Two-step Selection Procedure Research Articles

Associations between statewide prescription drug monitoring program (PDMP) requirement and physician patterns of prescribing opioid analgesics for patients with non-cancer chronic pain

ObjectiveState-level prescription drug monitoring programs (PDMPs) have been implemented in most states. PDMPs enable registered prescribers to obtain real-time information on patients' prescription history to reduce non-medical use of controlled drugs. This study examined whether PDMP implementation and different levels of PDMP requirements were associated with physicians' patterns of prescribing opioid analgesics for patients with non-cancer chronic pain. MethodsThis is a secondary analysis study using cross-sectional national data. Patients with non-cancer chronic pain from the 2012 National Ambulatory Medical Care Survey were included (weighted N=81,018,131; unweighted N=3295). Heckman two-step selection procedure employing two logistic regressions was used to explore the associations between PDMP requirements and physicians' prescribing behaviors, controlling for physician characteristics, patient characteristics, physician-healthcare system interaction, and physician-patient relationship, guided by the Eisenberg's model of physician decision making. ResultsState PDMP implementation status and requirement levels were not associated with physician opioid prescribing for non-cancer chronic pain treatment (p's ranged 0.30–0.32). Patients with Medicare coverage were more likely to be prescribed opioid analgesics than those with private health insurance (OR=1.55, p<0.01). Hispanic patients were less likely to be prescribed opioid analgesics than non-Hispanic white patients (OR=0.61, p<0.05). ConclusionsFindings indicated that the effectiveness of PDMPs on physicians' opioid prescribing tendency for non-cancer chronic pain treatment could not be supported. Policy makers should be aware of the need for redesigning PDMPs regarding requirements and enforcement for prescribers and related stakeholders. Future studies also are needed to identify characteristics contributing to PDMP effectiveness in reducing non-medical use of prescription opioids.

Variable selection in censored quantile regression with high dimensional data

We propose a two-step variable selection procedure for censored quantile regression with high dimensional predictors.To account for censoring data in high dimensional case, we employ effective dimension reduction and the ideas of informative subset idea. Under some regularity conditions, we show that our procedure enjoys the model selection consistency. Simulation study and real data analysis are conducted to evaluate the finite sample performance of the proposed approach.

Effects of the mental health parity and addictions equality act on depression treatment choice in primary care facilities.

Objective The Mental Health Parity and Addictions Equality Act (MHPAEA) of 2010 in the United States sought to expand mental health insurance benefits on par with medical benefits. As primary care facilities are often the first step in identifying mental health concerns, it is essential to examine the association of this policy with primary care physicians' choice on depression treatment. Method A retrospective cross-sectional study was conducted using data from the 2007-2012 National Ambulatory Medical Care Survey, including a weighted total of 162,699,930 depression patients. Using the Heckman two-step selection procedure, a logistic and a multinomial regression were conducted to examine the association of the MHPAEA with physicians' two-step process of deciding whether and which type of treatment was prescribed. Sociological factors were controlled. Results Treatment was significantly more likely to be provided after the MHPAEA. Psychotherapy was used for treatment for 10.0% of the sample while medication was used for 75.0% of the sample. Patient race/ethnicity, practice setting, physician specialty, and primary source of payment were associated with diverging likelihood of being prescribed depression treatment. Non-Hispanic White patients were more likely to be provided treatment than non-Hispanic Black patients. Patients were less likely to be prescribed only medication than only psychotherapy after the MHPAEA enactment. Conclusions The MHPAEA was associated with primary care providers' decision and choice on depression treatment. Educational and policy interventions aimed at improving physician's understanding of their own treatment tendencies and decreasing barriers to depression treatment may impact the disparities in underserved, minority, and older populations.

Two-step feature selection for predicting survival time of patients with metastatic castrate resistant prostate cancer.

