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Sample records for drug utilization study

  1. Socioeconomic factors, morbidity and drug utilization--an ecological study.

    PubMed

    Henricson, K; Stenberg, P; Rametsteiner, G; Ranstam, J; Hanson, B S; Melander, A

    1998-07-01

    The aim of the present study was to elucidate the relations between demographic and socioeconomic factors, morbidity and the utilization of major drug groups in an urban Swedish population. The study was performed as an ecological analysis during November 1991 in the 17 different districts of Malmö, the third largest Swedish city (235,000 inhabitants). The material comprised 86,228 ACT-coded drug items which corresponded to 76% of all prescriptions dispensed during the study month. Of these, 43,032, dispensed to patients aged 15-64 years, were analysed in the present work. Age standardized drug utilization was expressed as the number of dispensed Defined Daily Doses per 1000 inhabitants per day. Morbidity was measured in terms of reimbursed days on sick leave. The sociodemographic parameters used were socioeconomic status (SES), employment rate, median income per family, households on social allowance, and ethnicity. For four of the five major pharmacological groups (ATC-groups A, C, J, N and R, i.e. alimentation, circulation, infectious diseases, nervous system and respiration), most pronouncedly group N and least so group R, utilization correlated positively with not only the extent of morbidity but also with an unfavourable socioeconomic situation, high proportion of immigrants, and households on social allowance or with low income and/or with a low employment rate. The utilization of antibiotics (group J), however, instead correlated negatively with these parameters. For all five drug groups, these trends were similar among men and women, albeit with varying strength. In conclusion, socioeconomic factors may have a profound influence on the utilization of several major drug groups. At least in the case of antibiotics, the consequence of this influence is irrational drug use. PMID:15073988

  2. Drug utilization study in medical emergency unit of a tertiary care hospital in north India.

    PubMed

    Kaur, Sharonjeet; Rajagopalan, Sujit; Kaur, Navjot; Shafiq, Nusrat; Bhalla, Ashish; Pandhi, Promila; Malhotra, Samir

    2014-01-01

    Objective. To generate data on the drug utilization pattern and cost of drug treatment and to determine the rationality of prescriptions. Methods. A retrospective cross-sectional drug utilization study was conducted in the medical emergency unit of our hospital. Patient case records were reviewed to extract data on the pattern of drug use. Cost of drug treatment for the emergency visit was calculated by referring to the cost mentioned in Monthly Index of Medical Specialties and the rationality of prescriptions was evaluated using WHO core indicators of drug utilization. Results. 1100 case records were reviewed. Majority of patients received proton pump inhibitors followed by multivitamins. The median cost per prescription was 119.23$ (7.32$-7663.46$). Majority (49.9%) of drug cost was driven by antibiotics alone. An average of 4.9 drugs was prescribed per prescription. There were 14.89% encounters with antibiotics. 75.17% of the drugs were given as injectables and only 29.27% of the drugs were prescribed as generics. Conclusion. There is need to rationalize the drug therapy in terms of increasing prescribing of drugs by generic name and to avoid overuse of PPIs and multivitamins in emergency unit. Also the hospital pharmacy should be encouraged to procure more cost effective alternative antibiotics in future. PMID:24883208

  3. Comparative study of paediatric prescription drug utilization between the spanish and immigrant population

    PubMed Central

    2009-01-01

    Background The immigrant population has increased greatly in Spain in recent years to the point where immigrants made up 12% of the infant population in 2008. There is little information available on the profile of this group with regard to prescription drug utilization in universal public health care systems such as that operating in Spain. This work studies the overall and specific differences in prescription drug utilization between the immigrant and Spanish population. Methods Use was made of the Aragonese Health Service databases for 2006. The studied population comprises 159,908 children aged 0-14 years, 13.6% of whom are foreign nationals. Different utilization variables were calculated for each group. Prescription-drug consumption is measured in Defined Daily Doses (DDD) and DDD/1000 persons/day/(DID). Results A total of 833,223 prescriptions were studied. Utilization is lower for immigrant children than in Spanish children for both DID (66.27 v. 113.67) and average annual expense (€21.55 v. €41.14). Immigrant children consume fewer prescription drugs than Spanish children in all of the therapy groups, with the most prescribed (in DID) being: respiratory system, anti-infectives for systemic use, nervous system, sensory organs. Significant differences were observed in relation to the type of drugs and the geographical background of immigrants. Conclusion Prescription drug utilization is much greater in Spanish children than in immigrant children, particularly with reference to bronchodilators (montelukast and terbutaline) and attention-disorder hyperactivity drugs such as methylphenidate. There are important differences regarding drug type and depending on immigrants' geographical backgrounds that suggest there are social, cultural and access factors underlying these disparities. PMID:19995453

  4. Evaluation of utility of pharmacokinetic studies in phase I trials of two oncology drugs

    PubMed Central

    Wu, Kehua; House, Larry; Ramírez, Jacqueline; Seminerio, Michael J.; Ratain, Mark J.

    2013-01-01

    Purpose There are many phase I trials of oncology drug combinations, very few of which report clinically significant pharmacokinetic interactions. We hypothesized that the utility of such pharmacokinetic drug-drug interaction (DDI) studies is low in the absence of a mechanistic hypothesis. Experimental Design We retrospectively reviewed 152 phase I (2 drug) combination studies published in 2007–2011. Results Only 28 (18%) studies had an implicit or explicit rationale, either inhibition/induction of a drug metabolizing enzyme or transporter, co-substrates for the same enzyme or transporter, potential for end-organ toxicity, or protein binding. Only 12 (8%) studies demonstrated a statistically significant DDI, based on change in clearance (or area under the curve) of parent drug and/or active metabolite. There was a strong association between a rationale and a demonstrable drug interaction, as only 2% of studies without a rationale demonstrated a DDI, compared to 32% of studies with a rationale (Fisher’s exact test, p<10−6). Conclusion DDI studies should not be routinely performed as part of phase I trials of oncology combinations. PMID:24056785

  5. Study of drug utilization pattern in dental OPD at tertiary care teaching hospital.

    PubMed

    Rehan, H S; Singh, C; Tripathi, C D; Kela, A K

    2001-01-01

    Irrational prescribing is a global phenomenon. The objective of the study was to find out the prescribing practices of dental prescribers in a tertiary care teaching hospital with special emphasis on the utilization of antimicrobial agents. A prospective study was conducted in the month of March 2000. A total of 491 prescriptions were collected randomly. Prescribing pattern was analyzed using WHO basic drug indicators. The average number of drugs for prescription was 2.4. 78.8% of all prescriptions contained antimicrobial agents. It was most commonly prescribed (40.37%) group of drugs followed by anti-inflammatory and analgesics (33.8%). Fixed dose combination of ampicillin and cloxacillin was most commonly prescribed antimicrobial agents. Prophylactic use of AMA (78%) was more than therapeutic purpose (21.9%). Prophylactic use of antimicrobial agents was irrational in all the cases as duration for the use of antimicrobial agents was 5.1 +/- 0.5 days. Fixed dose combinations (45%), drugs by brand name (98.5%) were frequently used. Drug prescribed from Essential Drug List was maximum when one drug was prescribed. Results indicate that there is a scope for improving prescribing habits and minimizing the use of antimicrobial agents. This could be facilitated by periodic education to the prescribers.

  6. Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study

    PubMed Central

    Pottegård, Anton; Broe, Anne; Hallas, Jesper; de Muckadell, Ove B. Schaffalitzky; Lassen, Annmarie T.; Lødrup, Anders B.

    2016-01-01

    Background: The use of proton-pump inhibitors (PPIs) has increased over the last decade. The objective of this study was to provide detailed utilization data on PPI use over time, with special emphasis on duration of PPI use and concomitant use of ulcerogenic drugs. Methods: Using the nationwide Danish Prescription Registry, we identified all Danish adults filling a PPI between 2002 and 2014. Using descriptive statistics, we reported (i) the distribution of use between single PPI entities, (ii) the development in incidence and prevalence of use over time, (iii) measures of duration and intensity of treatment, and (iv) the prevalence of use of ulcerogenic drugs among users of PPIs. Results: We identified 1,617,614 adults using PPIs during the study period. The prevalence of PPI use increased fourfold during the study period to 7.4% of all Danish adults in 2014. PPI use showed strong age dependency, reaching more than 20% among those aged at least 80 years. The proportion of users maintaining treatment over time increased with increasing age, with less than10% of those aged 18–39 years using PPIs 2 years after their first prescription, compared with about 40% among those aged at least 80 years. The overall use of ulcerogenic drugs among PPI users increased moderately, from 35% of users of PPI in 2002 to 45% in 2014. Conclusions: The use of PPIs is extensive and increasing rapidly, especially among the elderly. PMID:27582879

  7. Prescription patterns of antihypertensives in a community health centre in Mexico City: a drug utilization study.

    PubMed

    Alba-Leonel, Adela; Carvajal, Alfonso; Fierro, Immaculada; Castillo-Nájera, Fernando; Campos-Ramos, Oscar; Villa-Romero, Antonio; Molina-Guarneros, Juan

    2016-06-01

    Hypertension is highly prevalent; in Mexico, the 2012 National Health and Nutrition Survey reported a prevalence of hypertension of 31.5% in the adult population. Pharmacological treatment is the commonest intervention and has been shown to reduce cardiovascular mortality and morbidity, and total mortality. Accordingly, the type and number of antihypertensives used and the outcome - in terms of blood pressure (BP) control - are important. Therefore, our purpose is to learn the pattern of antihypertensive drug prescription and explore the determinants of BP control in an urban population in Mexico. A retrospective cross-sectional drug utilization study was conducted. Medical records from a community health centre were searched to identify those corresponding to patients diagnosed with hypertension; information upon antihypertensives used and control of the disease was carefully retrieved. A logistic regression model was built to know the main determinants of BP control. A sample of 345 clinical records of interest was identified. Most patients received antihypertensives (86.4%); the leading medications used were angiotensin-converting enzyme inhibitors, 63.8%; beta-blockers (26.5%), diuretics (19.8%), angiotensin-receptor blockers (15.8%) and calcium-channel blockers (6.4%). Only the age (≥55 years) and BMI (>30) of the patients, and the age of the doctors (≥55 years), had an important influence on BP control. Obesity is a particular and important determinant of uncontrolled hypertension; it is worth to act on body weight, on an individual basis. As lack of control has been also tied to elderly doctors, an education programme could be envisaged. PMID:26787266

  8. Prescription patterns of antihypertensives in a community health centre in Mexico City: a drug utilization study.

    PubMed

    Alba-Leonel, Adela; Carvajal, Alfonso; Fierro, Immaculada; Castillo-Nájera, Fernando; Campos-Ramos, Oscar; Villa-Romero, Antonio; Molina-Guarneros, Juan

    2016-06-01

    Hypertension is highly prevalent; in Mexico, the 2012 National Health and Nutrition Survey reported a prevalence of hypertension of 31.5% in the adult population. Pharmacological treatment is the commonest intervention and has been shown to reduce cardiovascular mortality and morbidity, and total mortality. Accordingly, the type and number of antihypertensives used and the outcome - in terms of blood pressure (BP) control - are important. Therefore, our purpose is to learn the pattern of antihypertensive drug prescription and explore the determinants of BP control in an urban population in Mexico. A retrospective cross-sectional drug utilization study was conducted. Medical records from a community health centre were searched to identify those corresponding to patients diagnosed with hypertension; information upon antihypertensives used and control of the disease was carefully retrieved. A logistic regression model was built to know the main determinants of BP control. A sample of 345 clinical records of interest was identified. Most patients received antihypertensives (86.4%); the leading medications used were angiotensin-converting enzyme inhibitors, 63.8%; beta-blockers (26.5%), diuretics (19.8%), angiotensin-receptor blockers (15.8%) and calcium-channel blockers (6.4%). Only the age (≥55 years) and BMI (>30) of the patients, and the age of the doctors (≥55 years), had an important influence on BP control. Obesity is a particular and important determinant of uncontrolled hypertension; it is worth to act on body weight, on an individual basis. As lack of control has been also tied to elderly doctors, an education programme could be envisaged.

  9. Study of warfarin utilization in hospitalized patients: analysis of possible drug interactions.

    PubMed

    Guidoni, Camilo Molino; Camargo, Helen Palmira Miranda; Obreli-Neto, Paulo Roque; Girotto, Edmarlon; Pereira, Leonardo Regis Leira

    2016-10-01

    Background Drug-drug interactions in patients taking warfarin may contribute to a higher risk of adverse events. Objective To identify and evaluate the prevalence and characteristics of potential DDIs with warfarin. Methods A cross-sectional study was performed in a Brazilian tertiary hospital. The electronic prescriptions of the patients receiving warfarin between January 2004 and December 2010 were analyzed. Socio-demographic, clinical, and therapeutic variables were collected. Warfarin drug-drug interactions were classified as either risk A, B, C, D, or X according to the Lexi-Interact™ Online database. Results A total of 3048 patients were identified who were prescribed warfarin. Of the 154,161 total drug prescriptions issued, 42,120 (27.3 %) were for warfarin. Evaluation of the prescriptions showed that 63.1 and 0.1 % of patients received concomitant drugs classified as having class D or X risk. It was found that 20,539 (48.7 %) prescriptions had at least one drug with a D or X risk. Patients were prescribed an average of 1.4 (±0.4) concomitant medications with a class D or X warfarin-DDI risk, the most frequent being acetylsalicylic acid and amiodarone. Conclusion The results demonstrate a high prevalence of concomitant drug prescriptions with the potential for clinically relevant DDIs with warfarin, the most frequent being acetylsalicylic acid and amiodarone. PMID:27365092

  10. Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study

    PubMed Central

    Wang, Bo; Franklin, Jessica M; Darrow, Jonathan J

    2015-01-01

    Objective To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Design Cohort study. Setting FDA approved novel therapeutics between 1987 and 2014. Population Publicly available sources provided each drug’s year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA’s four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review. Main outcome measures Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not. Results The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P<0.001), and a 2.4% increase in the proportion of drugs associated with at least one such program (odds ratio 1.024, 95% confidence interval 1.006 to 1.043, P=0.009). Driving this trend was an increase in the proportion of approved, non-first in class drugs associated with at least one program for drugs (P=0.03 for interaction). Conclusions In the past two decades, drugs newly approved by the FDA have been associated with an

  11. Management of postoperative pain in abdominal surgery in Spain. A multicentre drug utilization study

    PubMed Central

    Vallano, Antonio; Aguilera, Cristina; Arnau, Josep Maria; Baños, Josep-Eladi; Laporte, Joan-Ramon

    1999-01-01

    Participating centres: Hospital Universitario San Juan, Alicante: Maria Jesús Olaso, Javier Agulló, Clara Faura. Hospital Torrecárdenas, Almería: Carmen Fernández Sánchez, Miguel Lorenzo Campos, Juan Manuel Rodríguez Alonso. Hospital Quirúrgic Adriano, Barcelona: Carmen Alerany Pardo, Paquita Alvarez González, Teresa Martín Benito. Hospital Universitari del Mar-IMIM, Barcelona: Magí Farré, Maite Terán. Corporació Sanitària Parc Taulí, Sabadell: Montserrat Cañellas, Sergio Zavala, Josep Planell. Hospital Universitari de la Santa Creu i Sant Pau: Gonzalo Calvo, Rosa Morros, Silvia Mateo. Hospital General Vall d’Hebron, Barcelona: Carmen Bosch, María José Martínez. Hospital Universitario Virgen de la Victoria, Málaga: Maribel Lucena, José Antonio González, Gabriel Carranque. Hospital Clínico Universitario San Carlos, Madrid: Emilio Vargas, Amparo Gil López-Oliva, Míriam García Mateos. Hospital Universitario Marqués de Valdecilla, Santander: Mario González, Antonio Cuadrado. Hospital Universitario Virgen de la Macarena, Sevilla: Juan Antonio Durán, Pilar Máyquez, María Isabel Serrano. Hospital Universitario Virgen del Rocío, Sevilla: Jaume Torelló, Juan Ramón Castillo, María de las Nieves Merino. Aims Postoperative pain is common in hospital-admitted patients. Its management is determined by different therapeutic traditions and by the attitudes of health professionals in each hospital. The aim of this study was to describe the patterns of prescription and administration of analgesic drugs used for postoperative pain after abdominal surgery in Spanish hospitals, to know the prevalence and the severity of postoperative pain, and to determine the extent of variability in the management of postoperative pain among the participating centres. Methods The study was a multicentre descriptive cross-sectional drug utilization study in 12 Spanish hospitals. The subjects were an unselected sample of consecutive patients undergoing abdominal

  12. Study of Drug Utilization Pattern for Skin Diseases in Dermatology OPD of an Indian Tertiary Care Hospital - A Prescription Survey

    PubMed Central

    Pathak, Anuj Kumar; Kumar, Subodh; Kumar, Manish; Dikshit, Harihar

    2016-01-01

    Introduction Skin diseases are the major contributors of disease burden in society. It affects individuals of all ages, neonates to elderly. Owing to its chronic nature, it causes serious impact on quality of life and financial status of the sufferer and his family. The problem gets compounded with the inappropriate and irrational use of medicines. Periodic prescription audit in form of drug utilization study is a way to improve the quality of prescription and curb the menace of irrational prescribing which has become a global phenomenon. Aim This study aims to determine the drug utilization pattern and assess the economic burden of the patient with skin disease. Materials and Methods It was a prospective, cross-sectional study conducted over a period of three months from January to March 2015 in newly diagnosed cases attending outpatient department of Skin and VD, IGIMS, Patna. The prescriptions were analysed with the help of descriptive statistics and results were expressed in percentage. Results Total 752 prescriptions were analysed during the study. Male patients were lesser as compared to female as male to female ratio was 0.88. Over 50% of patients were in adolescent age group i.e. 21-40 years. Acne (17.95%) was most common disease in the study population followed by eczema and Dermatophytosis. Among the drugs, antihistaminics (24.13%) were prescribed most frequently followed by antifungals and antibiotics. Topical agents constituted almost 60% of the total prescription and average number of drugs per prescription was 5.13, irrespective of the dosage forms prescribed. Conclusion This drug utilization study provides an insight to the prescriber regarding various issues related to polypharmacy, cost analysis and prevalent disease pattern in the region. This study also suggests periodic evaluation of prescription pattern to monitor and improve quality of prescription in other departments of the hospital. PMID:27042479

  13. Drug utilization patterns and reported health status in ethnic German migrants (Aussiedler) in Germany: a cross-sectional study

    PubMed Central

    2011-01-01

    Background Inadequate utilization of healthcare services by migrant populations is an important public health concern. Inadequate drug consumption and poor compliance to the therapeutic regimen are common manifestations of low health-care seeking behavior present in migrants even in the countries with well-established healthcare systems. There are few studies on the use of medicines among the different groups of migrants in Germany. The objective of this study is to investigate drug consumption patterns of ethnic German migrants (Aussiedler) and their current health status. Methods A cross-sectional study nested into a cohort of 18,621 individuals aged 20-70 years who migrated to Germany from the former Soviet Union between 1990 and 2005 was conducted. Data on consumption of drugs, drug handling, major health risk factors, and one-year disease prevalence were obtained for 114 individuals through a self-administered questionnaire and phone interviews. Results were compared to the data on the German population derived from the Disease Analyzer database and Robert Koch Institute (RKI) annual reports. Direct age standardization, test of differences, Chi-square test, and descriptive statistics were applied as appropriate. For drug classification the Anatomical Therapeutic Chemical (ATC) system was used. Results Of the respondents, 97% reported to have at least one disease within a 12-month period. The one-year prevalence of asthma (6.9%), hypertension (26.7%), chronic bronchitis (8.6%), and diabetes (4.9%) in migrants was similar to the general German population. 51% regularly took either over-the-counter (OTC) medication or prescription medicines. Six ATC groups were analyzed. The highest drug consumption was reported for the ATC cardiovascular (22%), nervous (9%), and muskulo-skeletal system (8%). 30% used OTC medicines obtained in the country of origin. Difficulties with drug handling were rare. Alcohol consumption did not differ from the German population (p = 0

  14. Patterns of finasteride use in the male populations of four Nordic countries: A cross-national drug utilization study.

    PubMed

    Kjærulff, T M; Ersbøll, A K; Green, A; Emneus, M; Pukkala, E; Bolin, K; Stavem, K; Iversen, P; Brasso, K; Hallas, J; Thygesen, L C

    2016-06-01

    Objective Finasteride 5 mg is a drug used to treat prostate hyperplasia. Little is known about its pattern of usage. This cross-national analysis of individual-level data from Denmark, Finland, Norway and Sweden was undertaken to appraise its usage and describe cross-national differences. Materials and methods Individual-level data from nationwide prescription registers in Denmark (1995-2009), Finland (1997-2010), Norway (2004-2009) and Sweden (July 2005-2011) were used to examine cross-national finasteride utilization patterns in the adult male population (≥15 years). The study presents period prevalences, incidence rates, waiting time distributions and Lorenz curves. Results During the study period, 295,620 men had at least one prescription redemption of finasteride 5 mg, and there were approximately 3 million dispensing events of finasteride prescriptions in the four Nordic countries. Different patterns of finasteride use were observed among the four Nordic countries. The period prevalence was markedly higher in Finland and Sweden than in Denmark and Norway. In 2009, period prevalences were 18.2/1000 males in Finland and 12.0/1000 males in Sweden compared to 6.7/1000 males in Norway and 4.9/1000 males in Denmark. Incidence rates of finasteride use for Finland, Norway and Sweden were about three times that for Denmark in 2008-2009. Long-term use of finasteride was found in all four Nordic countries with a high ratio between prevalent and incident users. Conclusion Despite resemblances regarding political systems and healthcare services in the Nordic countries, differences in finasteride utilization were found across Denmark, Finland, Norway and Sweden. PMID:26901820

  15. Rural drug users: factors associated with substance abuse treatment utilization.

    PubMed

    Oser, Carrie B; Leukefeld, Carl G; Tindall, Michele Staton; Garrity, Thomas F; Carlson, Robert G; Falck, Russel; Wang, Jichuan; Booth, Brenda M

    2011-06-01

    The purpose of this study is to use a modified version of Andersen's Behavioral Model of Health Services Use to identify the correlates of the number of substance abuse treatment episodes received by rural drug users. Data were collected from face-to-face interviews with 711 drug users in rural areas of Ohio, Arkansas, and Kentucky. Descriptive analyses examine rural drug users' substance use histories and retrospective substance abuse treatment service utilization patterns. A negative binomial regression model indicated that selected predisposing, historical health, and enabling factors were significantly associated with the utilization of substance abuse treatment among rural drug users. Despite high levels of recent and lifetime self-reported substance use among these rural drug users, treatment services were underutilized. Future studies are needed to examine the impact of the health care system and characteristics of the external environment associated with rural substance abuse treatment in order to increase utilization among drug users.

  16. Age- and Sex-related Prevalence and Drug Utilization Pattern in the Management of Type 2 Diabetes Mellitus and its Comorbidity with Cardiovascular Diseases: A Comparative Study.

    PubMed

    Das, S; Haroled Peter, P L; Bhavani, M Lakshmi; Naresh, P; Ramana, M V

    2015-01-01

    A cross-sectional study of 250 cases of type 2 diabetes management was conducted in a governmental tertiary care hospital of urban south India to determine the comparative prevalence of type 2 diabetes and its comorbidity with cardiovascular diseases in diabetic population, core drug use indicators and drug utilization pattern in the management of diabetics entirely and with cardiovascular diseases. Highest prevalent age group for type 2 diabetes/cardiovascular diseases (greater incidence in female than male) was 51-60 years. The 62.8% prevalence of cardiovascular diseases in the diabetic population ascertained in the study could provide an evidence-based rationale for the World Health Organization guidelines for the management of hypertension in type 2 diabetics. Incidence of polypharmacy (6.06, the mean number of total drug products prescribed); 59.26% of encounters prescribed antibiotics; 17.6 and 18.5 min of average consultation and dispensing time, respectively; 100% of drugs actually dispensed and adequately labeled; 81.26% of patients having knowledge of correct dosage and average drug cost of Indian Rupees 145.54 per prescription were the core drug use indicators found mainly. Moreover, drugs prescribed from the Essential Drug List were more than 90% and thereby indicated the drug use in this set-up quite rational. Around 71.09% of cardiovascular agents prescribed by generic name revealed the cost effective medical care. Among the agents in type 2 diabetes management, Actrapid(®) (35.43%) was the highest. Among the cardiovascular agents prescribed, lasix (19.37%) was the highest. Cardiovascular agents prescribed orally by 76.48% signified the good prescription habit indicating the improved patients' adherence to the treatment. The present study emphasizes the need of early detection of hypertension as a preliminary diagnostic parameter of cardiovascular diseases in diabetics and appropriate management through concomitant therapy of cardiovascular drugs to

  17. Age- and Sex-related Prevalence and Drug Utilization Pattern in the Management of Type 2 Diabetes Mellitus and its Comorbidity with Cardiovascular Diseases: A Comparative Study.

    PubMed

    Das, S; Haroled Peter, P L; Bhavani, M Lakshmi; Naresh, P; Ramana, M V

    2015-01-01

    A cross-sectional study of 250 cases of type 2 diabetes management was conducted in a governmental tertiary care hospital of urban south India to determine the comparative prevalence of type 2 diabetes and its comorbidity with cardiovascular diseases in diabetic population, core drug use indicators and drug utilization pattern in the management of diabetics entirely and with cardiovascular diseases. Highest prevalent age group for type 2 diabetes/cardiovascular diseases (greater incidence in female than male) was 51-60 years. The 62.8% prevalence of cardiovascular diseases in the diabetic population ascertained in the study could provide an evidence-based rationale for the World Health Organization guidelines for the management of hypertension in type 2 diabetics. Incidence of polypharmacy (6.06, the mean number of total drug products prescribed); 59.26% of encounters prescribed antibiotics; 17.6 and 18.5 min of average consultation and dispensing time, respectively; 100% of drugs actually dispensed and adequately labeled; 81.26% of patients having knowledge of correct dosage and average drug cost of Indian Rupees 145.54 per prescription were the core drug use indicators found mainly. Moreover, drugs prescribed from the Essential Drug List were more than 90% and thereby indicated the drug use in this set-up quite rational. Around 71.09% of cardiovascular agents prescribed by generic name revealed the cost effective medical care. Among the agents in type 2 diabetes management, Actrapid(®) (35.43%) was the highest. Among the cardiovascular agents prescribed, lasix (19.37%) was the highest. Cardiovascular agents prescribed orally by 76.48% signified the good prescription habit indicating the improved patients' adherence to the treatment. The present study emphasizes the need of early detection of hypertension as a preliminary diagnostic parameter of cardiovascular diseases in diabetics and appropriate management through concomitant therapy of cardiovascular drugs to

  18. Drug utilization and teratogenicity risk categories during pregnancy.

    PubMed

    Basgül, Alin; Akici, Ahmet; Uzuner, Arzu; Kalaça, Sibel; Kavak, Zehra N; Tural, Alper; Oktay, Sule

    2007-01-01

    A limited number of studies have investigated in detail the use of drugs during pregnancy. Researchers in the present study investigated the details of drug utilization in pregnant women during the month before pregnancy, at the time that they became aware of the pregnancy, and during the first trimester. Face-to-face interviews were conducted with 359 pregnant women who were admitted to the fetal medicine unit at a university hospital for diagnosis and follow-up. A questionnaire was used to document sociodemographic characteristics and details of drug use. Drugs were categorized according to the US Food and Drug Administration fetal risk classification. Mean maternal age was 29.9+/-5.1 y, and mean gestational age was 19.6+/-9.5 wk. Many of the pregnant women studied (46.6%) were university graduates, and most (61.9%) had a relatively high annual income. Mean gestational age when participants first learned of their pregnancy was 39.8+/-16.4 d. One hundred seventeen participants (32.6%) used drugs during the month before conception, 54 (15%) at the time when they learned of their pregnancy, 180 (50.1%) at the time of the interview, and 289 (80.5%) during the first trimester. The percentages of drugs in categories D and X used by these subjects were 14%, 13.5%, 2.9%, and 5.9%, respectively. Most of the drugs were hormones. The total rate of drug utilization was not high before and during the first trimester of pregnancy. A considerable number of women were using drugs from the D and X categories; however, these numbers decreased significantly when women learned of their pregnancies. Intake of folic acid, vitamins, and iron was very low during the preconception period and was not high enough during the first trimester; this suggests that particular attention should be paid to the use of beneficial "safe" drugs during the preconception and early pregnancy periods.

  19. Ten-Year Trends in the Morbidity of Diabetes Mellitus and Antidiabetic Drug Utilization in Croatia: A Study Based on Routinely Collected Data.

    PubMed

    Pavlov, Renata; Topličan, Ivančica; Vrcić Keglević, Mladenka

    2016-01-01

    Objectives. To investigate trends of diabetes mellitus (DM) morbidity and antidiabetic drug utilization in Croatian primary health care (PHC) from 2005 to 2014. Method. Routinely collected morbidity data from all PHC units, presented in Croatian health-statistics yearbooks, were retrieved. Data on drug utilization were retrieved from the Annual Reports of the Croatian Agency for Medicinal Products and Medical Devices (ATC/DDD, antidiabetic, A10). Results. Total morbidity increased by 33.3% and DM increased by 65.6%, mostly in patients over age 65 (from 50% to 57%). Estimated DM prevalence in adults increased from 3.9% to 6.4%. Increased morbidity was followed by an even higher increase in drug utilization (120%). Metformin was first, with a constant increase (from 18% to 39%), followed by glimepiride, while glibenclamide use decreased. Total utilization of insulin increased even more, mostly for aspart (600%) and newly introduced glargine and detemir, while human insulin usage sharply decreased. Spending also increased, mostly for aspart (from 21% to 61% of total). Conclusions. Increased DM is followed by a higher increase in antidiabetic drug utilization; this trend will continue in the future. In Croatian PHC, metformin has primacy along with insulin analogues. PMID:27462470

  20. Ten-Year Trends in the Morbidity of Diabetes Mellitus and Antidiabetic Drug Utilization in Croatia: A Study Based on Routinely Collected Data

    PubMed Central

    Topličan, Ivančica; Vrcić Keglević, Mladenka

    2016-01-01

    Objectives. To investigate trends of diabetes mellitus (DM) morbidity and antidiabetic drug utilization in Croatian primary health care (PHC) from 2005 to 2014. Method. Routinely collected morbidity data from all PHC units, presented in Croatian health-statistics yearbooks, were retrieved. Data on drug utilization were retrieved from the Annual Reports of the Croatian Agency for Medicinal Products and Medical Devices (ATC/DDD, antidiabetic, A10). Results. Total morbidity increased by 33.3% and DM increased by 65.6%, mostly in patients over age 65 (from 50% to 57%). Estimated DM prevalence in adults increased from 3.9% to 6.4%. Increased morbidity was followed by an even higher increase in drug utilization (120%). Metformin was first, with a constant increase (from 18% to 39%), followed by glimepiride, while glibenclamide use decreased. Total utilization of insulin increased even more, mostly for aspart (600%) and newly introduced glargine and detemir, while human insulin usage sharply decreased. Spending also increased, mostly for aspart (from 21% to 61% of total). Conclusions. Increased DM is followed by a higher increase in antidiabetic drug utilization; this trend will continue in the future. In Croatian PHC, metformin has primacy along with insulin analogues. PMID:27462470

  1. Can Walmart make us healthier? Prescription drug prices and health care utilization.

    PubMed

    Borrescio-Higa, Florencia

    2015-12-01

    This paper analyzes how prices in the retail pharmaceutical market affect health care utilization. Specifically, I study the impact of Walmart's $4 Prescription Drug Program on utilization of antihypertensive drugs and on hospitalizations for conditions amenable to drug therapy. Identification relies on the change in the availability of cheap drugs introduced by Walmart's program, exploiting variation in the distance to the nearest Walmart across ZIP codes in a difference-in-differences framework. I find that living close to a source of cheap drugs increases utilization of antihypertensive medications by 7 percent and decreases the probability of an avoidable hospitalization by 6.2 percent.

  2. Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.

    PubMed

    Fan, Fan; Hu, Rong; Munzli, Anke; Chen, Yuan; Dunn, Robert T; Weikl, Kerstin; Strauch, Simone; Schwandner, Ralf; Afshari, Cynthia A; Hamadeh, Hisham; Nioi, Paul

    2015-06-01

    Off-target effects of drugs on nuclear hormone receptors (NHRs) may result in adverse effects in multiple organs/physiological processes. Reliable assessments of the NHR activities for drug candidates are therefore crucial for drug development. However, the highly permissive structures of NHRs for vastly different ligands make it challenging to predict interactions by examining the chemical structures of the ligands. Here, we report a detailed investigation on the agonistic and antagonistic activities of 615 known drugs or drug candidates against a panel of 6 NHRs: androgen, progesterone, estrogen α/β, and thyroid hormone α/β receptors. Our study revealed that 4.7 and 12.4% compounds have agonistic and antagonistic activities, respectively, against this panel of NHRs. Nonetheless, potent, unintended NHR hits are relatively rare among the known drugs, indicating that such interactions are perhaps not tolerated during drug development. However, we uncovered examples of compounds that unintentionally agonize or antagonize NHRs. In addition, a number of compounds showed multi-NHR activities, suggesting that the cross-talk between multiple NHRs co-operate to elicit in vivo effects. These data highlight the merits of counter screening drug candidate against NHRs during drug discovery/development.

  3. Tribal Utility Feasibility Study

    SciTech Connect

    Engel, R. A.; Zoellick, J. J.

    2007-06-30

    The Schatz Energy Research Center (SERC) assisted the Yurok Tribe in investigating the feasibility of creating a permanent energy services program for the Tribe. The original purpose of the DOE grant that funded this project was to determine the feasibility of creating a full-blown Yurok Tribal electric utility to buy and sell electric power and own and maintain all electric power infrastructure on the Reservation. The original project consultant found this opportunity to be infeasible for the Tribe. When SERC took over as project consultant, we took a different approach. We explored opportunities for the Tribe to develop its own renewable energy resources for use on the Reservation and/or off-Reservation sales as a means of generating revenue for the Tribe. We also looked at ways the Tribe can provide energy services to its members and how to fund such efforts. We identified opportunities for the development of renewable energy resources and energy services on the Yurok Reservation that fall into five basic categories: • Demand-side management – This refers to efforts to reduce energy use through energy efficiency and conservation measures. • Off-grid, facility and household scale renewable energy systems – These systems can provide electricity to individual homes and Tribal facilities in areas of the Reservation that do not currently have access to the electric utility grid. • Village scale, micro-grid renewable energy systems - These are larger scale systems that can provide electricity to interconnected groups of homes and Tribal facilities in areas of the Reservation that do not have access to the conventional electric grid. This will require the development of miniature electric grids to serve these interconnected facilities. • Medium to large scale renewable energy development for sale to the grid – In areas where viable renewable energy resources exist and there is access to the conventional electric utility grid, these resources can be

  4. The anticipatory effects of Medicare Part D on drug utilization.

    PubMed

    Alpert, Abby

    2016-09-01

    While health care policies are frequently signed into law well before they are implemented, such lags are ignored in most empirical work. This paper demonstrates the importance of implementation lags in the context of Medicare Part D, the prescription drug benefit that took effect two years after it was signed into law. Exploiting the differential responses of chronic and acute drugs to anticipated future prices, I show that individuals reduced drug utilization for chronic but not acute drugs in anticipation of Part D's implementation. Accounting for this anticipatory response substantially reduces the estimated total treatment effect of Part D. PMID:27372577

  5. Emergency department utilization and subsequent prescription drug overdose death

    PubMed Central

    Brady, Joanne E.; DiMaggio, Charles J.; Keyes, Katherine M.; Doyle, John J.; Richardson, Lynne D.; Li, Guohua

    2015-01-01

    Purpose Prescription drug overdose (PDO) deaths are a critical public health problem in the United States. This study aims to assess the association between emergency department (ED) utilization patterns in a cohort of ED patients and the risk of subsequent unintentional PDO mortality. Methods Using data from the New York Statewide Planning and Research Cooperative System for 2006–2010, a nested case-control design was used to examine the relationship between ED utilization patterns in New York State residents of age 18–64 years and subsequent PDO death. Results The study sample consisted of 2732 case patients who died of PDO and 2732 control ED patients who were selected through incidence density sampling. With adjustment for demographic characteristics, and diagnoses of pain, substance abuse, and psychiatric disorders, the estimated odds ratios of PDO death relative to one ED visit or less in the previous year were 4.90 (95% confidence interval [CI]: 4.50–5.34) for those with two ED visits, 16.61 (95% CI: 14.72–18.75) for those with three ED visits, and 48.24 (95% CI: 43.23–53.83) for those with four ED visits or more. Conclusions Frequency of ED visits is strongly associated with the risk of subsequent PDO death. Intervention programs targeting frequent ED users are warranted to reduce PDO mortality. PMID:25935710

  6. Drug utilization in selected health facilities of South West Shoa Zone, Oromia Region, Ethiopia

    PubMed Central

    Kebede, Mengistu; Kebebe Borga, Dereje; Mulisa Bobasa, Eshetu

    2015-01-01

    Background Sustaining the availability and rational use of safe and effective drugs is a major problem in developing countries. Irrational drug use affects quality of health care more than accessibility of drugs. Objective To assess drug utilization in selected health facilities of South West Shoa Zone, Oromia Region, Ethiopia. Methods A cross-sectional study was conducted in selected health facilities of South West Shoa Zone from January 21–28, 2012 by using structured questionnaires. Results Of 50 prescribers and 30 dispensers, 58% and 83.3% were males, respectively. The result showed that majority of prescribers agreed on availability of essential drugs (72%) and had access to up-to-date drug information (76%). However, 43.3% of dispensers didn’t get access to up-to-date drug information. 86% and 88% of prescribers note cost of drugs and stick to standard treatment guidelines of Ethiopia during prescription, respectively. All drug dispensers check the name of the drug (100%), age of the patient (90%), the dosage form of drug (96.7%), the route of administration (90%), the duration of therapy (86.7%), and frequency of administration (86.7%) for prescription papers. Conclusion In general, drug utilization at the study sites was found to be good, although there are major deviations from the concept of rational drug use. PMID:26229506

  7. Forecasting drug utilization and expenditure in a metropolitan health region

    PubMed Central

    2010-01-01

    Background New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning), forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011. Methods Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee. Results The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs. Conclusions The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate of adoption of new

  8. Medical cost offsets from prescription drug utilization among Medicare beneficiaries.

    PubMed

    Roebuck, M Christopher

    2014-10-01

    This brief commentary extends earlier work on the value of adherence to derive medical cost offset estimates from prescription drug utilization. Among seniors with chronic vascular disease, 1% increases in condition-specific medication use were associated with significant (P  less than  0.001) reductions in gross nonpharmacy medical costs in the amounts of 0.63% for dyslipidemia, 0.77% for congestive heart failure, 0.83% for diabetes, and 1.17% for hypertension. PMID:25278321

  9. [Development of topical drug delivery systems utilizing polymeric materials].

