the antecubital flexure, mid-forearm) and determined the SCORing Atopic Dermatitis (SCORAD) score, Nottingham Eczema Severity Score (NESS), Children's Dermatology Life Quality Index (CDLQI) and the amount of emollient and cleanser usage over a 2-week period in consecutive new patients seen at the paediatric skin clinic of a teaching hospital. RESULTS: In total, 48 subjects and 19 controls were recruited. Patients with AE had significantly higher TEWL and lower SH in the studied sites. Emollient and cleanser usage was significantly higher (P = 0.001 and P = 0.041, respectively) in patients with AE than in controls. The amount of emollient usage was correlated with NESS, SCORAD, CDLQI, TEWL and mid-forearm SH. No such correlation was found with cleanser usage. Regardless of SCORAD, prescribing 130 g/m(2)/week of emollient met the requirement of 95.8% of patients, and 73 g/m(2)/week met that of 85.4%; for the cleanser, prescribing 136 g/m(2)/week met the requirement of 91.7% of patients. Although skin dryness and SH were improved, there was no significant improvement in SCORAD or TEWL after 2 weeks. In terms of global acceptability of treatment, three-quarters of patients with AE and controls rated the combination of cream and cleanser as 'good' or 'very good'. CONCLUSIONS: Adequate amounts of emollient and bathing cleanser should be prescribed to patients with AE. These amounts can be conveniently estimated based on body surface area instead of the less readily available tools for disease severity, degree of SH or skin integrity. However, liberal usage of emollients and bathing cleanser alone does not seem to alter disease severity or TEWL within 2 weeks, implying that additional treatments are necessary to manage AE.

Pharmacogenetics of esomeprazole or rabeprazole-based triple therapy in Helicobacter pylori eradication in Hong Kong non-ulcer dyspepsia Chinese subjects.

OBJECTIVE: Our study aimed to assess the effectiveness of esomeprazole or rabeprazole in combination with amoxicillin and clarithromycin for the eradication of Helicobacter pylori in Hong Kong non-ulcer dyspepsia (NUD) patients. METHODS: A prospective clinical trial was conducted at the Alice Ho Miu ling Nethersole Hospital outpatient endoscopy center from June 2004 to December 2005. Participants received amoxicillin 1 g, clarithromycin 500 mg, and, esomeprazole 20 mg (EAC) or rabeprazole 20 mg (RAC), all given twice daily for 1 week. The H. pylori status was determined by the [13C] urea breath test at least 4 weeks after completion of the treatment. Mutation status of CYP2C19 in exon 4 and exon 5 associated with the poor metabolizer phenotype was determined. RESULTS: The intention-to-treat eradication rates in patients treated with RAC and EAC were 77% and 84.6% respectively, and per protocol-based eradication rates were 83.7% and 88.9% respectively. The eradication rates did not vary with CYP2C19 phenotype found. For clarithromycin-sensitive strains, the cure rates were statistically significant regardless of CYP2C19 polymorphism (P < 0.0001). CONCLUSION: Triple therapy with either EAC or RAC is effective for Hong Kong Chinese NUD patients with H. pylori infection. Success eradication was related to clarithromycin resistance and not CYP2C19 genotype.

A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy.

OBJECTIVES: This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients. PATIENTS AND METHODS: Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE). RESULTS: Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048). CONCLUSION: The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

Cost of Type 2 Diabetes mellitus in Hong Kong Chinese.

