Cumulative Index

Diffuse liver disease is a growing problem and a major cause of death worldwide. In the final stages the treatment often involves liver resection or transplant and in deciding what course of action is to be taken it is crucial to have a correct assessment of the function of the liver. The current “gold standard” for this assessment is to take a liver biopsy which has a number of disadvantages. As an alternative, a method involving magnetic resonance imaging and mechanistic modeling of the liver has been developed at Linköping University. One of the obstacles for this method to overcome in order to reach clinical implementation is the speed of the parameter estimation. In this project the methodology of metamodeling is tested as a possible solution to this speed problem. Metamodeling involve making models of models using extensive model simulations and mathematical tools. With the use of regression methods, clustering algorithms, and optimization, different methods for parameter estimation have been evaluated. The results show that several, but not all, of the parameters could be accurately estimated using metamodeling and that metamodeling could be a highly useful tool when modeling biological systems. With further development, metamodeling could bring this non-invasive method for estimation of liver function a major step closer to application in the clinic

The spread of antimalarial drug resistance: A mathematical model with practical implications for ACT drug policies

Most malaria-endemic countries are implementing a change in antimalarial drug policy to artemisinin combination therapy (ACT). The impact of different drug choices and implementation strategies is uncertain. A comprehensive model was constructed incorporating important epidemiological and biological factors and used to illustrate the spread of resistance in low and high transmission settings. The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and that in low transmission areas ACTs slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. A major obstacle to achieving the benefits of high coverage is the current cost of the drugs. This argues strongly for a global subsidy to make ACTs generally available and affordable in endemic areas

Intermittent Presumptive Treatment for Malaria

A better understanding of the pharmacodynamics of intermittent presumptive treatment, says White, will guide more rational policymakin

The use of "no evidence" statements in public health

Public health communication makes extensive use of a linguistic formulation that will be called the "no evidence" statement. This is a written or spoken statement of the form "There is no evidence that P" where P stands for a proposition that typically describes a human health risk. Danger lurks in these expressions for the hearer or reader who is not logically perspicacious, as arguments that use them are only warranted under certain conditions. The extent to which members of the public are able to determine what those conditions are will be considered by examining data obtained from 879 subjects. The role of "no evidence" statements as cognitive heuristics in public health reasoning is considered

Is the HCV-HIV co-infection prevalence amongst injecting drug users a marker for the level of sexual and injection related HIV transmission?

BACKGROUND: Amongst injecting drug users (IDUs), HIV is transmitted sexually and parenterally, but HCV is transmitted primarily parenterally. We assess and model the antibody prevalence of HCV amongst HIV-infected IDUs (denoted as HCV-HIV co-infection prevalence) and consider whether it proxies the degree of sexual HIV transmission amongst IDUs. METHODS: HIV, HCV and HCV-HIV co-infection prevalence data amongst IDU was reviewed. An HIV/HCV transmission model was adapted. Multivariate model uncertainty analyses determined whether the model's ability to replicate observed data trends required the inclusion of sexual HIV transmission. The correlation between the model's HCV-HIV co-infection prevalence and estimated proportion of HIV infections due to injecting was evaluated. RESULTS: The median HCV-HIV co-infection prevalence (prevalence of HCV amongst HIV-infected IDUs) was 90% across 195 estimates from 43 countries. High HCV-HIV co-infection prevalences (>80%) occur in most (75%) settings, but can be lower in settings with low HIV prevalence (0.75). The model without sexual HIV transmission reproduced some data trends but could not reproduce any epidemics with high HIV/HCV prevalence ratios (>0.85) or low HCV-HIV co-infection prevalence (10%. The model with sexual HIV transmission reproduced data trends more closely. The proportion of HIV infections due to injecting correlated with HCV-HIV co-infection prevalence; suggesting that up to 80/60/90%. CONCLUSION: Substantial sexual HIV transmission may occur in many IDU populations; HCV-HIV co-infection prevalence could signify its importance

Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda.

BACKGROUND: Since drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation of the cluster randomized trial. METHODS: A survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district, central Uganda. A cluster was defined as a parish representing a cluster of drug shops. Data was collected using two structured questionnaires: a provider questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received. RESULTS: Among febrile patients seen at drug shops, 35% had a positive RDT result and 27% had a positive blood slide. Many patients (55%) had previously sought care from another drug shop prior to this consultation. Three quarters (73%) of all febrile patients seen at drug shops received an anti-malarial, of whom 39% received an ACT and 33% received quinine. The rest received another non-artemisinin monotherapy. Only one third (32%) of patients with a positive blood slide had received treatment with Coartem® while 34% of those with a negative blood slide had not received an anti-malarial. Overall appropriate treatment was 34 (95% CI: 28 - 40) with substantial between-cluster variation, ranging from 1% to 55%. CONCLUSION: In this setting, the proportion of malaria patients receiving appropriate ACT treatment at drug shops was low. This was due to the practice of presumptive treatment, inadequate training on malaria management and lack of knowledge that Coartem® was the recommended first-line treatment for malaria. There is urgent need for interventions to improve treatment of malaria at these outlets