    PubMed

    Machida, Y

    1993-05-01

    Topical drug delivery is important from the view points of improvement of therapeutic effect and reduction of systemic side effects. Utilization of polymeric materials seemed to be as a key for the development of new topical dosage forms including targeting drug delivery systems. Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose (HPC) according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content. Double-layered mucoadhesive sticks for the treatment of uterine cervix cancer were prepared by direct compression of powder mixture of bleomycin, HPC and carboxyvinyl polymer (CP). Drug release property of the sticks could be controlled by the weight of outer layer, drug combining ratio to each layer and coating of core layer. The results suggested a possibility of a "once-a-week" treatment that is preferable for the patients. Magnetic granules for the treatment of esophageal cancer were prepared using ferrite, HPC and CP. Magnetic guidance and retainment of the granules on esophageal mucosa were confirmed using rabbits in vivo. Buoyant sustained release preparations were prepared using chitosan, soybean protein, HPC and other polymers. Usefulness of the buoyant preparations was suggested from the results in vitro and in vivo. Insulin microspheres (IMS) for targeting delivery to the small intestine were prepared by the newly developed method. Employment of enteric coating material (Eudragit) and combination of protease inhibitor protected insulin from enzymatic attack and gave decreased levels of blood glucose by oral administration.

  10. Administrative Utility Analysis: Study Summary.

    ERIC Educational Resources Information Center

    Peat, Marwick, Mitchell and Co., San Juan, Puerto Rico.

    This document summarizes the recommendations made as a result of a study on administrative utility analysis and vocational education programs for Puerto Rico. The major recommendation was that the Area of Vocational and Technical Education (AVTE) in the Puerto Rico Department of Education be restructured at the central organizational level, for…

  11. Space platform utilities distribution study

    NASA Technical Reports Server (NTRS)

    Lefever, A. E.

    1980-01-01

    Generic concepts for the installation of power data and thermal fluid distribution lines on large space platforms were discussed. Connections with central utility subsystem modules and pallet interfaces were also considered. Three system concept study platforms were used as basepoints for the detail development. The tradeoff of high voltage low voltage power distribution and the impact of fiber optics as a data distribution mechanism were analyzed. Thermal expansion and temperature control of utility lines and ducts were considered. Technology developments required for implementation of the generic distribution concepts were identified.

  12. Utility of population pharmacokinetic modeling in the assessment of therapeutic protein-drug interactions.

    PubMed

    Chow, Andrew T; Earp, Justin C; Gupta, Manish; Hanley, William; Hu, Chuanpu; Wang, Diane D; Zajic, Stefan; Zhu, Min

    2014-05-01

    Assessment of pharmacokinetic (PK) based drug-drug interactions (DDI) is essential for ensuring patient safety and drug efficacy. With the substantial increase in therapeutic proteins (TP) entering the market and drug development, evaluation of TP-drug interaction (TPDI) has become increasingly important. Unlike for small molecule (e.g., chemical-based) drugs, conducting TPDI studies often presents logistical challenges, while the population PK (PPK) modeling may be a viable approach dealing with the issues. A working group was formed with members from the pharmaceutical industry and the FDA to assess the utility of PPK-based TPDI assessment including study designs, data analysis methods, and implementation strategy. This paper summarizes key issues for consideration as well as a proposed strategy with focuses on (1) PPK approach for exploratory assessment; (2) PPK approach for confirmatory assessment; (3) importance of data quality; (4) implementation strategy; and (5) potential regulatory implications. Advantages and limitations of the approach are also discussed.

  13. Internalized HIV and Drug Stigmas: Interacting Forces Threatening Health Status and Health Service Utilization Among People with HIV Who Inject Drugs in St. Petersburg, Russia.

    PubMed

    Calabrese, Sarah K; Burke, Sara E; Dovidio, John F; Levina, Olga S; Uusküla, Anneli; Niccolai, Linda M; Heimer, Robert

    2016-01-01

    Marked overlap between the HIV and injection drug use epidemics in St. Petersburg, Russia, puts many people in need of health services at risk for stigmatization based on both characteristics simultaneously. The current study examined the independent and interactive effects of internalized HIV and drug stigmas on health status and health service utilization among 383 people with HIV who inject drugs in St. Petersburg. Participants self-reported internalized HIV stigma, internalized drug stigma, health status (subjective rating and symptom count), health service utilization (HIV care and drug treatment), sociodemographic characteristics, and health/behavioral history. For both forms of internalized stigma, greater stigma was correlated with poorer health and lower likelihood of service utilization. HIV and drug stigmas interacted to predict symptom count, HIV care, and drug treatment such that individuals internalizing high levels of both stigmas were at elevated risk for experiencing poor health and less likely to access health services.

  14. Thermodynamic Studies for Drug Design and Screening

    PubMed Central

    Garbett, Nichola C.; Chaires, Jonathan B.

    2012-01-01

    Introduction A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. Areas covered This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 – 2011 using the Science Citation Index and PUBMED and the keywords listed below. Expert opinion The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically-driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development towards an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. PMID:22458502

  15. An informatics approach to assess pediatric pharmacotherapy: design and implementation of a hospital drug utilization system.

    PubMed

    Zuppa, Athena; Vijayakumar, Sundararajan; Jayaraman, Bhuvana; Patel, Dimple; Narayan, Mahesh; Vijayakumar, Kalpana; Mondick, John T; Barrett, Jeffrey S

    2007-09-01

    Drug utilization in the inpatient setting can provide a mechanism to assess drug prescribing trends, efficiency, and cost-effectiveness of hospital formularies and examine subpopulations for which prescribing habits may be different. Such data can be used to correlate trends with time-dependent or seasonal changes in clinical event rates or the introduction of new pharmaceuticals. It is now possible to provide a robust, dynamic analysis of drug utilization in a large pediatric inpatient setting through the creation of a Web-based hospital drug utilization system that retrieves source data from our accounting database. The production implementation provides a dynamic and historical account of drug utilization at the authors' institution. The existing application can easily be extended to accommodate a multi-institution environment. The creation of a national or even global drug utilization network would facilitate the examination of geographical and/or socioeconomic influences in drug utilization and prescribing practices in general. PMID:17656617

  16. Utilizing the protein corona around silica nanoparticles for dual drug loading and release

    NASA Astrophysics Data System (ADS)

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-01

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration

  17. The Association between Stimulant, Opioid, and Multiple Drug Use on Behavioral Healthcare Utilization in a Safety-Net Health System

    PubMed Central

    Calcaterra, Susan L; Keniston, Angela; Blum, Joshua; Crume, Tessa; Binswanger, Ingrid A

    2016-01-01

    Background Prior studies show an association between drug use and healthcare utilization. The relationship between specific drug type and emergent/urgent, inpatient, outpatient and behavioral healthcare utilization has not been examined. We aimed to determine if multiple drug use was associated with increased utilization of behavioral healthcare. Methods To assess healthcare utilization, we conducted a retrospective cohort study of patients who accessed healthcare at a safety-net medical center and affiliated clinics. Using electronic health records, we categorized patients who used stimulants, opioids, or multiple drugs based on urine toxicology screening tests and/or International Classification of Diseases, 9th Revision (ICD-9). Remaining patients were categorized as patients without identified drug use. Healthcare utilization by drug use group and visit type was determined using a negative binomial regression model. Associations were reported as incidence rate ratios. Utilization was described by rates of healthcare-related visits for inpatient, emergent/urgent, outpatient, and behavioral healthcare among patients who used drugs, categorized by drug types, compared to patients without identified drug use. Results Of 95,198 index visits, 4.6% (n=4,340) were by patients who used drugs. Opioid and multiple drug users had significantly higher rates of behavioral healthcare visits than patients without identified drug use (opioid incidence rate ratio [IRR]=7.2; 95% confidence interval [CI] 3.8–13.8; multiple drug use IRR=5.6, 95% CI 3.3–9.7). Patients who used stimulants were less likely to use behavioral health services (IRR=1.3, 95% CI 0.9–2.0) when compared to opioid and multiple drug users, but were more likely to use inpatient (IRR=1.6, 95% CI 1.4–1.8) and emergent/urgent care (IRR=1.4, 95% CI 1.3–1.5) services as compared to patients without identified drug use. Conclusions Integrated medical and mental healthcare and drug treatment may reduce

  18. TWRS LDUA utilization study report

    SciTech Connect

    Rieck, R.H.

    1994-09-01

    Tank Waste Remediation Systems functional requirements were reviewed. The Light Duty Utility Arm capabilities were considered as a means to support completion of these functional requirements. The recommendation is made to continue to develop the LDUA, integrating TWRS functional needs into the design to better support completion of TWRS mission needs.

  19. Undesirable blood pressure changes under naturalistic treatment with moclobemide, a reversible MAO-A inhibitor--results of the drug utilization observation studies.

    PubMed

    Delini-Stula, A; Baier, D; Kohnen, R; Laux, G; Philipp, M; Scholz, H J

    1999-03-01

    Blood pressure decrease, associated with postural hypotension, as well as spontaneous hypertension are considered to be typical side-effects of conventional, irreversible and nonselective MAO (A+B) inhibitors. The new generation of reversible MAO-A inhibitors is, however, expected to have negligible cardiovascular effects and low propensity to induce either blood pressure increases or decreases. But, the true incidence of such changes is largely unknown since observation studies, specifically assessing the frequency of blood pressure changes, in unselected population of patients treated in the practice, are lacking.

  20. Medical and psychosocial services in drug abuse treatment: do stronger linkages promote client utilization?

    PubMed Central

    Friedmann, P D; D'Aunno, T A; Jin, L; Alexander, J A

    2000-01-01

    OBJECTIVE: To examine the extent to which linkage mechanisms (on-site delivery, external arrangements, case management, and transportation assistance) are associated with increased utilization of medical and psychosocial services in outpatient drug abuse treatment units. DATA SOURCES: Survey of administrative directors and clinical supervisors from a nationally representative sample of 597 outpatient drug abuse treatment units in 1995. STUDY DESIGN: We generated separate two-stage multivariate generalized linear models to evaluate the correlation of on-site service delivery, formal external arrangements (joint program/venture or contract), referral agreements, case management, and transportation with the percentage of clients reported to have utilized eight services: physical examinations, routine medical care, tuberculosis screening, HIV treatment, mental health care, employment counseling, housing assistance, and financial counseling services. PRINCIPAL FINDINGS: On-site service delivery and transportation assistance were significantly associated with higher levels of client utilization of ancillary services. Referral agreements and formal external arrangements had no detectable relationship to most service utilization. On-site case management was related to increased clients' use of routine medical care, financial counseling, and housing assistance, but off-site case management was not correlated with utilization of most services. CONCLUSIONS: On-site service delivery appears to be the most reliable mechanism to link drug abuse treatment clients to ancillary services, while referral agreements and formal external mechanisms offer little detectable advantage over ad hoc referral. On-site case management might facilitate utilization of some services, but transportation seems a more important linkage mechanism overall. These findings imply that initiatives and policies to promote linkage of such clients to medical and psychosocial services should emphasize on

  1. Drug utilization and morbidity statistics for the evaluation of drug safety in Sweden.

    PubMed

    Wiholm, B E; Westerholm, B

    1984-01-01

    For a continuous monitoring and evaluation of drug safety problems in Sweden, the Department of Drugs of the National Board of Health and Welfare has access to a number of computerised patient-, drug-, and disease-oriented registers. The usefulness and limitations of these registers are presented by examples. A recent increase in asthma deaths is presently being analysed by comparing information from death certificates and case records with drug sales and prescription data. A recent analysis of the cancer register showed no increased risk of malignant thyroid tumors after diagnostic or therapeutic doses of I 131. Similarly no increased risk of malformations after occupational exposure to hexachlorophene could be detected by analysing the malformation and medical birth-record registers in relation to hospital hexachlorophene use. The register of patient discharge diagnoses has been repeatedly used to analyse the incidence and pattern of drug induced blood dyscrasias and thromboembolism associated with oral contraceptives (OC). These analyses have resulted i.a. in the withdrawal of dipyrone and tenalidine and a decrease of the estrogen-content of OCs. At the same time about 1/3 of these serious adverse drug reactions (ADR) was found to have been reported to the ADR-register. By combining sales and prescription data with ADR-reports the risk of inducing lactic acidosis was found to be significantly higher for phenformin than for metformin. Also the incidence of tardive dyskinesia from longterm use of metoclopramide was found to be much higher than hitherto recognized. By use of these registers it is possible to obtain valuable information about the safety of drugs. The raw data must, however, be interpreted with care and often be supplemented with in depth studies of the various problems. PMID:6430038

  2. Profile of drug utilization in the elderly living in Porto Alegre, Brazil

    PubMed Central

    Tôrres Faggiani, Fabiana; Schroeter, Guilherme; Luz Pacheco, Sandro; Araújo De Souza, Antônio Carlos; Werlang, Maria Cristina; Attílio De Carli, Geraldo; Bueno Morrone, Fernanda

    The elderly population is one of the most rapidly increasing populations in the world. Physiological alterations induced by the aging process make these individuals more susceptible to chronic diseases and, consequently, to increased drug utilization. Objective To describe the profile of drug utilization in the elderly living in Porto Alegre, RS, Brazil. Methods An observational and cross-sectional population-based study to investigate the characteristics of the population, sources of information and types of drugs used by the elderly was performed. Four hundred and eighty patients were recruited from data supplied by the City Hall of Porto Alegre. The elderly were interviewed individually during the period from January to May 2006 by trained interviewers. A validated pharmacotherapy questionnaire was used for data collection and data were tabulated and analyzed by the SPSS 11.5 computer program. Results Of the 480 patients interviewed, 13.8% did not use any medication. Cardiovascular system drugs represented the pharmacological class most used by the elderly (64.0%). When ill, 71.9% of these individuals visited the doctor, while 36.9% self-medicated. For the majority (50.2%), drugs were identified by their labels. Only 41.2% of the elderly understood medical prescriptions and 68.3% of the patients studied obtained the necessary information for the appropriate use of therapy from their doctors. Conclusions The present study suggests that a pharmaceutical care program for the treatment, prevention, and use of medications may provide a higher efficiency to elderly drug therapy. PMID:25170356

  3. Utility of Ion Mobility Mass Spectrometry for Drug-to-Antibody Ratio Measurements in Antibody-Drug Conjugates

    NASA Astrophysics Data System (ADS)

    Huang, Richard Y.-C.; Deyanova, Ekaterina G.; Passmore, David; Rangan, Vangipuram; Deshpande, Shrikant; Tymiak, Adrienne A.; Chen, Guodong

    2015-06-01

    Antibody-drug conjugates (ADCs) are emerging modalities in the pharmaceutical industry. Characterization of ADC's drug-to-antibody ratio (DAR) becomes a key assessment because of its importance in ADC efficacy and safety. DAR characterization by conventional intact protein MS analysis, however, is challenging because of high heterogeneity of ADC samples. The analysis often requires protein deglycosylation, disulfide-bond reduction, or partial fragmentation. In this study, we illustrate the practical utility of ion mobility mass spectrometry (IM-MS) in a routine LC/MS workflow for DAR measurements. This strategy allows analyte "cleanup" in the gas phase, providing significant improvement of signal-to-noise ratios of ADC intact mass spectra for accurate DAR measurements. In addition, protein drift time analysis offers a new dimension in monitoring the changes of DAR in lot-to-lot analysis.

  4. Utilizing the protein corona around silica nanoparticles for dual drug loading and release.

    PubMed

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-21

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.

  5. Impact of Pharmacy Benefit Design on Prescription Drug Utilization: A Fixed Effects Analysis of Plan Sponsor Data

    PubMed Central

    Roebuck, M Christopher; Liberman, Joshua N

    2009-01-01

    Objective To study the impact of various elements of pharmacy benefit design on both the absolute and relative utilization of generics, brands, retail pharmacy, and mail service. Data Source Panel data on 1,074 plan sponsors covering 21.6 million individuals over 12 calendar quarters (2005–2007). Study Design A retrospective analysis of pharmacy claims. Statistical Methods To control for potential endogeneity, linear fixed effects models were estimated for each of six dependent variables: the generic utilization rate, the brand utilization rate, the generic dispensing rate (GDR), the retail pharmacy utilization rate, the mail service utilization rate, and the mail distribution rate. Principal Findings Most member cost-share variables were nonlinearly associated with changes in prescription drug utilization. Marginal effects were generally greater in magnitude for brand out-of-pocket costs than for generic out-of-pocket costs. Time dummies, as well as other pharmacy benefit design elements, also yielded significant results. Conclusions Prior estimates of the effect of member cost sharing on prescription drug utilization may be biased if complex benefit designs, mail service fulfillment, and unmeasured factors such as pharmaceutical pipelines are not accounted for. Commonly cited relative utilization metrics, such as GDR, may be misleading if not examined alongside absolute prescription drug utilization. PMID:19187183

  6. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

    Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

    2012-01-01

    This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

  7. [Drug utilization in renal transplant patients: medication practices and representations].

    PubMed

    de Arruda, Guilherme Oliveira; Renovato, Rogério Dias

    2012-12-01

    Qualitative research approach, descriptive and exploratory with objective of to know the practices and representations of medication on the use of drugs by people transplanted kidney. 18 people participated in the Dourados (MS), through semistructured interview. The theoretical contributions of medication practices were Peter Conrad and representation of Stuart Hall. The definition of the categories of theoretical analysis was Michel Foucault. Respondents had a mean age of 53.5 years, 13 males and 5 females, with median time to transplant eight years. The medications predominantly used were immunosuppresssive. We developed three categories of analysis: the drug as part of everyday life, the central role of the drug and correlation with rejection, and medicine and the autonomy of the transplanted kidney. The drugs are part of everyday life and the representations of autonomy and quality enhance your daily use.

  8. Prescription drug monitoring program utilization in Kentucky community pharmacies

    PubMed Central

    Wixson, Sarah E.; Blumenschein, Karen; Goodin, Amie J.; Talbert, Jeffery; Freeman, Patricia R.

    2014-01-01

    Objective: Identify characteristics of Kentucky community pharmacists and community pharmacists’ practice environment associated with utilization of the Kentucky All Schedule Prescription Electronic Reporting Program (KASPER). Methods: Surveys were mailed to all 1,018 Kentucky pharmacists with a KASPER account and an additional 1,000 licensed pharmacists without an account. Bivariate analyses examined the association between KASPER utilization and practice type (independent or chain) and practice location (rural or urban). A multivariate Poisson regression model with robust error variance estimated risk ratios (RR) of KASPER utilization by characteristics of pharmacists’ practice environment. Results: Responses were received from 563 pharmacists (response rate 27.9%). Of these, 402 responses from community pharmacists were included in the analyses. A majority of responding pharmacists (84%) indicated they or someone in their pharmacy had requested a patient’s controlled substance history since KASPER’s inception. Bivariate results showed that pharmacists who practiced in independent pharmacies reported greater KASPER utilization (94%) than pharmacists in chain pharmacies (75%; p<0.001). Multivariate regression results found utilization of KASPER varied significantly among practice environments of community pharmacists with those who practiced in an urban location (RR: 1.11; [1.01–1.21]) or at an independent pharmacy (RR: 1.27; [1.14–1.40]) having an increased likelihood of KASPER utilization. Conclusion: Utilization of KASPER differs by community pharmacists’ practice environment, predominantly by practice type and location. Understanding characteristics of community pharmacists and community pharmacists’ practice environment associated with PDMP use is necessary to remove barriers to access and increase utilization thereby increasing PDMP effectiveness. PMID:26131042

  9. Drug Utilisation Study in a Tertiary Care Center: Recommendations for Improving Hospital Drug Dispensing Policies

    PubMed Central

    Mittal, Niti; Mittal, R.; Singh, I.; Shafiq, Nusrat; Malhotra, S.

    2014-01-01

    Drug therapy accounts for a major portion of health expenditure. A useful strategy for achieving cost efficient healthcare is drug utilisation research as it forms the basis for making amendments in drug policies and helps in rational drug use. The present observational study was conducted to generate data on drug utilization in inpatients of our tertiary care hospital to identify potential targets for improving drug prescribing patterns. Data was collected retrospectively from randomly selected 231 medical records of patients admitted in various wards of the hospital. WHO Anatomical Therapeutic Chemical/Defined Daily Dose methodology was used to assess drug utilisation data and drug prescriptions were analysed by WHO core drug indicators. Antibiotics were prescribed most frequently and also accounted for majority of drug costs. The prescribed daily dose for most of the antibiotics corresponded to defined daily dose reflecting adherence to international recommendations. Brand name prescribing and polypharmacy was very common.78% of the total drugs prescribed were from the National List of Essential Medicines 2003. Restricting the use of newer and costlier antibiotics, branded drugs and number of drugs per prescription could be considered as targets to cut down the cost of drug therapysignificantly. PMID:25284928

  10. Recent Advances in Ligand-Based Drug Design: Relevance and Utility of the Conformationally Sampled Pharmacophore Approach

    PubMed Central

    Acharya, Chayan; Coop, Andrew; Polli, James E.; MacKerell, Alexander D.

    2010-01-01

    In the absence of three-dimensional (3D) structures of potential drug targets, ligand-based drug design is one of the popular approaches for drug discovery and lead optimization. 3D structure-activity relationships (3D QSAR) and pharmacophore modeling are the most important and widely used tools in ligand-based drug design that can provide crucial insights into the nature of the interactions between drug target and ligand molecule and provide predictive models suitable for lead compound optimization. This review article will briefly discuss the features and potential application of recent advances in ligand-based drug design, with emphasis on a detailed description of a novel 3D QSAR method based on the conformationally sample pharmacophore (CSP) approach (denoted CSP-SAR). In addition, data from a published study is used to compare the CSP-SAR approach to the Catalyst method, emphasizing the utility of the CSP approach for ligand-based model development. PMID:20807187

  11. Experimental study and evaluation of radioprotective drugs

    NASA Technical Reports Server (NTRS)

    Smith, D. E.; Thomson, J. F.

    1968-01-01

    Experimental study evaluates radioprotective drugs administered before exposure either orally or intravenously. Specifically studied are the sources of radiation, choice of radiation dose, choice of animals, administration of drugs, the toxicity of protective agents and types of protective drug.

  12. A facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid base neutralization reactions

    NASA Astrophysics Data System (ADS)

    Chen, Huabing; Wan, Jiangling; Wang, Yirui; Mou, Dongsheng; Liu, Hongbin; Xu, Huibi; Yang, Xiangliang

    2008-09-01

    Nanonization strategies have been used to enhance the oral availability of numerous drugs that are poorly soluble in water. Exploring a facile nanonization strategy with highly practical potential is an attractive focus. Here, we report a novel facile nanoaggregation strategy for constructing drug nanoparticles of poorly soluble drugs with pH-dependent solubility by utilizing acid-base neutralization in aqueous solution, thus facilitating the exploration of nanonization in oral delivery for general applicability. We demonstrate that hydrophobic itraconazole dissolved in acid solution formed a growing core and aggregated into nanoparticles in the presence of stabilizers. The nanoparticles, with an average diameter of 279.3 nm and polydispersity index of 0.116, showed a higher dissolution rate when compared with the marketed formulation; the average dissolution was about 91.3%. The in vivo pharmacokinetic studies revealed that the nanoparticles had a rapid absorption and enhanced oral availability. The diet state also showed insignificant impact on the absorption of itraconazole from nanoparticles. This nanoaggregation strategy is a promising nanonization method with a facile process and avoidance of toxic organic solvents for oral delivery of poorly soluble drugs with pH-dependent solubility and reveals a highly practical potential in the pharmaceutical and chemical industries.

  13. Utility of coloured hair for the detection of drugs and alcohol.

    PubMed

    Agius, Ronald

    2014-06-01

    The aim of this paper is to assess the utility of coloured hair for the detection of drugs and alcohol in a large statistically significant population. The positivity rate, the 1st, 5th, 50th, 95th, and 99th percentiles of five amphetamines, cannabinoids, cocaine, four opiates, methadone, buprenorphine, seven benzodiazepines, and ethyl glucuronide (EtG) in 9488 non-treated and 1026 cosmetically treated (dyed or bleached) authentic hair samples was compared. Analytical methods used were accredited for forensic purposes at the cut-offs defined by the German driving licence re-granting medical and psychological assessment (MPA) guidelines. Considering only the drug classes for which at least 10 positive samples were detected, the positivity rate in non-treated hair was highest for alcohol (4.50%; measured using EtG at concentrations ≥ 7 pg/mg hair), followed by THC (2.00%), cocaine (1.75%), and amphetamine (0.59%). While the 1st to 99th percentile range was significantly lower for drugs in treated, compared to non-treated hair, no significant change was observed for EtG. Additionally, no significant difference in the positivity rate was observed between treated hair and non-treated hair for both drugs and EtG. This study is the first attempt to evaluate the influence of cosmetic treatment, mainly dying, on the positivity rate for both drugs and EtG in hair samples submitted routinely for abstinence testing and the first to indicate that dyed and eventually bleached hair is not necessarily useless in detecting drugs and/or alcohol consumption, thus making coloured hair analysis still useful, often being the only possibility to prove such misuse. PMID:24817056

  14. Expanding Medicaid drug formulary coverage. Effects on utilization of related services.

    PubMed

    Kozma, C M; Reeder, C E; Lingle, E W

    1990-10-01

    Effects on utilization and expenditures occurring concurrently with an expansion of coverage in the South Carolina Medicaid drug formulary were investigated. Data were collected for prescriptions, physician office visits, and outpatient and inpatient hospital visits. Data were evaluated for a cohort of 12,139 individuals who had at least one prescription claim and were continuously eligible for benefits during the two-year study. A repeated measures design was employed to control the differences between subjects. A multivariate analysis of variance was used to detect overall differences in utilization and expenditures. A priori comparisons of means were performed to detect changes in levels and rates of expenditures and utilization for each service. Increases were observed in the number of prescriptions, physician visits, and outpatient visits per person while the number of inpatient hospital admissions declined. Similarly, expenditures increased for all service areas except the inpatient hospital service. The proportion of variance explained by the formulary change was small in all service areas, but would be of practical significance because of the large number of Medicaid recipients affected. From a theoretical perspective, an association of a reduction in inpatient hospital use and expenditures following the elimination of drug formulary restrictions is particularly noteworthy. These findings support the thesis that medical care services should not be viewed in isolation but rather as a system of interrelated activities. Interventions in one portion of the system are mirrored by changes in utilization of other components. Frequently, private and public medical care programs are managed with organizationally distinct benefit budgets, which are controlled independently. In view of the results of this study, this organizational approach may lead to a suboptimal allocation of resources. PMID:2232926

  15. Utilizing Data from Cancer Patient & Survivor Studies

    Cancer.gov

    Utilizing Data from Cancer Patient & Survivor Studies and Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2011 workshop sponsored by the Epidemiology and Genomics Research Program.

  16. A Proposal for Better Drug Utilization and Education in Tompkins County (New York)

    ERIC Educational Resources Information Center

    Rivkin, Lawrence S.

    1976-01-01

    This proposal contains a mechanism to provide the population with useful drug information at the time of purchase. This mechanism may also provide the system with useful information concerning drug utilization by the consuming public. Such information is vital to health planners and others interested in health care delivery. (Author)

  17. The utilization of Arabic online drug information among adults in Saudi Arabia.

    PubMed

    Abanmy, Norah O; Al-Quait, Nouf A; Alami, Amani H; Al-Juhani, Meshaal H; Al-Aqeel, Sinaa

    2012-10-01

    In Saudi Arabia, the utilization of the world wide web has become increasingly popular. However, the exact figure of such use is unknown. This study aimed to determine the percentage of, and experience with, online Arabic drug information by Arabic-speaking adults in Saudi Arabia. A web based questionnaire was used. The questionnaire language was Arabic. Public were invited to participate in the survey through e-mails, Twitter, WhatsApp and Facebook in March 2012. The survey included 17 items examining the types of accessed Arabic drug information, the respondent's demographics, their ability to easily find and understand Arabic drug-related information, and their trustfulness and dependency on such information websites. Of the 422 Arabic speaking adults who answered the questionnaire, 88% stated that they used Arabic websites to answer drug-related questions. Of the respondents, 50% had a bachelor's degree, 44% were young adults, over half were female (60%), and 72% of them have a chronic disease. The ease of retrieving online information was the most common reason (69%) for consulting such websites. Google as a search engine was the most frequently (86%) accessible website. Although respondents reported different drug-related topics in their online searching, the search for adverse effects was the most common (68%). Respondents claimed that they could easily find (65%) and understand (49%) the drug-related information. Although a good number of respondents qualified this type of information as good, double-checking of information on other websites was highly recommended. Trustfulness was one of the important parameters to measure and 205 respondents (55%) claimed that they only trusted half of the information cited. Moreover, around 48% of respondents considered that finding the same information on more than one website increased its trustfulness. Surprisingly, 54% of respondents did not depend on Arabic information websites when making decisions on drug use

  18. Utilizing ambulatory blood pressure recordings to evaluate antihypertensive drug therapy.

    PubMed

    White, W B

    1992-04-30

    Until recently, the efficacy and pharmacodynamics of antihypertensive agents were assessed by resting blood pressure measurements in the doctor's office or a research clinic. The limitations of the office or clinic blood pressure measurement include the lack of representation (from recording only 1 point of time in the dosing schedule), the effects of the doctor's office on the patient's blood pressure, and, perhaps more relevant, observer bias. Ambulatory monitoring of the blood pressure has gained worldwide acceptance as an alternative method to assess antihypertensive drug efficacy and the time-effect relation of a drug. The ambulatory monitoring devices have been refined and are smaller, more precise, and more reliable than earlier recording models. Although there are no reference standards for analysis of ambulatory blood pressure data, international consensus groups are presently addressing this problem. Key roles for ambulatory blood pressure recordings in clinical trials of antihypertensive agents now include determination of the entry criteria for patients, improving the assessment of peak/trough pharmacodynamics in the patient's own environment (including nocturnal/sleep readings), and evaluating efficacy through calculation of the hypertensive burden, or blood pressure load. PMID:1575177

  19. 42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-utilization and under-utilization of prescribed medications; and (3) Provides CMS with information concerning... examination of claims data and other records, through computerized drug claims processing and information retrieval systems, in order to identify patterns of inappropriate or medically unnecessary care...

  20. Utilizing diversity-oriented synthesis in antimicrobial drug discovery.

    PubMed

    Comer, Eamon; Duvall, Jeremy R; duPont Lee, Maurice

    2014-01-01

    The development of resistance to existing antimicrobials has created a threat to human health that is not being addressed through our current drug pipeline. Limitations with the use of commercial vendor libraries and natural products have created a need for new types of small molecules to be screened in antimicrobial assays. Diversity oriented synthesis (DOS) is a strategy for the efficient generation of compound collections with a high degree of structural diversity. Diversity-oriented synthesis molecules occupy the middle ground of both complexity and efficiency of synthesis between natural products and commercial libraries. In this review we focus upon the use of diversity-oriented synthesis compound collections for the discovery of new antimicrobial agents. PMID:25495985

  1. Drug utilization of clarithromycin for gastrointestinal disease treatment

    PubMed Central

    Zhou, Quan; Zhu, Ling-Ling; Yan, Xiao-Feng; Pan, Wen-Sheng; Zeng, Su

    2008-01-01

    AIM: To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use. METHODS: Using a structured pro forma, we conducted a two-month survey of the electronic prescriptions containing immediate-release (IR) or sustained-release (SR) product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS: One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori (H pylori) therapy, triple therapy take the dominant position (91.8%), followed by quadruple therapy (4.3%) and dual therapy (3.9%). Amoxicillin was the most frequently co-prescribed antibiotic. Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR, and 6.4% of prescriptions of clarithromycin IR, were prescribed at inappropriate dosing intervals. Surprisingly, disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating H pylori infection although off-label use for this purpose was reported in literature. On the contrary, only one prescription (0.9%) of clarithromycin IR was prescribed for unapproved indication (i.e. gastro-oesophageal reflux disease). 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION: There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease, especially with regard to administration

  2. Mental Health Service and Drug Treatment Utilization: Adolescents with Substance Use/Mental Disorders and Dual Diagnosis

    ERIC Educational Resources Information Center

    Cheng, Tyrone C.; Lo, Celia C.

    2010-01-01

    This research is a secondary data analysis of the impact of adolescents' mental/substance-use disorders and dual diagnosis on their utilization of drug treatment and mental health services. By analyzing the same teenagers who participated in the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study, logistic…

  3. Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation.

    PubMed

    Wu, Shangquan; Liu, Xiaoli; Zhou, Xiarong; Liang, Xin M; Gao, Dayong; Liu, Hong; Zhao, Gang; Zhang, Qingchuan; Wu, Xiaoping

    2016-03-15

    Cancer is a serious threat to human health. Although numerous anti-cancer drugs are available clinically, many have shown toxic side effects due to poor tumor-selectivity, and reduced effectiveness due to cancers rapid development of resistance to treatment. The development of new highly efficient and practical methods to quantify cell viability and its change under drug treatment is thus of significant importance in both understanding of anti-cancer mechanism and anti-cancer drug screening. Here, we present an approach of utilizing a nanomechanical fluctuation based highly sensitive microcantilever sensor, which is capable of characterizing the viability of cells and quantitatively screening (within tens of minutes) their responses to a drug with the obvious advantages of a rapid, label-free, quantitative, noninvasive, real-time and in-situ assay. The microcantilever sensor operated in fluctuation mode was used in evaluating the paclitaxel effectiveness on breast cancer cell line MCF-7. This study demonstrated that the nanomechanical fluctuations of the microcantilever sensor are sensitive enough to detect the dynamic variation in cellular force which is provided by the cytoskeleton, using cell metabolism as its energy source, and the dynamic instability of microtubules plays an important role in the generation of the force. We propose that cell viability consists of two parts: biological viability and mechanical viability. Our experimental results suggest that paclitaxel has little effect on biological viability, but has a significant effect on mechanical viability. This new method provides a new concept and strategy for the evaluation of cell viability and the screening of anti-cancer drugs.

  4. Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation.

    PubMed

    Wu, Shangquan; Liu, Xiaoli; Zhou, Xiarong; Liang, Xin M; Gao, Dayong; Liu, Hong; Zhao, Gang; Zhang, Qingchuan; Wu, Xiaoping

    2016-03-15

    Cancer is a serious threat to human health. Although numerous anti-cancer drugs are available clinically, many have shown toxic side effects due to poor tumor-selectivity, and reduced effectiveness due to cancers rapid development of resistance to treatment. The development of new highly efficient and practical methods to quantify cell viability and its change under drug treatment is thus of significant importance in both understanding of anti-cancer mechanism and anti-cancer drug screening. Here, we present an approach of utilizing a nanomechanical fluctuation based highly sensitive microcantilever sensor, which is capable of characterizing the viability of cells and quantitatively screening (within tens of minutes) their responses to a drug with the obvious advantages of a rapid, label-free, quantitative, noninvasive, real-time and in-situ assay. The microcantilever sensor operated in fluctuation mode was used in evaluating the paclitaxel effectiveness on breast cancer cell line MCF-7. This study demonstrated that the nanomechanical fluctuations of the microcantilever sensor are sensitive enough to detect the dynamic variation in cellular force which is provided by the cytoskeleton, using cell metabolism as its energy source, and the dynamic instability of microtubules plays an important role in the generation of the force. We propose that cell viability consists of two parts: biological viability and mechanical viability. Our experimental results suggest that paclitaxel has little effect on biological viability, but has a significant effect on mechanical viability. This new method provides a new concept and strategy for the evaluation of cell viability and the screening of anti-cancer drugs. PMID:26406457

  5. Methods for comparing drug policies--the utility of composite drug harm indexes.

    PubMed

    Ritter, Alison

    2009-11-01

    One of the challenges for drug policy research is being able to compare policy options and outcomes. The development of indexes, such as the UK Drug Harm Index or the UNODC Illicit Drug Index is a way to systematically enable such comparisons. An Index is a single common metric that represents the diverse outcomes or consequences of drug use. An Index may be used for performance monitoring within one country/region over time; to establish societal benefit of drug policies as expressed in social costs saved; to compare countries or regions; or for comparative policy analysis. Clarity of purpose is important in how an Index is used. The consequences or outcomes that can be combined into a single Index include health consequences, crime consequences, public amenity, pain and suffering, labour market outcomes, and drug manufacture and trafficking activity. The choice of outcomes for inclusion is driven by the purpose but also often by practical considerations, such as data availability. The weighting of the consequences is an important consideration in translating the outcomes into a common metric. A monetary unit has a number of advantages: it is a unit that can be measured across diverse impacts; it gives implicit "weighting" of harms; and it is intuitive for policy makers and community. On the other hand, it represents an economic perspective. No one Index will be regarded as suitable and appropriate by every stakeholder and ongoing research effort on Indexes is an important foundational research activity to advance illicit drug policy. PMID:19356915

  6. Liquefaction chemistry and kinetics: Hydrogen utilization studies

    SciTech Connect

    Rothenberger, K.S.; Warzinski, R.P.; Cugini, A.V.

    1995-12-31

    The objectives of this project are to investigate the chemistry and kinetics that occur in the initial stages of coal liquefaction and to determine the effects of hydrogen pressure, catalyst activity, and solvent type on the quantity and quality of the products produced. The project comprises three tasks: (1) preconversion chemistry and kinetics, (2) hydrogen utilization studies, and (3) assessment of kinetic models for liquefaction. The hydrogen utilization studies work will be the main topic of this report. However, the other tasks are briefly described.

  7. Catanionic mixtures involving a drug: a rather general concept that can be utilized for prolonged drug release from gels.