Metastatic castrate resistant prostate cancer (mCRPC) is the major cause of death in prostate cancer patients. Even though some options for treatment of mCRPC have been developed, the most effective therapies remain unclear. Thus finding key patient clinical variables related with mCRPC is an important issue for understanding the disease progression mechanism of mCRPC and clinical decision making for these patients. The Prostate Cancer DREAM Challenge is a crowd-based competition to tackle this essential challenge using new large clinical datasets. This paper proposes an effective procedure for predicting global risks and survival times of these patients, aimed at sub-challenge 1a and 1b of the Prostate Cancer DREAM challenge. The procedure implements a two-step feature selection procedure, which first implements sparse feature selection for numerical clinical variables and statistical hypothesis testing of differences between survival curves caused by categorical clinical variables, and then implements a forward feature selection to narrow the list of informative features. Using Cox's proportional hazards model with these selected features, this method predicted global risk and survival time of patients using a linear model whose input is a median time computed from the hazard model. The challenge results demonstrated that the proposed procedure outperforms the state of the art model by correctly selecting more informative features on both the global risk prediction and the survival time prediction.

Iodine Value and Fatty Acids Determination on Pig Fat Samples by FT-NIR Spectroscopy: Benefits of Variable Selection in the Perspective of Industrial Applications

In this work, FT-NIR spectroscopy was employed to determine iodine value (IV) and fatty acids (FA) content of pig fat samples, through the combined use of signal preprocessing, multivariate calibration, and variable selection methods. In particular, the main focus was on the use of variable selection methods, both in order to improve the predictive performance of the calibration models, and to identify relevant wavelengths that could be subsequently used for the development of simple, fast, and cheap hand-held devices, able to measure IV and FA content directly on the fat without the need of any sample pretreatment. Firstly, for each property of interest, partial least squares (PLS) multivariate calibration models were calculated considering the whole spectral range and testing different signal preprocessing methods. Then, once chosen the optimal signal preprocessing method, a two-step variable selection procedure was applied. In the first step, the interval-PLS variable selection algorithm was used to calculate a set of calibration models, whose outcomes were considered altogether in the second step, in order to select the optimal calibration model. The variable selection procedure allowed to lower the number of spectral variables retained by the model, and often led to an increase of the performance in prediction of the external test set samples.

Explaining asymmetries in bilateral FDI flows

This paper constructs a two-stage monopolistic competition model that explains the large number of zeros and missing bilateral FDI flows, as well as positive bilateral FDI flows we observe in the data. A Heckman two-step selection procedure is used to empirically estimate the model by employing data for 101 countries from 1995 to 2002. I show that certain characteristics previously considered important to determine FDI flows in traditional OLS estimations may only matter for multinationals selecting into FDI relationships, and in some cases, they may even negatively affect FDI flows.

The cost-utility of left ventricular assist devices for end-stage heart failure patients ineligible for cardiac transplantation: a systematic review and critical appraisal of economic evaluations.

A health technology assessment (HTA) of left ventricular assist devices (LVADs) as destination therapy in patients with end-stage heart failure was commissioned by the Dutch Health Care Insurance Board [College voor Zorgverzekeringen (CVZ)]. In this context, a systematic review of the economic literature was performed to assess the procedure's value for money. A systematic search (updated in December 2013) for economic evaluations was performed by consulting various databases: the HTA database produced by the Centre for Reviews and Dissemination (CRD HTA), websites of HTA institutes, CRD's National Health Service Economic Evaluation Database (NHS EED), Medline (OVID) and EMBASE. No time or language restrictions were imposed and pre-defined selection criteria were used. The two-step selection procedure was performed by two people. References of the selected studies were checked for additional relevant citations. Six relevant studies were selected. Four economic evaluations relied on the results of the REMATCH trial to compare a pulsatile-flow LVAD with optimal medical therapy (OMT). These evaluations were performed before the publication of the HeartMate II (HM-II) Destination Therapy Trial which compared a pulsatile-flow with a continuous-flow LVAD. Two more recent economic evaluations combined the results of both trials to make an indirect comparison of a continuous-flow LVAD with OMT. In all studies, the largest part of the incremental cost was due to the reimplantation cost of an LVAD, with a device cost of €58,000-€75,000 and about €55,000 for the surgical procedure. The survival gain was highest with a continuous-flow LVAD, up to about three life-years gained (LYG) versus OMT in the most optimistic study. Quality of life (QoL) was improved but measures with a generic utility instrument were lacking, making estimates on quality-adjusted life-years (QALYs) gained more uncertain. Incremental cost-effectiveness ratios of the two most recent studies were on average €107,600 and $198,184 (ca.€145,800) per QALY gained. Although LVAD destination therapy improves survival and QoL, it remains questionable as to whether it offers value for money. This conclusion may alter if the price of the device/procedure decreases sufficiently, in combination with further improved outcomes for mortality, adverse events and QoL.

