Identification of a new GLDC gene alternative splicing variant and its protumorigenic roles in lung cancer.

Aim: To clarify the regulatory roles of GLDCV1, the first identified truncated glycine decarboxylase (GLDC), on cancer stem cells and tumorigenesis. Materials & methods: RT-PCR or RT-qPCR, immunoblotting and immunohistochemical staining were applied to assess gene expression. MTT, BrdU incorporation and colony formation assays were used to examine cell proliferation capacity. Soft agar colony formation and in vivo transplantation were applied to evaluate cellular transformation and tumorigenesis. Results & conclusion: Expression of GLDCV1 or GLDC was enhanced in non-small-cell lung cancer cell line and clinical samples. GLDCV1 overexpression induced MRC5 cell proliferation, transformation and tumorigenesis. Additionally, GLDCV1 increased lactate production and cancer stem cell marker expression and activated ERK and P38 pathways. Our study gained deeper insight into GLDC oncogene.

Quantification of missing prescriptions in commercial claims databases: results of a cohort study.

PURPOSE: This study aims to quantify the magnitude of missed dispensings in commercial claims databases. METHODS: A retrospective cohort study has been used linking PharMetrics, a commercial claims database, to a prescription database (LRx) that captures pharmacy dispensings independently of payment method, including cash transactions. We included adults with dispensings for opioids, diuretics, antiplatelet medications, or anticoagulants. To determine the degree of capture of dispensings, we calculated the number of subjects with the following: (1) same number of dispensings in both databases; (2) at least one dispensing, but not all dispensings, missed in PharMetrics; and (3) all dispensings missing in PharMetrics. Similar analyses were conducted using dispensings as the unit of analysis. To assess whether a dispensing in LRx was in PharMetrics, the dispensing in PharMetrics had to be for the same medication class and within ±7 days in LRx. RESULTS: A total of 1 426 498 subjects were included. Overall, 68% of subjects had the same number of dispensings in both databases. In 13% of subjects, PharMetrics identified ≥1 dispensing but also missed ≥1 dispensing. In 19% of the subjects, PharMetrics missed all the dispensings. Taking dispensings as the unit of analysis, 25% of the dispensings present in LRx were not captured in PharMetrics. These patterns were similar across all four classes of medications. Of the dispensings missing in PharMetrics, 48% involved a subject who had >1 health insurance plan. CONCLUSIONS: Commercial claims databases provide an incomplete picture of all prescriptions dispensed to patients. The lack of capture goes beyond cash transactions and potentially introduces substantial misclassification bias. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Doctor shopping for medications used in the treatment of attention deficit hyperactivity disorder: shoppers often pay in cash and cross state lines.

BACKGROUND: Doctor shopping, defined by filling overlapping prescriptions from more than one prescriber at more than two pharmacies, is a way to obtain scheduled medications for diversion or abuse. Little is known about how far attention deficit hyperactivity disorder (ADHD) medication shoppers travel, how often they cross state lines to fill their ADHD prescriptions and how often they pay for their medication in cash, i.e. entirely out of pocket. OBJECTIVE: We sought to describe the pattern of doctor shopping for ADHD medications: how far shoppers travel, how often they cross state lines to fill their prescriptions, and how often they pay in cash. METHODS: Retrospective cohort study using LRx, a large US retail prescription database. We included subjects with any ADHD medication dispensed between 2011 and 2012. Subjects were followed for 18 months. RESULTS: Of a total of 4 402 464 subjects exposed to ADHD medications, 0.4% developed shopping behavior. Women were more likely to become shoppers. Shoppers travelled a median of 91.9 miles and non-shoppers 0.2 miles to fill their ADHD prescriptions. Almost 28% of the shoppers filled prescriptions in >1 state compared with 4.3% of non-shoppers. Of the shoppers, 27.3% paid at least one prescription in cash compared to 14.4% of the non-shoppers. CONCLUSIONS: Shoppers travelled larger distances, visited more states and paid in cash for ADHD medications more often than non-shoppers. Data sharing among prescriptions monitoring programs can improve their effectiveness and drug utilization studies should take account of cash purchases.

Pathogenicity of Ureaplasma urealyticum and Ureaplasma parvum in the lower genital tract of female BALB/c mice.