    PubMed

    Bramer, Tobias; Dew, Noel; Edsman, Katarina

    2006-04-01

    The aim of this work was to study at what extent mixtures of drug substances and oppositely charged surfactants form catanionic aggregates and to apply these as a means of obtaining prolonged drug release from a gel. The properties of traditional catanionic mixtures are relatively well known, but only recently we found that not only traditional surfactants form these mixtures, but also structurally more complex surface active drug compounds. In this study, several different compositions of catanionic mixtures were studied visually, by cryogenic transmission electron microscopy (cryo-TEM) and rheologically using a Bohlin VOR Rheometer. Some of the catanionic vesicle and micelle phases were incorporated in and released from gels using the USP paddle method. The drug compounds investigated were lidocaine, ibuprofen, naproxen, alprenolol, propranolol, and orphenadrine. Of the six drug molecules used in this study, five, both positively and negatively charged, were capable of forming catanionic vesicles and/or micelles with oppositely charged surfactants. The drug release studies show that catanionic drug surfactant mixtures are beneficial for obtaining prolonged release from gels, as the drug release using catanionic vesicles and micelles was prolonged between 10 and 100 times compared to the release of pure drug substance from the gel.

  8. Drug and alcohol abuse: the bases for employee assistance programs in the nuclear-utility industry

    SciTech Connect

    Radford, L.R.; Rankin, W.L.; Barnes, V.; McGuire, M.V.; Hope, A.M.

    1983-07-01

    This report describes the nature, prevalence, and trends of drug and alcohol abuse among members of the US adult population and among personnel in non-nuclear industries. Analogous data specific to the nuclear utility industry are not available, so these data were gathered in order to provide a basis for regulatory planning. The nature, prevalence, and trend inforamtion was gathered using a computerized literature, telephone discussions with experts, and interviews with employee assistance program representatives from the Seattle area. This report also evaluates the possible impacts that drugs and alcohol might have on nuclear-related job performance, based on currently available nuclear utility job descriptions and on the scientific literature regarding the impairing effects of drugs and alcohol on human performance. Employee assistance programs, which can be used to minimize or eliminate job performance decrements resulting from drug or alcohol abuse, are also discussed.

  9. Stadium Site Utilization Study. University of Cincinnati.

    ERIC Educational Resources Information Center

    Caudill, Rowlett, and Scott, New York, NY.

    An evaluative study of the University of Cincinnati stadium site shows its potential with relation to the existing campus. Conclusions and recommendations concerning its future utilization are presented, based upon consideration of the following--(1) basic university planning policies, (2) assets and liabilities of the site, (3) the decision to…

  10. Chemical and genetic validation of thiamine utilization as an antimalarial drug target.

    PubMed

    Chan, Xie Wah Audrey; Wrenger, Carsten; Stahl, Katharina; Bergmann, Bärbel; Winterberg, Markus; Müller, Ingrid B; Saliba, Kevin J

    2013-01-01

    Thiamine is metabolized into an essential cofactor for several enzymes. Here we show that oxythiamine, a thiamine analog, inhibits proliferation of the malaria parasite Plasmodium falciparum in vitro via a thiamine-related pathway and significantly reduces parasite growth in a mouse malaria model. Overexpression of thiamine pyrophosphokinase (the enzyme that converts thiamine into its active form, thiamine pyrophosphate) hypersensitizes parasites to oxythiamine by up to 1,700-fold, consistent with oxythiamine being a substrate for thiamine pyrophosphokinase and its conversion into an antimetabolite. We show that parasites overexpressing the thiamine pyrophosphate-dependent enzymes oxoglutarate dehydrogenase and pyruvate dehydrogenase are up to 15-fold more resistant to oxythiamine, consistent with the antimetabolite inactivating thiamine pyrophosphate-dependent enzymes. Our studies therefore validate thiamine utilization as an antimalarial drug target and demonstrate that a single antimalarial can simultaneously target several enzymes located within distinct organelles.

  11. Utility of cerebrospinal fluid drug concentration as a surrogate for unbound brain concentration in nonhuman primates.

    PubMed

    Nagaya, Yoko; Nozaki, Yoshitane; Kobayashi, Kazumasa; Takenaka, Osamu; Nakatani, Yosuke; Kusano, Kazutomi; Yoshimura, Tsutomu; Kusuhara, Hiroyuki

    2014-01-01

    In central nervous system drug discovery, cerebrospinal fluid (CSF) drug concentration (C(CSF)) has been widely used as a surrogate for unbound brain concentrations (C(u,brain)). However, previous rodent studies demonstrated that when drugs undergo active efflux by transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier, the C(CSF) overestimates the corresponding C(u,brain). To investigate the utility of C(CSF) as a surrogate for interstitial fluid (ISF) concentration (C(ISF)) in nonhuman primates, this study simultaneously determined the C(CSF) and C(ISF) of 12 compounds, including P-gp substrates, under steady-state conditions in cynomolgus monkeys using intracerebral microdialysis coupled with cisternal CSF sampling. Unbound plasma concentrations of non- or weak P-gp substrates were within 2.2-fold of the C(ISF) or C(CSF), whereas typical P-gp substrates (risperidone, verapamil, desloratadine, and quinidine) showed ISF-to-plasma unbound (K(p,uu,ISF)) and CSF-to-plasma unbound concentration ratios (K(p,uu,CSF)) that were appreciably lower than unity. Although the K(p,uu,CSF) of quinidine, verapamil, and desloratadine showed a trend of overestimating the K(p,uu,ISF), K(p,uu,CSF) showed a good agreement with K(p,uu,ISF) within 3-fold variations for all compounds examined. C(u,brain) of some basic compounds, as determined using brain homogenates, overestimated the C(ISF) and C(CSF). Therefore, C(CSF) could be used as a surrogate for C(ISF) in nonhuman primates.

  12. Effects of gamma-aminobutyric acid agonist and antagonist drugs on local cerebral glucose utilization

    SciTech Connect

    Palacios, J.M.; Kuhar, M.J.; Rapoport, S.I.; London, E.D.

    1982-07-01

    The (/sup 14/C)2-deoxy-D-glucose method of Sokoloff et al. was used to study local cerebral glucose utilization (LCGU) in rats treated with gamma-aminobutyric acid (GABA) agonist (muscimol and 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyridin-3-ol, THIP) and antagonist (bicuculline) drugs. It was of interest to determine if the pattern of LCGU responses to GABA agonists and antagonists administered systemically in vivo would reflect the known distributions of markers for central GABAergic synapses. The patterns of LCGU responses to muscimol and THIP generally were similar. Most brain regions showed dose-dependent decreases in LCGU; others showed no effects; but the red nucleus showed an increase. The GABA antagonist bicuculline produced convulsions and variable LCGU responses, depending on the time of administration. Bicuculline also partially antagonized the depressant effects of muscimol of LCGU. The magnitudes and distribution of in vivo cerebral metabolic responses to specific GABA agonists were not correlated simply with markers for GABAergic synapses. This lack of correlation indicates that additional factors, such as neural circuitry, regulate the LCGU responses to GABAergic drugs.

  13. ChEMBL web services: streamlining access to drug discovery data and utilities.

    PubMed

    Davies, Mark; Nowotka, Michał; Papadatos, George; Dedman, Nathan; Gaulton, Anna; Atkinson, Francis; Bellis, Louisa; Overington, John P

    2015-07-01

    ChEMBL is now a well-established resource in the fields of drug discovery and medicinal chemistry research. The ChEMBL database curates and stores standardized bioactivity, molecule, target and drug data extracted from multiple sources, including the primary medicinal chemistry literature. Programmatic access to ChEMBL data has been improved by a recent update to the ChEMBL web services (version 2.0.x, https://www.ebi.ac.uk/chembl/api/data/docs), which exposes significantly more data from the underlying database and introduces new functionality. To complement the data-focused services, a utility service (version 1.0.x, https://www.ebi.ac.uk/chembl/api/utils/docs), which provides RESTful access to commonly used cheminformatics methods, has also been concurrently developed. The ChEMBL web services can be used together or independently to build applications and data processing workflows relevant to drug discovery and chemical biology.

  14. Short-term Efficacy of a Brief Intervention to Reduce Drug Misuse and Increase Drug Treatment Utilization Among Adult Emergency Department Patients

    PubMed Central

    Merchant, Roland C.; Baird, Janette R.; Liu, Tao

    2016-01-01

    Objectives Although brief interventions (BIs) have shown some success for smoking cessation and alcohol misuse, it is not known if they can be applied in the emergency department (ED) to drug use and misuse. The objectives of this investigation were to assess the 3-month efficacy of a BI to reduce drug use and misuse, increase drug treatment services utilization among adult ED patients, and identify subgroups more likely to benefit from the BI. Methods This randomized, controlled trial enrolled 18- to 64-year-old English- or Spanish-speaking patients from two urban, academic EDs whose responses to the Alcohol, Smoking, and Substance Involvement Screening Test indicated a need for a brief or intensive intervention. Treatment participants received a tailored BI, while control participants only completed the study questionnaires. At the 3-month follow-up, each participant’s past 3-month drug use and misuse and treatment utilization were compared to his or her baseline enrollment data. Regression modeling was used to identify subgroups of patients (per demographic and clinical factors) more likely to stop or reduce their drug use or misuse or engage in drug treatment by the 3-month follow-up assessment. Results Of the 1,030 participants, the median age was 30 years (interquartile range = 24 to 42 years), and 46% were female; 57% were white/non-Hispanic, 24.9% were black/non-Hispanic, and 15% were Hispanic. The most commonly misused drugs were marijuana, prescription opioids, cocaine/crack, and benzodiazepines. Although at follow-up the proportions of participants reporting any past 3-month drug misuse had decreased in both study arms (control 84% vs. treatment 78%), the decreases were similar between the two study arms (Δ−6.3%; 95% confidence interval [CI] = −13.0% to 0.0). In addition, at follow-up there were no differences between study arms in those who were currently receiving drug treatment (Δ1.8; 95% CI = −3.5 to 6.8), who had received treatment during

  15. Spirocyclic sulfamides as β-secretase 1 (BACE-1) inhibitors for the treatment of Alzheimer's disease: utilization of structure based drug design, WaterMap, and CNS penetration studies to identify centrally efficacious inhibitors.

    PubMed

    Brodney, Michael A; Barreiro, Gabriela; Ogilvie, Kevin; Hajos-Korcsok, Eva; Murray, John; Vajdos, Felix; Ambroise, Claude; Christoffersen, Curt; Fisher, Katherine; Lanyon, Lorraine; Liu, Jianhua; Nolan, Charles E; Withka, Jane M; Borzilleri, Kris A; Efremov, Ivan; Oborski, Christine E; Varghese, Alison; O'Neill, Brian T

    2012-11-01

    β-Secretase 1 (BACE-1) is an attractive therapeutic target for the treatment and prevention of Alzheimer's disease (AD). Herein, we describe the discovery of a novel class of BACE-1 inhibitors represented by sulfamide 14g, using a medicinal chemistry strategy to optimize central nervous system (CNS) penetration by minimizing hydrogen bond donors (HBDs) and reducing P-glycoprotein (P-gp) mediated efflux. We have also taken advantage of the combination of structure based drug design (SBDD) to guide the optimization of the sulfamide analogues and the in silico tool WaterMap to explain the observed SAR. Compound 14g is a potent inhibitor of BACE-1 with excellent permeability and a moderate P-gp liability. Administration of 14g to mice produced a significant, dose-dependent reduction in central Aβ(X-40) levels at a free drug exposure equivalent to the whole cell IC(50) (100 nM). Furthermore, studies of the P-gp knockout mouse provided evidence that efflux transporters affected the amount of Aβ lowering versus that observed in wild-type (WT) mouse at an equivalent dose. PMID:22984865

  16. Drugs foresight 2020: a Delphi expert panel study

    PubMed Central

    2014-01-01

    Background Historically substance misuse has been relatively common in western countries, but comparatively few Finns report drug use. The Drugs 2020 study aimed at foreseeing changes in the drug situation in Finland by the year 2020. Methods The Delphi method was used, utilizing drug experts of the EU national network in Finland. Results Marked growth was foreseen in drug use, especially in synthetic designer drugs and misuse of medicinal drugs. Significant increase was also expected in growing cannabis at home. However, the control of drug market was expected to shift more into the hands of organized crime. No consensus was reached on how drug prices will develop in the time period. Drug use is likely to remain punishable although the use and possession of cannabis may be treated less severely. It seems likely that health and social services resources will be directed towards medicinal treatment. Conclusions Foresight can be utilized in preparing for the future; desirable developments can be fostered, and measures can be taken to curb probable but undesirable lines of development. Based on the results of this study, the experts’ view is that it is highly likely that the Finnish society will have to prepare for an increase in the demand for drug-related care, both in terms of content of the care and financing the services. Also, the forecasted increase in the role of legal prescription medicine used as intoxicants will call for efforts not only in changing prescription practices but in border and police control measures, as well. Parallel developments have been foreseen in the UK and Sweden, and it is likely that similar trends will actualize also in other western countries. PMID:24885142

  17. [Study methods of drugs in Alzheimer disease].

    PubMed

    Dubois, B; Stehlé, B; Lehner, J P; Derouesné, C; Bourin, M; Lamour, Y; Blin, O; Jourdain, G; Alperovitch, A

    1996-01-01

    The availability of new drugs for Alzheimer's disease, with different pharmacological profiles, leads to a redefinition the relevant methodology for developing drugs in this indication, including the inclusion/exclusion criteria, the duration of the studies, and therefore, the relevant guidelines. This was the purpose of the Giens Round-table devoted to the new methodology for drug development in Alzheimer disease.

  18. Cost-utility analyses of drug therapies in breast cancer: a systematic review.

    PubMed

    Nerich, Virginie; Saing, Sopany; Gamper, Eva Maria; Kemmler, Georg; Daval, Franck; Pivot, Xavier; Holzner, Bernhard

    2016-10-01

    The economic evaluation (EE) of health care products has become a necessity. Their quality must be high in order to trust the results and make informed decisions. While cost-utility analyses (CUAs) should be preferred to cost-effectiveness analyses in the oncology area, the quality of breast cancer (BC)-related CUA has been given little attention so far. Thus, firstly, a systematic review of published CUA related to drug therapies for BC, gene expression profiling, and HER2 status testing was performed. Secondly, the quality of selected CUA was assessed and the factors associated with a high-quality CUA identified. The systematic literature search was conducted in PubMed, MEDLINE/EMBASE, and Cochrane to identify published CUA between 2000 and 2014. After screening and data extraction, the quality of each selected CUA was assessed by two independent reviewers, using the checklist proposed by Drummond et al. The analysis of factors associated with a high-quality CUA (defined as a Drummond score ≥7) was performed using a two-step approach. Our systematic review was based on 140 CUAs and showed a wide variety of methodological approaches, including differences in the perspective adopted, the time horizon, measurement of cost and effectiveness, and more specially health-state utility values (HSUVs). The median Drummond score was 7 [range 3-10]. Only one in two of the CUA (n = 74) had a Drummond score ≥7, synonymous of "high quality." The statistically significant predictors of a high-quality CUA were article with "gene expression profiling" topic (p = 0.001), consulting or pharmaceutical company as main location of first author (p = 0.004), and articles with both incremental cost-utility ratio and incremental cost-effectiveness ratio as outcomes of EE (p = 0.02). Our systematic review identified only 140 CUAs published over the past 15 years with one in two of high quality. It showed a wide variety of methodological approaches, especially focused on HSUVs. A

  19. Cost-utility analyses of drug therapies in breast cancer: a systematic review.

    PubMed

    Nerich, Virginie; Saing, Sopany; Gamper, Eva Maria; Kemmler, Georg; Daval, Franck; Pivot, Xavier; Holzner, Bernhard

    2016-10-01

    The economic evaluation (EE) of health care products has become a necessity. Their quality must be high in order to trust the results and make informed decisions. While cost-utility analyses (CUAs) should be preferred to cost-effectiveness analyses in the oncology area, the quality of breast cancer (BC)-related CUA has been given little attention so far. Thus, firstly, a systematic review of published CUA related to drug therapies for BC, gene expression profiling, and HER2 status testing was performed. Secondly, the quality of selected CUA was assessed and the factors associated with a high-quality CUA identified. The systematic literature search was conducted in PubMed, MEDLINE/EMBASE, and Cochrane to identify published CUA between 2000 and 2014. After screening and data extraction, the quality of each selected CUA was assessed by two independent reviewers, using the checklist proposed by Drummond et al. The analysis of factors associated with a high-quality CUA (defined as a Drummond score ≥7) was performed using a two-step approach. Our systematic review was based on 140 CUAs and showed a wide variety of methodological approaches, including differences in the perspective adopted, the time horizon, measurement of cost and effectiveness, and more specially health-state utility values (HSUVs). The median Drummond score was 7 [range 3-10]. Only one in two of the CUA (n = 74) had a Drummond score ≥7, synonymous of "high quality." The statistically significant predictors of a high-quality CUA were article with "gene expression profiling" topic (p = 0.001), consulting or pharmaceutical company as main location of first author (p = 0.004), and articles with both incremental cost-utility ratio and incremental cost-effectiveness ratio as outcomes of EE (p = 0.02). Our systematic review identified only 140 CUAs published over the past 15 years with one in two of high quality. It showed a wide variety of methodological approaches, especially focused on HSUVs. A

  20. Applicability, Commercial Utility and Recent Patents on Starch and Starch Derivative as Pharmaceutical Drug Delivery Carrier.

    PubMed

    Pandey, Shreya; Malviya, Rishabha; Sharma, Pramod K

    2015-01-01

    Natural polymers are widely utilized in pharmaceutical and food industries. Starch, a major carbohydrate is a staple food in human and animal diets which is simply extractable from various sources, like potato, maize, corn, wheat, etc. It is widely used as a raw material in various food and non food industries as well as in paper, textile and other industries. This article summarizes the starch and modification of starch and to produce a novel molecule with various applications in industries including number of advances in pharmaceutical industry. The unique characteristics of starch and their modified form can be successfully used as drug delivery carriers in various pharmaceutical preparations. It is widely used as controlled and sustained release polymer, tablet disintegrant, drug delivery carrier, plasma volume expander and also finds its applicability in bone tissue engineering and in artificial red cells. It also includes the patents related to starch and modified starch based products and their commercial utility. PMID:26205680

  1. Case studies in electric utility competition litigation

    SciTech Connect

    Orr, J.A.; Hawks, B.K.

    1994-12-31

    Although electric utilities in the US in many ways operate as highly regulated monopolies, federal and state regulation has not eliminated competition in the electric utility industry. This article describes trends in utility competition litigation as they have evolved in Georgia and other parts of the country.

  2. Legitimacy and modernity via policy transfer: the utility of the 2003 Afghan National Drug Control Strategy.

    PubMed

    Bewley-Taylor, David R

    2014-09-01

    Very much an exercise in historical reconstruction, this article is concerned with the development of the first version of the Afghan NDCS. It is hoped that this domain of enquiry will contribute to discussions around the 'governance of drug policy' in this special issue of the International Journal of Drug Policy by focusing on how different policy actors operate in influencing the policy process; or parts thereof. More specifically, exploration of the formulation of the Strategy does much to help us understand not only the origins and shifting nature of ownership of drug policy within Afghanistan but also the relationship between the NDCS and the broader normative expectations of what has been referred to as the global drug prohibition regime (Andreas & Nadelmann, 2006, p. 38). As will be discussed, while indisputably the product of a process of policy transfer involving a number of non-Afghan actors - and as such arguably not always appropriate to the peculiarities of the drug market within the country - it can be argued that the 2003 National Drug Control Strategy fulfilled a useful functional role that in many ways exceeded its utility as a guiding document beyond the confines of Kabul.

  3. Exploring the limits and utility of operant conditioning in the treatment of drug addiction.

    PubMed

    Silverman, Kenneth

    2004-01-01

    This article describes a research program to develop an operant treatment for cocaine addiction in low-income, treatment-resistant methadone patients. The treatment's central feature is an abstinence reinforcement contingency in which patients earn monetary reinforcement for providing cocaine-free urine samples. Success and failure of this contingency appear to be an orderly function of familiar parameters of operant conditioning. Increasing reinforcement magnitude and duration can increase effectiveness, and sustaining the contingency can prevent relapse. Initial development of a potentially practical application of this technology suggests that it may be possible to integrate abstinence reinforcement into employment settings using salary for work to reinforce drug abstinence. This research illustrates the potential utility and current limitations of an operant approach to the treatment of drug addiction. Similar research programs are needed to explore the limits of the operant approach and to develop practical applications that can be used widely in society for the treatment of drug addiction.

  4. Watching the monitors: "PAID" prescriptions, fiscal intermediaries and drug-utilization review.

    PubMed

    Morgan, J P

    1977-02-01

    Prescription monitoring evolved from the need of drug firms to obtain marketing information. Today, extensive monitoring is also done by fiscal intermediaries who administer prepaid drug benefit plans, both private and governmental, particularly Medicaid. The most important such agent is PAID Prescriptions. Under various contracts, PAID monitors physician, pharmacy, and patient behavior related to prescriptions and uses review processes that evaluate certain kinds of behavior for appropriateness. The criteria of appropriateness are essentially those that save money. PAID negotiates a program fee with the insurer (public or private) and applies constraints so that prescription and administrative costs do not overrun that fee. PAID and other monitors have contemplated expansion into the realm of defining and encouraging appropriate prescribing under the concept of "drugutilization review." The actual practices of PAID, particularly the background of fiscal enforcement, may impede the development of an actual drug-utilization review process.

  5. A cost-utility analysis of drug treatments in patients with HBeAg-positive chronic hepatitis B in Thailand

    PubMed Central

    2014-01-01

    Background Only lamivudine has been included for patients with chronic hepatitis B (CHB) in the National List of Essential Drugs (NLED), a pharmaceutical reimbursement list in Thailand. There have also been no economic evaluation studies of CHB drug treatments conducted in Thailand yet. In order to fill this gap in policy research, the objective of this study was to compare the cost-utility of each drug therapy (Figure 1) with palliative care in patients with HBeAg-positive CHB. Methods A cost-utility analysis using an economic evaluation model was performed to compare each drug treatment for HBeAg-positive CHB patients. A Markov model was used to estimate the relevant costs and health outcomes during a lifetime horizon based on a societal perspective. Direct medical costs, direct non-medical costs, and indirect costs were included, and health outcomes were denoted in life years (LYs) and quality-adjusted life years (QALYs). The results were presented as an incremental cost effectiveness ratio (ICER) in Thai baht (THB) per LY or QALY gained. One-way sensitivity and probabilistic sensitivity analyses were applied to investigate the effects of model parameter uncertainties. Results The ICER values of providing generic lamivudine with the addition of tenofovir when drug resistance occurred, generic lamivudine with the addition of tenofovir based on the road map guideline, and tenofovir monotherapy were -14,000 (USD -467), -8,000 (USD -267) , and -5,000 (USD -167) THB per QALY gained, respectively. However, when taking into account all parameter uncertainties in the model, providing generic lamivudine with the addition of tenofovir when drug resistance occurred (78% and 75%) and tenofovir monotherapy (18% and 24%) would yield higher probabilities of being cost-effective at the societal willingness to pay thresholds of 100,000 (USD 3,333) and 300,000 (USD 10,000) THB per QALY gained in Thailand, respectively. Conclusions Based on the policy recommendations from this

  6. Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997–2003

    PubMed Central

    Walley, T; Folino-Gallo, P; Stephens, P; Van Ganse, E

    2005-01-01

    Aims To describe trends in utilization and prescribing of statins and other lipid lowering drugs across Europe from data in routine administrative databases. Methods Observational study in EU member states and Norway. Comparison of annual utilization data for lipid lowering agents by class and drug from national administrative databases for reimbursement over the period 1997–2003, measured in DDDs per 1000 inhabitants/day. Prescribed daily doses (PDD) of statins obtained from a commercial database (IMS Health) for 2000 and 2003, and used to calculate numbers of ‘patient treatment days’ (PTD) in each country in each year. Analysis of PTD to explain increased utilization of statins. Results Use of lipid lowering agents varied among countries (in 2003, highest in Ireland and Norway, and lowest in Italy), but increased in all countries studied (between 2000 and 2003 by 274%in Ireland and by 56%in France). This increase was entirely due to increases in statin use. Prescribed daily doses of statins increased in all countries for which data was available between 2000 and 2003, but still usually fell below the doses used in the major trials of statins. As a result, the numbers of PTDs increased to a lesser extent than suggested by utilization (e.g. by 192% in Ireland and by 35% in France). One-third of the total rise in utilization was explained by increased PDD, and two-thirds by an increase in numbers of PTDs. Statins dominated the markets in all countries, although fibrates remained strong in France and Belgium (approximately 25% of all lipid lowering agents) and to a lesser extent Germany (10%). Conclusions Use of statins across Europe has increased hugely over the study period. Some of the increase in use is due to higher prescribed daily doses, but two-thirds is due to increases in numbers of patient days of treatment, either due to more patients treated or less likely to better compliance. PMID:16236045

  7. Cost-Utility Analysis of IEV Drug Regimen Versus ESHAP Drug Regimen for the Patients With Relapsed and Refractory Hodgkin and Non-Hodgkin’s Lymphoma in Iran

    PubMed Central

    Hatam, Nahid; Dehghani, Mehdi; Habibian, Mostafa; Jafari, Abdosaleh

    2015-01-01

    Background: Chemotherapy for lymph nodes cancer is often composed of several drugs that are used in a treatment program. Objectives: The aim of this study was to perform a cost-utility analysis of IEV regimen (ifosfamide, epirubicin and etoposide) versus ESHAP regimen (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in patients with lymphoma in the south of Iran. Patients and Methods: This was a cost-utility analysis done as a cross-sectional study in the south of Iran. Using decision tree, expected costs, quality -adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) were estimated. In addition, the robustness of results was examined by sensitivity analysis. Results: The results of this study indicated that the total lymphoma patients were about 65 people that 27 patients received IEV regimen and 38 patients ESHAP (43 patients with Hodgkin’s and 22 with non-Hodgkin lymphoma). The results of decision tree showed that in the IEV arm, the expected cost was $20952.93 and the expected QALYs was 3.89 and in the ESHAP arm, the expected cost was $31691.74 and the expected QALYs was 3.86. Based on the results of the study, IEV regimen was cost-effective alternative to the ESHAP regimen. Conclusions: According to the results of this study, it is recommended that oncologists use IEV instead of ESHAP in the treatment of patients with lymphoma and because of high costs of IEV drug costs, it is suggested that IEV drugs should be covered by insurance. PMID:26634115

  8. An Oral Contraceptive Drug Interaction Study

    ERIC Educational Resources Information Center

    Bradstreet, Thomas E.; Panebianco, Deborah L.

    2004-01-01

    This article focuses on a two treatment, two period, two treatment sequence crossover drug interaction study of a new drug and a standard oral contraceptive therapy. Both normal theory and distribution-free statistical analyses are provided along with a notable amount of graphical insight into the dataset. For one of the variables, the decision on…

  9. Utility of AIRS Retrievals for Climate Studies

    NASA Technical Reports Server (NTRS)

    Molnar, Guyla I.; Susskind, Joel

    2007-01-01

    Satellites provide an ideal platform to study the Earth-atmosphere system on practically all spatial and temporal scales. Thus, one may expect that their rapidly growing datasets could provide crucial insights not only for short-term weather processes/predictions but into ongoing and future climate change processes as well. Though Earth-observing satellites have been around for decades, extracting climatically reliable information from their widely varying datasets faces rather formidable challenges. AIRS/AMSU is a state of the art infrared/microwave sounding system that was launched on the EOS Aqua platform on May 4, 2002, and has been providing operational quality measurements since September 2002. In addition to temperature and atmospheric constituent profiles, outgoing longwave radiation and basic cloud parameters are also derived from the AIRS/AMSU observations. However, so far the AIRS products have not been rigorously evaluated and/or validated on a large scale. Here we present preliminary assessments of monthly and 8-day mean AIRS "Version 4.0" retrieved products (available to the public through the DAAC at NASA/GSFC) to assess their utility for climate studies. First we present "consistency checks" by evaluating the time series of means, and "anomalies" (relative to the first 4 full years' worth of AIRS "climate statistics") of several climatically important retrieved parameters. Finally, we also present preliminary results regarding interrelationships of some of these geophysical variables, to assess to what extent they are consistent with the known physics of climate variability/change. In particular, we find at least one observed relationship which contradicts current general circulation climate (GCM) model results: the global water vapor climate feedback which is expected to be strongly positive is deduced to be slightly negative (shades of the "Lindzen effect"?). Though the current AIRS climatology covers only -4.5 years, it will hopefully extend much

  10. Ophthalmic drug delivery utilizing two-photon absorption: a novel approach to treat posterior capsule opacification

    NASA Astrophysics Data System (ADS)

    Kim, H.-C.; Träger, J.; Zorn, M.; Haberkorn, N.; Hampp, N.

    2007-07-01

    Intraocular lens (IOL) implantation is the standard technique to treat cataract. Despite recent progress in surgical procedures, posterior capsule opacification is one of the sill remaining postoperative complications of cataract surgery. We present a novel strategy to reduce the incidence of posterior capsule opacification. A drug delivery polymer suitable for manufacturing intraocular lenses has been developed which enables repeated drug release in a non-invasive and controlled manner. The therapeutic molecules are attached through a UV light sensitive linkage to the polymer backbone which is mainly responsible for the optical properties of the intraocular lenses. However, UV light can not trigger the release of drug from the polymer due to the high absorption of the cornea. We developed linkers which enable drug release by two-photon absorption induced cleavage of the linker structure. Since the two-photon absorption requires high photon densities, this does not occur in ambient light conditions in daily life, but is easily triggered by focused laser beams from a pulsed laser. In this proof-of-principle study we have employed a cyclobutane type linker and investigated the properties of the therapeutic system with the approved drugs 5-fluorouracil and chlorambucil. The controlled drug delivery was successfully demonstrated in vitro and additional cell tests confirmed that the device itself shows no cytotoxicity until photochemical activation. This presented concept can provide a powerful method in ophthalmic drug delivery.

  11. Monitoring Adverse Drug Reactions: A Preliminary Study

    PubMed Central

    Reynolds, J. L.

    1981-01-01

    The feasibility of family physicians functioning as monitors of adverse drug reactions (ADR) was examined over one month in ten practices. This was done as a preliminary trial, before attempting to use the 200 family physicians of the National Reporting System of the College of Family Physicians of Canada to monitor ADRs on a national basis. Both of these trials were designed to examine the feasibility of family physicians acting as prospective monitors of ADRs in newly marketed drugs and to identify a drug group suitable for monitoring. This study examined the detection of ADRs, prescribing and practice profiles. No firm conclusion could be reached as to the value of family doctors monitoring ADRs. This study supports the evidence that older patients receive more drugs and are at even greater risk of an ADR. Antibiotics, cardiovascular, anti-inflammatory or antidepressant drugs are suggested as those most suitable for prospective monitoring in a family practice setting. PMID:21289786

  12. Health-related service utilization and HIV risk behaviors among HIV infected injection drug users and crack smokers.

    PubMed

    Booth, R E; Kwiatkowski, C F; Weissman, G

    1999-06-01

    This study was designed to assess utilization of health-related services and HIV risk related behaviors by HIV infected drug users one year prior to and two years following the availability of Ryan White Title I funding. Using a cross-sectional design, a total of 777 drug injectors and crack smokers from five US cities were surveyed, over three waves of data collection, about their use of drug treatment, medical services, housing, mental health, and case management and about their sex and drug-related risk behaviors. For all service categories and in each wave, including the year prior to Title I funding, HIV risk behaviors were lower among those who used health-related services, with the exception of housing. Use of services did not increase significantly following the disbursement of Title I funds except for housing and case management. These findings suggest that it may be necessary to increase the attractiveness of health-related services, not just funding for services, for HIV infected substance abusers. PMID:10402151

  13. Kauai Island Utility Cooperative energy storage study.

    SciTech Connect

    Akhil, Abbas Ali; Yamane, Mike; Murray, Aaron T.

    2009-06-01

    Sandia National Laboratories performed an assessment of the benefits of energy storage for the Kauai Island Utility Cooperative. This report documents the methodology and results of this study from a generation and production-side benefits perspective only. The KIUC energy storage study focused on the economic impact of using energy storage to shave the system peak, which reduces generator run time and consequently reduces fuel and operation and maintenance (O&M) costs. It was determined that a 16-MWh energy storage system would suit KIUC's needs, taking into account the size of the 13 individual generation units in the KIUC system and a system peak of 78 MW. The analysis shows that an energy storage system substantially reduces the run time of Units D1, D2, D3, and D5 - the four smallest and oldest diesel generators at the Port Allen generating plant. The availability of stored energy also evens the diurnal variability of the remaining generation units during the off- and on-peak periods. However, the net economic benefit is insufficient to justify a load-leveling type of energy storage system at this time. While the presence of storage helps reduce the run time of the smaller and older units, the economic dispatch changes and the largest most efficient unit in the KIUC system, the 27.5-MW steam-injected combustion turbine at Kapaia, is run for extra hours to provide the recharge energy for the storage system. The economic benefits of the storage is significantly reduced because the charging energy for the storage is derived from the same fuel source as the peak generation source it displaces. This situation would be substantially different if there were a renewable energy source available to charge the storage. Especially, if there is a wind generation resource introduced in the KIUC system, there may be a potential of capturing the load-leveling benefits as well as using the storage to dampen the dynamic instability that the wind generation could introduce into

  14. Torsadogenic Risk of Antipsychotics: Combining Adverse Event Reports with Drug Utilization Data across Europe

    PubMed Central

    Raschi, Emanuel; Poluzzi, Elisabetta; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Bennie, Marion; Barbui, Corrado; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

    2013-01-01

    Background Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. Methods FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled) to group E (unclear/uncertain signal: only 2/5 criteria). Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID). Results Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone). In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia) to 13.99 (France, 2009). Considerable increment of Group A agents was found in several Countries (+3.47 in France): the exposure to olanzapine increased across all Countries (+1.84 in France) and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009). Among Group B drugs, levomepromazine peaked 3.78 (Serbia); fluphenazine 1.61 (Slovenia). Conclusions This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  15. Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design.

    PubMed

    Massey, Andrew J; Stokes, Stephen; Browne, Helen; Foloppe, Nicolas; Fiumana, Andreá; Scrace, Simon; Fallowfield, Mandy; Bedford, Simon; Webb, Paul; Baker, Lisa; Christie, Mark; Drysdale, Martin J; Wood, Mike

    2015-11-01

    Chk1 kinase is a critical component of the DNA damage response checkpoint especially in cancer cells and targeting Chk1 is a potential therapeutic opportunity for potentiating the anti-tumor activity of DNA damaging chemotherapy drugs. Fragment elaboration by structure guided design was utilized to identify and develop a novel series of Chk1 inhibitors culminating in the identification of V158411, a potent ATP-competitive inhibitor of the Chk1 and Chk2 kinases. V158411 abrogated gemcitabine and camptothecin induced cell cycle checkpoints, resulting in the expected modulation of cell cycle proteins and increased cell death in cancer cells. V158411 potentiated the cytotoxicity of gemcitabine, cisplatin, SN38 and camptothecin in a variety of p53 deficient human tumor cell lines in vitro, p53 proficient cells were unaffected. In nude mice, V158411 showed minimal toxicity as a single agent and in combination with irinotecan. In tumor bearing animals, V158411 was detected at high levels in the tumor with a long elimination half-life; no pharmacologically significant in vivo drug-drug interactions with irinotecan were identified through analysis of the pharmacokinetic profiles. V158411 potentiated the anti-tumor activity of irinotecan in a variety of human colon tumor xenograft models without additional systemic toxicity. These results demonstrate the opportunity for combining V158411 with standard of care chemotherapeutic agents to potentiate the therapeutic efficacy of these agents without increasing their toxicity to normal cells. Thus, V158411 would warrant further clinical evaluation. PMID:26437226

  16. Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design

    PubMed Central

    Massey, Andrew J.; Stokes, Stephen; Browne, Helen; Foloppe, Nicolas; Fiumana, Andreá; Scrace, Simon; Fallowfield, Mandy; Bedford, Simon; Webb, Paul; Baker, Lisa; Christie, Mark; Drysdale, Martin J.; Wood, Mike

    2015-01-01

    Chk1 kinase is a critical component of the DNA damage response checkpoint especially in cancer cells and targeting Chk1 is a potential therapeutic opportunity for potentiating the anti-tumor activity of DNA damaging chemotherapy drugs. Fragment elaboration by structure guided design was utilized to identify and develop a novel series of Chk1 inhibitors culminating in the identification of V158411, a potent ATP-competitive inhibitor of the Chk1 and Chk2 kinases. V158411 abrogated gemcitabine and camptothecin induced cell cycle checkpoints, resulting in the expected modulation of cell cycle proteins and increased cell death in cancer cells. V158411 potentiated the cytotoxicity of gemcitabine, cisplatin, SN38 and camptothecin in a variety of p53 deficient human tumor cell lines in vitro, p53 proficient cells were unaffected. In nude mice, V158411 showed minimal toxicity as a single agent and in combination with irinotecan. In tumor bearing animals, V158411 was detected at high levels in the tumor with a long elimination half-life; no pharmacologically significant in vivo drug-drug interactions with irinotecan were identified through analysis of the pharmacokinetic profiles. V158411 potentiated the anti-tumor activity of irinotecan in a variety of human colon tumor xenograft models without additional systemic toxicity. These results demonstrate the opportunity for combining V158411 with standard of care chemotherapeutic agents to potentiate the therapeutic efficacy of these agents without increasing their toxicity to normal cells. Thus, V158411 would warrant further clinical evaluation. PMID:26437226

  17. Innovative Recruitment Using Online Networks: Lessons Learned From an Online Study of Alcohol and Other Drug Use Utilizing a Web-Based, Respondent-Driven Sampling (webRDS) Strategy

    PubMed Central

    Bauermeister, José A.; Zimmerman, Marc A.; Johns, Michelle M.; Glowacki, Pietreck; Stoddard, Sarah; Volz, Erik

    2012-01-01

    Objective: We used a web version of Respondent-Driven Sampling (webRDS) to recruit a sample of young adults (ages 18–24) and examined whether this strategy would result in alcohol and other drug (AOD) prevalence estimates comparable to national estimates (National Survey on Drug Use and Health [NSDUH]). Method: We recruited 22 initial participants (seeds) via Facebook to complete a web survey examining AOD risk correlates. Sequential, incentivized recruitment continued until our desired sample size was achieved. After correcting for webRDS clustering effects, we contrasted our AOD prevalence estimates (past 30 days) to NSDUH estimates by comparing the 95% confidence intervals of prevalence estimates. Results: We found comparable AOD prevalence estimates between our sample and NSDUH for the past 30 days for alcohol, marijuana, cocaine, Ecstasy (3,4-methylenedioxymethamphetamine, or MDMA), and hallucinogens. Cigarette use was lower than NSDUH estimates. Conclusions: WebRDS may be a suitable strategy to recruit young adults online. We discuss the unique strengths and challenges that may be encountered by public health researchers using webRDS methods. PMID:22846248

  18. Vaccine and Drug Ontology Studies (VDOS 2014).

    PubMed

    Tao, Cui; He, Yongqun; Arabandi, Sivaram

    2016-01-01

    The "Vaccine and Drug Ontology Studies" (VDOS) international workshop series focuses on vaccine- and drug-related ontology modeling and applications. Drugs and vaccines have been critical to prevent and treat human and animal diseases. Work in both (drugs and vaccines) areas is closely related - from preclinical research and development to manufacturing, clinical trials, government approval and regulation, and post-licensure usage surveillance and monitoring. Over the last decade, tremendous efforts have been made in the biomedical ontology community to ontologically represent various areas associated with vaccines and drugs - extending existing clinical terminology systems such as SNOMED, RxNorm, NDF-RT, and MedDRA, developing new models such as the Vaccine Ontology (VO) and Ontology of Adverse Events (OAE), vernacular medical terminologies such as the Consumer Health Vocabulary (CHV). The VDOS workshop series provides a platform for discussing innovative solutions as well as the challenges in the development and applications of biomedical ontologies for representing and analyzing drugs and vaccines, their administration, host immune responses, adverse events, and other related topics. The five full-length papers included in this 2014 thematic issue focus on two main themes: (i) General vaccine/drug-related ontology development and exploration, and (ii) Interaction and network-related ontology studies.

