Menoci: lightweight extensible web portal enhancing data management for biomedical research projects.

BACKGROUND: Biomedical research projects deal with data management requirements from multiple sources like funding agencies' guidelines, publisher policies, discipline best practices, and their own users' needs. We describe functional and quality requirements based on many years of experience implementing data management for the CRC 1002 and CRC 1190. A fully equipped data management software should improve documentation of experiments and materials, enable data storage and sharing according to the FAIR Guiding Principles while maximizing usability, information security, as well as software sustainability and reusability. RESULTS: We introduce the modular web portal software menoci for data collection, experiment documentation, data publication, sharing, and preservation in biomedical research projects. Menoci modules are based on the Drupal content management system which enables lightweight deployment and setup, and creates the possibility to combine research data management with a customisable project home page or collaboration platform. CONCLUSIONS: Management of research data and digital research artefacts is transforming from individual researcher or groups best practices towards project- or organisation-wide service infrastructures. To enable and support this structural transformation process, a vital ecosystem of open source software tools is needed. Menoci is a contribution to this ecosystem of research data management tools that is specifically designed to support biomedical research projects.

Optimising magnetic resonance imaging-based evaluation of the ossification of the medial clavicular epiphysis: a multi-centre study.

Evaluation of the ossification of the medial clavicular epiphysis plays a key role in forensic age estimation, particularly in determining whether the age of 18 has been attained. A key research objective in the forensic age estimation field at present is to establish non-X-ray methods for investigating the clavicle. This paper looks at the use of magnetic resonance imaging for evaluating the developmental state of the medial clavicular epiphysis. Clavicle specimens obtained from autopsies of 125 female and 270 male subjects aged from 10 to 30 were examined using a 3-T magnetic resonance scanner. One FFE-3D-T1 gradient echo sequence and one 2D-T2 turbo spin echo sequence were acquired. In each case, two investigators undertook a consensual determination of the ossification stage of the medial clavicular epiphysis using recognised classification systems. To determine intra-observer and inter-observer agreement, 80 clavicle specimens were subjected to repeat evaluation. We present statistics relating to the ossification stages. The inclusion of established sub-stages of clavicular ossification offers an additional option for determining whether a subject has attained the age of 18 which is applicable in both sexes. For both sexes, the minimum ages for ossification stages 4 and 5 allow conclusions to be drawn about a subject's age at a point in time lying several years in the past. Magnetic resonance imaging is a valid investigatory procedure for determining the ossification stage of the medial clavicular epiphysis. This paper makes a contribution to expanding the range of methods available for forensic age estimation.

Surprising prenatal toxicity of epidermal lipoxygenase-3.

Metabolites of the epidermal lipoxygenase-3 (eLOX-3) are involved in various metabolic pathways. Most unexpectedly, intra-amniotic delivery of eLOX-3 to mice at gestational day 14.5, both via an adenoviral vector and as recombinant protein, resulted in fetal growth restriction and intrauterine death. Periodic acid-Schiff staining and RT-PCR analysis of placentae from fetuses exposed to eLOX-3 indicated a lack of glycogen trophoblasts in the junctional zone. Placenta-specific gene expression was altered. Thus, the observed prenatal toxicity of eLOX-3 could be due to a strong effect on placental development.

Strength and endurance training in the treatment of lung cancer patients in stages IIIA/IIIB/IV.

PURPOSE: This randomized controlled trial tested the effects of a specially designed strength and endurance training on the independence and quality of life in lung cancer patients in stages IIIA/IIIB/IV during palliative chemotherapy. METHODS: Between August 2010 and December 2011, 46 patients were randomized into two groups receiving either conventional physiotherapy or special physiotherapeutic training. The Barthel Index served as primary endpoint. The secondary endpoints were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ C-30/LC-13) questionnaire, the 6-Minute Walk Test (6MWT), stair walking, the Modified Borg Scale, and muscle strength. Nonparametrical data were analyzed with the Wilcoxon and Mann-Whitney U test. For parametric, data student t tests were used. A p value of ≤.05 was accepted. RESULTS: Twenty-nine patients completed the trial (Intervention group (IG), n = 18; control group (CG), n = 11). Significant differences were detectable in the Barthel Index (IGmean = 92.08; CGmean = 81.67; p = .041), in single scores of the EORTC QLQ C-30/LC-13 questionnaire (physical functioning, p = .025; hemoptysis, p = .019; pain in arms or shoulder, p = .048; peripheral neuropathy, p = .050; cognitive functioning, p = .050), in the 6MWT, stair walking, strength capacity, and in the patient's dyspnoea perception during submaximal walking activities (IG > CG). CONCLUSION: According to these findings, lung cancer patients should receive enhanced physical activity intervention during palliative chemotherapy.

