Ineffectiveness of the current strategy to prevent hepatitis A in travelers

BACKGROUND: Each year, a large number of Canadians travel to regions of the world where hepatitis A remains endemic. Many of these travelers are not immune and the current preventive strategy relies wholly on self-referral to a travel clinic. All of the costs associated with such a visit are assumed by the traveler. We estimated the effectiveness of this strategy. METHODS: This case-control study included 108 travel-related hepatitis A cases with onset of disease between 1997 and 1999 and 620 controls who traveled during the same period. RESULTS: Hepatitis A was strongly associated with high-risk travel (Odds Ratio = 7.2, 95% Confidence Interval 1.76-29.4), but only 7% of cases were found in this category. The risk of hepatitis A was 5 times lower in travelers who visited a travel clinic than in those who did not (80% efficacy). However, only 14% of the controls visited a travel clinic. As a result, the effectiveness of the current strategy is estimated to be 11% (80% of 14%). CONCLUSIONS: Hepatitis A in travelers can be prevented effectively by attendance at a travel clinic. Unfortunately, most travelers do not visit such clinics prior to departure. Even if all high-risk travelers were to visit a travel clinic and receive vaccination, this would have negligible impact on the number of travel-related hepatitis A cases (approximately 7% reduction). The current strategy for the prevention of hepatitis A in travelers is ineffective and should be reexamined.     

Risks of hepatitis B in travelers as compared to immunization status

BACKGROUND: Our objective was to determine the risks of infection with hepatitis B among European travelers and to compare this with the immunization status in various risk groups. METHODS: A cross-sectional telephone questionnaire survey of randomly selected subjects, in nine European study populations was used. A total of 9, 008 individuals were involved, with approximately 1,000 interviews conducted in each country in the native languages. Situations with a high risk of hepatitis B infection, such as invasive medical procedures, attending to a bleeding person, and skin perforating cosmetic practices, particularly when performed in countries with medium/high transmission risk, and vaccination status of travelers, were the main outcome measures. RESULTS: Depending upon the destination, 6.6-11.2% of travelers were classified as at high risk of hepatitis B, with 24.4% vaccinated; between 60.8-75.8% of travelers at potential risk, with 19.2% vaccinated; and 33.4% of travelers where no hepatitis B risk was identified. Significantly more travelers who only visited medium/high endemicity regions exposed themselves to a high risk of contracting hepatitis B, (40, 10.5%) compared to travelers who only visited low endemicity regions (225, 6.6%; p <.01). CONCLUSIONS: A significant proportion of travelers surveyed unwittingly exposed themselves to the risk of hepatitis B infection while at medium/high risk destinations. The majority of at-risk travelers had not been vaccinated, regardless of their destination. Improved advice and clear recommendations to avoid transmission are needed.     

An estimate of the incidence of hepatitis A in unimmunized Canadian travelers to developing countries

BACKGROUND: There is a paucity of data describing the risk of acquiring hepatitis A while traveling in the developing world. This paper uses available data to calculate the risk to Canadian travelers. METHODS: Information was gathered from Canadian and international sources on the following: the yearly incidence of hepatitis A among Canadians; the proportion of cases of hepatitis A associated with travel to developing countries; the number of days of such travel by Canadians per year; and the percentage of travelers immunized before departure. Calculations were performed on these figures to arrive at an estimated risk of infection for unimmunized Canadian travelers. RESULTS: The annual incidence of hepatitis A in Canada over the period 1996-2001, adjusted for underreporting, averaged 6.15 cases/100,000 people. During that time, Canadians traveled approximately 36.5 million days/year in developing countries. The literature shows that 4% to 28% (mean 16%) of cases are estimated to have been acquired abroad. It also shows that 14% to 24% (mean 19%) of such travelers are immunized before departure. Based on these figures, the risk of acquiring hepatitis A during 1 month of travel in the developing world is calculated to be approximately 1 case per 3,000 unimmunized travelers. CONCLUSION: Hepatitis A is an important travel-related disease, preventable by immunization. However, our calculations indicate that the risk of acquiring hepatitis A while traveling in the developing world is lower than some previously published estimates. The results represent an average for all types of travel to all such countries. The actual risk will vary considerably, depending on the destination and style of travel.     

