Economic Evaluation of Internet-Based Interventions for Harmful Alcohol Use Alongside a Pragmatic Randomized Controlled Trial

Background

Internet interventions with and without therapist support have been found to be effective treatment options for harmful alcohol users. Internet-based therapy (IT) leads to larger and longer-lasting positive effects than Internet-based self-help (IS), but it is also more costly to provide.

Objective

To evaluate the cost effectiveness and cost utility of Internet-based interventions for harmful use of alcohol through the assessment of the incremental cost effectiveness of IT compared with IS.

Methods

This study was performed in a substance abuse treatment center in Amsterdam, the Netherlands. We collected data over the years 2008–2009. A total of 136 participants were included, 70 (51%) were female, and mean age was 41.5 (SD 9.83) years. Reported alcohol consumption and Alcohol Use Disorders Identification Test (AUDIT) scores indicated harmful drinking behavior at baseline. We collected self-reported outcome data prospectively at baseline and 6 months after randomization. Cost data were extracted from the treatment center’s cost records, and sex- and age-specific mean productivity cost data for the Netherlands.

Results

The median incremental cost-effectiveness ratio was estimated at €3683 per additional treatment responder and €14,710 per quality-adjusted life-year (QALY) gained. At a willingness to pay €20,000 for 1 additional QALY, IT had a 60% likelihood of being more cost effective than IS. Sensitivity analyses attested to the robustness of the findings.

Conclusions

IT offers better value for money than IS and might therefore be considered as a treatment option, either as first-line treatment in a matched-care approach or as a second-line treatment in the context of a stepped-care approach.

Trial Registration

Netherlands Trial Register NTR-TC1155; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1155 (Archived by WebCite at http://www.webcitation.org/6AqnV4eTU)     

Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: the problem of treatment selection bias

AIMS: In several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial. METHODS AND RESULTS: The study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58%) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37-0.96] and 0.46 (95% CI 0.31-0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95% CI 0.70-1.74) for death and 1.27 (95% CI 0.88-1.85) for death or spontaneous MI. CONCLUSION: The ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies.     

Differential transport of platinum compounds by the human organic cation transporter hOCT2 (hSLC22A2)

Background:

Solute carriers (SLCs), in particular organic cation transporters (OCTs), have been implicated in the cellular uptake of platinum-containing anticancer compounds. The activity of these carriers may determine the pharmacokinetics and the severity of side effects, including neuro- and nephrotoxicity of platinum-based chemotherapy. As decreased drug accumulation is a key mechanism of platinum resistance, SLCs may also contribute to the development of resistance. Here, we define the role of hSLC22A2 (OCT2) in the cellular uptake of platinum compounds.

Experimental approach:

Human embryonic kidney (HEK) 293 cells stably expressing the hSLC22A2 gene (HEK293/hSLC22A2) were used in platinum accumulation studies. Following a 2 h exposure to various platinum compounds (100 µM), intracellular platinum levels were determined by flameless atomic absorption spectrometry.

Key results:

HEK293/hSLC22A2 cells, compared with HEK293/Neo control cells, displayed significant increases in oxaliplatin (28.6-fold), Pt[DACH]Cl₂ (20.6-fold), ormaplatin (8.1-fold), tetraplatin (4.5-fold), transplatin (3.7-fold) and cisplatin (1.3-fold), but not carboplatin. SLC22A2-mediated transport could be inhibited by 1-methyl-4-phenylpyridinium. Furthermore, hSLC22A2-mediated oxaliplatin and cisplatin accumulation was time- and concentration-dependent, but non-saturable. Expression of hSLC22A2 in HEK293 cells resulted in enhanced sensitivity to oxaliplatin (12-fold) and cisplatin (1.8-fold). Although, hSLC22A2 mRNA expression was frequently found in ovarian cancer cell lines, its expression in clinical ovarian cancer specimens (n= 80) was low and did not correlate with the treatment outcome of platinum-based regimens.

Conclusions and implications:

The hSLC22A2 drug transporter is a critical determinant in the uptake and cytotoxicity of various platinum compounds, particularly oxaliplatin.     

Continuous versus intermittent exercise effects on urinary excretion of albumin and total protein

Several studies have reported post-exercise increases of urinary concentrations of plasma proteins. However, under normal conditions, through mechanisms of size and electrical charge selection, the kidney restricts the clearance of molecules as large as albumin. Post-exercise increases in albuminuria occur following the physiological stress of intense exercise, most likely as a result of the exercise induced blood acidity changes which lead to a change in the arrangement of the albumin molecule, and subsequently the filtration characteristics of the glomerular capillary wall. The purpose of the present study was therefore to determine the extent to which different types of exercise could induce a transient condition of post-exercise increases in the urinary output of total protein and albumin. All 14 males, who agreed to participate in the study, performed a continuous and an intermittent cycling protocol on a stationary bicycle ergometer. The results showed that: a) intermittent exercise had a greater influence than continuous exercise on the total output of urine albumin, and of urine total protein; b) concentrations of blood pH and blood lactate, were associated with changes in the clearance of urine albumin and urine total protein. Post-exercise proteinuria response seems to be transient and therefore renal trauma is not suspected at the early stages of observation. Furthermore, these results indicate that the kidney undergoes distinct physiological adjustments during exercise, and that these adjustments are relative to the intensity of the exercise stress.     

Antimicrobial activities of pomegranate rind extracts: enhancement by addition of metal salts and vitamin C

Background

Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course.

Methods/Design

The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis.

Discussion

This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia.

Trial registration

Current Controlled Trials ISRCTN01897462.     

Attenuation of experimental retrograde amnesia through pretraining administration of a dissimilar amnestic agent

Experiment 1 found that pretraining administration of electroconvulsive shock (ECS) attenuated ECS-induced amnesia of one-trial passive avoidance training in rats. Similarly, pretraining injections of cycloheximide (CXM) attenuated the amnestic effects of CXM at training. Experiment 2 demonstrated the ability of pretraining ECS to attenuate CXM-induced amnesia and pretraining CXM to attenuate ECS-induced amnesia. These studies join others in observing comparable behavioral effects of ECS-like amnestic agents and antimetabolite-like amnestic agents despite their different means of primary action. Collectively, these studies support the view that the two families of amnestic agents produce amnesia through a common mechanism.     

A National Study of Veterans Treatment Court Participants: Who Benefits and Who Recidivates

Although there are now over 400 veterans treatment courts (VTCs) in the country, there have been few studies on participant outcomes in functional domains. Using national data on 7931 veterans in the Veterans Affairs (VA) Veterans Justice Outreach program across 115 VA sites who entered a VTC from 2011 to 2015, we examined the housing, employment, income, and criminal justice outcomes of VTC participants; and identified veteran characteristics predictive of outcomes. VTC participants spent an average of nearly a year in the program and 14% experienced a new incarceration. From program admission to exit, 10% more participants were in their own housing, 12% more were receiving VA benefits, but only 1% more were employed. Controlling for background characteristics, a history of incarceration predicted poor criminal justice, housing, and employment outcomes. Participants with property offenses or probation/parole violations and those with substance use disorders were more likely to experience a new incarceration. Participants with more mental health problems were more likely to be receiving VA benefits and less likely to be employed at program exit. Together, these findings highlight the importance of proper substance abuse treatment as well as employment services for VTC participants so that they can benefit from the diversion process.