Self-sampling in the diagnosis of recurrent vulvovaginal candidosis.

OBJECTIVE: This study aimed to determine the accuracy and feasibility of self-sampling in patients suspected of having recurrent vulvovaginal candidosis (RVC). MATERIALS AND METHODS: Of 441 patients with symptoms suggestive of RVC presenting during an 8-year period (January 2000 to December 2007) at a dermatology clinic, 277 were instructed to perform weekly vaginal self-sampling for a period of up to 8 weeks. Demographic charactervistics, medical history, physical examination, culture results, and therapeutic efficacy were analyzed with Fisher exact, χ test, or Student t test. RESULTS: When only considering the results of the culture taken at consultation, 17.1% (20/117) of RVC cases could be confirmed. Positive cultures from self-sampling confirmed another 97 cases of RVC (82.9%). The sensitivity of a single Candida culture ranged from 18% to 53%, depending on the cutoff level of growth intensity of the yeast recovered. Specificity ranged from 97% to 100%, and the positive predictive value ranged from 92% to 100%. The number of positive cultures obtained was not associated with the duration of earlier vaginal complaints or with the efficacy of prophylactic treatment. Prophylactic treatment was equally effective in patients taking fluconazole once (8/13, 61.5%) or twice (48/74, 64.9%) a month, but treatment regimes were not randomized. CONCLUSIONS: The diagnosis of RVC can be improved dramatically by self-sampling, enabling a sooner start of adequate treatment. Multiple positive cultures were not associated with disease of longer duration or more severe disease and did not influence the response to prophylactic treatment.

Patients with cervical cancer: why did screening not prevent these cases?

OBJECTIVE: The objective of the study was to assess the screening history of women with cervical cancer and review normal cervical smears 5 years preceding the diagnosis. STUDY DESIGN: Cytological and histological results of 401 women treated for invasive cervical cancer between 1991 and 2008 at the Radboud University Nijmegen Medical Center were studied. Ninety-eight normal smears were reviewed. RESULTS: Of the 401 women, 269 (67%) received at least 1 invitation for the national screening program for cervical cancer (NCSP). One- third fell outside the target age of the NCSP. Seventeen percent never responded to the invitation(s). Twenty-one percent had 1 or more normal smears within 5 years preceding the diagnosis. After review, only 39% of those smears were reviewed as a normal smear. CONCLUSION: Half of the women with cervical cancer were never screened because of the limited target age range or nonattendance. Twenty-one percent had a normal smear within 5 years preceding the diagnosis, caused by interpretation and/or sampling errors.

[Illustrations of visceral referred pain. "Head-less" Head's zones]. / Illustrationen zum übertragenen Schmerz. Wie viel von Head steckt in den Head-Zonen?

Reviewing anatomical, physiological and neurological standard literature for illustrations of referred visceral pain only one type of illustration can frequently be found, which is referred to as Treves and Keith. In fact, the original illustration as a model for most current pictures stems from the German edition of Sir Frederick Treves' famous book "Surgical Applied Anatomy" from 1914, which was reillustrated for didactical reasons for the German readership. While neither Treves and Keith nor the German illustrator Otto Kleinschmidt ever published any work on referred pain this illustration must have been adapted or copied from older sources by the illustrator. Therefore the comprehensive systematic original works before 1914 were reviewed, namely those of Sir Henry Head and Sir James Mackenzie. Due to the name of the phenomenon in the German literature of Head's zones, the illustrations were expected to be based mainly on Head's work. However, a comparison of all available illustrations led to the conclusion that Kleinschmidt chiefly used information from Mackenzie as a model for his illustration. Due to the inexact reproduction of Mackenzie's work by the illustrator some important features were lost that had been reported by the original authors. These include the phenomenon of Head's maximum points, which nowadays has fallen into oblivion.Therefore current charts, based on the illustration by Kleinschmidt from 1914, lack experimental evidence and appear to be a simplification of the observational results of both Head's and Mackenzie's original systematic works.