Eradicating hepatitis C: Are novel screening strategies for people who inject drugs cost-effective?

Background: In developed countries, people who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV), yet they are often under-diagnosed. The World Health Organization has set 2030 as a target year for HCV elimination. To meet this target, improving screening in convenient community settings in order to reach infected undiagnosed individuals is a priority. This study assesses the cost-effectiveness of alternative novel strategies for diagnosing HCV infection in PWID. Methods: A cost-effectiveness analysis was undertaken to compare HCV screening at needle exchange centres, substance misuse services and at community pharmacies, with the standard practice of detection during general practitioners’ consultations. A decision tree model was developed to assess the incremental cost per positive diagnosis, and a Markov model explored the net monetary benefit (NMB) and the cost per Quality Adjusted Life Years (QALYs) gained over a lifetime horizon. Results: Needle exchange services provided a 7.45-fold increase in detecting positive individuals and an incremental cost of £12,336 per QALY gained against current practice (NMB £163,827), making this the most cost-effective strategy over a lifetime horizon. Screening at substance misuse services and pharmacies was cost-effective only at a £30,000/QALY threshold. With a 24% discount to HCV treatment list prices, all three screening strategies become cost-effective at £20,000/QALY. Conclusions: Targeting PWID populations with screening at needle exchange services is a highly cost-effective strategy for reaching undiagnosed HCV patients. When applying realistic discounts to list prices of drug treatments, all three strategies were highly cost-effective from a UK NHS perspective. All of these strategies have the potential to make a cost-effective contribution to the eradication of HCV by 2030.     

战略联盟--医药企业发展战略新选择

面对日益激烈的市场竞争,面对世界著名制药公司在规模、管理、产品等各方面的优势,我国的医药企业急需通过增强自身实力、提高生产经营规模、发展独特的核心竞争力来参与竞争。但是,目前我国医药企业普遍规模偏小,资金实力有限,如果通过传统的方式进行扩张的话,必然面临人力、物力、财力等资源的限制。因此,我国医药企业如何寻找一种适合中国国情的超常规发展之路就成为理论界和企业界都非常关心的问题。本文结合战略联盟理论,对我国医药产业现状进行分析后,对这一问题进行一些初步的探讨。     

The use of resonance energy transfer in high-throughput screening: BRET versus FRET

Bioluminescence resonance energy transfer has developed in recent years as a new technique to study protein-protein interactions. Protein partners of interest are tagged with either luciferase or green fluorescent protein (GFP). Non-radiative energy transfer between the excited luciferase and the GFP permits the study of spatial relationships between the two partners. This technique constitutes an important tool for the study of the functional activity of different types of receptors, and can be used in sensitive, homogenous high-throughput screening assays.     