The aim of this study was to establish a murine model of lower genital tract infection by Ureaplasma urealyticum and Ureaplasma parvum and evaluate differences in pathogenicity of five serotypes. BALB/c female mice were divided into seven groups (five mice in each group), including five groups infected in the lower genital tract after treatment with estradiol with U. urealyticum serotypes 4 and 8 and U. parvum serotypes 1, 3, and 6, respectively, and two control groups of untreated mice and estradiol treated mice. The presence of infection was determined on solid and liquid culture media. Tumor necrosis factor-alpha (TNF-α) expression in lower genital tract secretions was determined by PCR, and morphological and histological changes of the lower genital tract were observed. The genital secretions of all inoculated mice were positive for U. urealyticum and U. parvum on culture in both liquid and solid media. TNF-α expression at 7 and 14 days after infection was markedly increased as compared with that of the controls. Morphological changes of the external genitalia included hair loss and erosions, and histological examination revealed infiltration by inflammatory cells. The five serotypes tested were all found to be pathogenic, and the pathogenicity varied with serotype 4 showing the greatest pathogenicity.

Assessing the impact of the extended-release/long-acting opioid an-algesics risk evaluation and mitigation strategies on opioid prescrip-tion volume.

OBJECTIVE: The Food and Drug Administration approved the extended-release/long-acting (ER/LA) opioid analgesics risk evaluation and mitigation strategies (REMS) in July 2012 to educate healthcare providers and patients about safe and appropriate opioid analgesic use. The authors evaluated the impact of the REMS on ER/LA opioid analgesic utilization, overall and stratified by patient characteristics and prescriber type associated with greater expected need for analgesia. DESIGN: Retrospective repeated cross-sectional study. QuintilesIMS's National Prescription Audit™ and LifeLink™ patient-level longitudinal prescription databases measured prescription volumes, projected to national estimates. MAIN OUTCOME MEASURES: Changes were assessed in ER/LA opioid analgesic prescriptions dispensed from the 2-year pre-REMS implementation (July 2010 to June 2012) to the 18-month post-REMS implementation (July 2013 to December 2014) periods (with 12-month transitional implementation period in between). RESULTS: Average quarterly ER/LA opioid prescription volume significantly decreased by 4.3 percent from Preimple-mentation to the Active Period (5.58 vs 5.34 million, p < 0.001). Differences in prescription volume change were observed between age, gender, and payer types. Prescription volume either significantly decreased or remained stable from Preimplementation to the Active Period among most provider specialties evaluated. The largest volume decreases were observed for dentists (-48.5 percent) and emergency medicine specialists (-25.5 percent) (both p < 0.001). The largest increases were observed for nurse practitioners (+33.7 percent) and physician assistants (+31.2 percent; both p < 0.001), whose overall prescribing of nonopioid medications also increased. CONCLUSIONS: A significant decrease in dispensed ER/LA opioid prescriptions was observed following REMS implementation compared to Preimplementation. The impact on volume varied by patient characteristics and prescriber specialty. The REMS program, in conjunction with other healthcare policies and initiatives, likely influenced these observations.

Possible Opioid Shopping and its Correlates.

BACKGROUND: We created an operational definition of possible opioid shopping in US commercial health insurance data and examined its correlates. METHODS: The population consisted of 264,204 treatment courses in persons with a fill for an opioid or diuretic prescription in 2012 and a second within 18 months. We examined counts of prescribers and pharmacies and the numbers of fills and overlaps for ability to discriminate courses of opioids from diuretics, which were a negative control. The most discriminatory measure, indicating possible shopping behavior, was cross-tabulated against other prescriptions filled and diagnoses as found in insurance claims. The associations between claims characteristics and shopping behavior were assessed in a logistic regression. RESULTS: A definition that classified possible "moderate" or "extensive" shopping when a person obtained drug through at least 3 practices and at least 3 pharmacies over 18 months was highly discriminatory between opioid and diuretic treatment. Overlaps between fills and number of fills did not improve the discrimination. Data from insurance claims strongly predicted moderate-to-extensive levels of possible shopping (c=0.82). Prominent among 20 significant predictors were: state of residence; amount of opioid dispensed; self-payment; use of nonspecialist prescribers; high use of anxiolytics, hypnotics, psychostimulants, and antipsychotics; and use of both immediate release and extended-release or long-acting opioids. CONCLUSIONS: The use of ≥3 prescribing practices and ≥3 dispensing pharmacies over 18 months sharply discriminated courses of opioid treatment from courses of diuretics. This pattern of fills was additionally associated with the numbers of nonspecialist and self-paid fills, the total morphine milligram equivalents dispensed, and heavier use of drugs for anxiety, sleep, attention, and psychosis.