Anthropometric approximation of body weight in unresponsive stroke patients.

BACKGROUND AND PURPOSE: Thrombolysis of acute ischaemic stroke is based strictly on body weight to ensure efficacy and to prevent bleeding complications. Many candidate stroke patients are unable to communicate their body weight, and there is often neither the means nor the time to weigh the patient. Instead, weight is estimated visually by the attending physician, but this is known to be inaccurate. METHODS: Based on a large general population sample of nearly 7000 subjects, we constructed approximation formulae for estimating body weight from simple anthropometric measurements (body height, and waist and hip circumference). These formulae were validated in a sample of 178 consecutive inpatients admitted to our stroke unit, and their accuracy was compared with the best visual estimation of two experienced physicians. RESULTS: The simplest formula gave the most accurate approximation (mean absolute difference 3.1 (2.6) kg), which was considerably better than the best visual estimation (physician 1: 6.5 (5.2) kg; physician 2: 7.4 (5.7) kg). It reduced the proportion of weight approximations mismatched by >10% from 31.5% and 40.4% (physicians 1 and 2, respectively) to 6.2% (anthropometric approximation). Only the patient's own estimation was more accurate (mean absolute difference 2.7 (2.4) kg). CONCLUSIONS: By using an approximation formula based on simple anthropometric measurements (body height, and waist and hip circumference), it is possible to obtain a quick and accurate approximation of body weight. In situations where the exact weight of unresponsive patients cannot be ascertained quickly, we recommend using this approximation method rather than visual estimation.

Assessing contaminant sensitivity of endangered and threatened aquatic species: part III. Effluent toxicity tests.

Toxicity tests using standard effluent test procedures described by the U.S. Environmental Protection Agency were conducted with Ceriodaphnia dubia, fathead minnows (Pimephales promelas), and seven threatened and endangered (listed) fish species from four families: (1) Acipenseridae: shortnose sturgeon (Acipenser brevirostrum); (2) Catostomidae; razorback sucker (Xyrauchen texanus); (3) Cyprinidae: bonytail chub (Gila elegans), Cape Fear shiner (Notropis mekistocholas) Colorado pikeminnow (Ptychocheilus lucius), and spotfin chub (Cyprinella monacha); and (4) Poecillidae: Gila topminnow (Poeciliopsis occidentalis). We conducted 7-day survival and growth studies with embryo-larval fathead minnows and analogous exposures using the listed species. Survival and reproduction were also determined with C. dubia. Tests were conducted with carbaryl, ammonia--or a simulated effluent complex mixture of carbaryl, copper, 4-nonylphenol, pentachlorophenol and permethrin at equitoxic proportions. In addition, Cape Fear shiners and spotfin chub were tested using diazinon, copper, and chlorine. Toxicity tests were also conducted with field-collected effluents from domestic or industrial facilities. Bonytail chub and razorback suckers were tested with effluents collected in Arizona whereas effluent samples collected from North Carolina were tested with Cape Fear shiner, spotfin chub, and shortnose sturgeon. The fathead minnow 7-day effluent test was often a reliable estimator of toxic effects to the listed fishes. However, in 21 % of the tests, a listed species was more sensitive than fathead minnows. More sensitive species results varied by test so that usually no species was always more or less sensitive than fathead minnows. Only the Gila topminnow was consistently less sensitive than the fathead minnow. Listed fish species were protected 96% of the time when results for both fathead minnows and C. dubia were considered, thus reinforcing the value of standard whole-effluent toxicity tests using those two species. If the responses of specific listed species are important for management decisions, our study supports the value in developing culture and testing procedures for those species.

Assessing contaminant sensitivity of endangered and threatened aquatic species: part I. Acute toxicity of five chemicals.