OBJECTIVE: Hong Kong (HK) is a special administrative region of China as well as being a metropolitan city. In HK, like in many developed countries, Diabetes mellitus, with over 97% of diabetic patients having Type 2 Diabetes mellitus (Type 2 DM), is a growing public health problem but the local financial burden has never been investigated. The primary objectives of this study were to evaluate from the social perspective the costs of Type 2 DM, to identify the major cost drivers, and the proportion of the burden shared by the government, patient and the society. The study was carried out in a group of Hong Kong Chinese patients attending a government hospital. The economic impact of Type 2 DM on local and governmental healthcare expenditure was also examined. METHODS: A retrospective cohort observational study was conducted in Type 2 DM patients attending the Diabetes Mellitus Outpatient Clinic at a public hospital in the period January 2004 to May 2004, in which 204 patients were randomly selected and invited to join this study. A total of 147 patients were subsequently enrolled giving an inclusion rate of 72%. RESULTS: Annual total cost of Type 2 DM in a patient was US$ 1,725 +/- 2,044 (HK$ 13,457 +/- 15,943) with direct costs accounting for > 87.9%. The government was the major payer with over 78.4% of the total costs. Annual total direct medical costs per patient were US$ 1,492 +/- 1,716 (HK$ 11,638 +/- 13,386) of which the government paid 90.6%. Direct medical costs increased markedly if complications were present. In patients with microvascular or macrovascular complications only, the costs increased 1.1-fold compared to those for patients without complications. If both microvascular and macrovascular complications were present in the same patient, the costs were 1.3-fold higher than in patients without complications. CONCLUSION: Costs of Type 2 DM have a significant impact on the local healthcare budget. It contributed in 2004 up to 3.9% of the total HK healthcare expenditure and 6.4% of the HK Hospital Authority's (public sector) expenditures on health.

Helicobacter pylori eradication prior to initiation of long-term non-steroidal anti-inflammatory drug therapy in Chinese patients-a cost-effectiveness analysis.

BACKGROUND: Recent randomized clinical trials suggested that eradication of Helicobacter pylori prior to initiation of non-steroidal anti-inflammatory drug (NSAID) therapy would reduce the rate of peptic ulcer disease (PUD). OBJECTIVE: To analyze the cost-effectiveness of H. pylori eradication prior to initiation of long-term NSAID therapy for prevention of NSAID-induced PUD in a cohort of Chinese patients at high risk for PUD. METHODS: Clinical and economic data of 100 participants from a previously reported clinical trial conducted in Hong Kong were analyzed. Patients with a history of peptic ulcers were randomized to 1-week omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg twice daily (eradication group; n = 51) or 1-week omeprazole 20 mg twice daily (omeprazole group; n = 49) before initiation of diclofenac 100 mg daily for 6 months. The rates of PUD and healthcare utilization for routine follow-up as well as for management of symptomatic PUD of the 2 groups were retrieved from medical records. RESULTS: The rate of symptomatic ulcers in eradication group and omeprazole group were 3.9% and 18%, respectively. The mean direct medical cost of the eradication group was significantly lower than that of the omeprazole group by 30% (US dollar 797 (95% CI = 685 - 909) versus US dollar 1,128 (95% CI = 879 - 1,377)) (p = 0.018). The results were robust to variation of all the cost items. CONCLUSIONS: H. pylori eradication prior to initiation of NSAID therapy appeared to reduce the ulcer rate and mean direct medical cost when compared to no eradication for Chinese H. pylori-infected NSAID users at high risk for PUD.

Arthritis treatment in Hong Kong--cost analysis of celecoxib versus conventional NSAIDS, with or without gastroprotective agents.

BACKGROUND: Selective cyclo-oxygenase-2 inhibitors have been reported to cause fewer gastrointestinal complications when compared with conventional, non-selective, non-steroidal anti-inflammatory drugs (NSAIDs). AIM: To analyse the cost of celecoxib (selective cyclo-oxygenase-2 inhibitor) and conventional NSAID regimens for the treatment of osteoarthritis and rheumatoid arthritis from the perspective of a public health organization in Hong Kong. METHODS: A decision tree was used to analyse the cost of celecoxib, NSAID alone, NSAID plus histamine2-receptor antagonist, NSAID plus misoprostol and NSAID plus proton pump inhibitor over 6 months. Model outcomes were no gastrointestinal toxicity, gastrointestinal discomfort, symptomatic ulcer, anaemia with occult bleeding and serious gastrointestinal complications. The clinical probabilities were estimated from clinical trials. Resource utilization for gastrointestinal events was determined locally. Sensitivity analysis was performed. RESULTS: The 6-month costs per base-case analysis were as follows: NSAID plus histamine2-receptor antagonist, 1404 HK dollars (1 US dollar = 7.8 HK dollars); celecoxib, 1545 HK dollars; NSAID alone, 1610 HK dollars; NSAID plus misoprostol, 2213 HK dollars; NSAID plus proton pump inhibitor, 2857 HK dollars. The model was sensitive to the patients' underlying gastrointestinal risk scores, daily cost of NSAID regimen, risk ratio of NSAID plus histamine2-receptor antagonist for symptomatic ulcer, daily cost of celecoxib and daily cost of histamine2-receptor antagonist. CONCLUSIONS: Celecoxib appeared to be the least costly alternative in patients with intermediate to high gastrointestinal risk for the treatment of osteoarthritis and rheumatoid arthritis in Hong Kong.