The cost-utility of catheter ablation of atrial fibrillation: a systematic review and critical appraisal of economic evaluations.

BackgroundA health technology assessment (HTA) of catheter ablation for atrial fibrillation (CA-AF) was commissioned by the Belgian government and performed by the Belgian Health Care Knowledge Centre (KCE). In this context, a systematic review of the economic literature was performed to assess the procedure’s value for money.MethodsA systematic search for economic literature about the cost-effectiveness of CA-AF was performed by consulting various databases: CRD (Centre for Reviews and Dissemination) HTA and CDSR (Cochrane Database of Systematic Reviews) Technology Assessment, websites of HTA institutes, NHS EED (NHS Economic Evaluation Database), Medline (OVID), EMBASE and EconLit. No time or language restrictions were imposed and pre-defined selection criteria were used. The two-step selection procedure was performed by two persons. References of the selected studies were checked for additional relevant citations.ResultsOut of 697 references, seven relevant studies were selected. Based on current evidence and economic considerations, the rationale to support catheter ablation as first-line treatment was lacking.The economic evaluations for second-line catheter ablation included several assumptions that make the results rather optimistic or subject to large uncertainty. First, overall AAD (antiarrhythmic drugs) use after ablation was higher in reality than assumed in the economic evaluations, which had its impact on costs and effects. Second, several models focused on the impact of ablation on preventing stroke. This was questionable because there was no direct hard evidence from RCTs to support this assumption. An indirect impact through stroke on mortality should also be regarded with caution. Furthermore, all models included an impact on quality of life (QoL)/utility and assumed a long-term impact. Unfortunately, none of the RCTs measured QoL with a generic utility instrument and information on the long-term impact on both mortality and QoL was lacking.ConclusionsCatheter ablation is associated with high initial costs and may lead to life-threatening complications. Its cost-effectiveness depends on the belief one places on the impact on utility and/or preventing stroke, and the duration of these effects. Having no hard evidence for these important variables is rather troublesome. Although the technique is widely spread, the scientific evidence is insufficient for drawing conclusions about the intervention’s cost-effectiveness.

Zero-inflated and overdispersed: what's one to do?

Zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models are recommended for handling excessive zeros in count data. For various reasons, researchers may not address zero inflation. This paper helps educate researchers on (1) the importance of accounting for zero inflation and (2) the consequences of misspecifying the statistical model. Using simulations, we found that when the zero inflation in the data was ignored, estimation was poor and statistically significant findings were missed. When overdispersion within the zero-inflated data was ignored, poor estimation and inflated Type I errors resulted. Recommendations on when to use the ZINB and ZIP models are provided. In an illustration using a two-step model selection procedure (likelihood ratio test and the Vuong test), the ZIP model was correctly identified only when the distributions had moderate means and sample sizes and did not correctly identify the ZINB model or the zero inflation in the ZIP and ZINB distributions.

