Effectiveness Of Different Treatment Strategies Research Articles

The effectiveness of different intervention strategies for the prevention of zoonotic metacercariae infection in cultured fish

Fish-borne zoonotic trematodes (FZT) are a major public health problem. It is estimated that in Vietnam 26,366 “disability-adjusted life years” (DALYs) are lost due to FZT. Fish from aquaculture are a main source of protein and of great economic importance in both rural and urban areas. The objective of this study was to compare the impact on transmission of FZT to juvenile fish of drug treatment intervention of final hosts, and pond management interventions on fingerlings produced in nurseries producing Rohu carp in Northern Vietnam. The study design was a parallel group design of nurseries with two intervention groups; a drug treatment of human and animal groups and a farm management group (control of snail vectors and fecal pollution of pond). A third group (non-intervention) served as control. Fish were examined for FZT metacercariae prevalence and intensity before and after interventions, along with density of potential host pond snails. Fecal exams for FZT infections in farm household humans, dogs and cats were also performed. The results showed that although FZT prevalence in fish was not significantly reduced, the intensity of metacercariae in fish from ponds receiving management interventions was reduced 91.7% compared to before interventions. The intensity of FZT was also significantly lower in the pond management group, compared to the drug treatment group and the control group after interventions. The results demonstrate that improving farm and pond management practices can be effective in reducing FZT infections without using drug treatment. This study also highlighted certain obstacles to attaining higher levels of protection for which more research is needed. A major challenge is the ability to completely isolate (or bio-secure) the pond from its surrounding environment, especially surrounding water sources which may harbor snails and cercariae that can contaminate the pond through water resupply or runoff. Another is the unknown risk from piscivorous birds, host for intestinal FZT. The strategies employed in this study now need long-term evaluation on a regional basis, the outcome of which could be the development of good management practices crucial to ensuring a good quality product that benefits farmers and the consumers.

Clinical integration of software tool VEDO for adaptive and quantitative application of phased array hyperthermia in the head and neck

Background and purpose: In Rotterdam, patient-specific hyperthermia (HT) treatment planning (HTP) is applied for all deep head and neck (H&N) HT treatments. In this paper we introduce VEDO (the Visualisation Tool for Electromagnetic Dosimetry and Optimisation), the software tool required, and demonstrate its value for HTP-guided online complaint-adaptive (CA) steering based on specific absorption rate (SAR) optimisation during a H&N HT treatment.Materials and methods: VEDO integrates CA steering, visualisation of the SAR patterns and mean tumour SAR (SARtarget) optimisation in a single screen. The pre-calculated electromagnetic fields are loaded into VEDO. During treatment, VEDO shows the SAR pattern, overlaid on the patients’ CT-scan, corresponding to the actually applied power settings and it can (re-)optimise the SAR pattern to minimise SAR at regions where the patient senses discomfort while maintaining a high SARtarget.Results: The potential of the quantitative SAR steering approach using VEDO is demonstrated by analysis of the first treatment in which VEDO was used for two patients using the HYPERcollar.These cases show that VEDO allows response to power-related complaints of the patient and to quantify the change in absolute SAR: increasing either SARtarget from 96 to 178 W/kg (case 1); or show that the first SAR distribution was already optimum (case 2).Conclusion: This analysis shows that VEDO facilitates a quantitative treatment strategy allowing standardised application of HT by technicians of different HT centres, which will potentially lead to improved treatment quality and the possibility of tracking the effectiveness of different treatment strategies.

