Agnes L. F. Chan

Transdermal Delivery of Treatment for Alzheimer's Disease : Development, Clinical Performance and Future Prospects

There is increasing interest in the potential of transdermal drug delivery systems for the treatment of neurological disorders, especially in the elderly. In this population, the higher incidence of chronic diseases, such as diabetes mellitus, cardiovascular disease, neurological disease and chronic pain, has dramatically increased the need for long-term medications. Additionally, elderly patients often have a combination of several chronic diseases, meaning drug delivery, drug-drug interactions, absorption/blood concentrations, toxicity and compliance are of concern for patients as well as for their caregivers and physicians. Recent efforts have focused on developing pharmaceutical preparations that overcome these issues. For example, rate-controlled drug delivery systems have been under active development. Transdermal drug delivery systems have been developed to deliver phenserine, rivastigmine, nicotine and estradiol for the management of cognitive and behavioural dysfunctions in patients with Alzheimer’s disease because this form of administration has several advantages, including maintenance of sustained therapeutic plasma concentrations of drugs, easy application and reduced systemic adverse effects. Thus, transdermal drug delivery for elderly patients offers promise as the ideal therapeutic approach to treating Alzheimer’s disease.This article reviews the technical principles underlying the development of transdermal drug delivery systems, focusing on cholinesterase inhibitors, and the prospects for future development. The clinical performance of transdermal patches, again with emphasis on cholinesterase inhibitors, is also reviewed.

Multivitamin Supplement Use and Risk of Breast Cancer: A Meta-Analysis

Background The association between consumption of multivitamins and breast cancer is inconsistent in epidemiologic studies. Objective: To perform a meta-analysis of cohort and case-control studies to evaluate multivitamin intake and its relationship with breast cancer risk. Methods: The published literature was systematically searched and reviewed using MEDLINE (1950 through July 2010), EMBASE (1980 through July 2010). and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010 issue 1). Studies that included specific risk estimates were pooled using a random-effects model. The bias and quality of these studies were assessed with REVMAN statistical software (version 5.0) and the GRADE method of the Cochrane Collaboration. Results: Eight of 27 studies that included 355,080 subjects were available for analysis. The total duration of multivitamin use in these trials ranged from 3 to 10 years. The frequency of current use in these studies ranged from 2 to 6 times/week. In analyses by duration of use 10 years or longer or 3 years or longer and by frequency 7 or more times/week that were reported in these studies, multivitamin use was not significantly associated with the risk of breast cancer. Only 1 recent Swedish cohort study concluded that multivitamin use is associated with an increased risk of breast cancer. The results of a meta-analysis that pooled data from 5 cohort studies and 3 case-control studies indicated that the overall multivariable relative risk and odds ratio were 0.10 (95% CI 0.60 to 1.63; p = 0.98) and 1.00 (95% CI 0.51 to 1.00; p = 1.00), respectively. The association was not statistically significant. Conclusions: Multivitamin use is likely not associated with a significant increased or decreased risk of breast cancer, but these results highlight the need for more case-control studies or randomized controlled clinical trials to further examine this relationship.

Cost-Effectiveness of Trastuzumab as Adjuvant Therapy for Early Breast Cancer: A Systematic Review

Objective: To identify published, original, cost-effectiveness analyses presenting cost/quality-adjusted life year (QALY) ratios for trastuzumab used as an adjuvant treatment for HER2-positive early breast cancer and to evaluate the quality of reporting the favorable cost-effectiveness ratios. Data Sources: The terms trastuzumab adjuvant therapy, cost-effectiveness, quality-adjusted, QALY, and early breast cancer were searched in MEDLINE, PubMed, Embase, and CancerLit, as well as in Cochrane economic evaluation and reference lists from 1998 to June 2008. Only English-language publications were eligible. Study Selection and Data Extraction: All published studies examining cost-effectiveness outcomes on the basis of modeling or clinical trials were included. Cost-effectiveness analysis that measured health effects in units other than QALY, life year gained, neoadjuvant data, reviews, and comments were excluded. Each study was assessed independently by 2 trained reviewers. Data Synthesis: Thirteen of the 239 articles identified met the inclusion criteria, with 23 cost-effectiveness ratios pertaining to treatment of early breast cancer. These ratios ranged from