Academic and non-academic selection criteria in predicting medical school performance

Background: A two-step selection procedure, consisting of a non-academic and an academic step, was recently shown to select students with a 2.6 times lower risk of early dropout and a higher clerkship Grade Point Average (GPA) than lottery-admitted controls.Aim: To determine the relative contribution of the non-academic and academic steps to differences found in student performance.Method: Lottery-admitted students (n = 653) and three groups of selection procedure participants were compared on early dropout rate and clerkship GPA: (1) all participants (n = 1676), (2) participants who passed step 1, and (3) participants who passed step 2.Results: Selection procedure participation resulted in a 4.4% lower dropout rate than lottery admission and this difference increased to 5.2% after step 1 and to 8.7% after step 2. Clerkship GPA was significantly higher for participants who passed step 1 than for their lottery-admitted controls. This difference remained significant after the rejection of students on academic criteria in step 2.Conclusion: The lower dropout rate of selected students is related to both self-selection of participants before the start of the selection procedure and the academic part of the selection procedure. The higher clerkship GPA of selected students is almost exclusively related to the non-academic selection criteria.

FunSAV: Predicting the Functional Effect of Single Amino Acid Variants Using a Two-Stage Random Forest Model

Single amino acid variants (SAVs) are the most abundant form of known genetic variations associated with human disease. Successful prediction of the functional impact of SAVs from sequences can thus lead to an improved understanding of the underlying mechanisms of why a SAV may be associated with certain disease. In this work, we constructed a high-quality structural dataset that contained 679 high-quality protein structures with 2,048 SAVs by collecting the human genetic variant data from multiple resources and dividing them into two categories, i.e., disease-associated and neutral variants. We built a two-stage random forest (RF) model, termed as FunSAV, to predict the functional effect of SAVs by combining sequence, structure and residue-contact network features with other additional features that were not explored in previous studies. Importantly, a two-step feature selection procedure was proposed to select the most important and informative features that contribute to the prediction of disease association of SAVs. In cross-validation experiments on the benchmark dataset, FunSAV achieved a good prediction performance with the area under the curve (AUC) of 0.882, which is competitive with and in some cases better than other existing tools including SIFT, SNAP, Polyphen2, PANTHER, nsSNPAnalyzer and PhD-SNP. The sourcecodes of FunSAV and the datasets can be downloaded at http://sunflower.kuicr.kyoto-u.ac.jp/sjn/FunSAV.

Clustering the Winners: The French Policy of Competitiveness Clusters

In 2005 the French government launched a policy of competitiveness clusters, giving subsidies for innovative projects managed locally and collectively by firms, research centers and universities. This paper proposes an ex-ante analysis of the outcome of the selection process that took place before the implementation of the subsidies program, in order to assess whether the policy ended up in choosing winners or losers. We first ask how the clusters have been selected, and then focus on the selection of firms within the clusters, using export and productivity as a measure of performance. Our main conclusion is that public authorities have chosen the winners during the two-step selection procedure. Export premium, beyond what individual characteristics would predict, is however most visible within the category of clusters having no international ambition, where heterogeneity among firms is the largest.

Physician Prescribing Patterns of Innovative Antidepressants in the United States: The Case of MDD Patients 1993–2007

Innovative antidepressants such as SSRIs and SNRIs have been widely adopted. However, the differences in their adoption across patients' and physicians' characteristics, geographic regions, and insurance status need to be further explored. This study was trying to disentangle the patterns of physician antidepressant prescribing and medication choice for major depressive disorder treatment. A retrospective cross-sectional study was conducted using the 1993-2007 National Ambulatory Medical Care Survey database. A multinomial logistic regression with the Heckman two-step selection procedure was applied to capture the two-step nature of physician prescription decision making. The weighted logistic regression indicated that patients' race/ethnicity and primary source of payment for services, physician ownership status, and physicians' practice regions were associated with differential likelihood of physician' antidepressant prescribing. Non-Hispanic white patients were more likely to be prescribed antidepressants compared to Hispanic patients (OR = 1.52, 95% CI 1.24-1.87). Physicians' choice on antidepressant varied across with patient age and health insurance status. Compared to private insurance, patients who were primarily covered by Medicare were less likely to be prescribed only SSRIs/SNRIs or other newer antidepressants (RRRs = 0.42 and 0.39; 95% CIs 0.21-0.83 and 0.18-0.84, respectively). We observed strong associations between sociological factors and physicians' antidepressant prescribing patterns. Possible health disparities and gaps between optimal and suboptimal healthcare for patient mental health caused by systematic differences in sociological factors need to be mitigated. We need policy makers to design effective policy interventions to improve physician practice guidelines adherence to eliminate possible variations among physician practices.