Economic analysis of celecoxib versus diclofenac plus omeprazole for the treatment of arthritis in patients at risk of ulcer disease.

AIM: To evaluate the economic impact of celecoxib therapy vs. diclofenac plus omeprazole therapy for the treatment of arthritis in Chinese patients with a high risk of bleeding, from the perspective of a public health organization in Hong Kong. METHODS: The medical records of 287 Chinese arthritic patients with a history of bleeding ulcers who had previously participated in a randomised study of celecoxib 200 mg twice daily and extended-release diclofenac 75 mg twice daily plus 20 mg of omeprazole daily for 6 months were reviewed. RESULTS: Compared to the diclofenac plus omeprazole group, the average total direct cost per patient in the celecoxib group showed a significant reduction of 11%, from HK 10,915 (range HK dollars 10,915-57,899) to HK dollars 9714 (range HK dollars 9714-89,770) (P<0.0001) (1 US dollars=7.8 HK dollars). The median direct medical cost for routine management in the celecoxib group was significantly lower (11%) than that for the diclofenac plus omeprazole group [HK dollars 10,915 (range 10,915-28,048) vs. HK dollars 9714 (range HK dollars 6946-26,179) (P<0.0001)]. In patients who experienced recurrent bleeding, the celecoxib group showed a significantly higher median cost of management of recurrent bleeding than the diclofenac plus omeprazole group [HK dollars 8466 (range 572-29,851) vs. HK dollars 23,210 (range HK dollars 12,318-65,823)] (P=0.036). CONCLUSIONS: Celecoxib therapy appears to cost less compared with diclofenac plus omeprazole for treatment of arthritis in Chinese patients with a high risk of bleeding.

Vertebral body corner oedema vs gadolinium enhancement as biomarkers of active spinal inflammation in ankylosing spondylitis.

OBJECTIVE: To investigate the relative performance of T(2) weighted short tau inversion-recovery (STIR) and fat-suppressed T(1) weighted gadolinium contrast-enhanced sequences in depicting active inflammatory lesions in ankylosing spondylitis (AS). METHODS: Whole-spine MRI was performed on 32 patients with AS, who participated in a clinical trial of infliximab treatment, by STIR and contrast-enhanced sequences at baseline and after 30 weeks. The AS spine MRI-activity (ASspiMRI-a) scoring method was used. The images from these two imaging techniques were evaluated separately by two independent readers. RESULTS: For the pre-treatment lesion status, the intraclass correlation coefficients comparing STIR readings and contrast-enhanced readings were 0.69±0.23 for Reader 1 and 0.65±0.21 for Reader 2. At baseline, the mean ASspiMRI-a score was 15.4% and 17.7% higher for contrast-enhanced images than for STIR images for Reader 1 and Reader 2, respectively. After infliximab treatment, Reader 1 rated an ASspiMRI-a score reduction of 50.8±33.6% and 25.3±35.3% for STIR images and contrast-enhanced images, respectively, whereas Reader 2 rated an ASspiMRI-a score reduction of 42.4±50.4% and 32.9±35.6% for STIR images and contrast-enhanced images, respectively. CONCLUSION: While both contrast-enhanced and STIR sequences showed sensitivity to change over a short period of time after infliximab treatment, these two sequences may reflect different disease mechanisms.