Noninvasive visualization of tumor growth in a human colorectal liver metastases xenograft model using bioluminescence in vivo imaging

BackgroundBioluminescence imaging (BLI) is an ideal tool for noninvasive, quantitative monitoring of tumor progression/regression in animal models. The effectiveness of different treatment strategies is displayed by an altered intensity of bioluminescence, demonstrating a change of the tumor burden. The aim of this study was to establish a reliable, reproducible colorectal hepatic metastases cancer animal model. MethodsCells of the human colon carcinoma cell line HCT-116 Lucpos expressing the firefly luciferase enzyme gene were used. HCT-116 Lucpos cells (2.5 × 106) were injected through the portal vein into the liver of immunoincompetent nude mice. BLI was used to analyze intrahepatic tumor burden and growth kinetic. ResultsHCT-116 Lucpos cells demonstrated a progressive and reproducible growth in the liver after intraportal injection. Four days after injection, the animals were analyzed for tumor growth by BLI, and mice without or too low bioluminescence signals were excluded (between 10% and 20% animals). HCT-116 Lucpos intrahepatic tumors responded successfully to different dosages (5 and 10 mg/kg) of 5-fluorouracil. ConclusionsBLI is an important tool with many potential advantages for investigators. The measurement of intrahepatic tumor growth by imaging luciferase activity noninvasively provides valuable information on tumor burden and effectiveness of therapy. Thus, the presented intrahepatic metastases model based on the growth of HCT-116 Lucpos cells is suitable for in vivo testing of different cancer therapy strategies.

Cost Effectiveness of Different Treatment Strategies in the Treatment of Patients with Moderate to Severe Rheumatoid Arthritis in China

BackgroundTo analyse the cost-effectiveness of traditional disease-modifying anti-rheumatic drugs (tDMARDs) compared to biological therapies from the perspective of Chinese society.Methodology/Principal FindingsA mathematical model was developed by incorporating the clinical trial data and Chinese unit costs and treatment sequences from a lifetime perspective. Hypothetical cohorts with moderate to severe RA were simulated. The primary outcome measure–quality-adjusted life years (QALYs)–was derived from disease severity (HAQ scores). Primary analysis included drug costs, monitoring costs, and other costs. Probabilistic and one-way sensitivity analyses were performed. Treatment sequences that included TNF antagonists and rituximab produced a greater number of QALYs than tDMARDs alone or TNF antagonists plus DMARDs. In comparison with tDMARDs, the incremental cost-effectiveness ratios (ICERs) for etanercept, infliximab, and adalimumab without rituximab were $77,357.7, $26,562.4 and $57,838.4 per QALY and $66,422.9, $28,780.6 and $50,937.6 per QALY, for etanercept, infliximab, and adalimumab with rituximab. No biotherapy was cost-effective under the willingness to pay threshold when the threshold was 3 times the per capita GDP of China. When 3 times the per capita GDP of Shanghai used as the threshold, infliximab and rituximab could yield nearly 90% cost-effective simulations in probabilistic sensitivity analysis.Conclusions/SignificancetDMARD was the most cost-effective option in the Chinese healthcare setting. In some relatively developed regions in China, infliximab and rituximab may be a favorable cost-effective alternative for moderate to severe RA.

Stable or not, woman or man: is there a difference?

This editorial refers to ‘Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry’, by P.G. Steg et al. , doi:10.1093/eurheartj/ehs289 In 2010 a dedicated group of researchers interested in women's hearts, gathered in Brussels for a workshop discussing gender differences in cardiovascular disease (CVD).1 The workshop was undertaken as a result of an earlier report the same year from the European Heart Health Strategy (Euro-Heart) project showing that women are still under-represented in many cardiovascular clinical trials.2 Fewer women than men have been included in cardiovascular trials and, consequently, the evidence base is less firm for women regarding several treatments. The mean percentage of women enrolled in cardiovascular clinical trials since 2006 was 30%, while only 50% of trials reported results by gender analysis. Fewer evidence-based preventive, diagnostic, and therapeutic options for women with CVD may lead to undertreatment and a lower quality of care in comparison with men. Prospective studies to elucidate whether there are true differences in the effects of different treatment strategies according to gender and outcome are greatly needed to identify the most appropriate treatment for men and women, respectively ( Table …

Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study

Objective To evaluate the effect of different treatment strategies on enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome.Design Multicentre retrospective case-control study.Setting 23 hospitals in northern Germany.Participants 298 adults with...

