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Biomedical subjects

Gregory Cheng

Publications and source records attributed to Gregory Cheng.

17 recordsLinked to original sources

Management of Chinese patients on warfarin therapy in two models of anticoagulation service - a prospective randomized trial.

AIM: To compare the treatment outcomes of a clinical pharmacist-managed anticoagulation service with physician-managed service in Chinese patients. METHODS: A prospective, randomized clinical trial was conducted at the anticoagulation clinic of a teaching hospital in Hong Kong. Patients aged > or = 18 years who would required warfarin therapy for at least 3 months were recruited. Patients were randomized to the pharmacist-managed or physician-managed group. Primary clinical outcome was assessed by the percentage of patient time spent within the target international normalized ratio (INR) range. The incidence of major thromboembolic events (TEs) and major bleeding was assessed as secondary clinical outcomes. The cost per patient per month (cPPPM) was calculated and patient satisfaction was assessed by patient satisfaction questionnaire (PSQ)-18. RESULTS: One hundred and forty-one patients were recruited at the anticoagulation clinic and 137 patients completed the study. Patients in the pharmacist-managed group (n = 68) were in the target INR 64% of patient time vs. 59% in the physician-managed group (n = 69) (P < 0.001). There was no significant difference in incidence of major TEs or bleeding. The cPPPM in the pharmacist-managed group (76 +/- 95 US dollar) (43 +/- 53 British pound) was lower than in the physician-managed group (98 +/- 158 US dollar) (55 +/- 89 British pound) (P < 0.001). The PSQ-18 score of the pharmacist-managed group (3.8 +/- 0.2) was higher than that of the physician-managed group (3.6 +/- 0.3) (P < 0.001). CONCLUSION: The pharmacist-managed anticoagulation service was more effective and less costly than the physician-managed service in achieving target anticoagulation control for Chinese patients on warfarin therapy.

Anticoagulants↗

Cross-reactivity of antibody against SARS-coronavirus nucleocapsid protein with IL-11.

Infection of SARS-associated coronavirus (SARS-CoV) induced a strong anti-nucleocapsid (anti-N) antibody response. However, the pathophysiological significance of the anti-N antibodies in SARS pathogenesis is largely unknown. To profile the anti-N antibodies, a phage-displayed scFv library was prepared from mice immunized with heat-inactivated SARS-CoV-infected Vero E6 cell lysate. Specific anti-N scFvs were isolated by panning against a recombinant nucleocapsid protein and reactivity was confirmed with phage-ELISA. Sequence analysis indicated that two of the isolated anti-N scFv clones were identical and displayed a high homology with an scFv specific for interleukin 11 (IL-11), an anti-inflammatory cytokine derived from bone marrow stroma cells. In a neutralization assay, IL-11-induced STAT 3 phosphorylation in rat intestinal epithelial IEC-18 cells was completely suppressed by the anti-N scFv clone L9N01.

Animals↗

Factors affecting the maintenance stable warfarin dosage in Hong Kong Chinese patients.

BACKGROUND: Multiple factors can affect the anticoagulation effect of warfarin. The objective of this study was to determine the relationship between different clinical factors and outcomes of warfarin therapy in Hong Kong Chinese patients. METHODS: The study was conducted at the anticoagulation clinic of the Prince of Wales Hospital from 1 April to 31 December 2003. Clinical data collected included demographics, indications of warfarin, dietary vitamin K consumption, and drug-drug interactions. Blood samples were obtained for the genetic polymorphism analysis of CYP 2 C 9. Linear and multiple regression analysis were used for statistical analysis to determine the correlation between variables and the importance of various factors as the determinants of warfarin dosage requirement. RESULTS: A total of 63 patients were recruited. The mean warfarin dosage was 3.30+/-2.23 mg/day. The warfarin dosage ranged from 0.75 to 12 mg/day. The mean age was 59+/-14 years old. Age, dietary vitamin K consumption, chronic heart failure, atrial fibrillation, hypertension, smoking and drinking status were found to be factors statistically significant affecting warfarin dosage. We detected no single nucleotide polymorphism in CYP 2 C 9 exon 4. CONCLUSION: Age, dietary vitamin K consumption, warfarin indication for atrial fibrillation, co-morbid with CHF, smoking and drinking status were found to be the factors that affected the warfarin requirement in Hong Kong Chinese patients. However, the genetic polymorphism in exon 4 of CYP 2 C 9 may not be associated with the warfarin sensitivity in this patient population.

