Investigation of comparative effectiveness research in Asia,Europe, and North America

Comparative effectiveness research (CER) is an important branch of pharmacoeconomics that systematically studies and evaluates the cost-effectiveness of medical interventions. CER plays instrumental roles in guiding government public health policy programs and insurance. Countries throughout the world use different methods of CER to help make medical decisions based on providing optimal therapy at a reduced cost. Expenses to the healthcare system continue to rise, and CER is one-way in which expenses could be curbed in the future by applying cost-effectiveness evidence to clinical decisions. China, India, South Korea, and the United Kingdom are of essential focus because these country''s economies and health care expenses continue to expand. The structures and use of CER are diverse throughout these countries, and each is of prime importance. By conducting this thorough comparison of CER in different nations, strategies and organizational setups from different countries can be applied to help guide public health and medical decision-making in order to continue to expand the establishment and role of CER programs. The patient-centered medical home has been created to help reduce costs in the primary care sector and to help improve the effectiveness of therapy. Barriers to CER are also important as many stakeholders need to be able to work together to provide the best CER evidence. The advancement of CER in multiple countries throughout the world provides a possible way of reducing costs to the healthcare system in an age of expanding expenses.KEY WORDS: Comparative effectiveness research, health care costs, pharmacoeconomics     

The role of gasotransmitters NO,H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning,postconditioning and remote conditioning

Ischaemic heart disease is one of the leading causes of morbidity and mortality worldwide. The development of cardioprotective therapeutic agents remains a partly unmet need and a challenge for both medicine and industry, with significant financial and social implications. Protection of the myocardium can be achieved by mechanical vascular occlusions such as preconditioning (PC), when brief episodes of ischaemia/reperfusion (I/R) are experienced prior to ischaemia; postconditioning (PostC), when the brief episodes are experienced at the immediate onset of reperfusion; and remote conditioning (RC), when the brief episodes are experienced in another vascular territory. The elucidation of the signalling pathways, which underlie the protective effects of PC, PostC and RC, would be expected to reveal novel molecular targets for cardioprotection that could be modulated by pharmacological agents to prevent reperfusion injury. Gasotransmitters including NO, hydrogen sulphide (H₂S) and carbon monoxide (CO) are a growing family of regulatory molecules that affect physiological and pathological functions. NO, H₂S and CO share several common properties; they are beneficial at low concentrations but hazardous in higher amounts; they relax smooth muscle cells, inhibit apoptosis and exert anti-inflammatory effects. In the cardiovascular system, NO, H₂S and CO induce vasorelaxation and promote cardioprotection. In this review article, we summarize current knowledge on the role of the gasotransmitters NO, H₂S and CO in myocardial I/R injury and cardioprotection provided by conditioning strategies and highlight future perspectives in cardioprotection by NO, H₂S, CO, as well as their donor molecules.

Linked Articles

This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6     

Loss of bone mineral density in Chinese pre-menopausal women with systemic lupus erythematosus treated with corticosteroids

The adverse effect of disease and chronic corticosteroid therapy on bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE) has been reported in several studies of Caucasian populations. As the factors controlling bone homeostasis may be different in Asian populations, we measured BMD in 52 pre-menopausal Chinese women (mean age 34.1 +/- 8.0 yr) with SLE (mean disease duration 6.4 +/- 4.5 yr) treated with prednisone (mean daily dose 11.4 +/- 10.8 mg/day). Lumbar spine, hip (total and subregions) and total body BMDs were measured in the SLE patients using dual-energy X-ray absorptiometry (DEXA), and compared with those from healthy controls matched for age, sex and body mass index. Compared to controls, SLE patients were found to have lower BMD (g/cm2) at several sites: the lumbar spine (0.98 vs 0.90, P = 0.001), Ward's triangle (0.72 vs 0.67, P = 0.03), total body (1.04 vs 1.01, P = 0.04) and total hip (0.87 vs 0.82, P = 0.05). There was no correlation between BMD at any region and duration of disease, activity of disease or prednisone therapy (mean daily dose, cumulative dose or treatment duration). When BMDs were compared between controls and SLE patients, subgrouped according to those not on calcium and those arbitrarily receiving calcium supplements (1 g/day), significantly lower BMDs were found in those not on calcium compared to both controls and SLE patients on calcium. BMDs in SLE patients on calcium were not different from those in controls. The low prevalence of osteoporosis in our SLE patients (4-6%) suggests significant loss of BMD in Chinese SLE patients on corticosteroid therapy is less than that reported in Caucasians (12-18%).      

von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene [published erratum appears in Blood 1995 Sep 15;86(6):2461]

An animal model for human type I von Willebrand disease (vWD) has been previously described in the inbred mouse strain RIIIS/J. Murine vWD is characterized by a prolonged bleeding time, normal von Willebrand factor (vWF) multimer distribution, autosomal dominant inheritance, and proportionately decreased plasma vWF antigen, ristocetin cofactor, and factor VIII (FVIII) activities. To study the molecular genetics of murine vWD, a portion of the vWF gene surrounding exon 28 was cloned, sequenced, and used to develop two informative DNA sequence polymorphisms for rapid genotyping by DNA polymerase chain reaction. RIIIS/J mice were crossed with PWK/Ph mice, an inbred line of Mus musculus musculus, and the F1 progeny backcrossed to the parental PWK/Ph strain. vWF antigen levels in F1 mice were not significantly different from the parental RIIIS/J strain but were markedly decreased compared with the parental PWK/Ph mice. Genetic linkage analysis of 104 backcross progeny showed no correlation between vWF antigen level and vWF genotype. These data indicate that murine vWD is caused by a defect at a novel genetic locus, distinct from the murine vWF gene. The distribution of vWF antigen levels among backcross progeny suggests the presence of one major dominant vWD gene in the RIIIS/J mouse with possible modifying contributions from one or more additional minor loci. These observations may provide new insights into the molecular basis and variable expressivity of human vWD.     