Model selection, estimation and forecasting in VAR models with short-run and long-run restrictions

We study the joint determination of the lag length, the dimension of the cointegrating space and the rank of the matrix of short-run parameters of a vector autoregressive (VAR) model using model selection criteria. We suggest a new two-step model selection procedure which is a hybrid of traditional criteria and criteria with data-dependant penalties and we prove its consistency. A Monte Carlo study explores the finite sample performance of this procedure and evaluates the forecasting accuracy of models selected by this procedure. Two empirical applications confirm the usefulness of the model selection procedure proposed here for forecasting.

New Protocol for the Enrichment of Untouched Human Dendritic Cells (144.14)

Abstract We have developed a new negative selection protocol for the enrichment of untouched human dendritic cells (DCs) from human blood. The protocol can be carried out in less than one hour, after PBMC enrichment, and is characterized as a two-step negative selection procedure, using two different cocktails of biotinylated antibodies that target non-DC lineage markers. DCs enriched with this protocol performed better in T cell proliferation assays, as compared to DCs enriched with a commercial kit. Flow cytometric analysis of the isolated cells show that 90% of the enriched cells are CD14-/CD19-/BDCA1+/BDCA2+/BDCA3+ (total DCs), as compared to less than 10% before cell enrichment. Within these isolated DCs 2-8% are plasmacytoid DCs (BDCA2+/CD45+) and 82-88% are myeloid DCs (20-40% BDCA1+/CD11c+, 20-40% BDCA3+/CD11c+, 15-20% CD16+/CD11c+ and 20-25% CD56+/MHCII+). On average 1 million DCs were isolated per 100 million PBMCs. The advantages of this protocol include: a) better performance in T cell proliferation assays, compared to DCs enriched with a commercially available kit, and b) higher myeloid DC heterogeneity in the enriched DC fraction. The above observations could be the result of the fact that the isolated DCs are not bound to antibodies that could initiate activation cascades, and that CD16+ and CD56+ DCs were absent from the cell population isolated with the commercial kit.

“One Ring to Bind Them All”—Part II: Identification of Promising G‐Quadruplex Ligands by Screening of Cyclophane‐Type Macrocycles

A collection of 26 polyammonium cyclophane-type macrocycles with a large structural diversity has been screened for G-quadruplex recognition. A two-step selection procedure based on the FRET-melting assay was carried out enabling identification of macrocycles of high affinity (ΔT1/2 up to 30°C) and high selectivity for the human telomeric G-quadruplex. The four selected hits possess sophisticated architectures, more particularly the presence of a pendant side-arm as well as the existence of a particular topological arrangement appear to be strong determinants of quadruplex binding. These compounds are thus likely to create multiple contacts with the target that may be at the origin of their high selectivity, thereby suggesting that this class of macrocycles offers unique advantages for targeting G-quadruplex-DNA.

Genetic Diversity of Bacteriophages Highly Specific for Streptococcus Thermophilus Strain Lbb.A