Shopping behavior for ADHD drugs: results of a cohort study in a pharmacy database.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) medications are subject to abuse, misuse, and diversion. Obtaining ADHD prescriptions from multiple prescribers or filled across multiple pharmacies, known as 'doctor shopping', may reflect such unsanctioned use. We sought to create a definition of shopping behavior that differentiated ADHD medications from medications with low risk of diversion, i.e. asthma medications, and describe the incidence, frequency, and demography of shopping behavior. METHODS: This was a retrospective cohort study in a pharmacy database-LRx-covering 65 % of US retail pharmacies. Subjects had ADHD or asthma medication dispensed between February 2011 and January 2012. We followed subjects for 18 months to assess the number with overlapping dispensings from different prescribers, and the number of prescribers and pharmacies involved in those dispensings. RESULTS: We included 4,402,464 subjects who were dispensed ADHD medications, and 6,128,025 subjects who were dispensed asthma medications. Overlapping prescriptions from two or more prescribers dispensed by three or more pharmacies was four times more frequent in the ADHD cohort than in the asthma cohort. Using this definition, ADHD medication shopping behavior was more common among experienced users than naïve users, and was most common in subjects aged 10-39 years. Among subjects who shopped, 57.4 % shopped only once (accounting for 22.4 % of episodes), and 9.2 % shopped six or more times (accounting for 42.0 % of episodes). Shoppers more often received stimulant ADHD drugs than non-stimulants. CONCLUSIONS: Overlapping prescriptions by different prescribers and filled at three or more pharmacies defines ADHD medication shopping. Shopping behavior is most common in adolescents and younger adults. A small proportion of shoppers is responsible for a large number of shopping episodes.

Comparison of the risks of shopping behavior and opioid abuse between tapentadol and oxycodone and association of shopping behavior and opioid abuse.

OBJECTIVES: This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. MATERIALS AND METHODS: This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. RESULTS: Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. DISCUSSION: Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone.

Distance traveled and frequency of interstate opioid dispensing in opioid shoppers and nonshoppers.

UNLABELLED: Little is known about how far opioid shoppers travel or how often they cross state lines to fill their opioid prescriptions. This retrospective cohort study evaluated these measures for opioid shoppers and nonshoppers using a large U.S. prescription database. Patients with ≥3 opioid dispensings were followed for 18 months. A subject was considered a shopper when he or she filled overlapping opioid prescriptions written by >1 prescriber at ≥3 pharmacies. A heavy shopper had ≥5 shopping episodes. Outcomes assessed were distance traveled among pharmacies and number of states visited to fill opioid prescriptions. A total of 10,910,451 subjects were included; .7% developed any shopping behavior and their prescriptions accounted for 8.6% of all opioid dispensings. Shoppers and heavy shoppers were younger than the nonshoppers. Shoppers traveled a median of 83.8 miles, heavy shoppers 199.5 miles, and nonshoppers 0 miles. Almost 20% of shoppers or heavy shoppers, but only 4% of nonshoppers, visited >1 state. Shoppers traveled greater distances and more often crossed state borders to fill opioid prescriptions than nonshoppers, and their dispensings accounted for a disproportionate number of opioid dispensings. Sharing of data among prescription-monitoring programs will likely strengthen those programs and may decrease shopping behavior. PERSPECTIVE: This study shows that opioid shoppers travel greater distances and more often cross state borders to fill opioid prescriptions than nonshoppers, and their dispensings accounted for a disproportionate number of opioid dispensings. The findings support the need for data sharing among prescription-monitoring programs to deter opioid shopping behavior.

Comparison of opioid doctor shopping for tapentadol and oxycodone: a cohort study.