  19. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease

    PubMed Central

    Khare, Shilpi; Roach, Steven L.; Barnes, S. Whitney; Hoepfner, Dominic; Walker, John R.; Chatterjee, Arnab K.; Neitz, R. Jeffrey; Arkin, Michelle R.; McNamara, Case W.; Ballard, Jaime; Lai, Yin; Fu, Yue; Molteni, Valentina; Yeh, Vince; McKerrow, James H.; Glynne, Richard J.; Supek, Frantisek

    2015-01-01

    Unbiased phenotypic screens enable identification of small molecules that inhibit pathogen growth by unanticipated mechanisms. These small molecules can be used as starting points for drug discovery programs that target such mechanisms. A major challenge of the approach is the identification of the cellular targets. Here we report GNF7686, a small molecule inhibitor of Trypanosoma cruzi, the causative agent of Chagas disease, and identification of cytochrome b as its target. Following discovery of GNF7686 in a parasite growth inhibition high throughput screen, we were able to evolve a GNF7686-resistant culture of T. cruzi epimastigotes. Clones from this culture bore a mutation coding for a substitution of leucine by phenylalanine at amino acid position 197 in cytochrome b. Cytochrome b is a component of complex III (cytochrome bc1) in the mitochondrial electron transport chain and catalyzes the transfer of electrons from ubiquinol to cytochrome c by a mechanism that utilizes two distinct catalytic sites, QN and QP. The L197F mutation is located in the QN site and confers resistance to GNF7686 in both parasite cell growth and biochemical cytochrome b assays. Additionally, the mutant cytochrome b confers resistance to antimycin A, another QN site inhibitor, but not to strobilurin or myxothiazol, which target the QP site. GNF7686 represents a promising starting point for Chagas disease drug discovery as it potently inhibits growth of intracellular T. cruzi amastigotes with a half maximal effective concentration (EC50) of 0.15 µM, and is highly specific for T. cruzi cytochrome b. No effect on the mammalian respiratory chain or mammalian cell proliferation was observed with up to 25 µM of GNF7686. Our approach, which combines T. cruzi chemical genetics with biochemical target validation, can be broadly applied to the discovery of additional novel drug targets and drug leads for Chagas disease. PMID:26186534

  20. The Affordable Care Act, health care reform, prescription drug formularies and utilization management tools.

    PubMed

    Ung, Brian L; Mullins, C Daniel

    2015-01-01

    The U.S. Patient Protection and Affordable Care Act (hence, Affordable Care Act, or ACA) was signed into law on March 23, 2010. Goals of the ACA include decreasing the number of uninsured people, controlling cost and spending on health care, increasing the quality of care provided, and increasing insurance coverage benefits. This manuscript focuses on how the ACA affects pharmacy benefit managers and consumers when they have prescriptions dispensed. PBMs use formularies and utilization control tools to steer drug usage toward cost-effective and efficacious agents. A logic model was developed to explain the effects of the new legislation. The model draws from peer-reviewed and gray literature commentary about current and future U.S. healthcare reform. Outcomes were identified as desired and undesired effects, and expected unintended consequences. The ACA extends health insurance benefits to almost 32 million people and provides financial assistance to those up to 400% of the poverty level. Increased access to care leads to a similar increase in overall health care demand and usage. This short-term increase is projected to decrease downstream spending on disease treatment and stunt the continued growth of health care costs, but may unintentionally exacerbate the current primary care physician shortage. The ACA eliminates limitations on insurance and increases the scope of benefits. Online health care insurance exchanges give patients a central location with multiple insurance options. Problems with prescription drug affordability and control utilization tools used by PBMs were not addressed by the ACA. Improving communication within the U.S. healthcare system either by innovative health care delivery models or increased usage of health information technology will help alleviate problems of health care spending and affordability. PMID:25217142

  1. The Affordable Care Act, health care reform, prescription drug formularies and utilization management tools.

    PubMed

    Ung, Brian L; Mullins, C Daniel

    2015-01-01

    The U.S. Patient Protection and Affordable Care Act (hence, Affordable Care Act, or ACA) was signed into law on March 23, 2010. Goals of the ACA include decreasing the number of uninsured people, controlling cost and spending on health care, increasing the quality of care provided, and increasing insurance coverage benefits. This manuscript focuses on how the ACA affects pharmacy benefit managers and consumers when they have prescriptions dispensed. PBMs use formularies and utilization control tools to steer drug usage toward cost-effective and efficacious agents. A logic model was developed to explain the effects of the new legislation. The model draws from peer-reviewed and gray literature commentary about current and future U.S. healthcare reform. Outcomes were identified as desired and undesired effects, and expected unintended consequences. The ACA extends health insurance benefits to almost 32 million people and provides financial assistance to those up to 400% of the poverty level. Increased access to care leads to a similar increase in overall health care demand and usage. This short-term increase is projected to decrease downstream spending on disease treatment and stunt the continued growth of health care costs, but may unintentionally exacerbate the current primary care physician shortage. The ACA eliminates limitations on insurance and increases the scope of benefits. Online health care insurance exchanges give patients a central location with multiple insurance options. Problems with prescription drug affordability and control utilization tools used by PBMs were not addressed by the ACA. Improving communication within the U.S. healthcare system either by innovative health care delivery models or increased usage of health information technology will help alleviate problems of health care spending and affordability.

  2. Erosive Burning Study Utilizing Ultrasonic Measurement Techniques

    NASA Technical Reports Server (NTRS)

    Furfaro, James A.

    2003-01-01

    A 6-segment subscale motor was developed to generate a range of internal environments from which multiple propellants could be characterized for erosive burning. The motor test bed was designed to provide a high Mach number, high mass flux environment. Propellant regression rates were monitored for each segment utilizing ultrasonic measurement techniques. These data were obtained for three propellants RSRM, ETM- 03, and Castor@ IVA, which span two propellant types, PBAN (polybutadiene acrylonitrile) and HTPB (hydroxyl terminated polybutadiene). The characterization of these propellants indicates a remarkably similar erosive burning response to the induced flow environment. Propellant burnrates for each type had a conventional response with respect to pressure up to a bulk flow velocity threshold. Each propellant, however, had a unique threshold at which it would experience an increase in observed propellant burn rate. Above the observed threshold each propellant again demonstrated a similar enhanced burn rate response corresponding to the local flow environment.

  3. Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan

    PubMed Central

    2012-01-01

    Background A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. Methods Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. Results The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (

  4. A Case Report of Clonazepam Dependence: Utilization of Therapeutic Drug Monitoring During Withdrawal Period.

    PubMed

    Kacirova, Ivana; Grundmann, Milan; Silhan, Petr; Brozmanova, Hana

    2016-03-01

    Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse. We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia. It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence. PMID:26945373

  5. Specific systems studies of battery energy storage for electric utilities

    SciTech Connect

    Akhil, A.A.; Lachenmeyer, L.; Jabbour, S.J.; Clark, H.K.

    1993-08-01

    Sandia National Laboratories, New Mexico, conducts the Utility Battery Storage Systems Program, which is sponsored by the US Department of Energy`s Office of Energy Management. As a part of this program, four utility-specific systems studies were conducted to identify potential battery energy storage applications within each utility network and estimate the related benefits. This report contains the results of these systems studies.

  6. Dynamic SIMS utilizing SF 5+ polyatomic primary ion beams for drug delivery applications

    NASA Astrophysics Data System (ADS)

    Mahoney, Christine M.; Roberson, Sonya; Gillen, Greg

    2004-06-01

    The behavior of various biodegradable polymer films (e.g. polylactic acid, polyglycolic acid and polycaprolactone) as well as some model drugs (theophylline and 4-acetamidophenol) under dynamic SF 5+ primary ion bombardment is explored. A series of polylactic acid films containing varying concentrations of 4-acetamidophenol are also analyzed under similar conditions. The resultant molecular depth profiles obtained from these polymer films doped with drug show very little degradation in molecular signal as a function of SF 5+ primary ion dose, and it was found that the molecular ion signals of both polymer and drug remained constant for ion doses up to ˜5×10 15 ions/cm 2. In addition, the polymer film/Si interface was well defined which may imply that sputter-induced topography formation was not a significant limitation. These results suggest that the structure of the biodegradable polymers studied here which all have the common main chain structural unit, RCOOR, allows for a greater ability to depth profile due to ease of bond cleavage. Most importantly, however, these results indicate that in these particular polymer systems, the distribution of the drug as a function of depth can be monitored.

  7. Inpatient drug utilization in Europe: nationwide data sources and a review of publications on a selected group of medicines (PROTECT project).

    PubMed

    Sabaté, Mònica; Ferrer, Pili; Ballarín, Elena; Rottenkolber, Marietta; Amelio, Justyne; Schmiedl, Sven; Reynolds, Robert; Klungel, Olaf; Ibáñez, Luisa

    2015-03-01

    Drug utilization (DU) studies in inpatient settings at a national level are rarely conducted. The main objective of this study was to review the general information on hospital medicine management in Europe and to report on the availability and characteristics of nationwide administrative drug consumption databases. A secondary objective was to perform a review of published studies on hospital DU of a group of selected drugs, focusing on methodological characteristics (ATC/DDD). General information on hospital drug management was retrieved from several websites, nationwide administrative drug consumption databases and reports published by governmental organizations. A PubMed search was conducted using keywords related to the selected group of drugs AND 'hospital drug utilization'. The data sources for hospital DU information varied widely and included 14 databases from 25 reviewed countries. Bulgaria, Croatia, Denmark, Estonia, Finland, France, Hungary, Iceland, Latvia, Norway and Sweden obtain information on inpatient DU at a national level from wholesalers/manufacturers. In Belgium, Italy and Portugal, drugs dispensed to patients in hospitals are registered at a national level. Data are freely available online only for Denmark and Iceland. From the PubMed search, of a total of 868 retrieved studies, only 13 studies used the ATC/DDD methodology. Although the number of DDD/100 bed-days was used in four studies, other units of measure were also used. The type of information provided for the inpatient sector allowed primarily for conducting DU research at an aggregated data level. The existence of national administrative structures to monitor hospital DU would contribute to promoting the rational use of medicines and improving the safety and quality of prescribing. PMID:25420967

  8. 42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Screening for potential drug therapy problems due to therapeutic duplication. (ii) Age/gender-related... dosage or duration of drug therapy. (vi) Drug-allergy contraindications. (vii) Clinical abuse/misuse....

  9. Investigation of utilization of nanosuspension formulation to enhance exposure of 1,3-dicyclohexylurea in rats: Preparation for PK/PD study via subcutaneous route of nanosuspension drug delivery

    NASA Astrophysics Data System (ADS)

    Chiang, Po-Chang; Ran, Yingqing; Chou, Kang-Jye; Cui, Yong; Wong, Harvey

    2011-06-01

    1,3-Dicyclohexylurea (DCU), a potent soluble epoxide hydrolase (sEH) inhibitor has been reported to lower systemic blood pressure in spontaneously hypertensive rats. One limitation of continual administration of DCU for in vivo studies is the compound's poor oral bioavailability. This phenomenon is mainly attributed to its poor dissolution rate and low aqueous solubility. Previously, wet-milled DCU nanosuspension has been reported to enhance the bioavailability of DCU. However, the prosperities and limitations of wet-milled nanosuspension have not been fully evaluated. Furthermore, the oral pharmacokinetics of DCU in rodent are such that the use of DCU to understand PK/PD relationships of sEH inhibitors in preclinical efficacy model is less than ideal. In this study, the limitation of orally delivered DCU nanosuspension was assessed by a surface area sensitive absorption model and pharmacokinetic modeling. It was found that dosing DCU nanosuspension did not provide the desired plasma profile needed for PK/PD investigation. Based on the model and in vivo data, a subcutaneous route of delivery of nanosuspension of DCU was evaluated and demonstrated to be appropriate for future PK/PD studies.

  10. Integration and utilization of different visualization methods and devices in a structure-based drug design process

    NASA Astrophysics Data System (ADS)

    Grohn, Matti T.; Nyronen, Tommi N.

    2003-05-01

    Molecular visualization techniques are used in various stages in the computer-aided drug design process. Here, we report on utilization of a four wall immersive virtual room in the visualization of protein - drug complexes. The advantage of a virtual room compared to desktop graphics is that it provides a high-resolution large field of view, helping the observers of the visualization to dissect the individual important structural features more easily than while using only conventional molecular graphics visualizations.

  11. [Adaptive clinical study methodologies in drug development].

    PubMed

    Antal, János

    2015-11-29

    The evolution of drug development in human, clinical phase studies triggers the overview of those technologies and procedures which are labelled as adaptive clinical trials. The most relevant procedural and operational aspects will be discussed in this overview from points of view of clinico-methodological aspect.

  12. Hospital Utilization for Injection Drug Use-Related Soft Tissue Infections in Urban versus Rural Counties in California

    PubMed Central

    Etzioni, David A.; Hurley, Brian; Holtom, Paul; Bluthenthal, Ricky N.; Asch, Steven M.

    2006-01-01

    Drug related-soft tissue infections (DR-STIs) are a significant source of hospital utilization in inner-city urban areas where injection drug use is common but the magnitude of hospital utilization for DR-STIs outside of inner-city urban areas is not known. We described the magnitude and characteristics of hospital utilization for DR-STIs in urban versus rural counties in California. All discharges from all nonfederal hospitals in California in 2000 with ICD-9 codes for a soft tissue infection and for drug dependence/abuse were abstracted from the California Office of Statewide Health Planning and Development discharge database. There were 4,152 DR-STI discharges in 2000 from hospitals in 49 of California's 58 counties. Residents of 12 large metropolitan counties accounted for 3,598 discharges (87% of total). The majority of DR-STI discharges were from urban safety net hospitals with county indigent programs and Medicaid as the expected payment source and opiate related discharge diagnoses. Hospital utilization for DR-STIs in California is highest in large urban metropolitan counties, although DR-STI discharges are widespread. Increased access to harm reduction services and drug treatment may reduce government health care expenditures by preventing unnecessary hospital utilization for DR-STIs. PMID:16736367

  13. Drug Dependence in Michigan Including A Study of Attitudes and Actions of the Young People of Michigan.

    ERIC Educational Resources Information Center

    Bogg, Richard A.; And Others

    A 1968 study was undertaken in Michigan with the following objectives: 1) to determine drug utilization rates for public high school seniors; 2) to determine demographic, sociological, and social-psychological correlates of drug utilization; and 3) to acquire information relevant to present and future health education programs. A questionnaire…

  14. Drug Utilization Pattern in Patients with Different Types of Dementia in Western India

    PubMed Central

    Patel, Mansi; Joshi, Anuradha; Suthar, Jalpa; Desai, Soaham

    2014-01-01

    Background. Dementia is one of the most frequent disorders among elderly patients, reaching to epidemic proportions with an estimated 4.6 million new cases globally annually. Partially effective treatments are available for dementia. Aims & Objectives. We aim to study drugs used in dementia and find out frequency of types of Dementia. Method. This was an observational study conducted at rurally based tertiary care hospital. Prospective data was collected from outpatient department, while retrospective data was collected from medical records. Descriptive statistics were used to analyze data. Result. Total 125 prescriptions of patients diagnosed with dementia were analyzed. Alzheimer's dementia was most common (65.6%), followed by vascular dementia (21.6%), and frontotemporal dementia (10.4%), with the rarest being Lewy body dementia in (2.4%) cases. 60.57% of patients were males. Mini Mental Score Examination mean score was 15.93 ± 1.37. Frontal Battery Assessment mean score was 4.75 ± 1.01. Prescribed drugs were Donepezil (68.49%), Rivastigmine (13.63%), Donepezil + Memantine (6.43%) and Galantamine (12.83%), Quetiapine (38.46%), Lorazepam (23.07%), Clozapine (11.53%), Escitalopram (10.25%), Haloperidol (3.84%), Zolpidem, Sertraline, Olanzepine (2.56%), Nitrazepine, Lamotrigine, Fluoxetine, Tianeptine (1.28%), Folic acid, and Vitamin B12, respectively. Conclusion. Alzheimer's is the most common type of dementia while Donepezil was the most frequent drug. PMID:25243092

  15. Drug utilization pattern in patients with different types of dementia in Western India.

    PubMed

    Patel, Mansi; Joshi, Anuradha; Suthar, Jalpa; Desai, Soaham

    2014-01-01

    Background. Dementia is one of the most frequent disorders among elderly patients, reaching to epidemic proportions with an estimated 4.6 million new cases globally annually. Partially effective treatments are available for dementia. Aims & Objectives. We aim to study drugs used in dementia and find out frequency of types of Dementia. Method. This was an observational study conducted at rurally based tertiary care hospital. Prospective data was collected from outpatient department, while retrospective data was collected from medical records. Descriptive statistics were used to analyze data. Result. Total 125 prescriptions of patients diagnosed with dementia were analyzed. Alzheimer's dementia was most common (65.6%), followed by vascular dementia (21.6%), and frontotemporal dementia (10.4%), with the rarest being Lewy body dementia in (2.4%) cases. 60.57% of patients were males. Mini Mental Score Examination mean score was 15.93 ± 1.37. Frontal Battery Assessment mean score was 4.75 ± 1.01. Prescribed drugs were Donepezil (68.49%), Rivastigmine (13.63%), Donepezil + Memantine (6.43%) and Galantamine (12.83%), Quetiapine (38.46%), Lorazepam (23.07%), Clozapine (11.53%), Escitalopram (10.25%), Haloperidol (3.84%), Zolpidem, Sertraline, Olanzepine (2.56%), Nitrazepine, Lamotrigine, Fluoxetine, Tianeptine (1.28%), Folic acid, and Vitamin B12, respectively. Conclusion. Alzheimer's is the most common type of dementia while Donepezil was the most frequent drug. PMID:25243092

  16. Space Station RT and E Utilization Study

    NASA Technical Reports Server (NTRS)

    Wunsch, P. K.; Anderson, P. H.

    1989-01-01

    Descriptive information on a set of 241 mission concepts was reviewed to establish preliminary Space Station outfitting needs for technology development missions. The missions studied covered the full range of in-space technology development activities envisioned for early Space Station operations and included both pressurized volume and attached payload requirements. Equipment needs were compared with outfitting plans for the life sciences and microgravity user communities, and a number of potential outfitting additions were identified. Outfitting implementation was addressed by selecting a strawman mission complement for each of seven technical themes, by organizing the missions into flight scenarios, and by assessing the associated outfitting buildup for planning impacts.

  17. Illicit drugs: contaminants in the environment and utility in forensic epidemiology.

    PubMed

    Daughton, Christian G

    2011-01-01

    bioconcentration i tissues. In contrast to pharmaceuticals, chemical monitoring surveys have revealed the presence of certain IDIs in air and monetary currencies--the latter being of interest for the forensic tracking of money used in drug trafficking. Another unknown with regard to IDIs is the accuracy of current knowledge regarding the complete scope of chemical identities of the numerous types of IDIs in actual use (particularly some of the continually evolving designer drugs new to forensic chemistry) as well as the total quantities being trafficked, consumed, or disposed. The major aspect unique to the study of IDI's in the environment is making use of their presence in the environment as a tool to obtain better estimates of the collective usage of illicit drugs across entire communities. First proposed in 2001, but under investigation with field applications only since 2005, this new modeling approach for estimating drug usage by monitoring the concentrations of IDIs (or certain unique metabolites) in untreated sewage has potential as an additional source of data to augment or corroborate the information-collection ability of conventional written and oral surveys of drug-user populations. This still evolving monitoring tool has been called "sewer epidemiology" but is referred to in this chapter by a more descriptive proposed term "FEUDS" (Forensic Epidemiology Using Drugs in Sewage). The major limitation of FEUDS surrounds the variables involved at various steps performed in FEUDS calculations. These variables are summarized and span sampling and chemical analysis to the final numeric calculations, which particularly require a better understanding of IDI pharmacokinetics than currently exists. Although little examined in the literature, the potential for abuse of FEUDS as a tool in law enforcement is briefly discussed. Finally, the growing interest in FEUDS as a methodological approach for estimating collective public usage of illicit drugs points to the feasibility of

  18. Design and utilization of the drug-excipient chemical compatibility automated system.

    PubMed

    Thomas, V Hayden; Naath, Maryanne

    2008-07-01

    To accelerate clinical formulation development, an excipient compatibility screen should be conducted as early as possible and it must be rapid, robust and resource sparing. This however, does not describe the traditional excipient compatibility testing approach, requiring many tedious and labor intensive manual operations. This study focused on transforming traditional practices into a completely automated screening process to increase sample throughput and realign resources to more urgent areas, while maintaining quality. Using the developed system, a complete on-line performance study was conducted whereby drug-excipient mixtures were weighed, blended and subjected to accelerated stress stability for up to 1 month, followed by sample extraction and HPLC analysis. Compared to off-line traditional study protocols, the system provided similar relative rank order results with equivalent precision and accuracy, while increasing sample throughput. The designed system offers a resource sparing primary screen for drug-excipient chemical compatibility for solid dosage form development. This approach allows risk assessment analysis, based upon formulation complexity, to be conducted prior to the commitment of resources and candidate selection for clinical development. PMID:18486368

  19. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    PubMed Central

    Pignatello, R.; Musumeci, T.; Basile, L.; Carbone, C.; Puglisi, G.

    2011-01-01

    Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy. PMID:21430952

  20. In vitro drug release mechanism and drug loading studies of cubic phase gels.

    PubMed

    Lara, Marilisa G; Bentley, M Vitória L B; Collett, John H

    2005-04-11

    Glyceryl monooleate/water cubic phase systems were investigated as drug delivery systems, using salicylic acid as a model drug. The liquid crystalline phases formed by the glyceryl monooleate (GMO)/water systems were characterized by polarizing microscopy. In vitro drug release studies were performed and the influences of initial water content, swelling and drug loading on the drug release properties were evaluated. Water uptake followed second-order swelling kinetics. In vitro release profiles showed Fickian diffusion control and were independent on the initial water content and drug loading, suggesting GMO cubic phase gels suitability for use as drug delivery system.

  1. PET IMAGING STUDIES IN DRUG ABUSE RESEARCH.

    SciTech Connect

    Fowler, J.S.; Volkow, N.D.; Ding, Y.S.; Logan, J.; Wang, G.J.

    2001-01-29

    . This will be followed by highlights of PET studies of the acute effects of the psychostimulant drugs cocaine and methylphenidate (ritalin) and studies of the chronic effects of cocaine and of tobacco smoke on the human brain. This chapter concludes with the description of a study which uses brain imaging coupled with a specific pharmacological challenge to address the age-old question of why some people who experiment with drugs become addicted while others do not.

  2. Pro-Arrhythmic Potential of Oral Antihistamines (H1): Combining Adverse Event Reports with Drug Utilization Data across Europe

    PubMed Central

    Poluzzi, Elisabetta; Raschi, Emanuel; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

    2015-01-01

    Background There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in ’90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines. Aim To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries. Methods We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance. Results Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible. Conclusions Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by

  3. Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital

    PubMed Central

    2013-01-01

    Background Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy. Methods This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis. Results Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the

  4. The Michigan regulatory incentives study for electric utilities

    SciTech Connect

    Reid, M.W.; Weaver, E.M. )

    1991-06-17

    This is the final report of Phase I of the Michigan Regulatory Incentives Study for Electric Utilities, a three-phase review of Michigan's regulatory system and its effects on resource selection by electric utilities. The goal of Phase I is to identify and analyze financial incentive mechanisms that encourage selection of resources in accord with the principles of integrated resource planning (IRP) or least-cost planning (LCP). Subsequent study phases will involve further analysis of options and possibly a collaborative formal effort to propose regulatory changes. The Phase I analysis proceeded in three steps: (1) identification and review of existing regulatory practices that affect utilities; selection of resources, particularly DSM; (2) preliminary analysis of ten financial mechanisms, and selection of three for further study; (3) detailed analysis of the three mechanisms, including consideration of how they could be implemented in Michigan and financial modeling of their likely impacts on utilities and ratepayers.

  5. Use of immobilized enzymes in drug metabolism studies.

    PubMed

    Dulik, D M; Fenselau, C

    1988-04-01

    The immobilization of drug-metabolizing enzymes onto polymeric supports offers several advantages over use of conventional microsomal or soluble enzyme preparations. These include increased storage stability, facilitated separation of products from the incubation mixture, the ability to recover and reuse the enzyme catalyst, and in many cases, stabilization of the tertiary structure of membrane-bound enzymes. Attachment of the protein to the solid support may be accomplished by adsorption, covalent bonding, or entrapment techniques. This methodology has been successfully utilized for studies with such enzymes as cytochrome P-450, UDP-glucuronyltransferases, glutathione S-transferases, S-methyltransferases, and N-acetyltransferases. Although often employed for the synthesis of xenobiotic metabolites, immobilized enzymes have been used for mechanistic and relative reactivity studies, limited kinetic studies, and extracorporeal detoxification. Co-immobilization of multiple drug-metabolizing enzyme systems has made possible the sequential formation of metabolites arising from oxidation followed by conjugation. Immobilized enzymes may also be used in the prediction of species-dependent metabolic pathways. The potential for large-scale synthesis of drug metabolites using this methodology has been explored. PMID:3127263

  6. Changes in Drug Utilization during a Gap in Insurance Coverage: An Examination of the Medicare Part D Coverage Gap

    PubMed Central

    Polinski, Jennifer M.; Shrank, William H.; Huskamp, Haiden A.; Glynn, Robert J.; Liberman, Joshua N.; Schneeweiss, Sebastian

    2011-01-01

    but not switching drugs in 2006 and 2007. Blunt cost-containment features such as the coverage gap have an adverse impact on drug utilization that may conceivably affect health outcomes. Please see later in the article for the Editors' Summary PMID:21857811

  7. Progress in the study of drug nanocrystals.

    PubMed

    Shi, Jing; Guo, Fei; Zheng, Aiping; Zhang, Xiaoyan; Sun, Jianxu

    2015-12-01

    The poor water solubility of many candidate drugs remains a major obstacle to their development and clinical use, especially for oral drug delivery. Nanocrystal technology can improve the solubility and dissolution rates of many poorly water-soluble drugs very effectively, significantly improving their oral bioavailability and decreasing the food effect. For this reason, this technology is becoming a key area of drug delivery research. This review presents much of the recent progress in nanocrystal drug pharmaceuticals, including the characteristics, composition, preparation technology, and clinical applications of these drugs. Finally, the effect of nanocrystal technology on insoluble drugs is quantified and described. PMID:26817271

  8. Drug Court Effectiveness: A Matched Cohort Study in the Dane County Drug Treatment Court

    ERIC Educational Resources Information Center

    Brown, Randall

    2011-01-01

    Drug treatment courts (DTCs) are widely viewed as effective diversion programs for drug-involved offenders; however, previous studies frequently used flawed comparison groups. In the current study, the author compared rates of recidivism for drug court participants to rates for a traditionally adjudicated comparison group matched on potentially…

  9. Utilization

    NASA Astrophysics Data System (ADS)

    Lu, Guozhi; Zhang, Ting-An; Zhu, Xiaofeng; Liu, Yan; Wang, Yanxiu; Guo, Fangfang; Zhao, Qiuyue; Zheng, Chaozhen

    2014-09-01

    In this study, a calcification-carbonation method is proposed to change the equilibrium structure of red mud produced from the Bayer process. The thermodynamics of both calcification and carbonation processes has been elucidated. In addition, the non-isothermal kinetics involved in the calcification process and the effects of different parameters on the hydrogarnet synthesis and carbonation decomposition are experimentally investigated using pure reagents. The results indicate that through a two-step carbonation treatment of calcified slag by the new method, the mass ratio of alumina to silica ( A/S) of the modified red mud has decreased to 0.44 and the Na2O content drops to 0.12 wt.% at the carbonation temperature of 120°C under the CO2 pressure of 1.2 MPa. The newly modified red mud could be directly used in the cement industry.

  10. Part I---Evaluating Effects of Oligomer Formation on Cytochrome P450 2C9 Electron Transfer and Drug Metabolism, Part II---Utilizing Molecular Modeling Techniques to Study the Src-Interacting Proteins Actin Filament Associated Protein of 110 kDa (AFAP-110) and Cortactin

    NASA Astrophysics Data System (ADS)

    Jett, John Edward, Jr.

    The dissertation has been divided into two parts to accurately reflect the two distinct areas of interest pursued during my matriculation in the School of Pharmacy at West Virginia University. In Part I, I discuss research probing the nature of electron transfer in the Cytochrome P450 family of proteins, a group of proteins well-known for their role in drug metabolism. In Part II, I focus on in silico and in vitro work developed in concert to probe protein structure and protein-protein interactions involved in actin filament reorganization and cellular motility. Part I. Cytochrome P450s (P450s) are an important class of enzymes known to metabolize a variety of endogenous and xenobiotic compounds. P450s are most commonly found in liver and intestinal endothelial cells and are responsible for the metabolism of approximately 75% of pharmaceutical drugs on the market. CYP2C9---one of the six major P450 isoforms---is responsible for ˜20% of drug metabolism. Elucidation of the factors that affect in vitro drug metabolism is crucial to the accurate prediction of in vivo drug metabolism kinetics. Currently, the two major techniques for studying in vitro drug metabolism are solution-based. However, it is known that the results of solution-based studies can vary from in vivo drug metabolism. One reason suggested to account for this variation is the state of P450 oligomer formation in solution compared to the in vivo environment, where P450s are membrane-bound. To understand the details of how oligomer formation affects in vitro drug metabolism, it is imperative that techniques be developed which will allow for the unequivocal control of oligomer formation without altering other experimental parameters. Our long term goal of this research is to develop methods to more accurately predict in vivo drug metabolism from in vitro data. This section of the dissertation will discuss the development of a platform consisting of a doped silicon surface containing a large array of gold

  11. The Utility of a Rodent Model in Detecting Pediatric Drug-Induced Nephrotoxicity

    PubMed Central

    Espandiari, Parvaneh; Zhang, Jun; Rosenzweig, Barry A.; Vaidya, Vishal S.; Sun, Jinchun; Schnackenberg, Laura; Herman, Eugene H.; Knapton, Alan; Bonventre, Joseph V.; Beger, Richard D.; Thompson, Karol L.; Hanig, Joseph

    2009-01-01

    A multi-age rat model was used to identify potential age-related differences in renal injury following exposure to gentamicin (GM). In this study, 10-, 25-, 40-, and 80-day-old Sprague-Dawley rats were dosed with GM at 0, 50, or 100 mg kg-1 body weight per day (mkd) sc for 6 or 14 days. Urine samples were collected up to 72 h after initial dosing. The maximum tolerated dose was lower in 10-day-old rats than for other ages (none survived 11 days of treatment). Eighty-day-old rats given the highest dose showed a diminished rate of growth and an increase in serum creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (Kim-1), and renal pathology. Ten- and 40-day-old rats given 100 mkd of GM for 6- or 14 days also had increased levels of serum BUN and Cr and renal pathology, whereas only mild renal alterations were found in 25-day-old rats. After 6 days of treatment with 100 mkd GM, significant increases in Havcr-1 (Kim-1) gene expression were detected only in 10- and 80-day-old rats. In urine samples, nuclear magnetic resonance and ultra performance liquid chromatography/mass spectrometry analysis detected changes related to GM efficacy (e.g., hippurate) and increases in metabolites related to antioxidant activity, which was greatest in the 80-day-old rats. The magnitude of the genomic, metabonomic, and serum chemistry changes appeared to correlate with the degree of nephropathy. These findings indicate that an experimental animal model that includes several developmental stages can detect age-related differences in drug-induced organ toxicities and may be a useful predictor of pediatric drug safety in preclinical studies. PMID:17636248

  12. The utility of a rodent model in detecting pediatric drug-induced nephrotoxicity.

    PubMed

    Espandiari, Parvaneh; Zhang, Jun; Rosenzweig, Barry A; Vaidya, Vishal S; Sun, Jinchun; Schnackenberg, Laura; Herman, Eugene H; Knapton, Alan; Bonventre, Joseph V; Beger, Richard D; Thompson, Karol L; Hanig, Joseph

    2007-10-01

    A multi-age rat model was used to identify potential age-related differences in renal injury following exposure to gentamicin (GM). In this study, 10-, 25-, 40-, and 80-day-old Sprague-Dawley rats were dosed with GM at 0, 50, or 100 mg kg(-1) body weight per day (mkd) sc for 6 or 14 days. Urine samples were collected up to 72 h after initial dosing. The maximum tolerated dose was lower in 10-day-old rats than for other ages (none survived 11 days of treatment). Eighty-day-old rats given the highest dose showed a diminished rate of growth and an increase in serum creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (Kim-1), and renal pathology. Ten- and 40-day-old rats given 100 mkd of GM for 6- or 14 days also had increased levels of serum BUN and Cr and renal pathology, whereas only mild renal alterations were found in 25-day-old rats. After 6 days of treatment with 100 mkd GM, significant increases in Havcr-1 (Kim-1) gene expression were detected only in 10- and 80-day-old rats. In urine samples, nuclear magnetic resonance and ultra performance liquid chromatography/mass spectrometry analysis detected changes related to GM efficacy (e.g., hippurate) and increases in metabolites related to antioxidant activity, which was greatest in the 80-day-old rats. The magnitude of the genomic, metabonomic, and serum chemistry changes appeared to correlate with the degree of nephropathy. These findings indicate that an experimental animal model that includes several developmental stages can detect age-related differences in drug-induced organ toxicities and may be a useful predictor of pediatric drug safety in preclinical studies.

  13. New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid

    PubMed Central

    Brigden, Grania; Hewison, Cathy; Varaine, Francis

    2015-01-01

    The current treatment for drug-resistant tuberculosis (TB) is long, complex, and associated with severe and life-threatening side effects and poor outcomes. For the first time in nearly 50 years, there have been two new drugs registered for use in multidrug-resistant TB (MDR-TB). Bedaquiline, a diarylquinoline, and delamanid, a nitromidoxazole, have received conditional stringent regulatory approval and have World Health Organization interim policy guidance for their use. As countries improve and scale up their diagnostic services, increasing number of patients with MDR-TB and extensively drug-resistant TB are identified. These two new drugs offer a real opportunity to improve the outcomes of these patients. This article reviews the evidence for these two new drugs and discusses the clinical questions raised as they are used outside clinical trial settings. It also reviews the importance of the accompanying drugs used with these new drugs. It is important that barriers hindering the use of these two new drugs are addressed and that the existing clinical experience in using these drugs is shared, such that their routine-use programmatic conditions is scaled up, ensuring maximum benefit for patients and countries battling the MDR-TB crisis. PMID:26586956

  14. Modelling Simple Experimental Platform for In Vitro Study of Drug Elution from Drug Eluting Stents (DES)

    NASA Astrophysics Data System (ADS)

    Kalachev, L. V.

    2016-06-01

    We present a simple model of experimental setup for in vitro study of drug release from drug eluting stents and drug propagation in artificial tissue samples representing blood vessels. The model is further reduced using the assumption on vastly different characteristic diffusion times in the stent coating and in the artificial tissue. The model is used to derive a relationship between the times at which the measurements have to be taken for two experimental platforms, with corresponding artificial tissue samples made of different materials with different drug diffusion coefficients, to properly compare the drug release characteristics of drug eluting stents.

  15. Arthritis Possible Side Effect of Certain Cancer Drugs: Study

    MedlinePlus

    ... Arthritis Possible Side Effect of Certain Cancer Drugs: Study Doctors should weigh the risk-benefit ratio, researcher ... of drugs that boost the immune system," said study author Dr. Laura Cappelli. She is a rheumatologist ...

  16. Study of hydrogen slush-hydrogen gel utilization

    NASA Technical Reports Server (NTRS)

    Keller, C. W.

    1967-01-01

    Study of hydrogen slush-hydrogen gel utilization is presented in two volume publication. The first volume contains the physical and thermal property data for hydrogen used in the study. In the second volume, details of the technical effort are presented including parametric analysis of effects on vehicle systems.

  17. Feasibility Study for a Hopi Utility-Scale Wind Project

    SciTech Connect

    Kendrick Lomayestewa

    2011-05-31

    The goal of this project was to investigate the feasibility for the generation of energy from wind and to parallel this work with the development of a tribal utility organization capable of undertaking potential joint ventures in utility businesses and projects on the Hopi reservation. The goal of this project was to investigate the feasibility for the generation of energy from wind and to parallel this work with the development of a tribal utility organization capable of undertaking potential joint ventures in utility businesses and projects on the Hopi reservation. Wind resource assessments were conducted at two study sites on Hopi fee simple lands located south of the city of Winslow. Reports from the study were recently completed and have not been compared to any existing historical wind data nor have they been processed under any wind assessment models to determine the output performance and the project economics of turbines at the wind study sites. Ongoing analysis of the wind data and project modeling will determine the feasibility of a tribal utility-scale wind energy generation.