Chemoprophylaxis use and the risk of malaria in travelers to Nepal

BACKGROUND: Malaria transmission in Nepal is focal and seasonal. Based on data in returning travelers the risk of malaria is low. Sources of advice give contradictory information regarding the need for chemoprophylaxis. As a result, a degree of confusion exists among visitors. The aim of this study was to describe chemoprophylactic practices among travelers to Nepal and to document differences in advice according to its source and the country in which it was given. METHODS: A questionnaire survey of tourists attending the CIWEC Clinic Travel Medicine Center, Kathmandu between June 2000 and May 2001. Resident expatriates and indigenous Nepalese were excluded. RESULTS: Completed questionnaires were obtained from 1,303 respondents. Two hundred and eighty-eight respondents were taking chemoprophylaxis specifically for their trip to Nepal (22%), whereas 958 were not. Travelers from the United Kingdom and Denmark were significantly more likely, and those from the United States and Germany significantly less likely, to be taking chemoprophylaxis. Most travelers sought pretravel advice (71%), and all sources were more likely to advise them not to take chemoprophylaxis than to take it. However, travelers advised by a family practitioner were significantly more likely to be taking chemoprophylaxis than those advised by a travel medicine specialist. Of those taking chemoprophylaxis, 53% were doing so for a visit to the Terai alone, 33% for all areas of Nepal, and 6% for the Kathmandu Valley. Nine different chemoprophylactic regimes were in use. Six hundred and forty respondents who were not taking chemoprophylaxis had been advised that it was not necessary; 276 had made the choice themselves; and 131 had been taking chemoprophylaxis but had stopped while in Nepal. Twenty-eight of these respondents had stopped because of side effects. The most common reason for choosing not to take chemoprophylaxis was either the occurrence of side effects or the fear of them (31%). CONCLUSIONS: The variable and ultimately low risk of contracting malaria in Nepal has resulted in a lack of consensus and a wide range of opinion regarding the need for chemoprophylaxis. There is a need for clarification and tighter definition of the malaria risk faced by travelers to Nepal to avoid unnecessary chemoprophylaxis use while protecting those at significant risk.     

Promoting adult hippocampal neurogenesis: a novel strategy for antidepressant drug screening

Major depression is a common mood disorder that affects overall health; currently, almost all of the available antidepressants have the same core mechanisms of action through promotion of serotonin or noradrenaline function in the brain. The major limitation of today's antidepressants is that chronic treatment (3 - 6 weeks) is required before a therapeutic benefit is achieved. More effective and faster treatments for depression are needed. Adult neurogenesis is the birth of new neurons, which continues postnatally and into adulthood in the brains of multiple species, including humans. Recently, a large body of evidence gives rise to the hypothesis that the antidepressant effect and increases in adult hippocampal neurogenesis may be causally related. Multiple classes of antidepressants increase hippocampal neurogenesis in a chronic, but not acute, time course. This effect corresponds to the therapeutic time lag associated with current antidepressants. In addition, antidepressants are not effective in behavioral models of depression when hippocampal neurogenesis is prevented. This review examines the current understanding of adult neurogenesis and the evidence of the causal relationship between antidepressant effects and adult hippocampal neurogenesis. We also present our recent research findings, which support a promising strategy for enhancing adult hippocampal neurogenesis that might be a new approach for the development of novel antidepressants.     

Immunogenicity of booster vaccination with a virosomal hepatitis A vaccine after primary immunization with an aluminum-adsorbed hepatitis A vaccine

BACKGROUND: Increasing numbers of individuals are traveling to areas of high hepatitis A endemicity and require immunization against the hepatitis A virus (HAV). The option of using a virosomal, aluminum-free, HAV vaccine (Epaxal) for booster immunization following primary vaccination with an aluminum-adsorbed vaccine has been assessed. METHODS: In total, 142 healthy subjects, 79 men and 63 women, aged 12 to 72 years, were injected intramuscularly with a booster dose of Epaxal (0.5 mL containing < or =500 RIA units of HAV antigen) 6 to 24 months after primary vaccination with Havrix (0.5 or 1.0 mL containing 720 or 1440 ELISA units of HAV antigen, respectively, adsorbed onto aluminum hydroxide). Anti-HAV antibody titers were measured on days 0 and 28 by an enzyme immunoassay. Adverse events were recorded for 1 month postinjection. RESULTS: Overall, 98/118 subjects (83%) with no serologic evidence of past HAV infection were still seroprotected at enrolment (anti-HAV antibody titer < or = 20 mIU/mL). The seroprotection rate was 87% in those primed with Havrix 1440 6 to 12 months earlier (n=93) and 60% in those primed < or =12 months before enrolment (n=20, mean 16 months). The geometric mean anti-HAV antibody titer increased from 65 mIU/mL at day 0 to 1,722 mIU/mL at day 28 after a single booster dose with Epaxal in evaluable subjects who were primarily vaccinated with either a single dose of Havrix 1440 (n=111) or two separate doses of Havrix 720 (n=4). All subjects were seroprotected at day 28, and 98% showed at least a four-fold increase in anti-HAV antibody titer. Epaxal was well tolerated and no serious adverse events were reported. At day 28, the tolerability of the vaccination was judged as either "very good" or "good" by 96% of vaccinees and by all investigators. CONCLUSION: Epaxal can be successfully used to boost immunization following primary vaccination with an aluminum-adsorbed vaccine, and is well tolerated.     