Assessment of contaminant impacts to federally identified endangered, threatened and candidate, and state-identified endangered species (collectively referred to as "listed" species) requires understanding of a species' sensitivities to particular chemicals. The most direct approach would be to determine the sensitivity of a listed species to a particular contaminant or perturbation. An indirect approach for aquatic species would be application of toxicity data obtained from standard test procedures and species commonly used in laboratory toxicity tests. Common test species (fathead minnow, Pimephales promelas; sheepshead minnow, Cyprinodon variegatus; and rainbow trout, Oncorhynchus mykiss) and 17 listed or closely related species were tested in acute 96-hour water exposures with five chemicals (carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin) representing a broad range of toxic modes of action. No single species was the most sensitive to all chemicals. For the three standard test species evaluated, the rainbow trout was more sensitive than either the fathead minnow or sheepshead minnow and was equal to or more sensitive than listed and related species 81% of the time. To estimate an LC50 for a listed species, a factor of 0.63 can be applied to the geometric mean LC50 of rainbow trout toxicity data, and more conservative factors can be determined using variance estimates (0.46 based on 1 SD of the mean and 0.33 based on 2 SD of the mean). Additionally, a low- or no-acute effect concentration can be estimated by multiplying the respective LC50 by a factor of approximately 0.56, which supports the United States Environmental Protection Agency approach of multiplying the final acute value by 0.5 (division by 2). When captive or locally abundant populations of listed fish are available, consideration should be given to direct testing. When direct toxicity testing cannot be performed, approaches for developing protective measures using common test species toxicity data are available.

Cost of treatment for onychomycosis. Data from a 9-month observational study.

OBJECTIVES: To estimate component and total costs of treatment and to examine differences in cost and cost effectiveness between oral antifungal medication and local therapy for patients with toenail onychomycosis. DESIGN: Prospective, observational study of patients with onychomycosis who visited dermatologists and podiatrists in the US. Physicians provided data on clinical management, disease severity, nail improvement and resource utilisation. Patients completed questionnaires on resource utilisation and symptoms at base-line, 4 and 9 months. To estimate costs, reported utilisation was multiplied by unit costs expressed in 1997 US dollars ($US) and derived in 2 ways: first, using Medicare fees; and second, using standard physician fees. RESULTS: After adjustment for key demographic and clinical variables, participants receiving oral medication had higher total costs based on standard fees ($US794 vs $US575) and medication costs ($US564 vs $US109), lower procedure costs ($US0 vs $US122) and physician visit costs ($US200 vs $US330), and greater clinical effectiveness as measured by global improvement rating (86 vs 35%) and Toenail Symptom Index (94 vs 49%). For participants receiving oral medication, 90% of total costs were incurred during the first 4 months of follow-up, whereas for those receiving local therapy, costs were more evenly distributed throughout the study period. Incremental cost-effectiveness analysis showed $US304 to $US491 per additional case improved with oral medication over a 9-month timeframe. Extrapolation of these results using 2 time-points (months 4 and 9) suggested that cost equivalence would be reached 17 to 21 months following the initiation of treatment. CONCLUSIONS: During 9 months of follow-up in patients with toenail onychomycosis, the use of oral antifungal medication resulted in superior patient outcomes, but at higher total cost compared with local therapy.

Relationship of first-year costs of treating localized prostate cancer to initial choice of therapy and stage at diagnosis: results from the CAPSURE database.

OBJECTIVES: To determine the relationship among the initial choice of therapy, stage at presentation, and first-year treatment costs in men with newly diagnosed localized prostate cancer. METHODS: First-year resource use and clinical data were collected for 235 subjects with newly diagnosed localized prostate cancer. The costs were estimated from the standard Medicare payment schedules. The relationship among the initial therapy, stage at presentation, and overall cost was examined for the entire cohort and in the subgroup of patients who underwent radical prostatectomy. In addition, the inpatient, outpatient, and medication cost components were evaluated separately to determine what influenced the changes in cost by stage. RESULTS: The mean first-year cost of treating localized prostate cancer in CaPSURE was $6375. When broken down by stage, the mean first-year cost for patients with Stage T1c was $5731, with T2a/b was $6426, and with Stage T2c was $6810 (P = 0.059). The initial treatment choice was significantly associated with the total first-year costs (P <0.001). The mean cost specifically for radical prostatectomy patients with Stage T1c disease was $6881, with T2a/b was $7216, and with T2c was $8027 (P = 0.004). The increases in the first-year cost with higher stage appeared to primarily be associated with increased inpatient resource use and the greater use of adjuvant hormonal therapy. CONCLUSIONS: The first-year costs of treating localized prostate cancer in CaPSURE are associated with the choice of primary and adjuvant therapy. This supports the notion that cost savings may be possible with earlier detection of disease or by minimizing the use of hormonal adjuvant therapy.