Effects of Sequential and Simultaneous Applications of Bacteriophages on Populations of Pseudomonas aeruginosa In Vitro and in Wax Moth Larvae

Interest in using bacteriophages to treat bacterial infections (phage therapy) is growing, but there have been few experiments comparing the effects of different treatment strategies on both bacterial densities and resistance evolution. While it is established that multiphage therapy is typically more effective than the application of a single phage type, it is not clear if it is best to apply phages simultaneously or sequentially. We tried single- and multiphage therapy against Pseudomonas aeruginosa PAO1 in vitro, using different combinations of phages either simultaneously or sequentially. Across different phage combinations, simultaneous application was consistently equal or superior to sequential application in terms of reducing bacterial population density, and there was no difference (on average) in terms of minimizing resistance. Phage-resistant bacteria emerged in all experimental treatments and incurred significant fitness costs, expressed as reduced growth rate in the absence of phages. Finally, phage therapy increased the life span of wax moth larvae infected with P. aeruginosa, and a phage cocktail was the most effective short-term treatment. When the ratio of phages to bacteria was very high, phage cocktails cured otherwise lethal infections. These results suggest that while adding all available phages simultaneously tends to be the most successful short-term strategy, there are sequential strategies that are equally effective and potentially better over longer time scales.

Treatment of haemophilia A and B and von Willebrand’s disease: summary and conclusions of a systematic review as part of a Swedish health‐technology assessment

In an ongoing health-technology assessment of haemophilia treatment in Sweden, performed by the governmental agency Dental and Pharmaceutical Benefits Agency (TLV; tandvårds-och lākemedelsförmånsverket), the Swedish Council on Health Technology Assessment (SBU; statens beredning för medicinsk utvārdering) was called upon to evaluate treatment of haemophilia A and B and von Willebrand's disease (VWD) with clotting factor concentrates. To evaluate the following questions: What are the short-term and long-term effects of different treatment strategies? What methods are available to treat haemophilia patients that have developed inhibitors against factor concentrates? Based on the questions addressed by the project, a systematic database search was conducted in PubMed, NHSEED, Cochrane Library, EMBASE and other relevant databases. The literature search covered all studies in the field published from 1985 up to the spring of 2010. In most instances, the scientific evidence is insufficient for the questions raised in the review. Concentrates of coagulation factors have good haemostatic effects on acute bleeding and surgical intervention in haemophilia A and B and VWD, but conclusions cannot be drawn about possible differences in the effects of different dosing strategies for acute bleeding and surgery. Prophylaxis initiated at a young age can prevent future joint damage in persons with haemophilia. The available treatment options for inhibitors have been insufficiently assessed. The economic consequences of various treatment regimens have been insufficiently analysed. Introduction of national and international registries is important.

P1-S4.17 Interactive demonstration of a model to calculate costs and cost effectiveness of different strategies for chlamydia screening and partner notification

BackgroundWe have developed a model to calculate costs and cost effectiveness of different intervention strategies for chlamydia screening, which can be used by commissioners to evaluate and plan their local service provision. The model and an analysis of national data have been recently published in BMJ. Increasingly, financial constraints will mean that tools such as ours will be vital to provide value for money in healthcare.MethodWe will give a live demonstration of our spreadsheet model using the example from our recent study. We invite delegates to input their own data in real time to a laptop for comparison and testing against the national and international picture. We plan to promote this before the meeting.Main outcome measuresCost effectiveness of screening (as cost per individual tested, cost per positive diagnosis, total cost of screening, number screened, number infected, sex ratio of those tested and treated). We will show how to compare current programmes with a planned change eg, in screening coverage or partner notification efficacy.ResultsIn 2008−2009 screening was estimated to cost £46.3 m and £506 per infection treated. The model results suggest that increasing male screening coverage from 8% to 24% (to match female coverage) would cost an extra £22.9 m and increase the cost per infection treated to £528. Increasing partner notification efficacy from 0.4 to 0.8 partners per index case would cost an extra £3.3 m and reduce the cost per infection diagnosed to £449.ConclusionsThe results are broadly representative of the national picture, but further evaluation of the cost effectiveness of partner notification and screening is urgently needed. We encourage practitioners who want to test this tool in their own setting to contact us (katy.turner@bristol.ac.uk).BMJ2011; 342:c725010.1136/bmj.c7250.