ABSTRACTEight virulent bacteriophages φA1, φA2, φA5, φA6, φDmA, φSfA, φPtA and φA7, that showed high specificity for Streptococcus thermophilus strain LBB.A, the streptococcal component of an industrial yogurt starter, were isolated. The comparison of the HindIII and EcoRV restriction patterns of the phage DNA revealed limited relatedness between the isolates, clustering together only φA5 with φA6 and indicating similarity between φSfA, φPtA and φA7. All eight bacteriophages were classified as costype phages. An internal region within a conserved 2.2 kbp EcoRI DNA fragment typical for the majority of S. thermophilus bacteriophages was present in six of the phage isolates and was absent in φDmA and φA1. PCR amplification of the VR2 region of the antireceptor gene yielded an 800 bp product for seven of the phages and a 700 bp product for φA2. The genome size of the eight phage isolates was in the range of 33.4–37.3 kbp. Of a total of 62 other S. thermophilus cultures φA1, φDmA and φPtA were able to infect only two strains with reduced effectiveness of plaquing. Despite the broad genetic diversity of phages of S. thermophilus strain LBB.A, a two-step selection procedure, involving successive challenge of the bacterial culture with φA1 and φA7, was sufficient to obtain mutants resistant to all eight phases.

DNA-Encoded Chemical Libraries for the Discovery of MMP-3 Inhibitors

Encoded self-assembling chemical (ESAC) libraries are characterized by the covalent display of chemical moieties at the extremity of self-assembling oligonucleotides carrying a unique DNA sequence for the identification of the corresponding chemical moiety. We have used ESAC library technology in a two-step selection procedure for the identification of novel inhibitors of stromelysin-1 (MMP-3), a matrix metalloproteinase involved in both physiological and pathological tissue remodeling processes, yielding novel inhibitors with micromolar potency.

Trauma experience in individuals with idiopathic environmental intolerance and individuals with somatoform disorders

Objective Results from previous studies suggest that past trauma experience increases the risk for medically unexplained somatic symptoms and somatoform disorders (SFD). This cross-sectional study examined the link between various lifetime traumas, idiopathic environmental intolerance (IEI), and SFD. Methods Two clinical groups of 54 subjects with IEI and 44 subjects with SFD were compared to 54 subjects (comparison group, CG) free from both IEI and SFD regarding self-reported traumas. The subjects were mainly recruited via advertisements in local newspapers. From 970 individuals screened for IEI and multiple somatic symptoms, 152 were included through a two-step selection procedure consisting of screening questionnaires, a medical examination, and structured interviews for IEI and mental disorders. Results In all three groups at least one potential traumatic event was reported rather frequently (CG: 70%; IEI: 82%; SFD: 73%). But contrary to our expectation, significant group differences were neither found in regard to the proportion of subjects with any trauma, nor traumas fulfilling DSM-IV criteria (CG: 41%; IEI: 48%; SFD: 59%), nor multiple traumas (CG: 43%, IEI: 56%, SFD: 39%). Only two trauma categories were endorsed more frequently by the two clinical groups than by the CG: the unspecified ‘other’ category (IEI, SFD>CG) and ‘life-threatening illness’ (IEI>CG). Conclusion No clear evidence was found for increased rates of trauma experience in IEI and SFD. However, the results of this exploratory study should be considered as preliminary. Comparing larger IEI and SFD groups with a representative population-based sample may yield different results.

Homotypic interactions among bacteriophage φKMV early proteins

Little is known about the bacteriophage proteins expressed immediately after infection of the host cell. Most of these early proteins are probably involved in bacteriophage-host interactions redirecting the bacterial metabolism to phage production. Interaction analysis of the first 16 phiKMV gene products (gp) identified homotypic interactions of gp7, gp9 and gp15. Two related yeast two-hybrid procedures, a matrix and a minilibrary approach, were applied to detect protein-protein interactions. A two-step selection procedure enabled drastic reduction of the background. Interactions were confirmed by drop tests. Multimerization of gp15 is consistent with its putative function as a DNA helicase involved in DNA replication. Homotypic interaction of gp7 and gp9 suggests they function as dimers or multimers. The absence of heterotypic interactions among early phiKMV proteins hints at their functional independence from other early phage proteins and their involvement in phage-host interactions that are important for creating optimal conditions for phage propagation. Besides, these results demonstrate the compatibility of phiKMV early gene products with the yeast two-hybrid system. Therefore, they are promising candidates to screen for interactions with host proteins.