  18. Capacity Utilization Study for Aviation Security Cargo Inspection Queuing System

    SciTech Connect

    Allgood, Glenn O; Olama, Mohammed M; Lake, Joe E; Brumback, Daryl L

    2010-01-01

    In this paper, we conduct performance evaluation study for an aviation security cargo inspection queuing system for material flow and accountability. The queuing model employed in our study is based on discrete-event simulation and processes various types of cargo simultaneously. Onsite measurements are collected in an airport facility to validate the queuing model. The overall performance of the aviation security cargo inspection system is computed, analyzed, and optimized for the different system dynamics. Various performance measures are considered such as system capacity, residual capacity, throughput, capacity utilization, subscribed capacity utilization, resources capacity utilization, subscribed resources capacity utilization, and number of cargo pieces (or pallets) in the different queues. These metrics are performance indicators of the system s ability to service current needs and response capacity to additional requests. We studied and analyzed different scenarios by changing various model parameters such as number of pieces per pallet, number of TSA inspectors and ATS personnel, number of forklifts, number of explosives trace detection (ETD) and explosives detection system (EDS) inspection machines, inspection modality distribution, alarm rate, and cargo closeout time. The increased physical understanding resulting from execution of the queuing model utilizing these vetted performance measures should reduce the overall cost and shipping delays associated with new inspection requirements.

  19. Illicit Drugs: Contaminants in the Environment and Utility in Forensic Epidemiology

    EPA Science Inventory

    The published literature surrounding the origin, occurrence, fate, and effects of illicit drug ingredients (IDIs) in the environment is examined. Similarities exist with medical pharmaceuticals, particularly with regard to the basic processes by which these ingredients enter the ...

  20. Potential utility of precision medicine for older adults with polypharmacy: a case series study.

    PubMed

    Finkelstein, Joseph; Friedman, Carol; Hripcsak, George; Cabrera, Manuel

    2016-01-01

    Pharmacogenomic (PGx) testing has been increasingly used to optimize drug regimens; however, its potential in older adults with polypharmacy has not been systematically studied. In this hypothesis-generating study, we employed a case series design to explore potential utility of PGx testing in older adults with polypharmacy and to highlight barriers in implementing this methodology in routine clinical practice. Three patients with concurrent chronic heart and lung disease aged 74, 78, and 83 years and whose medication regimen comprised 26, 17, and 18 drugs, correspondingly, served as cases for this study. PGx testing identified major genetic polymorphisms in the first two cases. The first case was identified as "CYP3A4/CYP3A5 poor metabolizer", which affected metabolism of eleven prescribed drugs. The second case had "CYP2D6 rapid metabolizer" status affecting three prescribed medications, two of which were key drugs for managing this patient's chronic conditions. Both these patients also had VKORC1 allele *A, resulting in higher sensitivity to warfarin. All cases demonstrated a significant number of potential drug-drug interactions. Both patients with significant drug-gene interactions had a history of frequent hospitalizations (six and 23, respectively), whereas the person without impaired cytochrome P450 enzyme activity had only two acute episodes in the last 5 years, although he was older and had multiple comorbidities. Since all patients received guideline-concordant therapy from the same providers and were adherent to their drug regimen, we hypothesized that genetic polymorphism may represent an additional risk factor for higher hospitalization rates in older adults with polypharmacy. However, evidence to support or reject this hypothesis is yet to be established. Studies evaluating clinical impact of PGx testing in older adults with polypharmacy are warranted. For practical implementation of pharmacogenomics in routine clinical care, besides providing

  1. Potential utility of precision medicine for older adults with polypharmacy: a case series study.

    PubMed

    Finkelstein, Joseph; Friedman, Carol; Hripcsak, George; Cabrera, Manuel

    2016-01-01

    Pharmacogenomic (PGx) testing has been increasingly used to optimize drug regimens; however, its potential in older adults with polypharmacy has not been systematically studied. In this hypothesis-generating study, we employed a case series design to explore potential utility of PGx testing in older adults with polypharmacy and to highlight barriers in implementing this methodology in routine clinical practice. Three patients with concurrent chronic heart and lung disease aged 74, 78, and 83 years and whose medication regimen comprised 26, 17, and 18 drugs, correspondingly, served as cases for this study. PGx testing identified major genetic polymorphisms in the first two cases. The first case was identified as "CYP3A4/CYP3A5 poor metabolizer", which affected metabolism of eleven prescribed drugs. The second case had "CYP2D6 rapid metabolizer" status affecting three prescribed medications, two of which were key drugs for managing this patient's chronic conditions. Both these patients also had VKORC1 allele *A, resulting in higher sensitivity to warfarin. All cases demonstrated a significant number of potential drug-drug interactions. Both patients with significant drug-gene interactions had a history of frequent hospitalizations (six and 23, respectively), whereas the person without impaired cytochrome P450 enzyme activity had only two acute episodes in the last 5 years, although he was older and had multiple comorbidities. Since all patients received guideline-concordant therapy from the same providers and were adherent to their drug regimen, we hypothesized that genetic polymorphism may represent an additional risk factor for higher hospitalization rates in older adults with polypharmacy. However, evidence to support or reject this hypothesis is yet to be established. Studies evaluating clinical impact of PGx testing in older adults with polypharmacy are warranted. For practical implementation of pharmacogenomics in routine clinical care, besides providing

  2. Utility of drug-eluting stents in complex lesions and high-risk patients.

    PubMed

    Nikolsky, Eugenia; Stone, Gregg W

    2007-02-01

    Drug-eluting stents represent a breakthrough technology designed to deliver high concentrations of a bioactive agent locally to an atherosclerotic lesion, thereby minimizing systemic side effects of the drug. The safety and efficacy of drug-eluting stents have clearly been demonstrated in noncomplex lesions. This article presents an evidence-based analysis of the current experience with CYPHER sirolimus-eluting stents (Cordis Corp., Miami Lakes, FL) and TAXUS paclitaxel-eluting stents (Boston Scientific, Natick, MA) in a broad spectrum of high-risk and/or complex subsets of patients and lesions, including those with diabetes mellitus, multivessel disease, diffuse disease, very small vessels, lesions in saphenous vein grafts, chronic total occlusions, in-stent restenosis, ostial and bifurcation lesions, unprotected left main disease, and acute myocardial infarction. Emerging data in several of these subsets suggest that drug-eluting stents are safe and effective, and their use may currently be recommended, whereas in other groups of patients and lesions the efficacy and/or safety of drug-eluting stents remains to be determined, thus warranting caution. It is anticipated that penetration of drug-eluting stents will continue to increase, and fewer patients will require surgical revascularization to achieve sustained event-free survival.

  3. Impact of China's Public Hospital Reform on Healthcare Expenditures and Utilization: A Case Study in ZJ Province

    PubMed Central

    Zhang, Hao; Hu, Huimei; Wu, Christina; Yu, Hai; Dong, Hengjin

    2015-01-01

    Background High drug costs due to supplier-induced demand (SID) obstruct healthcare accessibility in China. Drug prescriptions can generate markup-related profits, and the low prices of other medical services can lead to labor-force underestimations; therefore, physicians are keen to prescribe drugs rather than services. Thus, in China, a public hospital reform has been instituted to cancel markups and increase service prices. Methods A retrospective pre/post-reform study was conducted in ZJ province to assess the impact of the reform on healthcare expenditures and utilization, ultimately to inform policy development and decision-making. The main indicators are healthcare expenditures and utilization. Results Post-reform, drug expenditures per visit decreased by 8.2% and 15.36% in outpatient and inpatient care, respectively; service expenditures per visit increased by 23.03% and 27.69% in outpatient and inpatient care, respectively. Drug utilization per visit increased by 5.58% in outpatient care and underwent no significant change in inpatient care. Both were lower than the theoretical drug-utilization level, which may move along the demand curve because of patient-initiated demand (PID); this indicates that SID-promoted drug utilization may decrease. Finally, service utilization per visit increased by 6% in outpatient care and by 13.10% in inpatient care; both were higher than the theoretical level moving along the demand curve, and this indicates that SID-promoted service utilization may increase. Conclusion The reform reduces drug-prescription profits by eliminating drug markups; additionally, it compensates for service costs by increasing service prices. Post-reform, the SID of drug prescriptions decreased, which may reduce drug-resource waste. The SID of services increased, with potentially positive and negative effects: accessibility to services may be promoted when physicians provide more services, but the risk of resource waste may also increase. This

  4. Combo Drug for Childhood Asthma Appears Safe in Study

    MedlinePlus

    ... news/fullstory_160721.html Combo Drug for Childhood Asthma Appears Safe in Study FDA to review findings, ... 2016 (HealthDay News) -- Lingering safety concerns regarding an asthma drug for children may be put to rest ...

  5. STS/Spacelab payload utilization planning study: Executive summary

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The planning process recommended to meet the orbital flight requirements for the Space Transportation System and payload development, procurement, operations, and support leading to authorization and funding of STS and payload project activities is described. The rationale and rp primary products of STS utilization planning are summarized along with the implementation of the system. Major recommendations of the study are included.

  6. Utility of spatially-resolved atmospheric pressure surface sampling and ionization techniques as alternatives to mass spectrometric imaging (MSI) in drug metabolism

    SciTech Connect

    Blatherwick, Eleanor Q.; Van Berkel, Gary J; Pickup, Kathryn; Johansson, Maria K.; Beaudoin, Marie-Eve; Cole, Roderic; Day, Jennifer M.; Iverson, Suzanne; Wilson, Ian D.; Scrivens, James H.; Weston, Daniel J.

    2011-01-01

    1. Tissue distribution studies of drug molecules play an essential role in the pharmaceutical industry and are commonly undertaken using quantitative whole body autoradiography (QWBA) methods. 2. The growing need for complementary methods to address some scientific gaps around radiography methods has led to increased use of mass spectrometric imaging (MSI) technology over the last 5 to 10 years. More recently, the development of novel mass spectrometric techniques for ambient surface sampling has redefined what can be regarded as fit-for-purpose for MSI in a drug metabolism and disposition arena. 3. Together with a review of these novel alternatives, this paper details the use of two liquid microjunction (LMJ)- based mass spectrometric surface sampling technologies. These approaches are used to provide qualitative determination of parent drug in rat liver tissue slices using liquid extraction surface analysis (LESA) and to assess the performance of a LMJ surface sampling probe (LMJ-SSP) interface for quantitative assessment of parent drug in brain, liver and muscle tissue slices. 4. An assessment of the utility of these spatially-resolved sampling methods is given, showing interdependence between mass spectrometric and QWBA methods, in particular there emerges a reason to question typical MSI workflows for drug metabolism; suggesting the expedient use of profile or region analysis may be more appropriate, rather than generating time-intensive molecular images of the entire tissue section.

  7. Drug utilization and prescribing patterns in a skilled nursing facility: the need for a rational approach to therapeutics.

    PubMed

    Segal, J L; Thompson, J F; Floyd, R A

    1979-03-01

    A study was made of 50 patients drawn at random from a Skilled Nursing Facility (SNF) attended by seven physicians. For 59 percent of these patients, polypharmacy was practiced but no substantiating diagnoses were recorded. Approximately half of the drugs were administered pro re nata. More drugs were prescribed in potentially toxic dosages than in subtherapeutic dosages. The risk of an adverse drug reaction (ADR) was most often associated with anticholinergic agents, sedative-hypnotic drugs, and neuroleptics (thioridazine and chlorpromazine), particularly when prescribed concurrently. Risk of an ADR was highest when a drug was prescribed without recording a definite diagnostic indication. Lack of consistency by individual physicians in their approaches to the therapy of similar disease entities in comparable patients tended to support the concept of peer review in SNFs and also the need for teaching a rational approach to therapeutics in SNFs based on clinical pharmacology as applied to the elderly. PMID:429730

  8. Ground-source heat pump case studies and utility programs

    SciTech Connect

    Lienau, P.J.; Boyd, T.L.; Rogers, R.L.

    1995-04-01

    Ground-source heat pump systems are one of the promising new energy technologies that has shown rapid increase in usage over the past ten years in the United States. These systems offer substantial benefits to consumers and utilities in energy (kWh) and demand (kW) savings. The purpose of this study was to determine what existing monitored data was available mainly from electric utilities on heat pump performance, energy savings and demand reduction for residential, school and commercial building applications. In order to verify the performance, information was collected for 253 case studies from mainly utilities throughout the United States. The case studies were compiled into a database. The database was organized into general information, system information, ground system information, system performance, and additional information. Information was developed on the status of demand-side management of ground-source heat pump programs for about 60 electric utility and rural electric cooperatives on marketing, incentive programs, barriers to market penetration, number units installed in service area, and benefits.

  9. Health Services Utilization and Payments in Patients With Cancer Pain: A Comparison of Intrathecal Drug Delivery vs. Conventional Medical Management

    PubMed Central

    Stearns, Lisa J.; Hammond, Krisstin; Berryman, Eric; Janjan, Nora A.

    2016-01-01

    Introduction To compare health services utilization and payments for cancer patients who received an implantable intrathecal drug delivery (IDD) system, consisting of a pump and catheter, vs. conventional medical management (CMM) for the treatment of cancer‐related pain. Methods This retrospective claims‐data analysis compared health services utilization and payments in a population of patients receiving either IDD or CMM for treatment of cancer pain. Patients were propensity score‐matched 1:1 based on characteristics including, but not limited to, age, gender, cancer type, comorbid conditions, and health care utilization and payments. Results From a sample of 142 IDD patients and 3188 CMM patients who met all inclusion/exclusion criteria, 73 matched pairs were obtained. In the year following implant, IDD patients had a consistent trend of lower medical utilization, and total payments that were $3195 lower compared to CMM. Conclusions Despite the high initial cost of IDD, this analysis suggests that patients with IDD incur lower medical utilization and payments over the first year post‐implant. Further analysis comprised of a larger, longitudinal sample would contribute to health economics and outcomes research, and assist with future practice guideline development. PMID:26816205

  10. Differences in utilization of drug-eluting stents by race and payer.

    PubMed

    Hannan, Edward L; Racz, Michael; Walford, Gary; Clark, Luther T; Holmes, David R; King, Spencer B; Sharma, Samin

    2007-10-15

    Numerous disparities in access to health care by race and gender have been identified in the literature. This study examines differences in the use of drug-eluting stents (DES) versus bare-metal stents (BMS) by race, payer, and income level. Data from New York State's Percutaneous Coronary Intervention Reporting System from July 2003 to December 2004 were used to examine use of DES (20,165 patients) relative to BMS (4,547 patients) by race, payer, and annual income level, controlling for a variety of patient and hospital characteristics. African-Americans were found to be less likely to receive DES than other races between July 2003 and March 2004 (adjusted odds ratio [OR] 0.56, 95% confidence interval [CI] 0.50 to 0.65) and between April 2004 and December 2004 (adjusted OR 0.74, 95% CI 0.61 to 0.90). These disparities were reduced (respective adjusted ORs 0.67, 95% CI 0.58 to 0.77 and 0.81, 95% CI 0.66 to 0.91) when controlling for admitting hospital and hospital volume, but were still significant. Medicaid/self-pay patients, and patients living in zip codes with median annual incomes between $20,000 and $30,000 were also less likely to receive DES in the first time period (adjusted respective ORs 0.80, 95% CI 0.68 to 0.93) and 0.85, 95% CI 0.75 to 0.96). In conclusion, African-Americans and low income groups receive DES less frequently than their counterparts compared with BMS. This is related to the hospitals where they are admitted, but not entirely.

  11. Automated method for study of drug metabolism

    NASA Technical Reports Server (NTRS)

    Furner, R. L.; Feller, D. D.

    1973-01-01

    Commercially available equipment can be modified to provide automated system for assaying drug metabolism by continuous flow-through. System includes steps and devices for mixing drug with enzyme and cofactor in the presence of pure oxygen, dialyzing resulting metabolite against buffer, and determining amount of metabolite by colorimetric method.

  12. Active controlled studies in antibiotic drug development.

    PubMed

    Dane, Aaron

    2011-01-01

    The increasing concern of antibacterial resistance has been well documented, as has the relative lack of antibiotic development. This paradox is in part due to challenges with clinical development of antibiotics. Because of their rapid progression, untreated bacterial infections are associated with significant morbidity and mortality. As a consequence, placebo-controlled studies of new agents are unethical. Rather, pivotal development studies are mostly conducted using non-inferiority designs versus an active comparator. Further, infections because of comparator-resistant isolates must usually be excluded from the trial programme. Unfortunately, the placebo-controlled data classically used in support of non-inferiority designs are largely unavailable for antibiotics. The only available data are from the 1930s and 1940s and their use is associated with significant concerns regarding constancy and assay sensitivity. Extended public debate on this challenge has led to proposed solutions by some in which these concerns are addressed by using very conservative approaches to trial design, endpoints and non-inferiority margins, in some cases leading to potentially impractical studies. To compound this challenge, different Regulatory Authorities seem to be taking different approaches to these key issues. If harmonisation does not occur, antibiotic development will become increasingly challenging, with the risk of further decreases in the amount of antibiotic drug development. However with clarity on Regulatory requirements and an ability to feasibly conduct global development programmes, it should be possible to bring much needed additional antibiotics to patients.

  13. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes

    NASA Astrophysics Data System (ADS)

    Hamlekhan, Azhang; Sinha-Ray, Suman; Takoudis, Christos; Mathew, Mathew T.; Sukotjo, Cortino; Yarin, Alexander L.; Shokuhfar, Tolou

    2015-06-01

    Formation of titanium dioxide nanotubes (TNTs) on a titanium surface holds great potential for promoting desirable cellular response. However, prolongation of drug release from these nano-reservoirs remains to be a challenge. In our previous work TNTs were successfully loaded with a drug. In this study the effect of TNTs dimensions on prolongation of drug release is quantified aiming at the introduction of a simple novel technique which overcomes complications of previously introduced methods. Different groups of TNTs with different lengths and diameters are fabricated. Samples are loaded with a model drug and rate of drug release over time is monitored. The relation of the drug release rate to the TNT dimensions (diameter, length, aspect ratio and volume) is established. The results show that an increase in any of these parameters increases the duration of the release process. However, the strongest parameter affecting the drug release is the aspect ratio. In fact, TNTs with higher aspect ratios release drug slower. It is revealed that drug release from TNT is a diffusion-limited process. Assuming that diffusion of drug in (Phosphate-Buffered Saline) PBS follows one-dimensional Fick’s law, the theoretical predictions for drug release profile is compatible with our experimental data for release from a single TNT.

  14. Alcohol and Drug Use among "Street" Adolescents: An Exploratory Study.

    ERIC Educational Resources Information Center

    McKirnan, David J.; Johnson, Tina

    Although adolescent alcohol and drug use is decreasing, many teenagers continue to use alcohol and drugs. Studies of adolescent alcohol use typically sample intact high school populations, excluding dropouts and adolescents alienated from straight high school populations. Alcohol and drug use and alcohol related attitudes were measured in 62…

  15. Utilizing Business, University, and Community Resources to Target Adolescent Prescription Drug Abuse

    ERIC Educational Resources Information Center

    Wade-Mdivanian, R.; Anderson-Butcher, D.; Hale, K.; Kwiek, N.; Smock, J.; Radigan, D.; Lineberger, J.

    2012-01-01

    "Generation Rx" is a prescription drug abuse prevention strategy which includes a "toolkit" designed to be used with youth. Developed by Cardinal Health Foundation and the Ohio State University, it provides health care providers (especially pharmacists), parents, teachers, youth workers, and other community leaders with interactive tools and…

  16. Parent Drug Education: A Participatory Action Research Study into Effective Communication about Drugs between Parents and Unrelated Young People

    ERIC Educational Resources Information Center

    Mallick, Jane

    2007-01-01

    Parent drug education is considered a key aspect of drug prevention. Effective communication acts as protective factor for drug misuse in young people. This study is a Participatory Action Research study of "Drugsbridge", a drug education programme that has an emphasis on facilitating intergenerational communication about drugs between parents and…

  17. 78 FR 68461 - Guidance for Industry: Studies To Evaluate the Utility of Anti-Salmonella Chemical Food Additives...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-14

    ... Anti- Salmonella Chemical Food Additives in Feeds; Request for Comments AGENCY: Food and Drug... Chemical Food Additives in Feeds,'' and is seeking comments on this guidance before revisions are made... Guidance for Industry: Studies to Evaluate the Utility of Anti-Salmonella Chemical Food Additives in...

  18. Turning the gun on cancer: Utilizing lysosomal P-glycoprotein as a new strategy to overcome multi-drug resistance.

    PubMed

    Seebacher, Nicole; Lane, Darius J R; Richardson, Des R; Jansson, Patric J

    2016-07-01

    Oxidative stress plays a role in the development of drug resistance in cancer cells. Cancer cells must constantly and rapidly adapt to changes in the tumor microenvironment, due to alterations in the availability of nutrients, such as glucose, oxygen and key transition metals (e.g., iron and copper). This nutrient flux is typically a consequence of rapid growth, poor vascularization and necrosis. It has been demonstrated that stress factors, such as hypoxia and glucose deprivation up-regulate master transcription factors, namely hypoxia inducible factor-1α (HIF-1α), which transcriptionally regulate the multi-drug resistance (MDR), transmembrane drug efflux transporter, P-glycoprotein (Pgp). Interestingly, in addition to the established role of plasma membrane Pgp in MDR, a new paradigm of intracellular resistance has emerged that is premised on the ability of lysosomal Pgp to transport cytotoxic agents into this organelle. This mechanism is enabled by the topological inversion of Pgp via endocytosis resulting in the transporter actively pumping agents into the lysosome. In this way, classical Pgp substrates, such as doxorubicin (DOX), can be actively transported into this organelle. Within the lysosome, DOX becomes protonated upon acidification of the lysosomal lumen, causing its accumulation. This mechanism efficiently traps DOX, preventing its cytotoxic interaction with nuclear DNA. This review discusses these effects and highlights a novel mechanism by which redox-active and protonatable Pgp substrates can utilize lysosomal Pgp to gain access to this compartment, resulting in catastrophic lysosomal membrane permeabilization and cell death. Hence, a key MDR mechanism that utilizes Pgp (the "gun") to sequester protonatable drug substrates safely within lysosomes can be "turned on" MDR cancer cells to destroy them from within.

  19. Turning the gun on cancer: Utilizing lysosomal P-glycoprotein as a new strategy to overcome multi-drug resistance.

    PubMed

    Seebacher, Nicole; Lane, Darius J R; Richardson, Des R; Jansson, Patric J

    2016-07-01

    Oxidative stress plays a role in the development of drug resistance in cancer cells. Cancer cells must constantly and rapidly adapt to changes in the tumor microenvironment, due to alterations in the availability of nutrients, such as glucose, oxygen and key transition metals (e.g., iron and copper). This nutrient flux is typically a consequence of rapid growth, poor vascularization and necrosis. It has been demonstrated that stress factors, such as hypoxia and glucose deprivation up-regulate master transcription factors, namely hypoxia inducible factor-1α (HIF-1α), which transcriptionally regulate the multi-drug resistance (MDR), transmembrane drug efflux transporter, P-glycoprotein (Pgp). Interestingly, in addition to the established role of plasma membrane Pgp in MDR, a new paradigm of intracellular resistance has emerged that is premised on the ability of lysosomal Pgp to transport cytotoxic agents into this organelle. This mechanism is enabled by the topological inversion of Pgp via endocytosis resulting in the transporter actively pumping agents into the lysosome. In this way, classical Pgp substrates, such as doxorubicin (DOX), can be actively transported into this organelle. Within the lysosome, DOX becomes protonated upon acidification of the lysosomal lumen, causing its accumulation. This mechanism efficiently traps DOX, preventing its cytotoxic interaction with nuclear DNA. This review discusses these effects and highlights a novel mechanism by which redox-active and protonatable Pgp substrates can utilize lysosomal Pgp to gain access to this compartment, resulting in catastrophic lysosomal membrane permeabilization and cell death. Hence, a key MDR mechanism that utilizes Pgp (the "gun") to sequester protonatable drug substrates safely within lysosomes can be "turned on" MDR cancer cells to destroy them from within. PMID:27154979

  20. Drug abuse in Costa Rica: a review of several studies.

    PubMed

    Alfaro Murillo, E

    1990-01-01

    This article provides a review of drug use surveys conducted by Costa Rica's Institute on Alcoholism and Drug Dependence during the years 1983-1987. These studies dealt with a wide range of subjects--residents of marginal neighborhoods, juvenile male and adult female detainees, and high school students--as well as with the general population. Overall, the studies indicated that the most commonly used illicit drug was marijuana, that the bulk of the drug users (excluding alcohol and tobacco users) were young males, that relevant levels of cocaine use were starting to occur, and that the country's general drug abuse picture poses a problem in need of immediate attention. PMID:2331555

  1. Study of Lyndon B. Johnson Space Center utility systems

    NASA Technical Reports Server (NTRS)

    Redding, T. E.; Huber, W. C.

    1977-01-01

    The results of an engineering study of potential energy saving utility system modifications for the NASA Lyndon B. Johnson Space Center are presented. The objective of the study was to define and analyze utility options that would provide facility energy savings in addition to the approximately 25 percent already achieved through an energy loads reduction program. A systems engineering approach was used to determine total system energy and cost savings resulting from each of the ten major options investigated. The results reported include detailed cost analyses and cost comparisons of various options. Cost are projected to the year 2000. Also included are a brief description of a mathematical model used for the analysis and the rationale used for a site survey to select buildings suitable for analysis.

  2. Enterprise utilization of "always on-line" diagnostic study archive.

    PubMed

    McEnery, Kevin W; Suitor, Charles T; Thompson, Stephen K; Shepard, Jeffrey S; Murphy, William A

    2002-01-01

    To meet demands for enterprise image distribution, an "always on-line" image storage archive architecture was implemented before soft copy interpretation. It was presumed that instant availability of historical diagnostic studies would elicit a substantial utilization. Beginning November 1, 2000 an enterprise distribution archive was activated (Stentor, SanFrancisco, CA). As of August 8, 2001, 83,052 studies were available for immediate access without the need for retrieval from long-term archive. Image storage and retrieval logs for the period from June 12, 2001 to August 8, 2001 were analyzed. A total of 41,337 retrieval requests were noted for the 83,052 studies available as August 8, 2001. Computed radiography represented 16.8% of retrieval requests; digital radiography, 16.9%; computed tomography (CT), 44.5%; magnetic resonance (MR), 19.2%; and ultrasonography, 2.6%. A total of 51.5% of study retrievals were for studies less than 72 hours old. Study requests for cases greater than 100 days old represented 9.9% of all accessions, 9.7% of CT accessions, and 15.4% of MR accessions. Utilization of the archive indicates a substantial proportion of study retrievals for studies less than 72 hours after study completion. However, significant interest in historical CT and MR examinations was shown. PMID:12105703

  3. Impact of Participatory Design for Drug-Drug Interaction Alerts. A Comparison Study Between Two Interfaces.

    PubMed

    Luna, Daniel; Otero, Carlos; Risk, Marcelo; Stanziola, Enrique; González Bernaldo de Quirós, Fernán

    2016-01-01

    Decision support systems for alert drug-drug interactions have been shown as valid strategy to reduce medical error. Even so the use of these systems has not been as expected, probably due to the lack of a suitable design. This study compares two interfaces, one of them developed using participatory design techniques (based on user centered design processes). This work showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction with the system.

  4. Utilizing Scanning Probe Microscopy to Study Organic Photovoltaic Materials

    NASA Astrophysics Data System (ADS)

    Kibel, Ashley; Bhattacharyya, Shreya; Liddell, Paul; Gust, Devens; Lindsay, Stuart

    2010-03-01

    Organic photovoltaics have the potential to provide cheaper alternatives to traditional silicon solar cells due to flexibility in design and engineering. Understanding how charge is transported in these materials is important for the future design and fabrication of efficient organic solar cells. We utilize scanning probe microscopy techniques to study the electrical properties of biomimetic organic molecules that have photovoltaic potential. We present results from conducting atomic force microscopy measurements performed on bare substrates commonly utilized in organic photovoltaic applications as well as measurements on organic thin films self assembled on these substrates. Furthermore, we present the results of single molecule conductivity experiments performed using a scanning tunneling microscope on novel donor-acceptor molecules. We discuss benefits, as well as challenges, to using scanning probe techniques on organic photovoltaic systems.

  5. Technology Utilization House Study Report. [For Energy Conservation

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The objectives of Project TECH are: (1) to construct a single family detached dwelling for demonstrating the application of advanced technology and minimizing the requirement for energy and utility services, and (2) to help influence future development in home construction by defining the interaction of integrated energy and water management systems with building configuration and construction materials. Components and methods expected to be cost effective over a 20 year span were studied. Emphasis was placed on the utilization of natural heating and cooling characteristics. Orientation and location of windows, landscaping, natural ventilation, and characteristics of the local climate and microclimate were intended to be used to best advantage. Energy conserving homes are most efficient when design for specific sites, therefore project TECH should not be considered a prototype design suitable for all locations. However, it does provide ideas and analytical methods which can be applied to some degree in all housing.

  6. A Study on Drug Safety Monitoring Program in India

    PubMed Central

    Ahmad, A.; Patel, Isha; Sanyal, Sudeepa; Balkrishnan, R.; Mohanta, G. P.

    2014-01-01

    Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers. PMID:25425751

  7. A study on drug safety monitoring program in India.

    PubMed

    Ahmad, A; Patel, Isha; Sanyal, Sudeepa; Balkrishnan, R; Mohanta, G P

    2014-09-01

    Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers.

  8. Pharmacogenomic study using bio- and nanobioelectrochemistry: Drug-DNA interaction.

    PubMed

    Hasanzadeh, Mohammad; Shadjou, Nasrin

    2016-04-01

    Small molecules that bind genomic DNA have proven that they can be effective anticancer, antibiotic and antiviral therapeutic agents that affect the well-being of millions of people worldwide. Drug-DNA interaction affects DNA replication and division; causes strand breaks, and mutations. Therefore, the investigation of drug-DNA interaction is needed to understand the mechanism of drug action as well as in designing DNA-targeted drugs. On the other hand, the interaction between DNA and drugs can cause chemical and conformational modifications and, thus, variation of the electrochemical properties of nucleobases. For this purpose, electrochemical methods/biosensors can be used toward detection of drug-DNA interactions. The present paper reviews the drug-DNA interactions, their types and applications of electrochemical techniques used to study interactions between DNA and drugs or small ligand molecules that are potentially of pharmaceutical interest. The results are used to determine drug binding sites and sequence preference, as well as conformational changes due to drug-DNA interactions. Also, the intention of this review is to give an overview of the present state of the drug-DNA interaction cognition. The applications of electrochemical techniques for investigation of drug-DNA interaction were reviewed and we have discussed the type of qualitative or quantitative information that can be obtained from the use of each technique.

  9. Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Brann, Tyler

    The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon

  10. The search for novel drug leads for predominately antitumor therapies by utilizing mother nature's pharmacophoric libraries.

    PubMed

    Kingston, David G I; Newman, David J

    2005-03-01

    Recent advances in the use of natural products and compounds derivedfrom natural products as agents for the treatment of cancer and other diseases are reviewed. The antitumor agents discussed include tubulin interactive agents, inhibitors of topoisomerases I and II, caspase activators, proteasome inhibitors, histone deacetylase inhibitors, heat shock protein 90 inhibitors, protein kinase inhibitors, and inhibitors of hypoxia inducible factor 1. It can be concluded that, despite a perceived lack of popularity in recent years, the use of natural product scaffolds in searching for drug leads is still being practiced.

  11. 76 FR 1174 - Drugs for Human Use; Drug Efficacy Study Implementation; Oral Prescription Drugs Offered for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-07

    ... and other parties in response to various DESI notices covering relevant products. \\3\\ 38 FR 34481 (December 14, 1973). \\4\\ 38 FR 4006 (February 9, 1973) and 37 FR 15022 (July 27, 1972). All drugs covered by... Federal Register on May 25, 1982 (47 FR 22606), FDA revoked the temporary exemption that permitted...

  12. 76 FR 11790 - Drugs for Human Use; Drug Efficacy Study Implementation; Oral Prescription Drugs Offered for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... . SUPPLEMENTARY INFORMATION: I. Background In a notice published in the Federal Register of January 7, 2011 (76 FR..., 1982 (47 FR 22610), FDA revoked the temporary exemption that permitted these drug products, and those... (49 FR 32681) that the Agency was withdrawing approval of NDAs 8-306, 8-604, and 11-265 pertaining...

  13. New Alert Override Codes for the Drug Utilization Review System Derived from Outpatient Prescription Data from a Tertiary Teaching Hospital in Korea

    PubMed Central

    Yoo, Ki-Bong; Kim, Woojae; Park, Man Young; Ahn, Eun Kyoung; Park, Rae Woong

    2016-01-01

    Objectives This paper proposes new alert override reason codes that are improvements on existing Drug Utilization Review (DUR) codes based on an analysis of DUR alert override cases in a tertiary medical institution. Methods Data were obtained from a tertiary teaching hospital covering the period from April 1, 2012 to January 15, 2013. We analyzed cases in which doctors had used the 11 overlapping prescription codes provided by the Health Insurance Review and Assessment Service (HIRA) or had provided free-text reasons. Results We identified 27,955 alert override cases. Among these, 7,772 (27.8%) utilized the HIRA codes, and 20,183 (72.2%) utilized free-text reasons. According to the free-text content analysis, 8,646 cases (42.8%) could be classified using the 11 HIRA codes, and 11,537 (57.2%) could not. In the unclassifiable cases, we identified the need for codes for "prescription relating to operation" and "emergency situations." Two overlapping prescription codes required removal because they were not used. Codes A, C, F, H, I, and J (for drug non-administration cases) explained surrounding situations in too much detail, making differentiation between them difficult. These 6 codes were merged into code J4: "patient was not taking/will not take the medications involved in the DDI." Of the 11 HIRA codes, 6 were merged into a single code, 2 were removed, and 2 were added, yielding 6 alert override codes. We could codify 23,550 (84.2%) alert override cases using these codes. Conclusions These new codes will facilitate the use of the drug–drug interactions alert override in the current DUR system. For further study, an appropriate evaluation should be conducted with prescribing clinicians. PMID:26893949

  14. Solid state drug-polymer miscibility studies using the model drug ABT-102.

    PubMed

    Jog, Rajan; Gokhale, Rajeev; Burgess, Diane J

    2016-07-25

    Amorphous solid dispersions typically suffer storage stability issues due to: their amorphous nature, high drug loading, uneven drug:stabilizer ratio and plasticization effects as a result of hygroscopic excipients. An extensive solid state miscibility study was conducted to aid in understanding the mechanisms involved in drug/stabilizer interactions. ABT-102 (model drug) and nine different polymers with different molecular weights and viscosities were selected to investigate drug/polymer miscibility. Three different polymer:drug ratios (1:3, 1:1 and 3:1, w/w) were analyzed using: DSC, FTIR and PXRD. Three different techniques were used to prepare the amorphous solid dispersions: serial dilution, solvent evaporation and spray drying. Spray drying was the best method to obtain amorphous solid dispersions. However, under certain conditions amorphous formulations could be obtained using solvent evaporation. Melting point depression was used to calculate interaction parameters and free energy of mixing for the various drug polymer mixtures. The spray dried solid dispersions yielded a negative free energy of mixing which indicated strong drug-polymer miscibility compared to the solvent evaporation and serial dilution method. Soluplus was the best stabilizer compared to PVP and HPMC, which is probably a consequence of strong hydrogen bonding between the two CO moieties of soluplus and the drug NH moieities.

  15. Scoping study of integrated resource planning needs in the public utility sector

    SciTech Connect

    Garrick, C J; Garrick, J M; Rue, D R

    1993-06-01

    Integrated resource planning (IRP) is an approach to utility resource planning that integrates the evaluation of supply- and demand-site options for providing energy services at the least cost. Many utilities practice IRP; however, most studies about IRP focus on investor-owned utilities (IOUs). This scoping study investigates the IRP activities and needs of public utilities (not-for-profit utilities, including federal, state, municipal, and cooperative utilities). This study (1) profiles IRP-related characteristics of the public utility sector, (2) articulates the needs of public utilities in understanding and implementing IRP, and (3) identifies strategies to advance IRP principles in public utility planning.

  16. Misuse of "study drugs:" prevalence, consequences, and implications for policy

    PubMed Central

    Sussman, Steve; Pentz, Mary Ann; Spruijt-Metz, Donna; Miller, Toby

    2006-01-01

    Background Non-medical/illegal use of prescription stimulants popularly have been referred to as "study drugs". This paper discusses the current prevalence and consequences of misuse of these drugs and implications of this information for drug policy. Results Study drugs are being misused annually by approximately 4% of older teens and emerging adults. Yet, there are numerous consequences of misuse of prescription stimulants including addiction, negative reactions to high dosages, and medical complications. Policy implications include continuing to limit access to study drugs, finding more safe prescription drug alternatives, interdiction, and public education. Conclusion Much more work is needed on prescription stimulant misuse assessment, identifying the extent of the social and economic costs of misuse, monitoring and reducing access, and developing prevention and cessation education efforts. PMID:16764722

  17. Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs

    PubMed Central

    Godman, Brian; Malmström, Rickard E.; Diogene, Eduardo; Jayathissa, Sisira; McTaggart, Stuart; Cars, Thomas; Alvarez-Madrazo, Samantha; Baumgärtel, Christoph; Brzezinska, Anna; Bucsics, Anna; Campbell, Stephen; Eriksson, Irene; Finlayson, Alexander; Fürst, Jurij; Garuoliene, Kristina; Gutiérrez-Ibarluzea, Iñaki; Hviding, Krystyna; Herholz, Harald; Joppi, Roberta; Kalaba, Marija; Laius, Ott; Malinowska, Kamila; Pedersen, Hanne B.; Markovic-Pekovic, Vanda; Piessnegger, Jutta; Selke, Gisbert; Sermet, Catherine; Spillane, Susan; Tomek, Dominik; Vončina, Luka; Vlahović-Palčevski, Vera; Wale, Janet; Wladysiuk, Magdalena; van Woerkom, Menno; Zara, Corinne; Gustafsson, Lars L.

    2014-01-01

    Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. Objective: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. Methodology: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding. PMID

  18. Use of Serotonergic Drugs in Canada for Gastrointestinal Motility Disorders: Results of a Retrospective Cohort Study

    PubMed Central

    Manji, Farouq; Lam, Jennifer; Taylor, Brian M.

    2016-01-01

    Background. Surgery for GI dysmotility is limited to those with severe refractory disease. Though effective, use of serotonergic promotility drugs has been restricted in Canada due to adverse events. We aimed to investigate utilization of promotility serotonergic drugs in patients under consideration for surgical management. Methods. A retrospective cohort study was conducted using prospectively collected data. The study population included consecutive patients referred to a motility clinic for consideration of bowel resection at a Canadian tertiary hospital (1996–2011). Univariable tests and multivariable logistic regression analyses were used to assess predictors of serotonergic drug use. Results. Of 128 patients, the majority (n = 98, 76.6%) had constipation-dominant symptoms. Only 25% (n = 32) had tried serotonergic promotility drugs. There was no association between use of these drugs and severity of constipation nor was there an association between serotonergic drug use and presence of diffuse dysmotility (all p > 0.05). The majority of patients (n = 97, 75.8%) underwent some type of surgical resection, which was associated with considerable morbidity (n = 13, 13.4%). Conclusions. Surgical management of GI dysmotility results in serious morbidity. Serotonergic promotility drugs may allow patients to avoid surgery but disease severity does not predict use of these drugs. PMID:27313955

  19. Utilizing a novel tandem oral dosing strategy to enhance exposure of low-solubility drug candidates in a preclinical setting.