Adult↗

Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population.

OBJECTIVE: To evaluate the association of VKORC1 genetic variants with warfarin dose requirements in a Hong Kong Chinese patient population. METHODS: A retrospective study of Hong Kong Chinese patients chronically maintained on warfarin was conducted. Single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 were genotyped. Stable warfarin dose data were retrieved from patient medical records. RESULTS: Sixty-nine patients were included in the analysis. VKORC1 haplotypes H1 (group A) and H7 (group B) were most common, accounting for 86% and 13% of all haplotypic variation in this cohort. Patients carrying at least one copy of a VKORC1 group B haplotype (n = 16) required a significantly higher stable warfarin dose (5.17+/-1.53 mg/day) than patients that were homozygous for group A haplotypes (n = 53; 2.93+/-1.22 mg; P < 0.001). In the VKORC1 A/A group, four patients (5.8%) were heterozygous for CYP2C9*3 and had a lower dose requirement (1.94+/-0.43 mg) than patients that exhibited the CYP2C9 *1/*1 genotype (3.01+/-1.23 mg), P = 0.004. In multivariate analysis, VKORC1 and CYP2C9 explained 31% and 7.9% of the variability in warfarin dose, respectively. CONCLUSIONS: VKORC1 genotype is the dominant genetic influence on inter-individual variability in warfarin dose in Hong Kong Chinese. The lower mean dose of warfarin in Chinese, relative to Europeans, appears to be a reflection of their preponderance of the 'low-dose' VKORC1 H1/H1 (homozygous group A) genotype.

Anticoagulants↗

A mathematical model for fresh frozen plasma transfusion strategies during major trauma resuscitation with ongoing hemorrhage.

BACKGROUND: Randomized controlled trials of how best to administer fresh frozen plasma (FFP) in the presence of ongoing severe traumatic hemorrhage are difficult to execute and have not been published. Meanwhile, coagulopathy remains a common occurrence during major trauma resuscitation and hemorrhage remains a major cause of traumatic deaths, suggesting that current coagulation factor replacement practices may be inadequate. METHODS: We used a pharmacokinetic model to simulate the dilutional component of coagulopathy during hemorrhage and compared different FFP transfusion strategies for the prevention or correction, or both, of dilutional coagulopathy. Assuming the rates of volume replacement and loss are roughly equal, we derived the hematocrit and plasma coagulation factor concentration over time based on the rate of blood loss and replacement, the hematocrit and coagulation factor concentration of the transfusate, and the hematocrit and plasma factor concentration at the time when FFP transfusion begins. RESULTS: Once excessive deficiency of factors has developed and bleeding is unabated, 1-1.5 units of FFP must be given for every unit of packed red blood cells (PRBC) transfused. If FFP transfusion should start before plasma factor concentration drops below 50% of normal, an FFP:PRBC transfusion ratio of 1:1 would prevent further dilution. CONCLUSION: During resuscitation of a patient who has undergone major trauma, the equivalent of whole-blood transfusion is required to correct or prevent dilutional coagulopathy.

Blood Coagulation Disorders↗

The potential clinical and economic outcomes of pharmacogenetics-oriented management of warfarin therapy - a decision analysis.