The effects of tirofiban on peripheral markers of oxidative stress and endothelial dysfunction in patients with acute coronary syndromes

BACKGROUND: Endothelial dysfunction and oxidative stress are believed to be central mechanisms in atherogenesis. We aimed to determine the effects of tirofiban on oxidative stress and neutrophil-endothelium interaction markers in patients with acute coronary syndromes (ACS). MATERIALS AND METHODS: We measured malondialdehyde (MDA), interleukin-6 (IL-6) and soluble endothelial intercellular and vascular adhesion molecules (sICAM-1 and sVCAM-1) on admission, at 48 and 72 h and on 5th day of hospitalization in 34 patients (age 66.5+/-1.8 years) with ACS. Patients with recurrent angina, changes on the electrocardiogram and/or elevated troponin I received intravenously tirofiban for 48 h and the others received normal saline. RESULTS: Baseline concentrations of all markers did not differ significantly and compared with placebo, tirofiban infusion markedly reduced MDA, IL-6, sICAM-1 and sVCAM-1 at 48 h (-31+/-6% vs. 84+/-49%, p=0.007, -12+/-14% vs. 23+/-10%, p=0.05, -20+/-6% vs. 36+/-25%, p=0.04 and -10+/-5% vs. 6+/-5%, p=0.02, respectively). Relative to baseline, significant reductions were observed for all 4 markers at 72 h and day 5 (p<0.05). CONCLUSION: Tirofiban potentiates the decline in oxidative stress and may reverse abnormal endothelial activation in patients with ACS. This benefit seems to remain over the following 5 days.     

Protection from postconditioning depends on the number of short ischemic insults in anesthetized pigs

Abstract Postconditioning in the early reperfusion period confers protection to the heart after a potentially lethal episode of prolonged ischemia. Protection from this novel intervention has been documented in rat, rabbit and canine hearts, but one group has reported that it is ineffective in pigs, a large-animal species that should be most relevant to humans. We hypothesized that this negative result was related to an inappropriate postconditioning protocol rather than the species. The present study, therefore, tested whether an effective postconditioning protocol could be identified that limits infarct size in anesthetized pigs. Domestic Landrace pigs weighing 25–29 kg were anesthetized, and after a mid-sternal thoracotomy and pericardiotomy the left anterior descending coronary artery was ligated for 60 min followed by 3 h of reperfusion. Three groups were studied: control group (n = 5) with no other intervention, 4–30 PostC group (n = 5) with 4 cycles of 30-s reperfusion/30-s ischemia, and 8–30 PostC group (n = 6) with 8 cycles of 30-s reperfusion/30-s ischemia. The two postconditioning protocols started immediately after termination of the 60-min coronary occlusion. Region at risk and infarct size were delineated with the aid of pre-mortem monastral blue injection and postmortem staining with triphenyltetrazolium chloride, respectively. In control hearts 33.5 ± 7.6% of the risk zone infarcted and 36.7 ± 3.7% in the 4–30 PostC group (P = NS). But there was only 10.5 ± 0.5% infarction in the 8–30 PostC group (P < 0.01 vs. the other two groups). Postconditioning confers protection in pigs but requires more than 4 ischemia/reperfusion cycles. Postconditioning may protect by inhibiting mitochondrial permeability transition pore formation by keeping the heart acidotic as it is reoxygenated. If true, then it would be difficult to employ too many occlusion cycles.     

Mortality is influenced by locality in a major HIV/AIDS epidemic

Objectives

The aim of the study was to compare the risks of death among HIV‐infected patients on highly active antiretroviral therapy (HAART) in two proximate, yet distinct neighbourhoods: a neighbourhood with a high concentration of gay men, and a neighbourhood with a high concentration of injecting drug users.

Methods

We compared the clinical and socioeconomic characteristics of HIV‐infected patients from the two neighbourhoods entering the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program from 1 September 1997 to 30 November 2005, using contingency table statistics. Cox survival models and Kaplan–Meier methods were used to estimate the cumulative mortality rates. Results We found significant differences between patients from the two neighbourhoods for all socioeconomic variables. Patients in the neighbourhood with a high concentration of injecting drug users were more likely to be female, have a history of injecting drug use, have a less HIV‐experienced physician and be less adherent. Patients in the neighbourhood with a high concentration of gay men were more likely to have AIDS. Mortality was significantly higher for patients in the neighbourhood with a high concentration of injecting drug users [hazard ratio (HR) 3.01; 95% confidence interval (CI) 1.73, 5.24].

Conclusions

A threefold increase was observed in the risk of death among HIV‐infected individuals on HAART in the neighbourhood with a high concentration of injecting drug users relative to the neighbourhood with a high concentration of gay men. The implications of this study should be assessed in similar HIV/AIDS epicentres.     

Association between myopia and diabetic retinopathy: a review of observational findings and potential mechanisms

A protective, but inconsistent association between myopia and a decreased risk of diabetic retinopathy (DR) has been suggested in several studies. However, it is unclear whether the structural, or the refractive components of myopia; or both, is the main contributor to this protective relationship. This paper provides a comprehensive review of existing evidence on the association between myopia, and its structural (axial length [AL], anterior chamber depth [ACD]) and refractive (lens biometry and corneal curvature [CC]) components, with DR. 11 studies consisting of 7230 subjects from 1960 to April 2012, were reviewed. A longer AL was the only variable associated with a lower risk and severity of DR. Therefore, the available evidence suggests that AL is the main contributor to the protective influence of myopia on DR observed in earlier studies. Further investigations are now needed to determine the mechanisms by which AL protects against DR.