Cost evaluation of adverse drug reactions in hospitalized patients in Taiwan: A prospective, descriptive, observational study

5020/QALY to

The evaluation of free influenza vaccination in health care workers in a medical center in Taiwan

134,610/QALY. Most studies reported favorable cost-effectiveness values (ie, below

Risk of Hemorrhage Associated with Co-Prescriptions for Ginkgo biloba and Antiplatelet or Anticoagulant Drugs

50,000/QALY). About 84.6% were conducted using a Markov model based on data from clinical trials and 15.3% were analyzed by other economic or cost models; 84.6% reported sensitivity analysis, 11 studies (84.6%) clearly described a justification of selecting study design, and only 15.3% noted study limitations. All studies mentioned their perspective; 92.3% did not show the funding source. Methods of reporting costs, effectiveness, and time-horizons for disease states varied significantly. Nine (69.2%) studies used a discount rate of 3%, 3 studies used a discount rate of 5%, and 1 study used 3.5%. The mean quality of the studies was 4.43. Conclusions: Most studies presenting the frequently proposed threshold of QALY suggest that trastuzumab may be cost-effective for treatment of early breast cancer in a 1-year treatment regimen.

Reliability of 95% confidence interval revealed by expected quality-of-life scores: an example of nasopharyngeal carcinoma patients after radiotherapy using EORTC QLQ-C 30

BACKGROUND Adverse drug reactions (AADRs) are a leading cause of morbidity and mortality. In the United States, ADR-related morbidity and mortality costs have been estimated at US

Celecoxib-Induced Deep-Vein Thrombosis

330 billion to US

Validation of a shortened Taiwanese version of an asthma quality-of-life questionnaire by Rasch model.

1130 billion annually. OBJECTIVES The aim of this study was to evaluate the incidence of ADRs in Taiwan, to identify the drug classes that are most commonly related to ADRs, and to determine the direct medical costs to hospitals associated with prolonged hospitalizations due to ADRs. METHODS In this prospective, descriptive, observational study, patients who experienced ADRs during their hospitalization at a Taiwan teaching hospital or who were admitted due to an ADR from January 1, 2002, through December 31, 2004, were included in the study. The patients were identified actively by clinical pharmacists and passively by physicians and nurses who reported ADRs. The World Health Organization (WWHO) definition of ADR severity was adopted, and degrees of probability for each ADR were determined using the Naranjo algorithm. The direct medical costs incurred to the hospital in the treatment of ADRs that prolonged hospitalization were calculated (ie, costs of emergency department [ED] visits, intensive care unit visits, extra days of hospitalization, monitoring and laboratory studies, pharmacist dispensing fees, physician fees, room charges, ED charges). RESULTS During the study period, 43 of the 142,295 hospitalized patients (00.03%)) were admitted because of an ADR. A total of 564 (00.40%)) of the hospitalized patients were verified to have ADRs. Three hundred eighteen of the patients (56.44%) with ADRs were male and the overall mean (SD) age was 66(2) years. The most common drug classes associated with the ADRs were antibiotics (219 patients [38.8% ]), analgesics (62 [11.0%]), and cardiovascular agents (56 [9.9%]). The systems most commonly involved in ADRs were cutaneous (296 patients [52.5%]), hematologic (61 [10.8%]), and cardiovascular (54 [9.66%]). The causes of the ADRs were anaphylactic (464 patients [82.3%]), drug overdose (78 [13.8%]), and drug-drug interactions (22 [3.9%]). Of the ADRs, 474 (884.0%) were idiosyncratic type B reactions (predictable). ADR-related costs, estimated at US

Pediatric Fatality Due to Anticonvulsant Hypersensitivity Syndrome

3489/ADR, were mostly due to prolonged length of stay. Based on the WHO definition, of the 564 ADRs, 330 (58.5%) and 40 (7.1%) were classified as moderate and severe, respectively. Two patients died of ADRs associated with allopurinol. CONCLUSION In this hospital, 0.40% of patients were identified as having ADRs that were associated with high direct costs, mostly due to extended hospitalizations.