Variant cytochrome P450 (CYP) 2C9 genotypes are associated with low maintenance dose requirement of warfarin therapy and increased risk of major bleeding events. The objective of the present study was to evaluate the potential clinical and economic outcomes of using CYP2C9 genotype data to guide the management of anticoagulation therapy and to identify influential factors affecting the cost-effectiveness of this treatment scheme. A decision tree was designed to simulate, over 12 months, the clinical and economic outcomes of patients newly started on warfarin associated with two alternatives: (1) no genotyping (non-genotyped group) and (2) CYP2C9 genotyping prior to initiation of warfarin therapy (genotyped group). Non-genotyped group patients would receive standard care of an anticoagulation clinic (AC). In the genotyped group, patients with at least one variant CYP2C9 allele would receive intensified anticoagulation service. Most of the clinical probabilities were derived from literature. The direct medical costs were estimated from the Diagnosis-Related Group charges and from literature. The total number of events and the direct medical cost per 100 patient-years in the genotyped and non-geno-typed groups were 9.58 and USD155,700, and, 10.48 and USD 150,500, respectively. The marginal cost per additional major bleeding averted in the genotyped group was USD 5,778. The model was sensitive to the variation of the cost and reduction of bleeding rate in the intensified anticoagulation service. In conclusion, the pharmacogenetics-oriented management of warfarin therapy is potentially more effective in preventing bleeding with a marginal cost. The cost-effectiveness of this treatment scheme depends on the relative cost and effectiveness of a pharmacogenetics-oriented intensified anticoagulation service comparing to the standard AC care.

Algorithms↗

The effects of nasal continuous positive airway pressure on platelet activation in obstructive sleep apnea syndrome.

OBJECTIVE: A case-controlled study to assess the effects of nasal continuous positive airway pressure (CPAP) on platelet activation in patients with obstructive sleep apnea (OSAS) syndrome. METHODS: We recruited 65 patients with suspected OSAS for this study. Blood samples were taken with the patient in the supine position in the morning immediately after polysomnography, and 1 night and 3 months after the start of nasal CPAP therapy to measure an index of platelet activation (IPA+), which reflected both the quantity and quality of platelet activation. Significant OSAS was defined as an apnea-hypopnea index (AHI) of > or = 10 events per hour. RESULTS: There were 42 patients with significant OSAS and 23 control subjects with AHI < 10 events per hour. The mean (+/- SD) age for the OSAS patients was 48 +/- 9 years, the mean body mass index was 30.7 +/- 4.8, the mean AHI was 47 +/- 25 events per hour, the mean arousal index (AI) was 37 +/- 23 events per hour, and the mean minimum arterial oxygen saturation was 74 +/- 11%. Following multiple linear regression analyses of the clinical and polysomnography parameters, AI was the independent factor that correlated best with the baseline IPA+ (beta-coefficient, 0.386; p = 0.006). Following nasal CPAP treatment with a mean objective CPAP compliance of 3.9 +/- 1.9 h per night, there was a significant decrease in IPA+ from 15.1 +/- 12.2 U (at baseline) to 12.2 +/- 5.2 U (p < 0.001) and 9.8 +/- 4.3 U (p = 0.005), respectively, after 1 night and 3 months, whereas no significant change was noted among the control subjects. Using univariate analysis of variance to compare the changes in IPA+ between the two groups at 3 months with adjustment for the baseline value, nasal CPAP reduced IPA+ by 5.63 (SE, 1.85), whereas IPA+ increased in control subjects by 1.33 (SE, 1.27) [least-squared mean difference between groups, 3.34; 95% confidence interval, 0.42 to 6.26; p = 0.026]. CONCLUSIONS: OSAS, through repeated episodes of arousals, may lead to platelet activation, which can be reduced by nasal CPAP therapy.

Case-Control Studies↗

Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone.

