The Effect of Financial Incentives on Patient Decisions to Undergo Low‐value Head Computed Tomography Scans

BackgroundExcessive diagnostic testing and defensive medicine contribute to billions of dollars in avoidable costs in the United States annually. Our objective was to determine the influence of financial incentives, accompanied with information regarding test risk and benefit, on patient preference for diagnostic testing.MethodsWe conducted a cross‐sectional survey of patients at the University of Michigan emergency department (ED). Each participant was presented with a hypothetical scenario involving an ED visit following minor traumatic brain injury. Participants were given information regarding potential benefit (detecting brain hemorrhage) and risk (developing cancer) of head computed tomography scan, as well as an incentive of $0 or$100 to forego testing. We used 0.1 and 1% for test benefit and risk, and values for risk, benefit, and financial incentive varied across participants. Our primary outcome was patient preference to undergo testing. We also collected demographic and numeracy information. We then used logistic regression to estimate odds ratios (ORs), which were adjusted for multiple potential confounders. Our sample size was designed to find at least 300 events (preference for testing) to allow for inclusion of up to 30 covariates in fully adjusted models. We had 85% to 90% power to detect a 10% absolute difference in testing rate across groups, assuming a 95% significance level.ResultsWe surveyed 913 patients. Increasing test benefit from 0.1% to 1% significantly increased test acceptance (adjusted OR [AOR] = 1.6, 95% confidence interval [CI] = 1.2 to 2.1) and increasing test risk from 0.1% to 1% significantly decreased test acceptance (AOR = 0.70, 95% CI = 0.52 to 0.93). Finally, a $100 incentive to forego low‐value testing significantly reduced test acceptance (AOR = 0.6; 95% CI = 0.4 to 0.8).ConclusionsProviding financial incentives to forego testing significantly decreased patient preference for testing, even when accounting for test benefit and risk. This work is preliminary and hypothetical and requires confirmation in larger patient cohorts facing these actual decisions.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151851/1/acem13823_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151851/2/acem13823-sup-0001-DataSupplementS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151851/3/acem13823.pd

Removal of PCR Error Products and Unincorporated Primers by Metal-Chelate Affinity Chromatography

Immobilized Metal Affinity Chromatography (IMAC) has been used for decades to purify proteins on the basis of amino acid content, especially surface-exposed histidines and “histidine tags” genetically added to recombinant proteins. We and others have extended the use of IMAC to purification of nucleic acids via interactions with the nucleotide bases, especially purines, of single-stranded RNA and DNA. We also have demonstrated the purification of plasmid DNA from contaminating genomic DNA by IMAC capture of selectively-denatured genomic DNA. Here we describe an efficient method of purifying PCR products by specifically removing error products, excess primers, and unincorporated dNTPs from PCR product mixtures using flow-through metal-chelate affinity adsorption. By flowing a PCR product mixture through a Cu2+-iminodiacetic acid (IDA) agarose spin column, 94–99% of the dNTPs and nearly all the primers can be removed. Many of the error products commonly formed by Taq polymerase also are removed. Sequencing of the IMAC-processed PCR product gave base-calling accuracy comparable to that obtained with a commercial PCR product purification method. The results show that IMAC matrices (specifically Cu2+-IDA agarose) can be used for the purification of PCR products. Due to the generality of the base-specific mechanism of adsorption, IMAC matrices may also be used in the purification of oligonucleotides, cDNA, mRNA and micro RNAs

Cost-effectiveness of fibronectin testing in a triage in women with threatened preterm labor: alleviation of pregnancy outcome by suspending tocolysis in early labor (APOSTEL-I trial)

BACKGROUND: At present, women with threatened preterm labor before 32 weeks of gestation are, after transfer to a perinatal center, treated with tocolytics and corticosteroids. Many of these women are treated unnecessarily. Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor. We will assess whether triage of these women with fibronectin testing, cervical length or their combination is cost-effective. METHODS/DESIGN: We will investigate a prospective cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes. All women will be tested for fibronectin and cervical length. Women with a cervical length <10 mm and women with a cervical length between 10-30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol. Women with a cervical length between 10-30 mm in combination with a negative fibronectin test will be randomised between treatment with nifedipine (intervention) and placebo (control) for 48 hours. Women with a cervical length > 30 mm will be managed according to local protocol. Corticosteroids may be given to all women at the discretion of the attending physician. Primary outcome measure will be delivery within 7 days. Secondary outcome measures will be neonatal morbidity and mortality, complications of tocolytics, costs and health related quality of life. The analysis will be according to the intention to treat principle. We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5%. Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5% (one sided test, beta 0.2, alpha 0.05). Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin. DISCUSSION: This study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor. TRIAL REGISTRATION: Nederlands Trial Register (NTR) number 1857, http://www.trialregister.nl

