Spatio-temporal modelling of disease incidence with missing covariate values.

The search for an association between disease incidence and possible risk factors using surveillance data needs to account for possible spatial and temporal correlations in underlying risk. This can be especially difficult if there are missing values for some important covariates. We present a case study to show how this problem can be overcome in a Bayesian analysis framework by adding to the usual spatio-temporal model a component for modelling the missing data.

BioJava: an open-source framework for bioinformatics.

SUMMARY: BioJava is a mature open-source project that provides a framework for processing of biological data. BioJava contains powerful analysis and statistical routines, tools for parsing common file formats and packages for manipulating sequences and 3D structures. It enables rapid bioinformatics application development in the Java programming language. AVAILABILITY: BioJava is an open-source project distributed under the Lesser GPL (LGPL). BioJava can be downloaded from the BioJava website (http://www.biojava.org). BioJava requires Java 1.5 or higher. All queries should be directed to the BioJava mailing lists. Details are available at http://biojava.org/wiki/BioJava:MailingLists.

To freeze or not to freeze: a cost-effectiveness analysis of wart treatment.

BACKGROUND: Several general practitioner (GP)-prescribed and over-the-counter therapies for warts and verrucae are available. However, the cost-effectiveness of these treatments is unknown. OBJECTIVES: To compare the cost-effectiveness of different treatments for cutaneous warts. METHODS: We designed a decision-analytic Markov simulation model based on systematic review evidence to estimate the cost-effectiveness of various treatments. The outcome measures studied are percentage of patients cured, cost of treatment and incremental cost-effectiveness ratio for each treatment, compared with no treatment, after 18 weeks. RESULTS: Duct tape was most cost-effective but published evidence of its effectiveness is sparse. Salicylic acid was the most cost-effective over-the-counter treatment commonly used. Cryotherapy administered by a GP was less cost-effective than GP-prescribed salicylic acid and less cost-effective than cryotherapy administered by a nurse. CONCLUSIONS: Duct tape could be adopted as the primary treatment for cutaneous warts if its effectiveness is verified by further rigorous trials. Nurse-administered cryotherapy is likely to be more cost-effective than GP-administered cryotherapy.

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts. An economic decision model.

OBJECTIVES: To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. DATA SOURCES: Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. REVIEW METHODS: Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GP-prescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. RESULTS: OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 pound/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 pound/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 pound/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 pound/% cured for OTC duct tape and 0.76 pound/% cured for OTC cryotherapy to 1.12 pound/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. CONCLUSIONS: Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more cost-effective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care.

Regulation of hepatic lanosterol 14 alpha-demethylase gene expression by dietary cholesterol and cholesterol-lowering agents.

Binding of sterol response element binding protein 1a to sterol response element-1 (SRE-1) in the promoter region of lanosterol 14 alpha-demethylase (14DM) has been demonstrated previously. Decreased 14DM activity has been shown to result in accumulation of the intermediate, 3 beta-hydroxy-lanost-8-en-32-al, a known translational downregulator of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Since it has also been demonstrated that feedback regulation of hepatic HMG-CoA reductase occurs primarily at the level of translation, the effects of dietary cholesterol and cholesterol lowering agents on levels of hepatic 14DM mRNA and immunoreactive protein were investigated. Addition of 1% cholesterol to a chow diet markedly decreased hepatic 14DM mRNA and protein levels in Sprague-Dawley rats. The extent and time course of this decrease in 14DM immunoreactive protein closely paralleled that of HMG-CoA reductase. Supplementation of the diet with the HMG-CoA reductase inhibitor, Lovastatin, to a level of 0.02%, raised 14DM mRNA and protein levels 2- to 3-fold. Addition of 2% Colestipol, a bile acid binding resin, to the chow diet caused smaller increases. The highest level of 14DM protein expression was observed in liver, the major site of feedback regulation of HMG-CoA reductase by cholesterol. Taken together, these observations suggest a critical role for 14DM in the feedback regulation of hepatic HMG-CoA reductase.