BACKGROUND: The role of high-dose dexamethasone in the treatment of immune thrombocytopenic purpura in adults is controversial. We assessed the effectiveness of high-dose dexamethasone as initial treatment in a series of consecutive adults with immune thrombocytopenic purpura. METHODS: Consecutive patients with newly diagnosed immune thrombocytopenic purpura and a platelet count of less than 20,000 per cubic millimeter or a platelet count of less than 50,000 per cubic millimeter and clinically significant bleeding were enrolled between January 1997 and December 2000. Oral dexamethasone at a dose of 40 mg per day for four consecutive days was the initial treatment. A response was defined as an increase in the platelet count of at least 30,000 per cubic millimeter and a platelet count of more than 50,000 per cubic millimeter by day 10 after the initiation of treatment. A sustained response was defined as a platelet count of more than 50,000 per cubic millimeter six months after the initial treatment. RESULTS: Of 157 consecutive patients, 125 were eligible. The mean (+/-SD) platelet count before treatment was 12,200+/-11,300 per cubic millimeter. A good initial response to high-dose dexamethasone occurred in 106 of the 125 patients (85 percent): the platelet count increased by at least 20,000 per cubic millimeter by the third day of treatment, and the mean platelet count was 101,400+/-53,200 per cubic millimeter (range, 50,000 to 260,000 per cubic millimeter) one week after the initiation of treatment. Among the 106 patients with a response, 53 (50 percent) had a sustained response; the other 53 (50 percent) had a relapse within six months, most of them (94 percent) within the first three months. A platelet count of less than 90,000 per cubic millimeter on day 10 was associated with a high risk of relapse. The treatment was well tolerated. CONCLUSIONS: A four-day course of high-dose dexamethasone is effective initial therapy for adults with immune thrombocytopenic purpura.

Administration, Oral↗

Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis.

OBJECTIVES: To evaluate the haematological findings of patients with severe acute respiratory syndrome (SARS). DESIGN: Analysis of the demographic, clinical, and laboratory characteristics of patients with SARS. SETTING: Prince of Wales Hospital, Hong Kong. Subjects All patients with a diagnosis of SARS between 11 March and 29 March 2003 who had no pre-existing haematological disorders. MAIN OUTCOME MEASURES: Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed to examine factors associated with adverse outcome. RESULTS: 64 male and 93 female patients were included in this study. The most common findings included lymphopenia in 153 (98%) of the 157 patients, neutrophilia in 129 (82%), thrombocytopenia in 87 patients (55%), followed by thrombocytosis in 77 (49%), and isolated prolonged activated partial thromboplastin time in 96 patients (63%). The haemoglobin count dropped by more than 20 g/l from baseline in 95 (61%) patients. Four patients (2.5%) developed disseminated intravascular coagulation. Lymphopenia was shown in haemato-lymphoid organs at postmortem examination. Multivariate analysis showed that advanced age and a high concentration of lactate dehydrogenase at presentation were independent predictors of an adverse outcome. Subsets of peripheral blood lymphocytes were analysed in 31 patients. The counts of CD4 positive and CD8 positive T cells fell early in the course of illness. Low counts of CD4 and CD8 cells at presentation were associated with adverse outcomes. CONCLUSIONS: Abnormal haematological variables were common among patients with SARS. Lymphopenia and the depletion of T lymphocyte subsets may be associated with disease activity.

Blood Coagulation↗

Cost-effectiveness of two models of management for patients on chronic warfarin therapy--a Markov model analysis.

Allocation of additional resources for establishing or expanding anticoagulation clinic (AC) services is a significant concern for healthcare decision-makers when the payer is also the provider of the healthcare system. The majority of anticoagulated patients in Hong Kong are managed by routine medical care (RMC) instead of ACs, possibly due to the lack of local cost-effectiveness analysis of the AC setting. The aim was to compare the clinical and economic outcomes of anticoagulated patients who were managed by AC or RMC from the perspective of a public health organization in Hong Kong. A Markov model was designed to simulate, over 10 years, the economic and clinical outcomes of patients receiving chronic warfarin therapy managed by AC or RMC. The transition probabilities were derived from literature. Resource utilization was retrieved from patients managed by AC and RMC in Hong Kong. Sensitivity analysis was conducted to examine the robustness of the model. The total number of events per 100 patient-years and the direct medical cost per patient-year in the AC and RMC groups were 9.5 and USD 840, and, 19.3 and USD 1,179, respectively. The results of the model were sensitive to the variation of the probability of major bleeding in the AC group. In conclusion, the coordinated care provided by an anticoagulation clinic appears to be more cost-effective than routine medical care in the management of warfarin therapy from the perspective of public health organization in Hong Kong.