A randomised clinical trial on cardiotocography plus fetal blood sampling versus cardiotocography plus ST-analysis of the fetal electrocardiogram (STAN®) for intrapartum monitoring

<p>Abstract</p> <p>Background</p> <p>Cardiotocography (CTG) is worldwide the method for fetal surveillance during labour. However, CTG alone shows many false positive test results and without fetal blood sampling (FBS), it results in an increase in operative deliveries without improvement of fetal outcome. FBS requires additional expertise, is invasive and has often to be repeated during labour. Two clinical trials have shown that a combination of CTG and ST-analysis of the fetal electrocardiogram (ECG) reduces the rates of metabolic acidosis and instrumental delivery. However, in both trials FBS was still performed in the ST-analysis arm, and it is therefore still unknown if the observed results were indeed due to the ST-analysis or to the use of FBS in combination with ST-analysis.</p> <p>Methods/Design</p> <p>We aim to evaluate the effectiveness of non-invasive monitoring (CTG + ST-analysis) as compared to normal care (CTG + FBS), in a multicentre randomised clinical trial setting. Secondary aims are: 1) to judge whether ST-analysis of fetal electrocardiogram can significantly decrease frequency of performance of FBS or even replace it; 2) perform a cost analysis to establish the economic impact of the two treatment options.</p> <p>Women in labour with a gestational age ≥ 36 weeks and an indication for CTG-monitoring can be included in the trial.</p> <p>Eligible women will be randomised for fetal surveillance with CTG and, if necessary, FBS or CTG combined with ST-analysis of the fetal ECG.</p> <p>The primary outcome of the study is the incidence of serious metabolic acidosis (defined as pH < 7.05 and Bd_ecf> 12 mmol/L in the umbilical cord artery). Secondary outcome measures are: instrumental delivery, neonatal outcome (Apgar score, admission to a neonatal ward), incidence of performance of FBS in both arms and cost-effectiveness of both monitoring strategies across hospitals.</p> <p>The analysis will follow the intention to treat principle. The incidence of metabolic acidosis will be compared across both groups. Assuming a reduction of metabolic acidosis from 3.5% to 2.1 %, using a two-sided test with an alpha of 0.05 and a power of 0.80, in favour of CTG plus ST-analysis, about 5100 women have to be randomised. Furthermore, the cost-effectiveness of CTG and ST-analysis as compared to CTG and FBS will be studied.</p> <p>Discussion</p> <p>This study will provide data about the use of intrapartum ST-analysis with a strict protocol for performance of FBS to limit its incidence. We aim to clarify to what extent intrapartum ST-analysis can be used without the performance of FBS and in which cases FBS is still needed.</p> <p>Trial Registration Number</p> <p>ISRCTN95732366</p

Assessing socioeconomic health care utilization inequity in Israel: impact of alternative approaches to morbidity adjustment

<p/> <p>Background</p> <p>The ability to accurately detect differential resource use between persons of different socioeconomic status relies on the accuracy of health-needs adjustment measures. This study tests different approaches to morbidity adjustment in explanation of health care utilization inequity.</p> <p>Methods</p> <p>A representative sample was selected of 10 percent (~270,000) adult enrolees of Clalit Health Services, Israel's largest health care organization. The Johns-Hopkins University Adjusted Clinical Groups^®were used to assess each person's overall morbidity burden based on one year's (2009) diagnostic information. The odds of above average health care resource use (primary care visits, specialty visits, diagnostic tests, or hospitalizations) were tested using multivariate logistic regression models, separately adjusting for levels of health-need using data on age and gender, comorbidity (using the Charlson Comorbidity Index), or morbidity burden (using the Adjusted Clinical Groups). Model fit was assessed using tests of the Area Under the Receiver Operating Characteristics Curve and the Akaike Information Criteria.</p> <p>Results</p> <p>Low socioeconomic status was associated with higher morbidity burden (1.5-fold difference). Adjusting for health needs using age and gender or the Charlson index, persons of low socioeconomic status had greater odds of above average resource use for all types of services examined (primary care and specialist visits, diagnostic tests, or hospitalizations). In contrast, after adjustment for overall morbidity burden (using Adjusted Clinical Groups), low socioeconomic status was no longer associated with greater odds of specialty care or diagnostic tests (OR: 0.95, CI: 0.94-0.99; and OR: 0.91, CI: 0.86-0.96, for specialty visits and diagnostic respectively). Tests of model fit showed that adjustment using the comprehensive morbidity burden measure provided a better fit than age and gender or the Charlson Index.</p> <p>Conclusions</p> <p>Identification of socioeconomic differences in health care utilization is an important step in disparity reduction efforts. Adjustment for health-needs using a comprehensive morbidity burden diagnoses-based measure, this study showed relative underutilization in use of specialist and diagnostic services, and thus allowed for identification of inequity in health resources use, which could not be detected with less comprehensive forms of health-needs adjustments.</p