An economic evaluation of a chlorhexidine chip for treating chronic periodontitis: the CHIP (chlorhexidine in periodontitis) study.

BACKGROUND: The authors previously suggested that an adjunctive, controlled-release chlorhexidine, or CHX, chip may reduce periodontal surgical needs at little additional cost. This article presents an economic analysis of the CHX chip in general dental practice. METHODS: In a one-year prospective clinical trial, 484 chronic periodontitis patients in 52 general practices across the United States were treated with either scaling and root planing, or SRP, plus any therapy prescribed by treating, unblinded dentists; or SRP plus other therapy as above but including the CHX chip. Economic data were collected from bills, case report forms and 12-month treatment recommendations from blinded periodontist evaluators. RESULTS: Total dental charges were higher for SRP + CHX chip patients vs. SRP patients when CHX chip costs were included (P = .027) but lower when CHX chip costs were excluded (P = .012). About one-half of the CHX chip acquisition cost was offset by savings in other charges. SRP + CHX chip patients were about 50 percent less likely to undergo surgical procedures than were SRP patients (P = .021). At the end of the trial, periodontist evaluators recommended similar additional procedures for both groups: SRP, about 46 percent; maintenance, about 37 percent; surgery, 56 percent for SRP alone and 63 percent for SRP + CHX chip. CONCLUSIONS: Adjunctive CHX chip use for general-practice patients with periodontitis increased costs but reduced surgeries over one year. At study's end, periodontists recommended similar additional surgical treatment for both groups. CLINICAL IMPLICATIONS: In general practice, routine use of the CHX chip suggests that costs will be partially offset by reduced surgery over at least one year.

Induction of lung fibroblast apoptosis by soluble fibronectin peptides.

Despite the importance of fibroproliferative lung disorders, no safe and effective therapies exist for reducing the size of the fibroblast population in existing fibrotic lesions. Recent work suggests that therapies that promote fibroblast apoptosis during the repair phase following lung injury may facilitate lung repair by eliminating excess fibrotic tissue. We report here our finding that three soluble fibronectin peptides (RGD, CS-1, and FN-C/H-V) induce apoptosis in lung fibroblasts. Fibroblast susceptibility to these peptides was dose and time dependent, with a maximal effect observed at 96 h (87 +/- 16% [mean +/- SEM] apoptosis). The peptides were able to induce fibroblast apoptosis in fibrin gels, an in vitro model of early fibroproliferative lesions. Fibroblasts were difficult to kill. All three peptides were required for maximal apoptosis of anchored cells. Apoptosis occurred by disruption of adhesion (anoikis). Treatment of fibroblasts with peptides caused proteolysis of pp125FAK, a tyrosine kinase involved in integrin-mediated signaling related to cell survival. These data show that soluble fibronectin peptides trigger nontransformed fibroblast apoptosis in routine culture and in fibrin gels by a mechanism that includes disruption of an integrin-mediated survival signaling pathway. The use of small fibronectin peptides to promote fibroblast apoptosis warrants further study as possible antifibrotic therapy.

An economic evaluation of levofloxacin versus cefuroxime axetil in the outpatient treatment of adults with community-acquired pneumonia.

OBJECTIVE: To examine treatment costs of community-acquired pneumonia (CAP) in adult outpatients given oral (p.o.) levofloxacin or cefuroxime axetil as initial therapy. STUDY DESIGN: Patients with a primary diagnosis of CAP were enrolled in a multicenter, prospective, randomized, open-label, active-controlled Phase III clinical trial. Both inpatients and outpatients were assigned to 1 of 2 treatment groups: (1) intravenous (i.v.) or p.o. levofloxacin; or (2) i.v. ceftriaxone and/or p.o. cefuroxime axetil. METHODS: To make legitimate and meaningful cost comparisons between similar types of patients receiving drugs via the same route of administration (i.e., orally), this outpatient economic study examined the resource utilization of the 211 patients enrolled as outpatients who received oral formulations as initial treatment (levofloxacin, 103 patients; cefuroxime axetil, 108 patients). Resource utilization data and clinical trial data were collected concurrently. To generate cost estimates, Medicare cost estimates for resources were multiplied by the resource units used by patients in each treatment arm. RESULTS: Cost estimates indicated a total cost difference that favored the levofloxacin group (base case: $169; sensitivity analysis: $223 [P = .008]). The results for the base case were not significant (P = .094). In addition, within the cost categories, there was a statistically significant study drug cost differential favoring levofloxacin ($86; P = .0001 for both the base case and sensitivity analysis). CONCLUSION: Oral levofloxacin is less costly than oral cefuroxime axetil in the outpatient treatment of adults with CAP.