    PubMed

    Chiang, Po-Chang; South, Sarah A; Foster, Kimberly A; Daniels, J Scott; Wene, Steve P; Albin, Lesley A; Thompson, David C

    2010-07-01

    Time and resource constraints necessitate increasingly early decision making to accelerate or stop preclinical drug discovery programs. Early discovery drug candidates may be potent inhibitors of new targets, but all too often exhibit poor pharmaceutical and pharmacokinetic properties that limit the in vivo exposure. Low solubility of a drug candidate often leads to poor oral bioavailability and poor dose linearity that creates an issue for efficacy and target safety studies, where high drug exposures are desired. When solubility issues are encountered, enabling formulations are often used to improve the exposure. However, this approach often requires a substantial and lengthy investment to develop the formulation. In our study, two drug candidates with poor aqueous solubility were dosed in rats as simple suspension formulations using a novel tandem dosing strategy, which employs dosing orally in 2.5 h increments up to three times to simulate an oral infusion by avoiding saturation of absorption associated with bolus dosing. These compounds were also dosed using the same suspension formulations and a standard dosing strategy. The resulting in vivo exposures were compared. It was found that this novel tandem dosing strategy significantly improved the in vivo exposures.

  20. Using Nonexperts for Annotating Pharmacokinetic Drug-Drug Interaction Mentions in Product Labeling: A Feasibility Study

    PubMed Central

    Ning, Yifan; Hernandez, Andres; Horn, John R; Jacobson, Rebecca; Boyce, Richard D

    2016-01-01

    labeling of annotated PDDIs across a broader range of drug product labels. Preannotation of drug mentions may ease the annotation task. However, preannotation of PDDIs, as operationalized in this study, presented the participants with difficulties. Future work should test if these issues can be addressed by the use of better performing NLP and a different approach to presenting the PDDI preannotations to users during the annotation workflow. PMID:27066806

  1. Drug abuse in Nigeria: a review of epidemiological studies.

    PubMed

    Pela, O A; Ebie, J C

    1982-01-01

    This paper reviews the available literature on the epidemiology of drug abuse in Nigeria. Depending on the definition used, substances which are abused include antibiotics, antidiarrhoeals, laxatives, pain-relieving drugs, sedatives, amphetamines and cannabis. This review is, however, limited to studies on substances which alter behaviour or mood. These drugs include cannabis, sedative-hypnotics, amphetamines and alcohol. For some classes of drugs there has been a noticeable shift in patterns of drug abuse, for example, from abuse of methaqualone to barbiturates. The abuse of volatile solvents and other substances has also been noted. The review shows that there is no age limit among drug abusers. Studies on the influence of social class have been contradictory. Factors which indicate a predisposition to initial drug use have been similar to those reported in other cultures. Although the studies agreed on the classes of drugs abused and the changing patterns of drug abuse, there has been no uniform reporting system. This situation is attributed to financial constraints. Large-scale surveys which should incorporate most of the core items in any epidemiological study on substance abuse have been suggested. PMID:6985029

  2. EMPADE Study: Evaluation of Medical Prescriptions and Adverse Drug Events in COPD Patients Admitted to Intensive Care Unit

    PubMed Central

    Khan, M. Amer; Khan, M. Nematullah; Sultan, Ihtisham; Khan, M. Aamer; Ali, S. Amir; Farooqui, Afroze

    2015-01-01

    Introduction Inappropriate drug usage may preclude ideal benefit due to increased medical cost, antimicrobial resistance, adverse effects and mortality. Therefore drug utilization studies have become a plausible means in evaluating the healthcare systems. COPD management usually involves more than one drug which may escalate the risk of ADEs (adverse drug events). Aim The present study was aimed at assessing the current drug practice and ADEs in COPD management in ICU. Materials and Methods A total of 1,044 patients admitted for the treatment of COPD were included in the study. Their prescriptions were recorded for evaluation of drug utilization and patients were counseled for assessing ADEs. Results were evaluated by Chi-square test and percentages. Result All-embracing 15,360 drugs were prescribed at an average of 14.71 drugs per patient, wherein β2-agonists were extensively prescribed agents followed by inhaled-corticosteroids and anti-cholinergics. 372 ADEs were reported in 252 patients, wherein restlessness was the most frequent ADE and theophylline was found to be associated with highest cases of ADEs. Conclusion Practitioners should prescribe least number of drugs to mitigate the likelihood of adverse outcomes in patients due to numerous drugs usage, which may be achieved by following GOLD guidelines. The present work may help in improving the current management of COPD by rectifying the flaws delineated in this article. PMID:26675667

  3. Lymphocyte transformation studies in drug hypersensitivity

    PubMed Central

    Warrington, R.J.; Tse, K.S.

    1979-01-01

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents. Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects. For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test. It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs. PMID:445303

  4. National study on the utilization of prophylactic antibiotics in surgery, Belgium, 1986

    PubMed Central

    Mertens, R.; Verbist, L.; Gordts, B.; Lauwers, S.; Potvliege, C.; Reybrouck, G.; Verschraegen, G.; Wauters, G.; Berghmans, L.; Dondeyne, F.; Stroobant, A.

    1989-01-01

    During the last week of May 1986, a 1-week prospective study on antibiotic utilization in surgical patients was held in 104 (42%) of the 247 Belgian acute care hospitals. All surgical patients with a post-operative stay of at least 3 days were studied, involving 3112 patients. Each patient was observed for 7 days, starting from the day before surgery. Antibiotics were administered to 71·9% of all patients; 21·9% received therapeutic antibiotics and 52·9% prophylactic antibiotics; 2·9% received both. Of the 1285 patients undergoing a surgical procedure with no indication for antimicrobial prophylaxis, 50·7% nevertheless received prophylaxis; 92·8% of patients with a generally recognized indication for prophylaxis received antibiotic prophylaxis. Less than one fifth (17·1%) of all prophylactic courses were stopped on the day of the intervention whilst 26·3% were continued up to the fifth post-operative day or beyond. The most frequently prescribed drugs for this indication included first and second generation cephalosporins and nitroimidazoles. The number of different generic drugs utilized per hospital ranged from 1 to 18 (mean: 7·7). PMID:2680549

  5. Membrane–drug interactions studied using model membrane systems

    PubMed Central

    Knobloch, Jacqueline; Suhendro, Daniel K.; Zieleniecki, Julius L.; Shapter, Joseph G.; Köper, Ingo

    2015-01-01

    The direct interaction of drugs with the cell membrane is often neglected when drug effects are studied. Systematic investigations are hindered by the complexity of the natural membrane and model membrane systems can offer a useful alternative. Here some examples are reviewed of how model membrane architectures including vesicles, Langmuir monolayers and solid supported membranes can be used to investigate the effects of drug molecules on the membrane structure, and how these interactions can translate into effects on embedded membrane proteins. PMID:26586998

  6. Very large virtual compound spaces: construction, storage and utility in drug discovery.

    PubMed

    Peng, Zhengwei

    2013-09-01

    Recent activities in the construction, storage and exploration of very large virtual compound spaces are reviewed by this report. As expected, the systematic exploration of compound spaces at the highest resolution (individual atoms and bonds) is intrinsically intractable. By contrast, by staying within a finite number of reactions and a finite number of reactants or fragments, several virtual compound spaces have been constructed in a combinatorial fashion with sizes ranging from 10(11)11 to 10(20)20 compounds. Multiple search methods have been developed to perform searches (e.g. similarity, exact and substructure) into those compound spaces without the need for full enumeration. The up-front investment spent on synthetic feasibility during the construction of some of those virtual compound spaces enables a wider adoption by medicinal chemists to design and synthesize important compounds for drug discovery. Recent activities in the area of exploring virtual compound spaces via the evolutionary approach based on Genetic Algorithm also suggests a positive shift of focus from method development to workflow, integration and ease of use, all of which are required for this approach to be widely adopted by medicinal chemists.

  7. Clinical utility of the Food and Drug Administration Electrocardiogram Warehouse: a paradigm for the critical pathway initiative.

    PubMed

    Cabell, Christopher H; Noto, Tory C; Krucoff, Mitchell W

    2005-10-01

    Although there are rising public expectations about the prospects for new therapies based on advances in biomedical discoveries, the rate of new product submissions to the Food and Drug Administration (FDA) has not been increasing. Alarmingly, over the past 6 years, there has been a 30% decline in submissions. The reasons for this are multifactorial and include new science not at its full potential, mergers/business arrangements have decreased candidates, chronic disease is harder to study, the failure rate has not improved, and rapidly escalating costs and complexity. Notably, societal investment in research and development to improve the drug approval process has been lacking in contrast to the large investments, both private and public, in basic research and specific product advances. The Critical Path Initiative has been developed by the FDA to combat many of these issues. This initiative is designed to be collaborative between government, academic, industry, and patient groups. The partnership is designed to expand product opportunities by sharing existing knowledge and data, allowing the development of enabling standards, to improve drug development and approval. A central tenant of Critical Path is a focus on the evaluative science of the drug approval process, including both efficacy and safety measures. The FDA Electrocardiogram Warehouse is 1 example where a government resource could be used by a confluence of groups to improve the science surrounding important components of the drug approval process such as cardiac safety evaluation.

  8. Concurrent Use of Conventional Drugs with Chinese Herbal Products in Taiwan: A Population-based Study.

    PubMed

    Chen, Ming-Chen; Lai, Jung-Nien; Chen, Pau-Chung; Wang, Jung-Der

    2013-10-01

    The increased use of Chinese herbal products (CHPs) worldwide has raised the concern of herb-drug interactions. The aim of this study was to determine the prevalence and utilization patterns of concurrent use of conventional drugs and CHPs in Taiwan. The usage and frequency of services in the co-prescription of a CHP and a conventional drug were evaluated. Subjects were recruited from a simple random sample of 1,000,000 subjects from over 22 million beneficiaries of the National Health Insurance in 2007. The logistic regression method was employed to estimate the odds ratios (ORs) for the co-prescription of a CHP and a conventional drug (CH + D) and a conventional drug alone (D-alone). The prevalence of the CH + D was 14.1%. Females, regular salary earners, and elderly (65 years and above) were more likely to consume a CHP and a conventional drug concurrently. Painkillers, especially acetaminophen, and anti-cough medicines were the top two conventional drugs that were most frequently co-prescribed with a CHP. Anti-cough medication is the most common conventional drug co-prescribed with CHP, after painkillers. We recommend that safety issues be investigated in future research and integrating both healthcare technologies may be beneficial for the overall health and quality of life of patients.

  9. Potential utility of precision medicine for older adults with polypharmacy: a case series study

    PubMed Central

    Finkelstein, Joseph; Friedman, Carol; Hripcsak, George; Cabrera, Manuel

    2016-01-01

    Pharmacogenomic (PGx) testing has been increasingly used to optimize drug regimens; however, its potential in older adults with polypharmacy has not been systematically studied. In this hypothesis-generating study, we employed a case series design to explore potential utility of PGx testing in older adults with polypharmacy and to highlight barriers in implementing this methodology in routine clinical practice. Three patients with concurrent chronic heart and lung disease aged 74, 78, and 83 years and whose medication regimen comprised 26, 17, and 18 drugs, correspondingly, served as cases for this study. PGx testing identified major genetic polymorphisms in the first two cases. The first case was identified as “CYP3A4/CYP3A5 poor metabolizer”, which affected metabolism of eleven prescribed drugs. The second case had “CYP2D6 rapid metabolizer” status affecting three prescribed medications, two of which were key drugs for managing this patient’s chronic conditions. Both these patients also had VKORC1 allele *A, resulting in higher sensitivity to warfarin. All cases demonstrated a significant number of potential drug–drug interactions. Both patients with significant drug–gene interactions had a history of frequent hospitalizations (six and 23, respectively), whereas the person without impaired cytochrome P450 enzyme activity had only two acute episodes in the last 5 years, although he was older and had multiple comorbidities. Since all patients received guideline-concordant therapy from the same providers and were adherent to their drug regimen, we hypothesized that genetic polymorphism may represent an additional risk factor for higher hospitalization rates in older adults with polypharmacy. However, evidence to support or reject this hypothesis is yet to be established. Studies evaluating clinical impact of PGx testing in older adults with polypharmacy are warranted. For practical implementation of pharmacogenomics in routine clinical care, besides

  10. Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni▿

    PubMed Central

    Manneck, Theresia; Braissant, Olivier; Haggenmüller, Yolanda; Keiser, Jennifer

    2011-01-01

    Alternative antischistosomal drugs are required since praziquantel is virtually the only drug available for treatment and morbidity control of schistosomiasis. Manual microscopic reading is the current “gold standard” to assess the in vitro antischistosomal properties of test drugs; however, it is labor-intensive, subjective, and difficult to standardize. Hence, there is a need to develop novel tools for antischistosomal drug discovery. The in vitro effects of praziquantel, oxamniquine, artesunate, and mefloquine on metabolic activity and parasite motility of Schistosoma mansoni (newly transformed schistosomula [NTS] and 49-day-old adult worms) were studied using isothermal microcalorimetry (IMC). Results were compared to morphological readouts of viability. Results obtained for the four drugs tested with phenotypic evaluation by microscopy and IMC showed a good correlation, but IMC also identified drug effects that were not visible by microscopic evaluation, and IMC precisely determined the onset of action of the test drugs. Similar sensitivities on NTS and adult schistosomes were observed for praziquantel and mefloquine, while slight differences in the drug susceptibilities of the two developmental stages were noted with oxamniquine and artesunate. IMC is a useful tool for antischistosomal drug discovery that should be further validated. In addition, our data support the use of NTS in in vitro antischistosomal drug assays. PMID:21270220

  11. Might Hallucinations Have Social Utility?: A Proposal for Scientific Study.

    PubMed

    Kauffman, Paul Richard

    2016-09-01

    There are many historical examples of people who heard voices or saw visions but were not classified as having a mental illness and who were supported by a religious community. The article offers a perspective for effective psychosocial supports for schizophrenia. The author analyzes data on 95 people who experienced verifiable persistent non-drug-assisted hallucinations in Europe, North America, and Australasia and discusses the life outcomes of 39 subjects. They include founders of religions, dysfunctional monarchs, persons with cosmological beliefs, and mental health workers. Their psychoses were intrinsic to their personalities and contributions. Hallucinations generated by psychosis were useful for cultural innovation, particularly in religion as many hallucinators were integrated into church history. Community, work, friendship, and supportive practices are discussed. A scientific study of effective psychosocial support to supplement medication for schizophrenia is outlined. PMID:27570899

  12. Screening studies of yeasts capable of utilizing petroleum fractions.

    PubMed

    El-Masry, H G; Foda, M S

    1979-01-01

    In these studies, 23 yeast cultures belonging to 10 genera of ascosporogenous, ballistosporogenous, and asporogenous yeasts, were screened with respect to their abilities of hydrocarbon utilization in synthetic media. Thus, kerosene, n-hexadecane, and wax distillate were compared as sole carbon sources in 2% final concentration. Kerosene exhibited marked inhibition on the growth of the majority of the strains, whereas active growth was observed with Debaryomyces vanrijii and many species of the genus Candida in media with n-hexadecane or wax distillate as sole source of carbon. In addition, some cultures belonging to the genera Sporobolomyces, Hansenula, Cryptococcus, and Trigonopsis could utilize some of these substrates, but to a lesser extent. Highest yield of cells and protein was obtained with Candida lipolytica NRRL 1094 in n-hexadecane medium, supplied with 0.03% yeast extract and trace element solutions. The results are discussed with respect to the possibilities of using new yeast genera, with special reference to the genus Debaryomyces, in microbiol protein production. PMID:44934

  13. Drug Monitoring Programs Do Curb Overdose Deaths: Study

    MedlinePlus

    ... html Drug Monitoring Programs Do Curb Overdose Deaths: Study Opioid epidemic demands such measures, researcher says To ... deaths from prescription painkillers called opioids, a new study finds. In an effort to curb overdose deaths ...

  14. Drug-drug interaction studies: regulatory guidance and an industry perspective.

    PubMed

    Prueksaritanont, Thomayant; Chu, Xiaoyan; Gibson, Christopher; Cui, Donghui; Yee, Ka Lai; Ballard, Jeanine; Cabalu, Tamara; Hochman, Jerome

    2013-07-01

    Recently, the US Food and Drug Administration and European Medicines Agency have issued new guidance for industry on drug interaction studies, which outline comprehensive recommendations on a broad range of in vitro and in vivo studies to evaluate drug-drug interaction (DDI) potential. This paper aims to provide an overview of these new recommendations and an in-depth scientifically based perspective on issues surrounding some of the recommended approaches in emerging areas, particularly, transporters and complex DDIs. We present a number of theoretical considerations and several case examples to demonstrate complexities in applying (1) the proposed transporter decision trees and associated criteria for studying a broad spectrum of transporters to derive actionable information and (2) the recommended model-based approaches at an early stage of drug development to prospectively predict DDIs involving time-dependent inhibition and mixed inhibition/induction of drug metabolizing enzymes. We hope to convey the need for conducting DDI studies on a case-by-case basis using a holistic scientifically based interrogative approach and to communicate the need for additional research to fill in knowledge gaps in these areas where the science is rapidly evolving to better ensure the safety and efficacy of new therapeutic agents. PMID:23543602

  15. RS-34 Phoenix (Peacekeeper Post Boost Propulsion System) Utilization Study

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Kos, Larry; Bruno, Cy

    2012-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) in conjunction with Pratt & Whitney Rocketdyne conducted a study to evaluate potential in-space applications for the Rocketdyne produced RS-34 propulsion system. The existing RS-34 propulsion system is a remaining asset from the decommissioned United States Air Force Peacekeeper ICBM program; specifically the pressure-fed storable bipropellant Stage IV Post Boost Propulsion System, renamed Phoenix. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in October 2009. RS-34 propulsion system components were harvested from stages supplied by the USAF and used on the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC is working closely with the USAF to obtain all the remaining RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Phoenix Utilization Study sought to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions: 1) small satellite delivery (SSD), 2) orbital debris removal (ODR), 3) ISS re-supply, 4) SLS kick stage, 5) manned GEO servicing precursor mission, and an Earth-Moon L-2 Waypoint mission. The small satellite delivery and orbital debris removal missions were found to closely mimic the heritage RS-34 mission. It is believed that this technology will enable a small, low-cost multiple satellite delivery to multiple orbital locations with a single

  16. RS-34 Phoenix (Peacekeeper Post Boost Propulsion System) Utilization Study

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Kos, Larry; Burnside, Christopher G.; Bruno, Cy

    2013-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) in conjunction with Pratt & Whitney Rocketdyne conducted a study to evaluate potential in-space applications for the Rocketdyne produced RS-34 propulsion system. The existing RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper ICBM program, specifically the pressure-fed storable bipropellant Stage IV Post Boost Propulsion System, renamed Phoenix. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in October 2009. RS-34 propulsion system components were harvested from stages supplied by the USAF and used on the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. MSFC is working closely with the USAF to obtain RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. As originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Phoenix Utilization Study sought to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions: 1) small satellite delivery (SSD), 2) orbital debris removal (ODR), 3) ISS re-supply, 4) SLS kick stage, 5) manned GEO servicing precursor mission, and an Earth-Moon L-2 Waypoint mission. The small satellite delivery and orbital debris removal missions were found to closely mimic the heritage RS-34 mission. It is believed that this technology will enable a small, low-cost multiple satellite delivery to multiple orbital locations with a single boost. For both the small

  17. Alternative approach for cavitation damage study utilizing repetitive laser pulses

    SciTech Connect

    Ren, Fei; Wang, Jy-An John; Wang, Hong

    2010-01-01

    Cavitation is a common phenomenon in fluid systems that can lead to dramatic degradation of solid materials surface in contact with the cavitating media. Study of cavitation damage has great significance in many engineering fields. Current techniques for cavitation damage study either require large scale equipments or tend to introduce damages from other mechanisms. In this project, we utilized the cavitation phenomenon induced by laser optical breakdown and developed a prototype apparatus for cavitation damage study. In our approach, cavitation was generated by the repetitive pressure waves induced by high-power laser pulses. As proof of principal study, stainless steel and aluminum samples were tested using the novel apparatus. Surface characterization via scanning electron microscopy revealed damages such as indentation and surface pitting, which were similar to those reported in literature using other state-of-the-art techniques. These preliminary results demonstrated the new device was capable of generating cavitation damages and could be used as an alternative method for cavitation damage study.

  18. FEASIBILITY OF MATCHING STUDY PARTICIPANT RESIDENCE WITH SPECIFIC WATER UTILITY TRIHALOMETHANE (THM) DATA IN EPIDEMIOLOGIC STUDIES

    EPA Science Inventory

    Many epidemiologic studies concerning by-products of water disinfection use utility monitoring data to estimate exposure. Use of such data requires linkage of residence location to a specific water utility and associated monitoring data during a given exposure period. The inabil...

  19. Drug Utilization, Dosing, and Costs After Implementation of Intravenous Acetaminophen Guidelines for Pediatric Patients

    PubMed Central

    Fusco, Nicholas M.; Parbuoni, Kristine; Morgan, Jill A.

    2014-01-01

    OBJECTIVES The objectives of this evaluation of medication use were to characterize the use of intravenous acetaminophen at our institution and to determine if acetaminophen was prescribed at age-appropriate dosages per institutional guidelines, as well as to evaluate compliance with restrictions for use. Total acquisition costs associated with intravenous acetaminophen usage is described as well. METHODS This retrospective study evaluated the use of acetaminophen in pediatric patients younger than 18 years of age, admitted to a tertiary care hospital, who received at least 1 dose of intravenous acet-aminophen between August 1, 2011, and January 31, 2012. RESULTS A total of 52 doses of intravenous acetaminophen were administered to 31 patients during the 6-month study period. Most patients were admitted to the otorhinolaryngology service (55%), and the majority of doses were administered either in the operating room (46%) or in the intensive care unit (46%). Nineteen doses (37%) of intravenous acetaminophen were administered to patients who did not meet institutional guidelines' eligibility criteria. Three patients received single doses of intravenous acetaminophen that were greater than the dose recommended for their age. One patient during the study period received more than the recommended 24-hour maximum cumulative dose for acetaminophen. Total acquisition cost of intravenous acetaminophen therapy over the 6-month study period was $530.40. CONCLUSIONS Intravenous acetaminophen was used most frequently among pediatric patients admitted to the otorhinolaryngology service during the perioperative period. Nineteen doses (37%) were administered to patients who did not meet the institutional guidelines' eligibility criteria. Our data support reinforcing the availability of institutional guidelines to promote cost-effective use of intravenous acetaminophen while minimizing the prescription of inappropriate doses. PMID:24782690

  20. Kauai Island Utility Co-op (KIUC) PV integration study.

    SciTech Connect

    Ellis, Abraham; Mousseau, Tom

    2011-08-01

    This report investigates the effects that increased distributed photovoltaic (PV) generation would have on the Kauai Island Utility Co-op (KIUC) system operating requirements. The study focused on determining reserve requirements needed to mitigate the impact of PV variability on system frequency, and the impact on operating costs. Scenarios of 5-MW, 10-MW, and 15-MW nameplate capacity of PV generation plants distributed across the Kauai Island were considered in this study. The analysis required synthesis of the PV solar resource data and modeling of the KIUC system inertia. Based on the results, some findings and conclusions could be drawn, including that the selection of units identified as marginal resources that are used for load following will change; PV penetration will displace energy generated by existing conventional units, thus reducing overall fuel consumption; PV penetration at any deployment level is not likely to reduce system peak load; and increasing PV penetration has little effect on load-following reserves. The study was performed by EnerNex under contract from Sandia National Laboratories with cooperation from KIUC.

  1. A pharmacokinetic drug-drug interaction study of venlafaxine and indinavir.

    PubMed

    Levin, G M; Nelson, L A; DeVane, C L; Preston, S L; Eisele, G; Carson, S W

    2001-01-01

    Depression is a common occurrence in the human immunodeficiency virus (HIV)-infected population. Complications in treating depressed HIV-infected individuals include the use of multiple medications, additive side effects, and potentially significant drug-drug interactions. Based on the pharmacologic characteristics of venlafaxine and indinavir, we hypothesized that significant pharmacokinetic drug-drug interactions would not occur when these drugs where taken concurrently. Nine healthy adult subjects were given a single 800 mg oral dose of indinavir and serial blood samples were collected for measurement of plasma drug concentrations. Over the next 9 days, venlafaxine was administered at a dosage of 50 mg every 8 hours following a brief titration. A venlafaxine trough plasma concentration and serial concentrations following venlafaxine administration were obtained on day 10. On day 11, venlafaxine and indinavir were administered together and serial blood sampling was repeated. Indinavir had no effect on venlafaxine plasma concentrations but resulted in a 7% decrease in plasma concentrations of O-desmethyl-venlafaxine (ODV)(P = 0.028). This effect is unlikely to be clinically significant. Venlafaxine coadministration resulted in a 28% decrease in the area under the concentration time curve (AUC) of plasma indinavir (P = 0.016) and a 36% decrease in its maximum plasma concentration (Cmax; P = 0.038). As the plasma concentration of protease inhibitors is a critical factor in maintaining efficacy and minimizing the potential for viral resistance, the decrease in both AUC and Cmax of indinavir from coadministration of venlafaxine is of concern. The clinical significance of these results obtained from a small number of healthy volunteers is unknown. Further studies are needed to substantiate or refute this apparent drug-drug interaction. Until such time, venlafaxine should be used cautiously in patients receiving indinavir.

  2. Genetic association studies in drug-induced liver injury.

    PubMed

    Daly, Ann K; Day, Chris P

    2009-11-01

    Genetic studies on drug-induced liver injury (DILI) have proved challenging, both because of their rarity and their difficulty in replicating observed effects. However, significant progress has now been achieved by both candidate-gene and genome-wide association studies. These two approaches are considered in detail, together with examples of DILI due to specific drugs where consistent associations have been reported. Particular consideration is given to associations between antituberculosis drug-related liver injury and the "slow acetylator" genotype for N-acetyltransferase 2, amoxicillin/clavulanate-related liver injury, and the human leukocyte antigen (HLA) class II DRB1*1501 allele and flucloxacillin-related injury and the HLA class I B*5701 allele. Although these associations are drug-specific, the possibility that additional, more general susceptibility genes for DILI exist requires further investigation, ideally by genome-wide association studies involving international collaboration. The possibility of interethnic variation in susceptibility to DILI also requires further study.

  3. Antimicrobial susceptibilities of canine Clostridium difficile and Clostridium perfringens isolates to commonly utilized antimicrobial drugs.

    PubMed

    Marks, Stanley L; Kather, Elizabeth J

    2003-06-24

    Clostridium difficile and Clostridium perfringens are anaerobic, Gram-positive bacilli that are common causes of enteritis and enterotoxemias in both domestic animals and humans. Both organisms have been associated with acute and chronic large and small bowel diarrhea, and acute hemorrhagic diarrheal syndrome in the dog. The objective of this study was to determine the in vitro antimicrobial susceptibilities of canine C. difficile and C. perfringens isolates in an effort to optimize antimicrobial therapy for dogs with clostridial-associated diarrhea. The minimum inhibitory concentrations (MIC) of antibiotics recommended for treating C. difficile (metronidazole, vancomycin) and C. perfringens-associated diarrhea in the dog (ampicillin, erythromycin, metronidazole, tetracycline, tylosin) were determined for 70 canine fecal C. difficile isolates and 131 C. perfringens isolates. All C. difficile isolates tested had an MIC of or=256 microg/ml for both erythromycin and tylosin. A third C. perfringens isolate had an MIC of 32 microg/ml for metronidazole. Based on the results of this study, ampicillin, erythromycin, metronidazole, and tylosin appear to be effective antibiotics for the treatment of C. perfringens-associated diarrhea, although resistant strains do exist. However, because there is limited information regarding breakpoints for veterinary anaerobes, and because intestinal concentrations are not known, in vitro results should be interpreted with caution. PMID:12742714

  4. The utility of the zebrafish model in conditioned place preference to assess the rewarding effects of drugs.

    PubMed

    Collier, Adam D; Echevarria, David J

    2013-09-01

    Substance abuse is a significant public health concern both domestically and worldwide. The persistent use of substances regardless of aversive consequences forces the user to give higher priority to the drug than to normal activities and obligations. The harmful and hazardous use of psychoactive substances can lead to a dependence syndrome. In this regard, the genetic and neurobiological underpinnings of reward-seeking behavior need to be fully understood in order to develop effective pharmacotherapies and other methods of treatment. Animal models are often implemented in preclinical screening for testing the efficacy of novel treatments. Several paradigms exist that model various facets of addiction including sensitization, tolerance, withdrawal, drug seeking, extinction, and relapse. Self-administration and, most notably, conditioned place preference (CPP) are relatively simple tests that serve as indicators of the aforementioned aspects of addiction by means of behavioral quantification. CPP is a commonly used technique to evaluate the motivational effects of compounds and experiences that have been associated with a positive or negative reward, which capitalizes on the basic principles of Pavlovian conditioning. During training, the unconditioned stimulus is consistently paired with a neutral set of environmental stimuli, which obtain, during conditioning, secondary motivational properties that elicit approach behavior in the absence of the unconditioned stimulus. For over 50 years, rodents have been the primary test subjects. However, the zebrafish (Danio rerio) is gaining favor as a valuable model organism in the fields of biology, genetics, and behavioral neuroscience. This paper presents a discussion on the merits, advantages, and limitations of the zebrafish model and its utility in relation to CPP.

  5. Utility of in vitro systems and preclinical data for the prediction of human intestinal first-pass metabolism during drug discovery and preclinical development.

    PubMed

    Karlsson, Fredrik H; Bouchene, Salim; Hilgendorf, Constanze; Dolgos, Hugues; Peters, Sheila Annie

    2013-12-01

    A growing awareness of the risks associated with extensive intestinal metabolism has triggered an interest in developing robust methods for its quantitative assessment. This study explored the utility of intestinal S9 fractions, human liver microsomes, and recombinant cytochromes P450 to quantify CYP3A-mediated intestinal extraction in humans for a selection of marketed drugs that are predominantly metabolized by CYP3A4. A simple competing rates model is used to estimate the fraction of drug escaping gut wall metabolism (fg) from in vitro intrinsic clearance in humans. The fg values extrapolated from the three in vitro systems used in this study, together with literature-derived fg from human intestinal microsomes, were validated against fg extracted from human in vivo pharmacokinetic (PK) profiles using a generic whole-body physiologically-based pharmacokinetic (PBPK) model. The utility of the rat as a model for human CYP3A-mediated intestinal metabolism was also evaluated. Human fg from PBPK compares well with that from the grapefruit juice method, justifying its use for the evaluation of human in vitro systems. Predictive performance of all human in vitro systems was comparable [root mean square error (RMSE) = 0.22-0.27; n = 10]. Rat fg derived from in vivo PK profiles using PBPK has the lowest RMSE (0.19; n = 11) for the prediction of human fg for the selected compounds, most of which have a fraction absorbed close to 1. On the basis of these evaluations, the combined use of fg from human in vitro systems and rats is recommended for the estimation of CYP3A4-mediated intestinal metabolism in lead optimization and preclinical development phases.

  6. A cohort mortality study among gas generator utility workers.

    PubMed

    Blot, W J; Fryzek, J P; Henderson, B E; Sadler, C J; McLaughlin, J K

    2000-02-01

    An earlier cohort study tracked the mortality experience through 1988 of male employees at five utility companies in the United States. Workers employed by the Pacific Gas and Electric Company (PG&E) were part of that study, but results for PG&E employees overall or for those involved in gas generator plant operations where hexavalent chromium compounds were used in open and closed systems from the 1950s to early 1980s were not reported. To evaluate risk of lung cancer and other diseases, a cohort of 51,899 PG&E male workers was followed for mortality from 1971 through 1997. Observed numbers of deaths were compared with those expected based on rates in the general California population, with standardized mortality ratios (SMR) and corresponding 95% confidence intervals (CI) calculated for the total cohort and for subsets defined by potential for gas generator plant exposure. A total of 10,591 deaths were observed, a number significantly less than expected (SMR, 0.89; 95% CI, 0.87 to 0.91). No significant excesses of total or specific cancers were observed, with SMR typically near or below 1.0. Lung cancer mortality in the entire cohort was close to expected (SMR, 0.98; 95% CI, 0.92 to 1.05), with no excess detected among persons who worked (SMR, 0.81; 95% CI, 0.35 to 1.60) or trained (SMR, 0.57; 95% CI, 0.12 to 1.67) at gas generator facilities. Furthermore, risk of lung cancer did not increase with increasing duration of employment or time since hire. The study thus provides no evidence that occupational exposures at PG&E facilities resulted in increased risk of lung cancer or any other cause of death. The results indicate that any chromium exposures were of insufficient magnitude to result in increased risk of lung cancer.

  7. Turbidity study of solar ponds utilizing seawater as salt source

    SciTech Connect

    Li, Nan; Sun, Wence; Shi, Yufeng; Yin, Fang; Zhang, Caihong

    2010-02-15

    A series of experiments were conducted to study the turbidity reduction in solar ponds utilizing seawater as salt source. The experiment on the turbidity reduction efficiency with chemicals indicates that alum (KAl(SO{sub 4}){sub 2}.12H{sub 2}O) has a better turbidity control property because of its strongly flocculating and also well depressing the growing of algae and bacteria in the seawater. In comparison with bittern and seawater, our experiment shows that the residual brine after desalination can keep limpidity for a long time even without any chemical in it. Experiments were also conducted on the diffusion of turbidity and salinity, which show that the turbidity did not diffuse upwards in the solution. In the experiment on subsidence of soil in the bittern and saline with the same salinity, it was found that soil subsided quite quickly in the pure saline water, but very slowly in the bittern. In this paper we also proposed an economical method to protect the solar pond from the damage of rain. Finally, thermal performance of a solar pond was simulated in the conditions of different turbidities using a thermal diffusion model. (author)

  8. An exploratory study of drug use in bar environments

    PubMed Central

    Trocki, Karen; Michalak, Laurence; McDaniel, Patricia

    2010-01-01

    The purpose of this paper is to explore the characteristics of bars where drug use was observed compared to those where no drug use was observed. The study was done through a combination of qualitative and quantitative techniques gleaned through observations and interviews. Among the most important of indicators were the type of activity (particularly dancing) and the level of rowdiness evident in the bars. In addition drug use bars had higher levels of other types of rule-breaking. Patron characteristics (more men) and behavioral patterns (more sexual risk-taking) also distinguished these bars. PMID:25221431

  9. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

  10. A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital

    PubMed Central

    MARTÍNEZ-MIR, I.; GARCÍA-LÓPEZ, M.; PALOP, V.; FERRER, J. M.; ESTAÑ, L.; RUBIO, E.; MORALES-OLIVAS, F. J.

    1996-01-01

    1A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). The proportion of suspected ADRs related to hospital admissions was 4.3%. 2The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37–2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72–5.42). 5The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group. PMID:8877022

  11. Theoretical and experimental studies of the stability of drug-drug interact

    NASA Astrophysics Data System (ADS)

    Soares, Monica F. R.; Alves, Lariza D. S.; Nadvorny, Daniela; Soares-Sobrinho, José L.; Rolim-Neto, Pedro J.

    2016-11-01

    Several factors can intervene in the molecular properties and consequently in the stability of drugs. The molecular complexes formation often occur due to favor the formation of hydrogen bonds, leading the system to configuration more energy stable. This work we aim to investigate through theoretical and experimental methods the relation between stability and properties of molecular complexes the molecular complex formed between the drugs, efavirenz (EFV), lamivudine (3TC) and zidovudine (AZT). With this study was possible determining the most stable complex formed between the compounds evaluated. In addition the energy and structural properties of the complex formed in relation to its individual components allowed us to evaluate the stability of the same.

  12. Insights into drug metabolism from modelling studies of cytochrome P450-drug interactions.

    PubMed

    Maréchal, Jean-Didier; Sutcliffe, Michael J

    2006-01-01

    The cytochromes P450 (CYPs) comprise a vast superfamily of enzymes found in virtually all life forms. In mammals, xenobiotic metabolising CYPs provide crucial protection from the harmful effects of exposure to a wide variety of chemicals, including environmental toxins and therapeutic drugs. Elucidating the structural features of CYPs that contribute to their metabolism of structurally diverse substrates impacts on the rational design of improved therapeutic drugs and specific inhibitors. Models capable of predicting the possible involvement of CYPs in the metabolism of drugs or drug candidates are thus important tools in drug discovery and development. Ideally, functional information would be obtained from crystal structures of all the CYPs of interest. Initially only crystal structures of distantly related bacterial CYPs were available - comparative modelling techniques were used to bridge the gap and produce structural models of human CYPs, and thereby obtain some useful functional information. A significant step forward in the reliability of these models came six years ago with the first crystal structure of a mammalian CYP, rabbit CYP2C5, followed by the structures of five human enzymes, CYP2A6, CYP2C8, CYP2C9, CYP2D6 and CYP3A4, and a second rabbit enzyme, CYP2B4. The evolution of a CYP2D6 model, leading to the validation of the model as an in silico tool for predicting binding and metabolism, is presented as a case study. PMID:16918473

  13. Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies

    PubMed Central

    Shahbazi, Sajad; Sahrawat, Tammanna R.; Ray, Monalisa; Dash, Swagatika; Kar, Dattatreya; Singh, Shikha

    2016-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent. PMID:27258084

  14. Isolation and Physical Property Optimization of an Amorphous Drug Substance Utilizing a High Surface Area Magnesium Aluminometasilicate (Neusilin(®) US2).