Mineral metabolism management in Canadian peritoneal dialysis patients

Abnormal mineral metabolism is associated with increased morbidity and mortality in dialysis patients. Therefore, the goal of this study was to compare a) mineral metabolism control among a cohort of Canadian peritoneal dialysis (PD) patients to K/DOQI-defined targets and b) the effect of different treatment strategies on mineral metabolism parameters. We looked at a cohort of 317 Canadian PD patients from 9 clinics that used the PhotoGraph™ software program which tracks mineral metabolism management. Serum phosphorus (P), calcium (Ca) and intact parathyroid hormone (iPTH) values were collected for the patients. Data were categorized and analyzed by the type of phosphate binder prescribed, vitamin D use, and dosing and reimbursement criteria for the phosphate binder, sevelamer. The majority of patients achieved K/DOQI-set targets for serum P. Patients who resided in Quebec (QC), which had greater access to sevelamer, had lower mean concentrations of P and Ca, were less likely to take Ca-based phosphate binders (CBBs) exclusively and were exposed to less exogenous Ca than in Ontario (ON). Availability of the phosphate binder sevelamer and reduced doses of elemental Ca were associated with more mineral metabolism parameters within suggested target ranges. Further studies that focus on patient outcomes are warranted.

Impact of a Comprehensive Worksite Wellness Program on Health Risk, Utilization, and Health Care Costs

In 2005, Blue Cross Blue Shield of Kansas City initiated a comprehensive worksite wellness program designed to impact employer culture and to assist healthy employees to stay at low risk and to reduce risk levels for those at moderate or high risk. Fifteen employer groups (9637 employees) participated in the A Healthier You (AHY) program for 3 consecutive years, 2006-2008. The results of health risk appraisals and biometric screening were used to evaluate program impact. Among the 4230 employees (44.0% of eligible employees) who completed health risk appraisals in all 3 years, 85.8% of individuals in the low-risk category in 2006 remained at low risk in 2008. There were also improvements in other risk categories, with 39.9% of those in the medium-risk category and 48.9% of those in the high-risk category in 2006 moving to a lower risk category in 2008. There were improvements in blood pressure control and total cholesterol, but no improvement in weight control. To assess financial and utilization outcomes, claims for the participating employer groups were compared to those for 7 employers (3800 employees) who did not participate in AHY in 2006-2008. Although none of the utilization measures was statistically different, the AHY groups had significantly smaller increases in both overall and emergency room costs per member per month. The AHY program now has over 180 employer groups, which will allow future evaluations to examine the impact of the program on a much larger population and to focus on the comparative effectiveness of different intervention strategies across implementations.

The cost effectiveness of radon mitigation in existing German dwellings – A decision theoretic analysis

Radon is a naturally occurring inert radioactive gas found in soils and rocks that can accumulate in dwellings, and is associated with an increased risk of lung cancer. This study aims to analyze the cost effectiveness of different intervention strategies to reduce radon concentrations in existing German dwellings. The cost effectiveness analysis (CEA) was conducted as a scenario analysis, where each scenario represents a specific regulatory regime. A decision theoretic model was developed, which reflects accepted recommendations for radon screening and mitigation and uses most up-to-date data on radon distribution and relative risks. The model was programmed to account for compliance with respect to the single steps of radon intervention, as well as data on the sensitivity/specificity of radon tests. A societal perspective was adopted to calculate costs and effects. All scenarios were calculated for different action levels. Cost effectiveness was measured in costs per averted case of lung cancer, costs per life year gained and costs per quality adjusted life year (QALY) gained. Univariate and multivariate deterministic and probabilistic sensitivity analyses (SA) were performed. Probabilistic sensitivity analyses were based on Monte Carlo simulations with 5000 model runs. The results show that legal regulations with mandatory screening and mitigation for indoor radon levels >100 Bq/m 3 are most cost effective. Incremental cost effectiveness compared to the no mitigation base case is 25,181 € (95% CI: 7371 €–90,593 €) per QALY gained. Other intervention strategies focussing primarily on the personal responsibility for screening and/or mitigative actions show considerably worse cost effectiveness ratios. However, targeting radon intervention to radon-prone areas is significantly more cost effective. Most of the uncertainty that surrounds the results can be ascribed to the relative risk of radon exposure. It can be concluded that in the light of international experience a legal regulation requiring radon screening and, if necessary, mitigation is justifiable under the terms of CEA.