Functional role of cyclin A on induction of fibroblast apoptosis due to ligation of CD44 matrix receptor by anti-CD44 antibody.

Ligation of cell surface matrix adhesion receptors such as integrins can increase expression of specific cell cycle regulatory proteins such as cyclin A, thereby regulating cell cycle progression. Disruption of cell surface matrix receptor interaction with the extracellular matrix can trigger apoptosis. Induction of apoptosis has been linked to unscheduled up-regulation of cyclin A and activation of cyclin-A-associated dependent kinase 2 activity due to cleavage of cyclin-dependent kinase inhibitors by caspases. We have found that ligation of the cell surface matrix adhesion receptor CD44 by anti-CD44 antibody induces cell detachment and triggers apoptosis. In this report we show that ligation of CD44 by anti-CD44 antibody increases the expression of cyclin A protein prior to activation of caspase-3-like activity and morphological changes of apoptosis. Down-regulation of cyclin A protein levels by cyclin A antisense oligonucleotides dramatically decreased fibroblast apoptosis in response to anti-CD44 antibody. These data identify an important functional role of cyclin A in the induction of fibroblast apoptosis due to the ligation of the cell surface adhesion receptor CD44 by anti-CD44 antibody.

Work loss costs due to peptic ulcer disease and gastroesophageal reflux disease in a health maintenance organization.

OBJECTIVE: The aim of this study was to estimate the value of work time and productivity loss because of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). METHODS: A total of 300 adult members of Northern California Kaiser Permanente Medical Care Program with outpatient diagnoses of PUD or GERD were randomly selected for a record review to confirm diagnosis. A telephone survey was conducted soliciting information about work loss because of their disease. Reported work losses were valued at self-reported hourly wage to derive work loss costs. A total of 117 PUD and 102 GERD patients participated. RESULTS: About 75% of each sample was employed full-time or part-time. In all, 42% of potentially working PUD patients and 41% of GERD patients reported some lost work productivity because of their disease. The average loss (per person working) was $606 for PUD and $237 for GERD over a 3-month period. Reduced productivity while at work and part-time work because of the disease were the most costly productivity losses for PUD, whereas time off for physician visits and reduced productivity while at work were the most costly losses for GERD. CONCLUSIONS: Work loss costs for patients with PUD and GERD may be nearly as large as direct medical care costs, and are consistent with the more acute nature of PUD and the chronic pattern of GERD. The work losses resulting from these diseases are large enough to warrant consideration in guideline development and policy decisions for patients with PUD and GERD.

A cost-effectiveness and cost-benefit analysis of contingency contracting-enhanced methadone detoxification treatment.

We examined treatment costs in an ongoing study in which 102 opioid-addicted patients had been randomly assigned to either 180-day methadone detoxification or the same treatment enhanced with contingency contracting. In the latter condition, study participants received regular reinforcers contingent on negative urine toxicology screens and breath analyses for a range of drugs and alcohol. Both conditions involved psychosocial treatment, and all participants were stabilized to a daily methadone dose of approximately 80 mg during the first 4 months, followed by a 2-month taper. Individuals participating in the enhanced condition were more likely to provide continuously drug-free urine samples and alcohol-free breath samples during the final month of treatment than were participants in the control condition. Cost of treatment was calculated individually for each participant based on actual services received. First, unit cost for each service was determined, including adjusted staff salaries for direct treatment and opportunity cost of facilities utilized during service delivery. Next, we valued each patient's use of services during the first 120 days of the study and then added the cost of methadone, laboratory work, and contingent reinforcers. A subsample (n = 45) also provided data on health care utilization during treatment, which we valued using standard Medicare unit costs. The marginal cost of enhancing the standard treatment with contingency contracting was approximately 8%. An incremental cost of $17.27 produced an additional 1% increase in the number of participants providing continuously substance-free urine and breath samples during month 4 of the study. For every additional dollar spent on treatment, a $4.87 health care cost offset was realized; however, this difference was statistically insignificant due to extreme variances and small subsample size.