Matrix Metalloproteinase-10 Is Required for Lung Cancer Stem Cell Maintenance, Tumor Initiation and Metastatic Potential

Matrix metalloproteinases (Mmps) stimulate tumor invasion and metastasis by degrading the extracellular matrix. Here we reveal an unexpected role for Mmp10 (stromelysin 2) in the maintenance and tumorigenicity of mouse lung cancer stem-like cells (CSC). Mmp10 is highly expressed in oncosphere cultures enriched in CSCs and RNAi-mediated knockdown of Mmp10 leads to a loss of stem cell marker gene expression and inhibition of oncosphere growth, clonal expansion, and transformed growth in vitro. Interestingly, clonal expansion of Mmp10 deficient oncospheres can be restored by addition of exogenous Mmp10 protein to the culture medium, demonstrating a direct role for Mmp10 in the proliferation of these cells. Oncospheres exhibit enhanced tumor-initiating and metastatic activity when injected orthotopically into syngeneic mice, whereas Mmp10-deficient cultures show a severe defect in tumor initiation. Conversely, oncospheres implanted into syngeneic non-transgenic or Mmp10−/− mice show no significant difference in tumor initiation, growth or metastasis, demonstrating the importance of Mmp10 produced by cancer cells rather than the tumor microenvironment in lung tumor initiation and maintenance. Analysis of gene expression data from human cancers reveals a strong positive correlation between tumor Mmp10 expression and metastatic behavior in many human tumor types. Thus, Mmp10 is required for maintenance of a highly tumorigenic, cancer-initiating, metastatic stem-like cell population in lung cancer. Our data demonstrate for the first time that Mmp10 is a critical lung cancer stem cell gene and novel therapeutic target for lung cancer stem cells

Remifentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial

Contains fulltext : 109349.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments. METHODS/DESIGN: The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia.Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief.Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects.The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared. DISCUSSION: This study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 women, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR2551, http://www.trialregister.nl

Targeting Lysophosphatidic Acid Signaling Retards Culture-Associated Senescence of Human Marrow Stromal Cells

Marrow stromal cells (MSCs) isolated from mesenchymal tissues can propagate in vitro to some extent and differentiate into various tissue lineages to be used for cell-based therapies. Cellular senescence, which occurs readily in continual MSC culture, leads to loss of these characteristic properties, representing one of the major limitations to achieving the potential of MSCs. In this study, we investigated the effect of lysophosphatidic acid (LPA), a ubiquitous metabolite in membrane phospholipid synthesis, on the senescence program of human MSCs. We show that MSCs preferentially express the LPA receptor subtype 1, and an abrogation of the receptor engagement with the antagonistic compound Ki16425 attenuates senescence induction in continually propagated human MSCs. This anti-aging effect of Ki16425 results in extended rounds of cellular proliferation, increased clonogenic potential, and retained plasticity for osteogenic and adipogenic differentiation. Expressions of p16Ink4a, Rb, p53, and p21Cip1, which have been associated with cellular senescence, were all reduced in human MSCs by the pharmacological inhibition of LPA signaling. Disruption of this signaling pathway was accompanied by morphological changes such as cell thinning and elongation as well as actin filament deformation through decreased phosphorylation of focal adhesion kinase. Prevention of LPA receptor engagement also promoted ubiquitination-mediated c-Myc elimination in MSCs, and consequently the entry into a quiescent state, G0 phase, of the cell cycle. Collectively, these results highlight the potential of pharmacological intervention against LPA signaling for blunting senescence-associated loss of function characteristic of human MSCs

Like Mother(-in-Law) Like Daughter? Influence of the Older Generation’s Fertility Behaviours on Women’s Desired Family Size in Bihar, India

This paper investigates the associations between preferred family size of women in rural Bihar, India and the fertility behaviours of their mother and mother-in-law. Scheduled interviews of 440 pairs of married women aged 16–34 years and their mothers-in-law were conducted in 2011. Preferred family size is first measured by Coombs scale, allowing us to capture latent desired number of children and then categorized into three categories (low, medium and high). Women’s preferred family size is estimated using ordered logistic regression. We find that the family size preferences are not associated with mother’s fertility but with mother’s education. Mother-in-law’s desired number of grandchildren is positively associated with women’s preferred family size. However, when the woman has higher education than her mother-in-law, her preferred family size gets smaller, suggesting that education provides women with greater autonomy in their decision-making on childbearing