    PubMed

    Allgeier, Matthew C; Piper, Jared L; Hinds, Jeremy; Yates, Matthew H; Kolodsick, Kevin J; Meury, Richard; Shaw, Bruce; Kulkarni, Mehuli R; Remick, David M

    2016-10-01

    Control and optimization of the physical properties of a drug substance (DS) are critical to the development of robust drug product manufacturing processes and performance. A lack of isolatable, for example, crystalline, DS solid forms can present challenges to achieving this control. In this study, an isolation scheme for an amorphous DS was developed and integrated into the synthetic route producing DS with optimized properties. An inert absorbent excipient (Neusilin® US2) was used to isolate the DS via a novel antisolvent scheme as the final step of the route. Isolation was executed at kilogram scale utilizing conventional equipment. The resulting 50 wt% DS:Neusilin complex had improved physical stability and exceptional micromeritic and tableting properties. Improved dissolution was observed and attributed to enhanced dispersion and increased surface area. Characterization data suggest a high degree of penetration of the DS into the Neusilin, with DS occupying 70% of mesopore and 12% of macropore volume. This approach has application in the isolation and particle engineering of difficult to isolate DS without additional unit operation, such as spray drying, and has the potential for a high degree of optimization and control of physical properties over the course of DS development. PMID:27492963

  15. An Exploration of the Utility of a Knowledge Utilization Framework to Study the Gap between Reading Disabilities Research and Practice

    ERIC Educational Resources Information Center

    Davidson, Katherine; Nowicki, Elizabeth

    2012-01-01

    This pre-pilot study explored the usefulness of a knowledge utilization framework comprised of Knott and Wildavsky's (1980) seven stages of knowledge use and Stone's (2002) three routes to knowledge use to investigate the gap between reading disabilities research and teachers' self-reported use of that research. Semi-structured interviews of ten…

  16. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  17. Pueblo of Laguna Utility Authority Renewable Energy Feasibility Study

    SciTech Connect

    Carolyn Stewart, Red Mountain Tribal Energy

    2008-03-31

    The project, “Renewable Energy Feasibility Study” was designed to expand upon previous work done by the Tribe in evaluating utility formation, generation development opportunities, examining options for creating self-sufficiency in energy matters, and integrating energy management with the Tribe’s economic development goals. The evaluation of project locations and economic analysis, led to a focus primarily on solar projects.

  18. Drug Utilization Review of Potassium Chloride Injection Formulations Available in a Private Hospital in Kuching, Sarawak, Malaysia

    PubMed Central

    MELISSA, Mohammad Hirman; AZMI, Sarriff

    2013-01-01

    Background: The concentrated potassium chloride injection is a high-alert medication and replacing it with a pre-mixed formulation can reduce the risks associated with its use. The aim of this study was to determine the clinical characteristics of patients receiving different potassium chloride formulations available at a private institution. The study also assessed the effectiveness and safety of pre-mixed formulations in the correction of hypokalaemia. Methods: This was a retrospective observational study consisting of 296 cases using concentrated and pre-mixed potassium chloride injections in 2011 in a private hospital in Kuching, Sarawak, Malaysia. Results: There were 135 (45.6%) cases that received concentrated potassium chloride, and 161 (54.4%) cases that received pre-mixed formulations. The patients’ clinical characteristics that were significantly related to the utilization of the different formulations were diagnosis (P < 0.001), potassium serum blood concentration (P < 0.05), and fluid overload risk (P < 0.05). The difference observed for the cases that achieved or maintained normokalaemia was statistically insignificant (P = 0.172). Infusion-related adverse effects were seen more in pre-mixes compared to concentrated formulations (6.8% versus 2.2%, P < 0.05). Conclusion: This study provides insight into the utilization of potassium chloride injections at this specific institution. The results support current recommendations to use pre-mixed formulations whenever possible. PMID:24043996

  19. Adverse drug reaction profile of microtubule-damaging antineoplastic drugs: A focused pharmacovigilance study in India

    PubMed Central

    Manohar, Hasitha Diana; Adiga, Shalini; Thomas, Joseph; Sharma, Ajitha

    2016-01-01

    Objectives: The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. Materials and Methods: Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. Results: A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The highest incidence of ADRs was reported among paclitaxel (54.6%), and vincristine (39.2%). Most of the reported ADRs were of milder nature and preventable. The WHO causality assessment scale indicated 71.1% possible reactions. Conclusions: This study showed that most ADRs are preventable with effective ADR monitoring. There is a great need to create awareness among healthcare professionals regarding the importance of the pharmacovigilance system. Judicious use of the preventive measures will lead to a reduction in the incidence of ADRs due to the drug armamentarium, thereby enabling additional economic benefit to the patient and society. PMID:27721535

  20. Screening and determination of drugs in human saliva utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry.

    PubMed

    Abdel-Rehim, Abbi; Abdel-Rehim, Mohamed

    2013-09-01

    This study presents a new method for collecting and handling saliva samples using an automated analytical microsyringe and microextraction by packed syringe (MEPS). The screening and determination of lidocaine in human saliva samples utilizing MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. An exact volume of saliva could be collected. The MEPS C8 -cartridge could be used for 50 extractions before it was discarded. The extraction recovery was about 60%. The pharmacokinetic curve of lidocaine in saliva using MEPS-LC-MS/MS is reported.

  1. Nitazoxanide: Nematicidal Mode of Action and Drug Combination Studies

    PubMed Central

    Somvanshi, Vishal S.; Ellis, Brian L.; Hu, Yan; Aroian, Raffi V.

    2014-01-01

    Intestinal nematodes or roundworms (aka soil-transmitted helminths or STHs) cause great disease. They infect upwards of two billion people, leading to high morbidity and a range of health problems, especially in infected children and pregnant women. Development of resistance to the two main classes of drugs used to treat intestinal nematode infections of humans has been reported. To fight STH infections, we need new and more effective drugs and ways to improve the efficacy of the old drugs. One promising alternative drug is nitazoxanide (NTZ). NTZ, approved for treating human protozoan infections, was serendipitously shown to have therapeutic activity against STHs. However, its mechanism of action against nematodes is not known. Using the laboratory nematode Caenorhabditis elegans, we show that NTZ acts on the nematodes through avr-14, an alpha-type subunit of a glutamate-gated chloride ion channel known for its role in ivermectin susceptibility. In addition, a forward genetic screen to select C. elegans mutants resistant to NTZ resulted in isolation of two NTZ resistant mutants that are not in avr-14, suggesting that additional mechanisms are involved in resistance to NTZ. We found that NTZ combines synergistically with other classes of anthelmintic drugs, i.e. albendazole and pyrantel, making it a good candidate for further studies on its use in drug combination therapy of STH infections. Given NTZ acts against a wide range of nematode parasites, our findings also validate avr-14 as an excellent target for pan-STH therapy. PMID:24412397

  2. 77 FR 9946 - Draft Guidance for Industry on Drug Interaction Studies-Study Design, Data Analysis, Implications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-21

    ... Federal Register of September 12, 2006 (71 FR 53696), FDA announced the availability of a draft guidance... in vivo studies of drug metabolism, drug transport, and drug-drug, or drug-therapeutic protein... metabolism and/or drug transport abruptly in individuals who previously had been receiving and tolerating...

  3. Can utilizing a computerized provider order entry (CPOE) system prevent hospital medical errors and adverse drug events?

    PubMed

    Charles, Krista; Cannon, Margaret; Hall, Robert; Coustasse, Alberto

    2014-01-01

    Computerized provider order entry (CPOE) systems allow physicians to prescribe patient services electronically. In hospitals, CPOE essentially eliminates the need for handwritten paper orders and achieves cost savings through increased efficiency. The purpose of this research study was to examine the benefits of and barriers to CPOE adoption in hospitals to determine the effects on medical errors and adverse drug events (ADEs) and examine cost and savings associated with the implementation of this newly mandated technology. This study followed a methodology using the basic principles of a systematic review and referenced 50 sources. CPOE systems in hospitals were found to be capable of reducing medical errors and ADEs, especially when CPOE systems are bundled with clinical decision support systems designed to alert physicians and other healthcare providers of pending lab or medical errors. However, CPOE systems face major barriers associated with adoption in a hospital system, mainly high implementation costs and physicians' resistance to change.

  4. Can Utilizing a Computerized Provider Order Entry (CPOE) System Prevent Hospital Medical Errors and Adverse Drug Events?

    PubMed Central

    Charles, Krista; Cannon, Margaret; Hall, Robert; Coustasse, Alberto

    2014-01-01

    Computerized provider order entry (CPOE) systems allow physicians to prescribe patient services electronically. In hospitals, CPOE essentially eliminates the need for handwritten paper orders and achieves cost savings through increased efficiency. The purpose of this research study was to examine the benefits of and barriers to CPOE adoption in hospitals to determine the effects on medical errors and adverse drug events (ADEs) and examine cost and savings associated with the implementation of this newly mandated technology. This study followed a methodology using the basic principles of a systematic review and referenced 50 sources. CPOE systems in hospitals were found to be capable of reducing medical errors and ADEs, especially when CPOE systems are bundled with clinical decision support systems designed to alert physicians and other healthcare providers of pending lab or medical errors. However, CPOE systems face major barriers associated with adoption in a hospital system, mainly high implementation costs and physicians’ resistance to change. PMID:25593568

  5. Propeller aircraft interior noise model utilization study and validation

    NASA Astrophysics Data System (ADS)

    Pope, L. D.

    1984-09-01

    Utilization and validation of a computer program designed for aircraft interior noise prediction is considered. The program, entitled PAIN (an acronym for Propeller Aircraft Interior Noise), permits (in theory) predictions of sound levels inside propeller driven aircraft arising from sidewall transmission. The objective of the work reported was to determine the practicality of making predictions for various airplanes and the extent of the program's capabilities. The ultimate purpose was to discern the quality of predictions for tonal levels inside an aircraft occurring at the propeller blade passage frequency and its harmonics. The effort involved three tasks: (1) program validation through comparisons of predictions with scale-model test results; (2) development of utilization schemes for large (full scale) fuselages; and (3) validation through comparisons of predictions with measurements taken in flight tests on a turboprop aircraft. Findings should enable future users of the program to efficiently undertake and correctly interpret predictions.

  6. Propeller aircraft interior noise model utilization study and validation

    NASA Technical Reports Server (NTRS)

    Pope, L. D.

    1984-01-01

    Utilization and validation of a computer program designed for aircraft interior noise prediction is considered. The program, entitled PAIN (an acronym for Propeller Aircraft Interior Noise), permits (in theory) predictions of sound levels inside propeller driven aircraft arising from sidewall transmission. The objective of the work reported was to determine the practicality of making predictions for various airplanes and the extent of the program's capabilities. The ultimate purpose was to discern the quality of predictions for tonal levels inside an aircraft occurring at the propeller blade passage frequency and its harmonics. The effort involved three tasks: (1) program validation through comparisons of predictions with scale-model test results; (2) development of utilization schemes for large (full scale) fuselages; and (3) validation through comparisons of predictions with measurements taken in flight tests on a turboprop aircraft. Findings should enable future users of the program to efficiently undertake and correctly interpret predictions.

  7. Nanobiological studies on drug design using molecular mechanic method

    PubMed Central

    Ghaheh, Hooria Seyedhosseini; Mousavi, Maryam; Araghi, Mahmood; Rasoolzadeh, Reza; Hosseini, Zahra

    2015-01-01

    Background: Influenza H1N1 is very important worldwide and point mutations that occur in the virus gene are a threat for the World Health Organization (WHO) and druggists, since they could make this virus resistant to the existing antibiotics. Influenza epidemics cause severe respiratory illness in 30 to 50 million people and kill 250,000 to 500,000 people worldwide every year. Nowadays, drug design is not done through trial and error because of its cost and waste of time; therefore bioinformatics studies is essential for designing drugs. Materials and Methods: This paper, infolds a study on binding site of Neuraminidase (NA) enzyme, (that is very important in drug design) in 310K temperature and different dielectrics, for the best drug design. Information of NA enzyme was extracted from Protein Data Bank (PDB) and National Center for Biotechnology Information (NCBI) websites. The new sequences of N1 were downloaded from the NCBI influenza virus sequence database. Drug binding sites were assimilated and homologized modeling using Argus lab 4.0, HyperChem 6.0 and Chem. D3 softwares. Their stability was assessed in different dielectrics and temperatures. Result: Measurements of potential energy (Kcal/mol) of binding sites of NA in different dielectrics and 310K temperature revealed that at time step size = 0 pSec drug binding sites have maximum energy level and at time step size = 100 pSec have maximum stability and minimum energy. Conclusions: Drug binding sites are more dependent on dielectric constants rather than on temperature and the optimum dielectric constant is 39/78. PMID:26605248

  8. AC biosusceptometry in the study of drug delivery.

    PubMed

    Corá, L A; Romeiro, F G; Stelzer, M; Américo, M F; Oliveira, R B; Baffa, O; Miranda, J R A

    2005-06-15

    Conventionally, pharmaceutical substances are administered orally because the gastrointestinal tract possesses the appropriate features for drug absorption. Nevertheless, the gastrointestinal tract physiology is complex and influenced by many factors. These factors must be completely understood for the optimization of oral drug delivery systems. Although in vitro tests provide information about release and drug absorption profiles, in vivo studies are essential, due to the biological variability. Several techniques have been employed in an attempt to conveniently characterize the behavior of solid dosage forms in vivo. The noninvasive biomagnetic technique of alternate current biosusceptometry (ACB) has been used in studies focusing on gastrointestinal motility and, more recently, to evaluate the performance of magnetic dosage forms. This article will discuss the main characteristics of AC biosusceptometry and its applicability for determination of the relationship between the human gastrointestinal tract and orally administered pharmaceutical dosage forms.

  9. Emergency Department Frequent Utilization for Non-Emergent Presentments: Results from a Regional Urban Trauma Center Study

    PubMed Central

    2016-01-01

    Objectives First, to test a model of the drivers of frequent emergency department utilization conceptualized as falling within predisposing, enabling, and need dimensions. Second, to extend the model to include social networks and service quality as predictors of frequent utilization. Third, to illustrate the variation in thresholds that define frequent utilization in terms of the number of emergency department encounters by the predictors within the model. Data Source Primary data collection over an eight week period within a level-1 trauma urban hospital’s emergency department. Study Design Representative randomized sample of 1,443 adult patients triaged ESI levels 4–5. Physicians and research staff interviewed patients as they received services. Relationships with the outcome variable, utilization, were tested using logistic regression to establish odds-ratios. Principal Findings 70.6 percent of patients have two or more, 48.3 percent have three or more, 25.3 percent have four or more, and 14.9 percent have five or more emergency department visits within 12 months. Factors associated with frequent utilization include gender, race, poor mental health, mental health drugs, prescription drug abuse, social networks, employment, perceptions of service quality, seriousness of condition, persistence of condition, and previous hospital admittance. Conclusions Interventions targeting associated factors will change global emergency department encounters, although the mutability varies. Policy interventions to address predisposing factors such as substance abuse or access to mental health treatment as well as interventions that speak to enabling factors such as promoting the resiliency of social networks may result in decreased frequency of emergency department utilization. PMID:26784515

  10. A Penalized Likelihood Approach for Investigating Gene-Drug Interactions in Pharmacogenetic Studies

    PubMed Central

    Neely, Megan L.; Bondell, Howard D.; Tzeng, Jung-Ying

    2015-01-01

    Summary Pharmacogenetics investigates the relationship between heritable genetic variation and the variation in how individuals respond to drug therapies. Often, gene-drug interactions play a primary role in this response, and identifying these effects can aid in the development of individualized treatment regimes. Haplotypes can hold key information in understanding the association between genetic variation and drug response. However, the standard approach for haplotype-based association analysis does not directly address the research questions dictated by individualized medicine. A complementary post-hoc analysis is required, and this post-hoc analysis is usually under powered after adjusting for multiple comparisons and may lead to seemingly contradictory conclusions. In this work, we propose a penalized likelihood approach that is able to overcome the drawbacks of the standard approach and yield the desired personalized output. We demonstrate the utility of our method by applying it to the Scottish Randomized Trial in Ovarian Cancer. We also conducted simulation studies and showed that the proposed penalized method has comparable or more power than the standard approach and maintains low Type I error rates for both binary and quantitative drug responses. The largest performance gains are seen when the haplotype frequency is low, the difference in effect sizes are small, or the true relationship among the drugs is more complex. PMID:25604216

  11. The role of metabolic biomarkers in drug toxicity studies.

    PubMed

    Schnackenberg, Laura K; Beger, Richard D

    2008-01-01

    ABSTRACT Metabolic profiling is a technique that can potentially provide more sensitive and specific biomarkers of toxicity than the current clinical measures benefiting preclinical and clinical drug studies. Both nuclear magnetic resonance (NMR) and mass spectrometry (MS) platforms have been used for metabolic profiling studies of drug toxicity. Not only can both techniques provide novel biomarker(s) of toxicity but the combination of both techniques gives a broader range of metabolites evaluated. Changes in metabolic patterns can provide insight into mechanism(s) of toxicity and help to eliminate a potentially toxic new chemical entity earlier in the developmental process. Metabolic profiling offers numerous advantages in toxicological research and screening as sample collection and preparation are relatively simple. Further, sample throughput, reproducibility, and accuracy are high. The area of drug toxicity of therapeutic compounds has already been impacted by metabolic profiling studies and will continue to be impacted as new, more specific biomarker(s) are found. In order for a biomarker or pattern of biomarkers to be accepted, it must be shown that they originate from the target tissue of interest. Metabolic profiling studies are amenable to any biofluid or tissue sample making it possible to link the changes noted in urine for instance as originating from renal injury. Additionally, the ease of sample collection makes it possible to follow a single animal or subject over time in order to determine whether and when the toxicity resolves itself. This review focuses on the advantages of metabolic profiling for drug toxicity studies.

  12. Utilization of H-bond interaction of nucleobase Uralic with antitumor methotrexate to design drug carrier with ultrahigh loading efficiency and pH-responsive drug release

    PubMed Central

    Cai, Teng-Teng; Lei, Qi; Yang, Bin; Jia, Hui-Zhen; Cheng, Hong; Liu, Li-Han; Zeng, Xuan; Feng, Jun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-01-01

    A novel Uralic (U)-rich linear-hyperbranched mono-methoxy poly (ethylene glycol)-hyperbranched polyglycerol-graft-Uralic (mPEG-HPG-g-U) nanoparticle (NP) was prepared as drug carrier for antitumor methotrexate (MTX). Due to the H-bond interaction of U with MTX and hydrophobic interaction, this NP exhibited high drug loading efficiency of up to 40%, which was significantly higher than that of traditional NPs based on U-absent copolymers (<15%). In addition, MTX-loaded mPEG-HPG-g-U NPs also demonstrated an acidity-accelerated drug release behavior. PMID:26816622

  13. Utilization of H-bond interaction of nucleobase Uralic with antitumor methotrexate to design drug carrier with ultrahigh loading efficiency and pH-responsive drug release.

    PubMed

    Cai, Teng-Teng; Lei, Qi; Yang, Bin; Jia, Hui-Zhen; Cheng, Hong; Liu, Li-Han; Zeng, Xuan; Feng, Jun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-11-01

    A novel Uralic (U)-rich linear-hyperbranched mono-methoxy poly (ethylene glycol)-hyperbranched polyglycerol-graft-Uralic (mPEG-HPG-g-U) nanoparticle (NP) was prepared as drug carrier for antitumor methotrexate (MTX). Due to the H-bond interaction of U with MTX and hydrophobic interaction, this NP exhibited high drug loading efficiency of up to 40%, which was significantly higher than that of traditional NPs based on U-absent copolymers (<15%). In addition, MTX-loaded mPEG-HPG-g-U NPs also demonstrated an acidity-accelerated drug release behavior.

  14. Study of Dynamic Characteristics of Aeroelastic Systems Utilizing Randomdec Signatures

    NASA Technical Reports Server (NTRS)

    Chang, C. S.

    1975-01-01

    The feasibility of utilizing the random decrement method in conjunction with a signature analysis procedure to determine the dynamic characteristics of an aeroelastic system for the purpose of on-line prediction of potential on-set of flutter was examined. Digital computer programs were developed to simulate sampled response signals of a two-mode aeroelastic system. Simulated response data were used to test the random decrement method. A special curve-fit approach was developed for analyzing the resulting signatures. A number of numerical 'experiments' were conducted on the combined processes. The method is capable of determining frequency and damping values accurately from randomdec signatures of carefully selected lengths.

  15. Medication Use and Medical Comorbidity in Patients with Chronic Hepatitis C from a U.S. Commercial Claims Database: High Utilization of Drugs with Interaction Potential

    PubMed Central

    Lauffenburger, Julie C.; Mayer, Christina L.; Hawke, Roy L.; Brouwer, Kim L. R.; Fried, Michael W.; Farley, Joel F.

    2014-01-01

    Background With the advent of the direct-acting antiviral agents (DAAs), significant drug-drug interaction (DDI) potential now exists for patients treated for chronic hepatitis C virus (HCV) infection. However, little is known about how often patients with HCV use medications that may interact with newer HCV treatments, especially those with CYP3A DDI potential. Methods Using a large United States commercial insurance database, medication use and comorbidity burden was examined among adult patients with a chronic HCV diagnosis from 2006-2010. Medications were examined by total number of prescription claims, proportion of patients exposed, and DDI potential with prototypical CYP3A DAAs, boceprevir and telaprevir, for which data were available. Results Patient comorbidity burden was high and increased over the study period. Medication use was investigated in 53,461 patients with chronic HCV. Twenty-one (53%) of the top 40 most utilized medications were classified as having interaction potential, with 62% of patients received at least one of the top 22 interacting medications by exposure. Of these, 59% and 41% were listed in a common DDI resource but not in medication prescribing information, 77% and 77% had not been investigated in DDI studies, 32% and 27% did not have clear recommendations for DDI management, and only 14% and 23% carried a recommendation to avoid coadministration for boceprevir and telaprevir, respectively. Conclusion Practitioners may expect a medication with CYP3A DDI potential in two-thirds of patients with HCV and almost one-half of the most frequently used medications. However, DDI potential may not be reflected in prescribing information. PMID:25014625

  16. Studies on pharmacokinetic drug interaction potential of vinpocetine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Vinpocetine, a semi-synthetic derivative of vincamine, is a popular dietary supplement used for the treatment of several central nervous system related disorders. Despite its wide use, no pharmacokinetic drug interaction studies are reported in literature. Due to increasing use of dietar...

  17. Drug Taking Beliefs of Australian Adolescents: A Pilot Study

    ERIC Educational Resources Information Center

    Skrzypiec, Grace; Owens, Laurence

    2013-01-01

    In this study adolescents offered their insights and perspectives of factors associated with adolescent illicit drug taking intentions. The factors explored were identified using a cross-disciplinary approach involving the Theory of Planned Behavior (TPB) and criminological theories, and these formed the framework for data analysis. Interviews…

  18. Quantitative Methods in the Study of Drug Use.

    ERIC Educational Resources Information Center

    Huba, George J.

    1983-01-01

    Addresses the use of data sources and multivariate data analysis methods for modeling naturally occurring data. Two studies in this special section deal with longitudinal perspectives on drug use and emotional adjustment and an application of log-linear model to examine the stress-buffering function of alcohol. (LLL)

  19. 21 CFR 330.12 - Status of over-the-counter (OTC) drugs previously reviewed under the Drug Efficacy Study (DESI).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Status of over-the-counter (OTC) drugs previously reviewed under the Drug Efficacy Study (DESI). 330.12 Section 330.12 Food and Drugs FOOD AND DRUG... Register concerning previously unpublished OTC drugs reviewed by the National Academy of...

  20. 21 CFR 310.303 - Continuation of long-term studies, records, and reports on certain drugs for which new drug...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... reports on certain drugs for which new drug applications have been approved. 310.303 Section 310.303 Food... HUMAN USE NEW DRUGS Records and Reports § 310.303 Continuation of long-term studies, records, and reports on certain drugs for which new drug applications have been approved. (a) A new drug may not...

  1. Theoretical and experimental studies of the stability of drug-drug interact.

    PubMed

    Soares, Monica F R; Alves, Lariza D S; Nadvorny, Daniela; Soares-Sobrinho, José L; Rolim-Neto, Pedro J

    2016-11-01

    Several factors can intervene in the molecular properties and consequently in the stability of drugs. The molecular complexes formation often occur due to favor the formation of hydrogen bonds, leading the system to configuration more energy stable. This work we aim to investigate through theoretical and experimental methods the relation between stability and properties of molecular complexes the molecular complex formed between the drugs, efavirenz (EFV), lamivudine (3TC) and zidovudine (AZT). With this study was possible determining the most stable complex formed between the compounds evaluated. In addition the energy and structural properties of the complex formed in relation to its individual components allowed us to evaluate the stability of the same. PMID:27267283

  2. [Comparative neurophysiological study of the nootropic drugs piracetam and centrophenoxine].

    PubMed

    Krapivin, S V; Voronina, T A

    1987-01-01

    Effects of nootropic drugs on transcallosal evoked potential (TEP) and EEG spectra of the animal brain cortex and hippocamp were studied. It was found that piracetam and centrophenoxine exert similar effects on the amplitude of the primary TEP components, produce its increase and also a rise and stabilization of the predominant peak in distribution of EEG power spectrum that corresponds to the improvement of theta rhythm organization. The drugs exert different effects on the secondary positive TEP component; centrophenoxine induces a change in non-basic rhythm of EEG in rats. Based on the results obtained, the authors consider possible neurophysiological mechanisms of the nootropic effect and make a comparative analysis of the actions of the drugs.

  3. Drug promotional practices in Mumbai: a qualitative study.

    PubMed

    Roy, Nobhojit; Madhiwalla, Neha; Pai, Sanjay A

    2007-01-01

    We conducted a qualitative study to determine the range of promotional practices influencing drug usage in Mumbai. Open-ended interviews were conducted with 15 senior executives in drug companies, 25 chemists and 25 doctors; focus group discussions were held with 36 medical representatives. The study provided a picture of what might be described as an unholy alliance: manufacturers, chemists and doctors conspire to make profits at the expense of consumers and the public's health, even as they negotiate with each other on their respective shares of these profits. Misleading information, incentives and unethical trade practices were identified as methods to increase the prescription and sale of drugs. Medical representatives provide incomplete medical information to influence prescribing practices; they also offer incentives including conference sponsorship. Doctors may also demand incentives, as when doctors' associations threaten to boycott companies that do not comply with their demands for sponsorship. Manufacturers, chemists and medical representatives use various unethical trade practices. Of particular interest was the finding that chemists are major players in this system, providing drug information directly to patients. The study also reinforced our impression that medical representatives are the least powerful of the four groups. PMID:18630221

  4. Electrophoretic Particle Guidance Significantly Enhances Olfactory Drug Delivery: A Feasibility Study

    PubMed Central

    Xi, Jinxiang; Si, Xiuhua A.; Gaide, Rachel

    2014-01-01

    Background Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and directly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has not yet been found. Methods In this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to the olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically accurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on the olfactory delivery efficiency. Findings Results showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly enhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of magnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril (i.e., partial release) led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By combining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more than 90% were observed as compared to the extremely low olfactory dosage (<1%) with conventional inhaler devices. Conclusion Results of this study have important implications in developing personalized olfactory delivery protocols for the treatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different pointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery. PMID:24497957

  5. Characterization and subsequent utilization of microbially solubilized coal: Preliminary studies

    SciTech Connect

    Davison, B.H.; Nicklaus, D.M.; Woodward, C.A.; Lewis, S.N.; Faison, B.D.

    1989-01-01

    The solubilization of low-ranked coals by fungi, such as Paecilomyces and Candida, in defined submerged culture systems has been demonstrated. Current efforts focus on the characterization of the aqueous solubilized coal products and the development of technologies for their subsequent utilization. Solubilized coal products have been fractionated, and preliminary characterizations performed. Differences in product composition have been detected with respect to the organism used in culture duration. Prospects for the conversion of the aerobically-solubilized coal into less-oxidized products have been developed which can remain active and viable in the presence of the aqueous coal product or vanillin, a coal model compound. The results suggest that a methanogenic consortium was able to produce methane and carbon dioxide from the product of coal biosolubilization by Paecilomyces as a sole carbon source. Work continues on the development of cultures able to convert the aqueous coal product and its various fractions into methane or fuel alcohols. 17 refs., 8 figs.

  6. A study of the potential impacts of space utilization

    NASA Technical Reports Server (NTRS)

    Cheston, T. S.; Chafer, C. M.; Chafer, S. B.; Webb, D. C.; Stadd, C. A.

    1979-01-01

    Because the demand for comprehensive impact analysis of space technologies will increase with the use of space shuttles, the academic social sciences/humanities community was surveyed in order to determine their interests in space utilization, to develop a list of current and planned courses, and to generate a preliminary matrix of relevant social sciences. The academic scope/focus of a proposed social science space-related journal was identified including the disciplines which should be represented in the editorial board/reviewer system. The time and funding necessary to develop a self-sustaining journal were assessed. Cost income, general organizational structure, marking/distribution and funding sources were analyzed. Recommendations based on the survey are included.

  7. Spectromicroscopy Study of the Organic Molecules Utilizing Polarized Radiation

    SciTech Connect

    Hsu, Y.J.; Wei, D.H.; Yin, G.C.; Chung, S.C.; Hu, W.S.; Tao, Y.T.

    2004-05-12

    Spectromicroscopy combined with polarized synchrotron radiation is a powerful tool for imaging and characterizing the molecular properties on surface. In this work we utilized the photoemission electron microscopy (PEEM) with linear polarized radiation provided by an elliptically polarized undulator to investigate the molecular orientations of pentacene on self-assembled monolayer (SAMs) modified gold surface and to observe the cluster domain of mixed monolayers after reorganization on silver. Varying the electric vector parallel or perpendicular to the surface, the relative intensity of {pi}* and {sigma}* transition in carbon K-edge can be used to determine the orientation of the planar-shaped pentacene molecule or long carbon chain of carboxylic acids which are important for organic semiconductor.

  8. 77 FR 48491 - Regulatory New Drug Review: Solutions for Study Data Exchange Standards; Notice of Meeting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I Regulatory New Drug Review: Solutions for... Administration (FDA) is announcing a meeting entitled ``Regulatory New Drug Review: Solutions for Study Data... Planning & Informatics, Center for Drug Evaluation and Research, Food and Drug Administration, 10903...

  9. Solvent drag effect in drug intestinal absorption. II. Studies on drug absorption clearance and water influx.

    PubMed

    Karino, A; Hayashi, M; Awazu, S; Hanano, M

    1982-09-01

    In order to study the solvent drag effect, it was shown that back flux of absorbed drug from blood to intestinal lumen can be ignored but the back flux of water cannot. Then, apparent water influx was calculated as a new measure of solvent drag based on the model in which the back flux of D2O from blood to lumen was considered during absorption. Consequently, the correlation between drug absorption clearance (CLdrug) and apparent water influx was highly significant for benzoic acid, salicylic acid, p-hydroxybenzoic acid, antipyrine, cephalexin (CEX) and cefroxadine (CXD), resulting the high solvent drag effects were detected. The mean values of the slopes in the regression lines of CLdrug versus apparent water influx, i.e., sieving coefficients, were smaller than one for benzoic acid and salicylic acid, but the values were not significantly different from one. The sieving coefficients of the other drugs were significantly smaller than one. From these results, the molecular size dependence in the reflection from the intestinal membrane during absorption was clearly shown. And the intercepts of the regression lines including diffusive permeabilities were found to be significantly different from zero in CEX and CXD. On the basis of the sieving coefficients and intercept values obtained in such ways, the appropriateness of this model was discussed.

  10. Utilization of formal and informal home care by AIDS patients in Boston: a comparison of intravenous drug users and homosexual males.

    PubMed

    Ettner, S L; Weissman, J

    1994-05-01

    The assumption that intravenous (i.v.) drug users have weaker informal support networks than homosexual men has led to opposing policy recommendations: one emphasizes outreach and more formal (paid) home care for i.v. drug users, whereas the other maintains that formal home care programs are less effective for this risk group due to the lack of informal (unpaid) caregivers to coordinate efforts. Data from interviews with a sample of 231 persons with AIDS in the Boston area were used to compare the use of formal and informal home care between the two largest risk groups, homosexual men and i.v. drug users. Multivariate regression analysis was also employed to adjust estimates and to determine the significance of population characteristics in explaining utilization differences. IV drug users received about twice as much formal and informal home care as homosexual men. Controlling for functional status, income and assets, insurance and potential caregiver supply, i.v. drug users obtained significantly fewer formal home care services, but more informal care. Overall, i.v. drug users received a greater number of adjusted home care hours. These findings cast doubt upon the previous assumptions of the literature and suggest that members of both risk groups are appropriate candidates for formal home care services.

  11. Mining hidden knowledge for drug safety assessment: topic modeling of LiverTox as a case study

    PubMed Central

    2014-01-01

    of them could be verified and confirmed. This study highlights the utility of topic modeling to leverage information within textual drug safety databases, which provides new opportunities in the big data era to assess drug safety. PMID:25559675

  12. Carer involvement with drug services: a qualitative study

    PubMed Central

    Orr, Linda C; Barbour, Rosaline S; Elliott, Lawrie

    2013-01-01

    BackgroundEmpirical research suggests that involving carers brings benefits to families and services. Consequently, drug-related policy and guidance has increasingly encouraged drug services to involve carers at all levels of service provision. ObjectiveTo explore the purpose and scope of carer involvement with adult drug services in North-east Scotland. Design, Setting and ParticipantsA total of 82 participants (20 informal carers, 43 service providers and 19 policy makers) were purposively selected to take part in a qualitative study. Eight focus groups and 32 interviews were conducted between 2007 and 2008. FindingsThree themes were identified through thematic coding: ‘Current levels of involvement’, ‘Use of the term carer’ and ‘Opportunities for change?’ Carer involvement was described as limited, unplanned and unstructured, and consisted largely of information and advice, practical and emotional support, and signposting of services. Although use of the term ‘carer’ was contested within and across the groups, caring in a drug context was considered the ‘same but different’ from caring in other contexts. Carers remained sceptical that services actually wanted to involve them in supporting their relative or to offer carers support in their own right. Many service providers and policy makers regarded carer involvement as an aspiration. ConclusionEncouraging carers, service providers and policy makers to reach a shared understanding of caring in a drug context may help translation of policy into practice. However, there is also a fundamental need for drug services to widen the level and type of involvement activities on offer to carers. PMID:23216899

  13. A challenge for diagnosing acute liver injury with concomitant/sequential exposure to multiple drugs: can causality assessment scales be utilized to identify the offending drug?

    PubMed

    Lim, Roxanne; Choudry, Hassan; Conner, Kim; Karnsakul, Wikrom

    2014-01-01

    Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only) drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM), Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis.

  14. Utilization study of antidiabetic agents in a teaching hospital of Sikkim and adherence to current standard treatment guidelines

    PubMed Central

    Satpathy, Sushrut Varun; Datta, Supratim; Upreti, Binu

    2016-01-01

    Objective: Diabetes has gradually emerged as one of the most serious public health problems in our country. This underlines the need for timely disease detection and decisive therapeutic intervention. This prospective cross-sectional observational study aims at analyzing the utilization pattern of antidiabetic agents in a remote North-East Indian tertiary care teaching hospital in the perspective of current standard treatment guidelines. Materials and Methods: Diabetic patients receiving antidiabetic medication, both as outpatients and inpatients in our hospital over a period of 12 months (May 2013–May 2014), were included in this study. The data obtained were sorted and analyzed on the basis of gender, type of therapy, and hospital setting. Results: A total of 310 patients were included in the study. Metformin was the single most frequently prescribed antidiabetic agent (66.8%) followed by the sulfonylureas group (37.4%). Insulin was prescribed in 23.2% of the patients. Combination antidiabetic drug therapy (65.1%) was used more frequently than monotherapy (34.8%). The use of biguanides (P < 0.0001) and sulfonylureas (P = 0.02) in combination was significant as compared to their use as monotherapy. A total of 48% of all antidiabetic combinations used, comprised metformin and sulfonylureas (n = 96). Insulin use was significantly higher as monotherapy and in inpatients (P < 0.0001). The utilization of drugs from the National List of Essential Medicines was 51.2%, while 11% of antidiabetics were prescribed by generic name. Conclusion: The pattern of utilization largely conforms to the current standard treatment guidelines. Increased use of generic drugs is an area with scope for improvement. PMID:27413351

  15. Medical databases in studies of drug teratogenicity: methodological issues.

    PubMed

    Ehrenstein, Vera; Sørensen, Henrik T; Bakketeig, Leiv S; Pedersen, Lars

    2010-01-01

    More than half of all pregnant women take prescription medications, raising concerns about fetal safety. Medical databases routinely collecting data from large populations are potentially valuable resources for cohort studies addressing teratogenicity of drugs. These include electronic medical records, administrative databases, population health registries, and teratogenicity information services. Medical databases allow estimation of prevalences of birth defects with enhanced precision, but systematic error remains a potentially serious problem. In this review, we first provide a brief description of types of North American and European medical databases suitable for studying teratogenicity of drugs and then discuss manifestation of systematic errors in teratogenicity studies based on such databases. Selection bias stems primarily from the inability to ascertain all reproductive outcomes. Information bias (misclassification) may be caused by paucity of recorded clinical details or incomplete documentation of medication use. Confounding, particularly confounding by indication, can rarely be ruled out. Bias that either masks teratogenicity or creates false appearance thereof, may have adverse consequences for the health of the child and the mother. Biases should be quantified and their potential impact on the study results should be assessed. Both theory and software are available for such estimation. Provided that methodological problems are understood and effectively handled, computerized medical databases are a valuable source of data for studies of teratogenicity of drugs.

  16. Stevens-Johnson syndrome and toxic epidermal necrolysis: an update on pharmacogenetics studies in drug-induced severe skin reaction.

    PubMed

    Rufini, Sara; Ciccacci, Cinzia; Politi, Cristina; Giardina, Emiliano; Novelli, Giuseppe; Borgiani, Paola

    2015-11-01

    Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, life-threatening drug reactions involving skin and membranes mucous, which are associated with significant morbidity and mortality and triggered, especially by drug exposure. Different studies have demonstrated that drug response is a multifactorial character and that the interindividual variability in this response depends on both environmental and genetic factors. The last ones have a relevant significance. In fact, the identification of new specific genetic markers involved in the response to drugs, will be of great utility to establish a more personalized therapeutic approach and to prevent the appearance of these adverse reactions. In this review, we summarize recent progresses in the Pharmacogenetics studies related to Stevens-Johnson syndrome/toxic epidermal necrolysis reporting the major genetic factors identified in the last years as associated with the disease and highlighting the use of some of these genomic variants in the clinical practice.

  17. Drugs of abuse in urban groundwater. A case study: Barcelona.

    NASA Astrophysics Data System (ADS)

    Jurado, A.; Mastroianni, N.; Vazquez-Suñe, E.; Carrera, J.; Tubau, I.; Pujades, E.; Postigo, C.; Lopez de Alda, M.; Barceló, D.