Glucose Control is Associated With Patient Survival in Diabetic Patients After Renal Transplantation

The efficacy of tight glycemic control for the prevention of death and renal failure in the general diabetic population is well established. However, in diabetic renal-allograft recipients, the effect of different treatment strategies on outcomes is undetermined. We conducted a cohort study of 798 diabetic, renal-allograft recipients transplanted at the Medical University of Vienna between 1990 and 2004. We studied the influence of glucose parameters and diabetes treatment on mortality and graft loss. Marginal-structural models and multivariable Cox regression analysis were used to control for confounding. Maximal glucose levels but not HbA1c were independently associated with mortality. Being in the highest quartile of maximal glucose increased the adjusted risk of death by a factor of 2.2 (P value for trend 0.009). Furthermore, in patients receiving insulin, the risk of death was increased 1.7-fold (95% confidence interval 0.9-3.1) compared with diet and 2.0-fold (95% confidence interval 1.1-3.7) compared with oral medication. Maximal glucose, HbA1c, or diabetes treatment did not influence death-censored functional graft survival. In conclusion, maximal glucose levels and insulin treatment were independently associated with higher rates of mortality in our cohort of diabetic, renal-allograft recipients. However, graft survival was unaffected.

A model of tuberculosis transmission and intervention strategies in an urban residential area

The model herein aims to explore the dynamics of the spread of tuberculosis (TB) in an informal settlement or township. The population is divided into households of various sizes and also based on commuting status. The model dynamics distinguishes between three distinct social patterns: the exposure of commuters during travel, random diurnal interaction and familial exposure at night. Following the general SLIR models, the population is further segmented into susceptible (S), exposed/latently infected (L), active/infectious (I), and recovered (R) individuals. During the daytime, commuters travel on public transport, while non-commuters randomly interact in the community to mimic chance encounters with infectious persons. At night, each family interacts and sleeps together in the home. The risk of exposure to TB is based on the proximity, duration, and frequency of encounters with infectious persons. The model is applied to a hypothetical population to explore the effects of different intervention strategies including vaccination, wearing of masks during the commute, prophylactic treatment of latent infections and more effective case-finding and treatment. The most important findings of the model are: (1) members of larger families are responsible for more disease transmissions than those from smaller families, (2) daily commutes on public transport provide ideal conditions for transmission of the disease, (3) improved diagnosis and treatment has the greatest impact on the spread of the disease, and (4) detecting TB at the first clinic visit, when patients are still smear negative, is key.

Evaluation of medical and health economic effectiveness of non-pharmacological secondary prevention of coronary heart disease.

Evaluation of medical and health economic effectiveness of non-pharmacological secondary prevention of coronary heart disease.

A Three-dimensional Method for Evaluating Changes in Acetabular Osteolytic Lesions in Response to Treatment

The treatment of asymptomatic osteolysis among well-fixed cementless cups remains controversial. To compare the effectiveness of different treatment strategies, an objective technique for evaluating bone remodeling would be useful. By matching and comparing serial CT images with the aid of a computer-assisted imaging program, we developed a method to evaluate three-dimensional mineralization changes within osteolytic defects. Preoperative, immediate postoperative, and followup CT images were normalized based on a phantom with known densities and matched using image registration so that the same region could be analyzed on each image. New bone mineralization within the preoperative osteolytic lesion volume was quantified based on a patient-specific trabecular bone density threshold. As a pilot study, we applied this technique in 10 patients treated by polyethylene liner exchange with débridement and grafting of periacetabular osteolytic lesions using a calcium sulfate bone graft substitute. Relative to the preoperative osteolytic lesion volume, an average of 43% (range, 8%-72%) of each defect was filled with graft at revision. After resorption of the graft, an average of 24% (range, 9%-44%) of the original defect volume demonstrated evidence of new mineralization at 1-year followup. The amount of new mineralization was directly proportional (r(2) = 0.70) to the defect filling achieved at revision. CT-based image analysis offers an objective method for quantifying three-dimensional bone remodeling and can be used to evaluate the effectiveness of osteolysis treatment strategies. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Validation of intervention strategies to control Escherichia coli O157:H7 and Salmonella typhimurium DT 104 in mechanically tenderized and brine-enhanced beef.