Algorithms↗

Relationship between patients' warfarin knowledge and anticoagulation control.

OBJECTIVE: To evaluate patients' knowledge of warfarin and its relationship to anticoagulation control. METHODS: From January to March 1999, 122 patients attending the warfarin clinic of the Prince of Wales Hospital in Hong Kong were interviewed. Their knowledge of warfarin therapy and adherence to medical advice were tested by 9 questions. A score (maximum 1.0) was calculated for each patient. The number of international normalized ratios (INRs) that was within the target range in the 4 most recent clinic visits was noted. RESULTS: Fifty-six men and 66 women participated in the study (mean +/- SD age 58.0 +/- 13.0, duration of treatment 43.1 +/- 39.8 mo). Patients' warfarin knowledge was poor, with an overall score of 0.48 +/- 0.18. Participants generally knew the colors of their warfarin tablets and took them regularly. They almost always informed their physicians and dentists of their warfarin therapy. Only 40-45% of patients knew the strengths of their warfarin tablets, the reason for taking warfarin, and its effect on the body. Their deficiencies in knowledge were even more obvious with respect to the possible consequences of under- or over-anticoagulation, drugs and medicated oils that might interact with warfarin, and management of a missed dose. Knowledge was related to age (r -0.43; p < 0.001) and duration of therapy (r 0.18; p = 0.044). Sixty patients (49.2%) had read the information booklet on warfarin and had better knowledge than those who had not (0.53 +/- 0.20 vs. 0.42 +/- 0.20; p < 0.001). Illiteracy was the main reason for not reading the booklet. There was a positive correlation between patients' warfarin knowledge and the number of INR values that was within the target range in the 4 most recent clinic visits (r 0.20; p = 0.024). CONCLUSIONS: Patients' warfarin knowledge, a determinant of anticoagulation control, was generally poor. More attention should be given to the education of elderly and illiterate patients.

Adult↗

Use of herbal medicines by patients receiving warfarin.

BACKGROUND: Patients receiving warfarin therapy are discouraged from taking herbal medicines. Whether patients adhere to this advice and, if they do not, the types of products they use, are not known. OBJECTIVE: The objective of this observational study was to estimate the magnitude of use of herbal medicines among Chinese patients attending the Warfarin Clinic of the Prince of Wales Hospital in Hong Kong. METHODS: A medical officer interviewed all patients who attended the Warfarin Clinic during May 2001. Patients were asked about the use of herbal medicines in the preceding week. Demographic data, indication and duration of warfarin therapy, and International Normalised Ratio (INR) value at the time of the visit were also noted. RESULTS: Of 107 patients interviewed, 28 (26%) claimed to have taken herbal medicines during the week prior to the clinic visit. The users of herbal medicines had lower INR values than non-users (mean INR value 2.41 +/- 0.65 vs 2.75 +/- 0.65, p = 0.019), possibly because of a lower warfarin dosage (mean dosage 2.93 mg/day +/- 1.23 vs 3.34 mg/day +/- 1.45; p = 0.185) and because a smaller proportion of such patients had heart valve replacement (21% vs 39%, p = 0.141). 'Herbal soup' (soup made at home from vegetables, meat and certain herbs for consumption with the main meals) and 'cool tea' (herbal decoction for the treatment of 'endogenous heat') were the most popular and were taken by 12 (11%) and 11 (10%) patients, respectively. Four patients took proprietary medicines each containing between one and three different herbs that could potentially enhance or antagonise the effects of warfarin. None of the patients in this study showed any evidence of thromboembolism or bleeding on the day of clinic visit. CONCLUSION: Among Chinese patients treated with warfarin at a Hong Kong clinic, the use of herbal medicines was relatively common. Healthcare professionals play an important role in educating the patients and updating the list of herbal medicines that should be avoided by patients taking warfarin.

Blood Coagulation↗