Enhancing the role of physicians in the cost-effective use of pharmaceuticals

The appropriate use of pharmaceuticals, like much else in medicine, is receiving increased public scrutiny. Health care practitioners are looking for ways to reduce costs without negatively influencing quality of care. This article reviews methods for physicians and pharmacists to work together to implement cost-effective prescribing practices and assess clinical outcomes. These methods include educational initiatives, administrative programs to restrict ordering practices, use of formularies and prescribing guidelines, financial incentives, and programs that support physician and pharmacist collaboration.     

The use of AUDIT as a screening tool for alcohol use in the police work-place

There has been little research examining the use of the Alcohol Use Disorders Identification Test (AUDIT) as a work-place screening tool. In the current study a large scale sample ( n = 4193) of police personnel completed the 10 AUDIT questions and two readiness-to-change questions. The sample represented 67% of all members of an Australian State Police organization. Analysis of AUDIT scores showed that 65% of the sample scored in the low risk of hazardous alcohol consumption range, 32% (33% of males and 24% of females) scored in the at risk for harmful alcohol consumption range and 3% scored in the range indicating risk of alcohol dependence. Age emerged as a clear risk factor of hazardous drinking patterns. The 18-25-year age group recorded higher average alcohol consumption, higher rates of risk of abnormal drinking behaviour, higher rates of adverse consequences from drinking alcohol and higher total AUDIT scores than other age groups. This was consistent for both males and females. Of those scoring in the at-risk range, 72.5% reported that they did not have a drinking problem. Sixty percent also reported that it would be easy to stop drinking. This study exemplifies how the AUDIT can be used to provide strong evidence for the need for work-based intervention programmes. Further, it can be used to target particular groups within the organization at risk of harmful alcohol use.     

Promoting the cost-effective utilization of cefoxitin with a drug use education program.

Concerns about cost containment in the health care industry have caused many hospital P & T Committees to focus on developing measures for curtailing drug costs, and antibiotics have been a principal area of this focus focus. The development of an educationally based program created to bring an awareness to physicians regarding the cost-effective use of specific antibiotics is described. The program, entitled a Drug Use Education (DUE) Program, began with development of specific criteria for utilization of cefoxitin sodium (Mefoxin). Subsequently, concurrent monitoring of all cefoxitin usage was initiated and its effectiveness evaluated. The DUE program was effective in significantly altering the use of cefoxitin and had a positive impact on overall parenteral antibiotic use.     

Biomolecular-chemical screening: a novel screening approach for the discovery of biologically active secondary metabolites. I. Screening strategy and validation

Chemical screening using thin-layer chromatography and various staining reagents offers the opportunity to visualize an almost complete picture of a microbial secondary metabolite pattern (metabolic finger-print). A thorough application of this strategy resulted in a number of biologically active new secondary metabolites, although the screening strategy is per se not correlated to any biological activity. In the present paper we report on a novel approach called biomolecular-chemical screening which combines the chemical screening strategy with binding studies of biological relevance. Making use of thin-layer chromatography (TLC) and subsequent staining, biomolecular-chemical screening allows to examine binding properties of low molecular weight metabolites to certain bio-macromolecules. The screening strategy itself, as well as independent validation of the results using DNA as selected bio-macromolecule are presented. The biomolecular-chemical screening method is useful to screen binding behaviour towards DNA of both, pure metabolites by one-dimensional TLC, and crude extracts by two-dimensional TLC. Investigation of pure secondary metabolites as well as screening of crude microbial extracts and new secondary metabolites obtained with this screening strategy are presented in accompanying papers.