UNLABELLED: Obtaining opioids from multiple prescribers, known as doctor shopping, is 1 example of opioid abuse and diversion. The dual mechanism of action of tapentadol could make tapentadol less likely to be abused than other opioids. The aim of this retrospective cohort study was to compare the risk of shopping behavior between tapentadol immediate release (IR) and oxycodone IR. Subjects exposed to tapentadol or oxycodone with no recent opioid use were included and followed for 1 year. The primary outcome was the proportion of subjects who developed shopping behavior defined as subjects who had opioid prescriptions written by >1 prescriber with ≥1 day of overlap filled at ≥3 pharmacies. The opioids involved in the shopping episodes were assessed. A total of 112,821 subjects were exposed to oxycodone and 42,940 to tapentadol. Shopping behavior was seen in .8% of the subjects in the oxycodone group and in .2% of the subjects in the tapentadol group, for an adjusted odds ratio of 3.5 (95% confidence interval, 2.8 to 4.4). In the oxycodone group, 28.0% of the shopping events involved exclusively oxycodone, whereas in the tapentadol group, .6% of the shopping events involved exclusively tapentadol. Results suggest that the risk of shopping behavior is substantially lower with tapentadol than with oxycodone. PERSPECTIVE: The risk of opioid doctor shopping, ie, obtaining opioid prescriptions from multiple prescribers, is lower with tapentadol than with oxycodone.

Characteristics of prescribers whose patients shop for opioids: results from a cohort study.

BACKGROUND: Little is known about the prevalence of opioid shoppers in clinical practices and the relation between prescriber characteristics and the risk of having opioid shoppers. OBJECTIVE: Describe the prevalence of opioid shoppers in prescribers' practices. Assess the relation between prescribers' characteristics and patient opioid shopping behavior. DESIGN: Retrospective cohort study using a large US retail prescription database. PATIENTS, PARTICIPANTS: Patients with ≥1 opioid dispensing were followed 18 months. These patients' prescribers are the focus of the study. MAIN OUTCOME MEASURES: A patient was a "shopper" if he or she had opioid prescriptions written by ≥1 prescriber with ≥1 day of overlap filled at ≥3 pharmacies and a "heavy shopper" if he or she had ≥5 shopping episodes. The proportions of shoppers by prescriber and the proportion of prescribers with ≥1 shopper or heavy shopper were calculated. RESULTS: Among 858,290 opioid prescribers, most (87 percent) had no shoppers and 98 percent had no heavy shoppers. Prescribers who were aged 70-79 years, male, or who prescribed schedule II opioids had an increased likelihood of having shoppers. As the number of patients for whom a prescriber prescribed opioids increased, the proportion of shoppers also increased. Prescribers with 66 or more patients receiving opioids, who represented 25 percent of prescribers, prescribed for 82 percent of all shoppers. CONCLUSION: The great majority of opioid prescribers appear to have no shoppers in their practice. Any educational program will be more cost effective if targeted to prescribers of schedule II opioids with a large volume of patients requiring opioids.

A comparison of drug formularies and the potential for cost-savings.

BACKGROUND: Brand-name drug costs have been escalating in the United States, and the reasons for this are not immediately clear. A lack of adequate and accurate information about drug effectiveness, safety, and cost has implications for drug utilization and cost. OBJECTIVE: To explore the extent to which health plan formularies were consistent with recommended drug listings and identify what would be the potential cost-savings on total drug expenditures if the utilization rate of the recommended therapies was increased. METHOD: This study compared publicly available recommended drug listings with the formularies of 8 major health plans in Minnesota. Data from 1 of the health plans underwent an in-depth case analysis to evaluate the potential impact on pharmaceutical expenditures, using increased utilization rate scenarios of the recommended drugs. RESULTS: Health plans were similar with respect to degree of coverage for the recommended drugs. However, the case analysis showed that by increasing the utilization rate of recommended drugs, a potential cost-savings of more than 50% could be realized for the evaluated health plan for some therapeutic categories. CONCLUSION: This study demonstrates an approach to assessing drug formularies using publicly available, recommended drug lists that incorporated evidence for effectiveness, safety, and cost. By using the application of this type of reliable information, formulary changes can be guided to incentivize value-based utilization for patient populations.