After three different outbreaks were linked to the consumption of nonintact meat products contaminated with Escherichia coli O157:H7, the U.S. Department of Agriculture, Food Safety and Inspection Service published notice requiring establishments producing mechanically tenderized and moisture-enhanced beef products to reassess their respective hazard analysis and critical control point system, due to potential risk to the consumers. The purpose of this study was to determine the effectiveness of different intervention strategies (lactic acid, lactic acid bacteria, and acidified sodium chlorite) to control E. coli O157:H7 and Salmonella enterica serotype Typhimurium definitive phage type 104 in mechanically tenderized and brine-enhanced beef strip loins when applied to the steaks prior to packaging and shipment for processing. After the mechanical process, translocation of E. coli O157:H7 and Salmonella Typhimurium DT 104 from the surface into the internal muscles occurred at levels between 2.0 and 4.0 log CFU/g (from an initial inoculation level of 5.0 log) after mechanical tenderization, and at levels of 1.0 to 3.0 log CFU/g after injection, with all the interventions consistently presenting lower microbial counts (P < 0.05) than did the controls. Lactic acid bacteria reduced internal E. coli O157:H7 loads 1.2 to > 2.2 log cycles, while the acidified sodium chlorite and lactic acid reduced them between 0.8 and 3.0 log, respectively. Salmonella Typhimurium DT 104 was also reduced internally after application of all interventions between 0.9 and 2.2 log. The application of antimicrobials to the steaks prior to packaging and shipment on day 0 was effective in reducing internalization of both pathogens in nonintact beef products stored for both 14 and 21 days.

Editor’s Choice

Editor’s Choice

Effect of Small‐World Networks on Epidemic Propagation and Intervention

The small‐world network, characterized by special structural properties of high connectivity and clustering, is one of the highlights in recent advances in network science and has the potential to model a variety of social contact networks. In an attempt to better understand how these structural properties of small‐world networks affect epidemic propagation and intervention, this article uses an agent‐based approach to investigate the interplay between an epidemic process and its underlying network structure. Small‐world networks are derived from a network “rewiring” process, which readjusts edges in a completely regular two‐dimensional network by different rewiring probabilities (0–1) to produce a spectrum of modified networks on which an agent‐based simulation of epidemic propagation can be conducted. A comparison of simulated epidemics discloses the effect of small‐world networks on epidemic propagation as well as the effectiveness of different intervention strategies, including mass vaccination, acquaintance vaccination, targeted vaccination, and contact tracing. Epidemics taking place on small‐world networks tend to reach large‐scale epidemic peaks within a short time period. Among the four intervention strategies tested, only one strategy—the targeted vaccination—proves to be effective for containing epidemics, a finding supported by a simulation of the severe acute respiratory syndrome epidemic in a large‐scale realistic social contact network in Portland, OR.

Clinical Implications of Antiretroviral Pharmacokinetics and Pharmacodynamics in the CNS

The prevalence of HIV-associated brain disease remains high in the combination antiretroviral era. Factors associated with the development of HIV-associated neurocognitive impairment remain poorly understood. The selection of an antiretroviral regimen that can successfully penetrate the CNS compartment and control cerebrospinal fluid HIV replication may prove a crucial strategy in preventing the emergence and progression of HIV-associated neurocognitive impairment. Different antiretroviral agents and drug classes vary in their ability to penetrate the CNS. In this review, data on the CNS penetration of antiretrovirals are evaluated, including the clinical studies examining their relevance. Prospective studies examining the effect of different treatment strategies on CNS clinical outcomes are needed.