    2012-04-01

    This study is concerned with drugs of abuse (DAs) and their metabolites in urban groundwater at field scale in relation to (1) the spatial distribution of the groundwater samples, (2) the depth of the groundwater sample, (3) the presence of DAs in recharge sources, and (4) the identification of processes affecting the fate of DAs in groundwater. To this end, urban groundwater samples were collected in the city of Barcelona and a total of 21 drugs were analyzed including cocainics, amphetamine-like compounds, opioids, lysergics and cannabinoids and the prescribed drugs benzodiazepines. Overall, the highest groundwater concentrations and the largest number of detected DAs were found in zones basically recharged by a river that receives large amounts of effluents from waste water treatment plants (WWTPs). In contrast, the urbanized areas yielded not only lower concentrations but also a much smaller number of drugs, which suggests a local origin. In fact, cocaine and its metabolite were dominant in more prosperous neighbourhoods, whereas the cheaper (MDMA) was the dominant DA in poorer districts. Concentrations of DAs estimated mainly from the waste water fraction in groundwater samples were consistently higher than the measured ones, suggesting that DAs undergo removal processes in both reducing and oxidizing conditions.

  18. Bioresorbable polymer coated drug eluting stent: a model study.

    PubMed

    Rossi, Filippo; Casalini, Tommaso; Raffa, Edoardo; Masi, Maurizio; Perale, Giuseppe

    2012-07-01

    In drug eluting stent technologies, an increased demand for better control, higher reliability, and enhanced performances of drug delivery systems emerged in the last years and thus offered the opportunity to introduce model-based approaches aimed to overcome the remarkable limits of trial-and-error methods. In this context a mathematical model was studied, based on detailed conservation equations and taking into account the main physical-chemical mechanisms involved in polymeric coating degradation, drug release, and restenosis inhibition. It allowed highlighting the interdependence between factors affecting each of these phenomena and, in particular, the influence of stent design parameters on drug antirestenotic efficacy. Therefore, the here-proposed model is aimed to simulate the diffusional release, for both in vitro and the in vivo conditions: results were verified against various literature data, confirming the reliability of the parameter estimation procedure. The hierarchical structure of this model also allows easily modifying the set of equations describing restenosis evolution to enhance model reliability and taking advantage of the deep understanding of physiological mechanisms governing the different stages of smooth muscle cell growth and proliferation. In addition, thanks to its simplicity and to the very low system requirements and central processing unit (CPU) time, our model allows obtaining immediate views of system behavior.

  19. "Let's Talk about Drugs": Pilot Study of a Community-Level Drug Prevention Intervention Based on Motivational Interviewing Principles

    ERIC Educational Resources Information Center

    Newbery, Natasha; McCambridge, Jim; Strang, John

    2007-01-01

    Purpose: The feasibility of a community-level drug prevention intervention based upon the principles of motivational interviewing within a further education college was investigated in a pilot study. Design/methodology/approach: The implementation over the course of a single term of "Let's Talk about Drugs" was studied with both action research…

  20. Postmarketing Safety Study Tool: A Web Based, Dynamic, and Interoperable System for Postmarketing Drug Surveillance Studies.

    PubMed

    Sinaci, A Anil; Laleci Erturkmen, Gokce B; Gonul, Suat; Yuksel, Mustafa; Invernizzi, Paolo; Thakrar, Bharat; Pacaci, Anil; Cinar, H Alper; Cicekli, Nihan Kesim

    2015-01-01

    Postmarketing drug surveillance is a crucial aspect of the clinical research activities in pharmacovigilance and pharmacoepidemiology. Successful utilization of available Electronic Health Record (EHR) data can complement and strengthen postmarketing safety studies. In terms of the secondary use of EHRs, access and analysis of patient data across different domains are a critical factor; we address this data interoperability problem between EHR systems and clinical research systems in this paper. We demonstrate that this problem can be solved in an upper level with the use of common data elements in a standardized fashion so that clinical researchers can work with different EHR systems independently of the underlying information model. Postmarketing Safety Study Tool lets the clinical researchers extract data from different EHR systems by designing data collection set schemas through common data elements. The tool interacts with a semantic metadata registry through IHE data element exchange profile. Postmarketing Safety Study Tool and its supporting components have been implemented and deployed on the central data warehouse of the Lombardy region, Italy, which contains anonymized records of about 16 million patients with over 10-year longitudinal data on average. Clinical researchers in Roche validate the tool with real life use cases. PMID:26543873

  1. Postmarketing Safety Study Tool: A Web Based, Dynamic, and Interoperable System for Postmarketing Drug Surveillance Studies

    PubMed Central

    Sinaci, A. Anil; Laleci Erturkmen, Gokce B.; Gonul, Suat; Yuksel, Mustafa; Invernizzi, Paolo; Thakrar, Bharat; Pacaci, Anil; Cinar, H. Alper; Cicekli, Nihan Kesim

    2015-01-01

    Postmarketing drug surveillance is a crucial aspect of the clinical research activities in pharmacovigilance and pharmacoepidemiology. Successful utilization of available Electronic Health Record (EHR) data can complement and strengthen postmarketing safety studies. In terms of the secondary use of EHRs, access and analysis of patient data across different domains are a critical factor; we address this data interoperability problem between EHR systems and clinical research systems in this paper. We demonstrate that this problem can be solved in an upper level with the use of common data elements in a standardized fashion so that clinical researchers can work with different EHR systems independently of the underlying information model. Postmarketing Safety Study Tool lets the clinical researchers extract data from different EHR systems by designing data collection set schemas through common data elements. The tool interacts with a semantic metadata registry through IHE data element exchange profile. Postmarketing Safety Study Tool and its supporting components have been implemented and deployed on the central data warehouse of the Lombardy region, Italy, which contains anonymized records of about 16 million patients with over 10-year longitudinal data on average. Clinical researchers in Roche validate the tool with real life use cases. PMID:26543873

  2. Comparison of continuous air monitor utilization: A case study

    SciTech Connect

    Rodgers, J.C.; Whicker, J.J.; Voss, J.T.

    1997-08-01

    The Chemical Metallurgy Research (CMR) building has been upgrading to different continuous air monitors (CAMs) over the past several years. During the transition, both the newer and older CAMs were positioned in the rooms for field testing and comparison. On December 19, 1996, an accidental release of plutonium aerosol occurred into a laboratory in the CMR building. The event occurred while the room was unoccupied, and no personnel were exposed from this incident. There were two fixed air samplers (FASs) and three CAMs operating in the room at the time the release occurred, including two of the recently installed Canberra Alpha Sentry CAMs and one older Eberline CAM. The apparent cause of the release was a procedure carried out in the basement involving the replacement of the HEPA filter in the ventilation exhaust of a slot-box in the laboratory. For a short period, the ventilation was disconnected from the slot-box in this room, but not from the chemical hood exhaust on the opposite side of the laboratory. Therefore, a condition was created where backflow could occur out of the slot-box and into the room. Eventually all three CAMs in the room alarmed, and the situation was successfully monitored and brought under control by health physics personnel. Data on CAM performance were logged, and Pu activity collected on CAM and FAS filters were measured. A comparison of the new and old continuous air monitoring programs was performed and many interesting lessons on CAM performance and CAM utilization were learned. Overall, this comparison showed the advantages of remote monitoring, timely spectral information, and concentration measurements resolved in time and space.

  3. The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs.

    PubMed

    Marek, Gerard J; Day, Mark; Hudzik, Thomas J

    2016-03-01

    Cognitive dysfunction may be a core feature of major depressive disorder, including affective processing bias, abnormal response to negative feedback, changes in decision making, and increased impulsivity. Accordingly, a translational medicine paradigm predicts clinical action of novel antidepressants by examining drug-induced changes in affective processing bias. With some exceptions, these concepts have not been systematically applied to preclinical models to test new chemical entities. The purpose of this review is to examine whether an empirically derived behavioral screen for antidepressant drugs may screen for compounds, at least in part, by modulating an impulsive biasing of responding and altered decision making. The differential-reinforcement-of-low-rate (DRL) 72-second schedule is an operant schedule with a documented fidelity for discriminating antidepressant drugs from nonantidepressant drugs. However, a theoretical basis for this empirical relationship has been lacking. Therefore, this review will discuss whether response bias toward impulsive behavior may be a critical screening characteristic of DRL behavior requiring long inter-response times to obtain rewards. This review will compare and contrast DRL behavior with the five-choice serial reaction time task, a test specifically designed for assessing motoric impulsivity, with respect to psychopharmacological testing and the neural basis of distributed macrocircuits underlying these tasks. This comparison suggests that the existing empirical basis for the DRL 72-second schedule as a pharmacological screen for antidepressant drugs is complemented by a novel hypothesis that altering impulsive response bias for rodents trained on this operant schedule is a previously unrecognized theoretical cornerstone for this screening paradigm. PMID:26699144

  4. Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein.

    PubMed

    Keogh, John P; Kunta, Jeevan R

    2006-04-01

    Regulatory interest is increasing for drug transporters generally and P-glycoprotein (Pgp) in particular, primarily in the area of drug-drug interactions. To aid in both identifying and discharging the potential liabilities associated with drug-transporter interactions, the pharmaceutical industry has a growing requirement for routine and robust non-clinical assays. An assay was designed, optimised and validated to determine the in vitro inhibitory potency of new chemical entities (NCEs) towards human Pgp-mediated transport. [3H]-Digoxin was established as a suitable probe substrate by investigating its characteristics in the in vitro system (MDCKII-MDR1 cells grown in 24-multiwell inserts). The inhibitory potencies (apparent IC50) of known Pgp inhibitors astemizole, GF120918, ketoconazole, itraconazole, quinidine, verapamil and quinine were determined over at least a 1000-fold concentration range. Validation was carried out using manual and automatic techniques. [3H]-Digoxin was found to be stable and have good mass balance in the system. In contrast to [A-->B] transport, [3H]-digoxin [B-->A] transport rates were readily measured with good reproducibility. There was no evidence of saturation of transport up to 10 microM digoxin and 30 nM digoxin was selected for routine assay use, reflecting clinical therapeutic concentrations. IC50 values ranged over approximately 100-fold with excellent reproducibility. Results from manual and automated versions were in close agreement. This method is suitable for routine use to assess the in vitro inhibitory potency of NCEs on Pgp-mediated digoxin transport. Comparison of IC50 values against clinical interaction profiles for the probe inhibitors indicated the in vitro assay is predictive of clinical digoxin-drug interactions mediated via Pgp.

  5. The utility of self-emulsifying oil formulation to improve the poor solubility of the anti HIV drug CSIC

    PubMed Central

    2013-01-01

    Background CSIC (5-chloro-3-phenylsulfonylindole-2-carboxamide), a non-nucleoside reverse transcriptase inhibitor (NNRTI) has not been advanced as a therapeutic anti-HIV candidate drug due to its low aqueous solubility and poor bioavailability. Objective The objective of this work was to formulate CSIC into self-emulsifying oil formulations for the purpose of improving its aqueous solubility and evaluating in vitro antiretroviral activity. Methods CSIC self-emulsifying oil formulations (SEFs) were formulated and evaluated for droplet size, zeta potential, polydispersity index (PDI), viscosity, emulsification time, stability and bioactivity. Results Results showed significantly improved solubility of CSIC in the SEFs.The concentration of co-surfactant affected the droplet size, zeta potential and polydispersity index. In vitro bioactivity studies showed that the CSIC SEFs retained full anti-HIV activity. Conclusion The in vitro data from this first attempt to formulate CSIC SEFs suggest that improvement on the aqueous solubility of CSIC through this delivery system may accentuate its antiretroviral effectiveness in vivo via bioavailability enhancement. The formulation is therefore intended as an oral anti-HIV agent for prophylactic and therapeutic uses. PMID:23721408

  6. Real-time mobile detection of drug use with wearable biosensors: a pilot study.

    PubMed

    Carreiro, Stephanie; Smelson, David; Ranney, Megan; Horvath, Keith J; Picard, R W; Boudreaux, Edwin D; Hayes, Rashelle; Boyer, Edward W

    2015-03-01

    While reliable detection of illicit drug use is paramount to the field of addiction, current methods involving self-report and urine drug screens have substantial limitations that hinder their utility. Wearable biosensors may fill a void by providing valuable objective data regarding the timing and contexts of drug use. This is a preliminary observational study of four emergency department patients receiving parenteral opioids and one individual using cocaine in a natural environment. A portable biosensor was placed on the inner wrist of each subject, to continuously measure electrodermal activity (EDA), skin temperature, and acceleration. Data were continuously recorded for at least 5 min prior to drug administration, during administration, and for at least 30 min afterward. Overall trends in biophysiometric parameters were assessed. Injection of opioids and cocaine use were associated with rises in EDA. Cocaine injection was also associated with a decrease in skin temperature. Opioid tolerance appeared to be associated with a blunted physiologic response as measured by the biosensor. Laterality may be an important factor, as magnitude of response varied between dominant and nondominant wrists in a single patient with bilateral wrist measurements. Changes in EDA and skin temperature are temporally associated with intravenous administration of opioids and cocaine; the intensity of response, however, may vary depending on history and extent of prior use. PMID:25330747

  7. A prospective study of adverse drug reactions in hospitalized children

    PubMed Central

    Martínez-Mir, Inocencia; García-López, Mercedes; Palop, Vicente; Ferrer, José M; Rubio, Elena; Morales-Olivas, Francisco J

    1999-01-01

    Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR = 1.66, 95% CI 1.03–2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. PMID:10383547

  8. Pharmacogenetic studies of epilepsy drugs: are we there yet?

    PubMed

    Spurr, Nigel K

    2006-05-01

    One of the mantras of scientists working in the field of pharmacogenetics is 'the right dose for the right patient'. A recent article has gone someway towards demonstrating that this goal can be achieved using genetic approaches. It is one of the first reports to show that a specific polymorphism can predict the maximum tolerated dose of two anti-epileptic drugs. However, further studies are necessary to validate these observations.

  9. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    PubMed

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  10. Quantitative ToF-SIMS studies of protein drug release from biodegradable polymer drug delivery membranes

    NASA Astrophysics Data System (ADS)

    Burns, Sarah A.; Gardella, Joseph A.

    2008-12-01

    Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/ z 467 and 421, respectively. These peaks were determined to be [AOT + Na +] and [AOT - Na +]. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution [C.M. Mahoney, J. Yu, A. Fahey, J.A.J. Gardella, SIMS depth profiling of polymer blends with protein based drugs, Appl. Surf. Sci. 252 (2006), 6609-6614.].

  11. Utilization of bio-degradable fermented tapioca to synthesized low toxicity of carbon nanotubes for drug delivery applications

    NASA Astrophysics Data System (ADS)

    Nurulhuda, I.; Poh, R.; Mazatulikhma, M. Z.; Salman, A. H. A.; Haseeb, A. K.; Rusop, M.

    2016-07-01

    Carbon nanotubes (CNT) have potential biomedical applications, and investigations are shifting towards the production of such nanotubes using renewable natural sources. CNTs were synthesized at various temperatures of 700, 750, 800, 850 and 900 °C, respectively, using a local fermented food known as "tapai ubi" or fermented tapioca as a precursor. The liquid part of this fermented food was heated separately at 80°C and channeled directly into the furnace system that employs the thermal chemical vapor deposition (CVD) method. Ferrocene, which was the catalyst was placed in furnace 1 in the thermal CVD process. The resulting CNTs produced from the process were studied using field emission scanning electron microscopy (FESEM) and raman spectroscopy. The FESEM images showed the growth morphology of the CNTs at the different temperatures employed. It was observed that the higher the synthesis temperature up to a point, the diameter of CNTs produced, after which the diameter increased. CNTs with helical structures were observed at 700 °C with a diameter range of 111 - 143 nm. A more straightened structure was observed at 750 °C with a diameter range of 59 - 121 nm. From 800 °C onwards, the diameters of the CNTs were less than 60 nm. Raman analysis revealed the present of D, G and G' peak were observed at 1227-1358, 1565-1582, and 2678-2695 cm-1, respectively. The highest degree of crystallity of the carbon nanotubes synthesized were obtained at 800 °C. The radial breathing mode (RBM) were in range between 212-220 and 279-292 cm-1. Carbon nanotubes also being functionalized with Polyethylene bis(amine) Mw2000 (PEG 2000-NH2) and showed highly cells viability compared to non-functionalized CNT. The nanotubes synthesized will be applied as drug delivery in future study.

  12. Use of benzodiazepines and related drugs in Manitoba: a population-based study

    PubMed Central

    Bolton, James M.; Enns, Murray W.; Dahl, Matthew; Collins, David M.; Chateau, Dan; Sareen, Jitender

    2014-01-01

    Background Despite their favourable toxicology profile, benzodiazepines and the related Z-drugs (zopiclone, zolpidem and zaleplon) have been associated with physiological tolerance, dependence and addiction. Evidence of harm (e.g., falls, motor vehicle collisions and cognitive disturbances) has been reported in older populations. The aim of this study was to determine the relation between users’ characteristics and the use of benzodiazepines and Z-drugs in Manitoba over a 16-year period. Methods This time-series analysis was based on prescription data from Apr. 1, 1996, to Mar. 31, 2012, obtained from the Drug Product Information Network database of Manitoba. We obtained sociodemographic information on benzodiazepine and Z-drug users from the Population Registry and determined changes in utilization rates over time using generalized estimating equations. Results Overall, the prevalence of benzodiazepine use remained stable at about 61.0 per 1000 population between 1996/97 and 2011/12; however, the prevalence of Z-drug use increased steadily from 10.9 to 37.0 per 1000 over the same period. In older people (≥ 65 years), the incidence of benzodiazepine use decreased from 55.5 to 30.3 users per 1000, whereas the incidence of Z-drug use increased from 7.3 to 20.3 users per 1000 over the study period. Among those 18–64 years of age, the incidence of benzodiazepine use decreased from 30.1 to 27.6 users per 1000, but the increase in incidence of Z-drug use was more than 2-fold. The youngest population (≤ 17 years) showed the lowest rates of use of these drugs. The highest rates of use were observed among older women and the low-income population. Interpretation Over the study period, benzodiazepines have been prescribed less frequently to older patients in Manitoba; however, zopiclone prescribing has continued to increase for all age groups. The reasons for this increase remain to be determined. PMID:25485245

  13. Computational Study of Anticancer Drug Resistance Caused by 10 Topisomerase I Mutations, Including 7 Camptothecin Analogs and Lucanthone.

    PubMed

    Mulholland, Kelly; Wu, Chun

    2016-09-26

    Although Camptothecin and its analogs as Topoisomerase I poisons can effectively treat cancers, serious drug resistance has been identified for this class of drugs. Recent computational studies have indicated that the mutations near the active binding site of the drug can significantly weaken the drug binding and cause drug resistance. However, only Topotecan and three mutations have been previously analyzed. Here we present a comprehensive binding study of 10 Topoisomerase I mutants (N722S, N722A, D533G, D533N, G503S, G717V, T729A, F361S, G363C, and R364H) and 8 poisons including 7 Camptothecin analogs as well as a new generation Topoisomerase I drug, Lucanthone. Utilizing Glide docking followed by MMGBSA calculations, we determined the binding energy for each complex. We examine the relative binding energy changes with reference to the wild type, which are linked to the degree of drug resistance. On this set of mutant complexes, Topotecan and Camptothecin showed much smaller binding energies than a set of new Camptothecin derivatives (Lurtotecan, SN38, Gimatecan, Exatecan, and Belotecan) currently under clinical trials. We observed that Lucanthone exhibited comparable results to Topotecan and Camptothecin, indicating that it may serve as a promising candidate for future studies as a Topoisomerase I poison. Our docked results on Topotecan were also validated by a set of molecular dynamics simulations. In addition to a good agreement on the MMGBSA binding energy change, our simulation data also shows there is larger conformation fluctuation upon the mutations. These results may be utilized to further advancements of Topoisomerase I drugs that are resistant to mutations.

  14. Validation of the Drug Abuse Screening Test (DAST-10): A study on illicit drug use among Chinese pregnant women

    PubMed Central

    Lam, Lap Po; Leung, Wing Cheong; Ip, Patrick; Chow, Chun Bong; Chan, Mei Fung; Ng, Judy Wai Ying; Sing, Chu; Lam, Ying Hoo; Mak, Wing Lai Tony; Chow, Kam Ming; Chin, Robert Kien Howe

    2015-01-01

    We assessed the Chinese version of the Drug Abuse Screening Test (DAST-10) for identifying illicit drug use during pregnancy among Chinese population. Chinese pregnant women attending their first antenatal visit or their first unbooked visit to the maternity ward were recruited during a 4-month study period in 2011. The participants completed self-administered questionnaires on demographic information, a single question on illicit drug use during pregnancy and the DAST-10. Urine samples screened positive by the urine Point-of-Care Test were confirmed by gas chromatography-mass spectrometry. DAST-10 performance was compared with three different gold standards: urinalysis, self-reported drug use, and evidence of drug use by urinalysis or self-report. 1214 Chinese pregnant women participated in the study and 1085 complete DAST-10 forms were collected. Women who had used illicit drugs had significantly different DAST-10 scores than those who had not. The sensitivity of DAST-10 for identify illicit drug use in pregnant women ranged from 79.2% to 33.3% and specificity ranged from 67.7% to 99.7% using cut-off scores from ≥1 to ≥3. The ~80% sensitivity of DAST-10 using a cut-off score of ≥1 should be sufficient for screening of illicit drug use in Chinese pregnant women, but validation tests for drug use are needed. PMID:26091290

  15. Validation of the Drug Abuse Screening Test (DAST-10): A study on illicit drug use among Chinese pregnant women.

    PubMed

    Lam, Lap Po; Leung, Wing Cheong; Ip, Patrick; Chow, Chun Bong; Chan, Mei Fung; Ng, Judy Wai Ying; Sing, Chu; Lam, Ying Hoo; Mak, Wing Lai Tony; Chow, Kam Ming; Chin, Robert Kien Howe

    2015-06-19

    We assessed the Chinese version of the Drug Abuse Screening Test (DAST-10) for identifying illicit drug use during pregnancy among Chinese population. Chinese pregnant women attending their first antenatal visit or their first unbooked visit to the maternity ward were recruited during a 4-month study period in 2011. The participants completed self-administered questionnaires on demographic information, a single question on illicit drug use during pregnancy and the DAST-10. Urine samples screened positive by the urine Point-of-Care Test were confirmed by gas chromatography-mass spectrometry. DAST-10 performance was compared with three different gold standards: urinalysis, self-reported drug use, and evidence of drug use by urinalysis or self-report. 1214 Chinese pregnant women participated in the study and 1085 complete DAST-10 forms were collected. Women who had used illicit drugs had significantly different DAST-10 scores than those who had not. The sensitivity of DAST-10 for identify illicit drug use in pregnant women ranged from 79.2% to 33.3% and specificity ranged from 67.7% to 99.7% using cut-off scores from ≥ 1 to ≥ 3. The ~ 80% sensitivity of DAST-10 using a cut-off score of ≥ 1 should be sufficient for screening of illicit drug use in Chinese pregnant women, but validation tests for drug use are needed.

  16. Validation of the Drug Abuse Screening Test (DAST-10): A study on illicit drug use among Chinese pregnant women.

    PubMed

    Lam, Lap Po; Leung, Wing Cheong; Ip, Patrick; Chow, Chun Bong; Chan, Mei Fung; Ng, Judy Wai Ying; Sing, Chu; Lam, Ying Hoo; Mak, Wing Lai Tony; Chow, Kam Ming; Chin, Robert Kien Howe

    2015-01-01

    We assessed the Chinese version of the Drug Abuse Screening Test (DAST-10) for identifying illicit drug use during pregnancy among Chinese population. Chinese pregnant women attending their first antenatal visit or their first unbooked visit to the maternity ward were recruited during a 4-month study period in 2011. The participants completed self-administered questionnaires on demographic information, a single question on illicit drug use during pregnancy and the DAST-10. Urine samples screened positive by the urine Point-of-Care Test were confirmed by gas chromatography-mass spectrometry. DAST-10 performance was compared with three different gold standards: urinalysis, self-reported drug use, and evidence of drug use by urinalysis or self-report. 1214 Chinese pregnant women participated in the study and 1085 complete DAST-10 forms were collected. Women who had used illicit drugs had significantly different DAST-10 scores than those who had not. The sensitivity of DAST-10 for identify illicit drug use in pregnant women ranged from 79.2% to 33.3% and specificity ranged from 67.7% to 99.7% using cut-off scores from ≥ 1 to ≥ 3. The ~ 80% sensitivity of DAST-10 using a cut-off score of ≥ 1 should be sufficient for screening of illicit drug use in Chinese pregnant women, but validation tests for drug use are needed. PMID:26091290

  17. Non interventional drug studies in oncology: Why we need them?

    PubMed

    Mishra, Divya; Vora, Jesal

    2010-10-01

    Oncology is a highly researched therapeutic area with an ever expanding armamentarium of drugs entering the market. It is unique in how the heterogeneity of tumor, patient and treatment factors is critical in determining outcomes of interventions. When it comes to decision making in the clinic, the practicing physician often seeks answers in populations with obvious deviations from the ideal selected populations included in the pivotal phase III randomized controlled trials (RCTs). While the randomized nature of the RCT ensures its high internal validity by removing bias, their 'controlled' nature casts a doubt on their generalizability to the real world population. It is for this reason that trials done in a naturalistic setting post the marketing authorization of a drug are increasingly required. This article discusses the importance of non interventional drug studies in oncology as an important tool in testing the external validity of controlled trial results and its value in generation of new hypothesis. It also discusses the limitations of such studies while outlining the steps in their effective conduct. PMID:21350727

  18. Progress of drug-loaded polymeric micelles into clinical studies.

    PubMed

    Cabral, Horacio; Kataoka, Kazunori

    2014-09-28

    Targeting tumors with long-circulating nano-scaled carriers is a promising strategy for systemic cancer treatment. Compared with free small therapeutic agents, nanocarriers can selectively accumulate in solid tumors through the enhanced permeability and retention (EPR) effect, which is characterized by leaky blood vessels and impaired lymphatic drainage in tumor tissues, and achieve superior therapeutic efficacy, while reducing side effects. In this way, drug-loaded polymeric micelles, i.e. self-assemblies of amphiphilic block copolymers consisting of a hydrophobic core as a drug reservoir and a poly(ethylene glycol) (PEG) hydrophilic shell, have demonstrated outstanding features as tumor-targeted nanocarriers with high translational potential, and several micelle formulations are currently under clinical evaluation. This review summarizes recent efforts in the development of these polymeric micelles and their performance in human studies, as well as our recent progress in polymeric micelles for the delivery of nucleic acids and imaging. PMID:24993430

  19. [Transesophageal electrophysiologic study: utility in the diagnosis of syncope].

    PubMed

    Hidalgo Ottolenghi, F

    2001-01-01

    Neurocardiogenic and arrhythmic syncope are very common and may be found in many patients in Emergency Departments or admitted to hospitals. Technologic advances now allow etiologic diagnosis to be determined but the importance of a detailed clinical history and physical examination can not be overemphasized in the evaluation of syncope, thereby to avoid some costly or invasive procedures. The recent introduction of the head-up tilt test alone or in combination with electrophysiologic studies, has significantly improved our ability to diagnose the etiology of syncope in many cases. Suspicion of an arrhythmic cause of syncope does not always require an invasive electrophysiologic study since the transesophageal electrophysiologic study is useful and provides a high diagnostic yield in the evaluation of non ventricular arrhythmic syncope, such as in the sick sinus syndrome, atrio-ventricular block or in supraventricular tachycardia and for the study of atrial stability. The transesophageal electrophysiologic study is an inexpensive non invasive procedure which does not require complex hospitalary installations. PMID:11535186

  20. A prospective study of adverse drug reactions to antiepileptic drugs in children

    PubMed Central

    Anderson, Mark; Egunsola, Oluwaseun; Cherrill, Janine; Millward, Claire; Fakis, Apostolos; Choonara, Imti

    2015-01-01

    Objectives To prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour. Setting A single centre prospective observational study. Participants Children (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit. Primary and secondary outcomes Primary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes. Results 180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR. Conclusions Behavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children. Trail registration number EudraCT (2007-000565-37). PMID:26033949

  1. EMERGENCY DEPARTMENT UTILIZATION AMONG A COHORT OF HIV-POSITIVE INJECTING DRUG USERS IN A CANADIAN SETTING

    PubMed Central

    Fairbairn, Nadia; Milloy, M-J; Zhang, Ruth; Lai, Calvin; Grafstein, Eric; Kerr, Thomas; Wood, Evan

    2011-01-01

    Background HIV-positive injection drug users (IDU) are known to be at risk for multiple medical problems that may necessitate emergency department (ED) use, however, the relative contribution of HIV disease versus injection-related complications have not been well described. Objectives We examined factors associated with ED use among a prospective cohort of HIV-positive IDU in a Canadian setting. Methods We enrolled HIV-positive IDU into a community-recruited prospective cohort study. We modeled factors associated with the time to first ED visit using Cox regression to determine factors independently associated with ED use. In sub-analyses, we examined ED diagnoses and subsequent hospital admission rates. Results Between December 5, 2005, and April 30, 2008, 428 HIV-positive IDU were enrolled, among whom the cumulative incidence of ED use was 63.7% (95% Confidence Interval [CI]: 59.1% – 68.3%) at 12 months after enrollment. Factors independently associated with time to first ED visit included: unstable housing (Hazard Ratio [HR] = 1.5, 95% CI: 1.1–2.0) and reporting being unable to obtain needed health care services (HR = 2.2, 95% CI: 1.2–4.1), whereas CD4 count and viral load were non-significant. Skin and soft tissue infections (SSTIs) accounted for the greatest proportion of ED visits (17%). Of the 2461 visits to the ED, 419 (17%) were admitted to hospital. Conclusions High rates of ED use were observed among HIV-positive IDU, a behavior that was predicted by unstable housing and limited access to primary care. Factors other than HIV infection appear to be driving ED use among this population in the post-HAART era. PMID:21719229

  2. Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction

    PubMed Central

    Engleman, Eric A.; Katner, Simon N.; Neal-Beliveau, Bethany S.

    2016-01-01

    Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH’s effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system–dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine

  3. Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction.

    PubMed

    Engleman, Eric A; Katner, Simon N; Neal-Beliveau, Bethany S

    2016-01-01

    Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH's effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system-dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission

  4. Corrosion and degradation studies utilizing X-ray photoelectron spectroscopy

    NASA Astrophysics Data System (ADS)

    Hixson, Holly Gwyndolen

    1997-08-01

    This dissertation involves studies of corrosion behavior at the surface of various metal samples, as well as the degradation of wool fibers obtained from the Star-Spangled Banner. Molybdenum metal and iron-zinc alloys were examined under corrosive conditions, and the degradation of the wool fibers was studied. The behavior of a polished molybdenum metal surface upon exposure to both aerated and deaerated water and 1.0 M NaCl solution was studied by X-ray Photoelectron Spectroscopy (XPS). Exposure to deaerated water and NaCl failed to produce oxidation of the metal surfaces, but exposing the polished metal surface to aerated water produced significant oxidation. Metal surfaces cleaned by argon-ion etching were found to be inert to oxidation by aerated water. The etching process also appears to passivate the metal surface. The behavior of molybdenum metal in 0.5 M Hsb2SOsb4 treated at various potentials has been studied using core and valence band XPS. The study indicates that Mosp{IV} and Mosp{VI} (including possibly Mosp{V} in some cases) were formed as the potential of the system was increased within the active range of molybdenum. The corrosive behavior of iron-zinc alloys that have been electroplated on plain steel in both aerated and deaerated quadruply-distilled water has been studied using XPS. Several different iron-zinc alloys were electroplated for comparative purposes: an iron-rich alloy, a zinc-rich alloy, and an alloy of similar iron and zinc composition. Treatment in aerated water produces oxidation for the iron-rich and similar composition alloys, but the oxide is reduced for the zinc-rich alloy. Degradation of the fibers in the original Star-Spangled Banner has been monitored using XPS and Scanning Electron Microscopy (SEM). Comparison of white and red wool fibers and linen fibers from the flag with new, mechanically-abraded, and chemically-treated white, red, and linen fibers, respectively, was performed in an attempt to determine the fibers' levels

  5. Utilization of remote sensing in Alaska permafrost studies

    NASA Technical Reports Server (NTRS)

    Hall, D. K.

    1981-01-01

    Permafrost related features such as: aufeis, tundra, thaw lakes and subsurface ice features were studied. LANDSAT imagery was used to measure the extent and distribution of aufeis in Arctic Slope rivers over a period of 7 years. Interannual extent of large aufeis fields was found to vary significantly. Digital LANDSAT data were used to study the short term effects of a tundra fire which burned a 48 sq km area in northwestern Alaska. Vegetation regrowth was inferred from Landsat spectral reflectance increases and compared to in-situ measurements. Aircraft SAR (Synethic Aperture Radar) imagery was used in conjunction with LANDSAT imagery used in conjunction with LANDSAT imagery to qualitatively determine depth categories for thaw lakes in northern Alaska.

  6. The utilization of Computer Mediated Communication for case study collaboration.

    PubMed

    Gwozdek, Anne E; Klausner, Christine P; Kerschbaum, Wendy E

    2008-01-01

    Computer Mediated Communication (CMC) can be used as an effective tool for student communication and collaboration. First-year, first-semester dental hygiene students self-selected groups to develop dental hygiene process of care treatment plans, written reports, and oral case presentations based on assigned clinical cases. In consultation with the University of Michigan (UM) Digital Media Commons Collaborative Technologies Teams, CMC options were identified. Two chat rooms were established within the UM's Course Management System (CTools) to provide opportunities for synchronous (simultaneous, real-time) communication. One course blog site and 8 case blog sites were developed to provide students and instructors with electronic asynchronous (nonsimultaneous) communication formats. The purpose of this study was to evaluate the effectiveness of these technologies during group case study projects. CMC has the potential to provide an effective means of collaboration and communication when the technologies align with the purpose of the project and compliment the dynamics of student groups.

  7. Utilizing Cloud Computing to Improve Climate Modeling and Studies

    NASA Astrophysics Data System (ADS)

    Li, Z.; Yang, C.; Liu, K.; Sun, M.; XIA, J.; Huang, Q.

    2013-12-01

    Climate studies have become increasingly important due to the global climate change, one of the biggest challenges for the human in the 21st century. Climate data, not only observations data collected from various sensors but also simulated data generated from diverse climate models, are essential for scientists to explore the potential climate change patterns and analyze the complex climate dynamics. Climate modeling and simulation, a critical methodology for simulating the past and predicting the future climate conditions, can produce huge amount of data that contains potentially valuable information for climate studies. However, using modeling method in climate studies poses at least two challenges for scientists. First, running climate models is a computing intensive process, which requires large amounts of computation resources. Second, running climate models is also a data intensive process generating Big geospatial Data (model output), which demands large storage for managing the data and large computing power to process and analyze these data. This presentation introduces a novel framework to tackle the two challenges by 1) running climate models in a cloud environment in an automated fashion, and 2) managing and parallel processing Big model output Data by leveraging cloud computing technologies. A prototype system is developed based on the framework using ModelE as the climate model. Experiment results show that this framework can improve climate modeling in the research cycle by accelerating big data generation (model simulation), big data management (storage and processing) and on demand big data analytics.

  8. Comparing Utility Scores in Common Spinal Radiculopathies: Results of a Prospective Valuation Study.

    PubMed

    Nayak, Nikhil R; Stephen, James H; Abdullah, Kalil G; Stein, Sherman C; Malhotra, Neil R

    2016-05-01

    Study Design Prospective observational study. Objective To determine whether preference-based health utility scores for common spinal radiculopathies vary by specific spinal level. Methods We employed a standard gamble study using the general public to calculate individual preference-based quality of life for four common radiculopathies: C6, C7, L5, and S1. We compared utility scores obtained for each level of radiculopathy with analysis of variance and t test. Multivariable regression was used to test the effects of the covariates age, sex, and years of education. We also reviewed the literature for publications reporting EuroQol-5 Dimensions (EQ-5D) scores for patients with radiculopathy. Results Two hundred participants were included in the study. Average utility for the four spinal levels fell within a narrow range (0.748 to 0.796). There were no statistically significant differences between lumbar and cervical radiculopathies, nor were there significant differences among the different spinal levels (F = 0.0850, p = 0.086). Age and sex had no significant effect on utility scores. There was a significant correlation between years of education and utility values for S1 radiculopathy (p = 0.037). On review of the literature, no study separated utility values by specific spinal level. EQ-5D utilities for both cervical and lumbar radiculopathy were considerably lower than the results of our study. Conclusions Utility values associated with the most common levels of cervical and lumbar radiculopathy do not significantly differ from each other, validating the current practice of grouping utility by spinal segment rather than by specific root levels. The discrepancy in average utility values between our study and the EQ-5D highlights the need to be mindful of the underlying instruments used when assessing outcomes studies from different sources. PMID:27099818

  9. Comparing Utility Scores in Common Spinal Radiculopathies: Results of a Prospective Valuation Study.

    PubMed

    Nayak, Nikhil R; Stephen, James H; Abdullah, Kalil G; Stein, Sherman C; Malhotra, Neil R

    2016-05-01

    Study Design Prospective observational study. Objective To determine whether preference-based health utility scores for common spinal radiculopathies vary by specific spinal level. Methods We employed a standard gamble study using the general public to calculate individual preference-based quality of life for four common radiculopathies: C6, C7, L5, and S1. We compared utility scores obtained for each level of radiculopathy with analysis of variance and t test. Multivariable regression was used to test the effects of the covariates age, sex, and years of education. We also reviewed the literature for publications reporting EuroQol-5 Dimensions (EQ-5D) scores for patients with radiculopathy. Results Two hundred participants were included in the study. Average utility for the four spinal levels fell within a narrow range (0.748 to 0.796). There were no statistically significant differences between lumbar and cervical radiculopathies, nor were there significant differences among the different spinal levels (F = 0.0850, p = 0.086). Age and sex had no significant effect on utility scores. There was a significant correlation between years of education and utility values for S1 radiculopathy (p = 0.037). On review of the literature, no study separated utility values by specific spinal level. EQ-5D utilities for both cervical and lumbar radiculopathy were considerably lower than the results of our study. Conclusions Utility values associated with the most common levels of cervical and lumbar radiculopathy do not significantly differ from each other, validating the current practice of grouping utility by spinal segment rather than by specific root levels. The discrepancy in average utility values between our study and the EQ-5D highlights the need to be mindful of the underlying instruments used when assessing outcomes studies from different sources.

  10. Epidemiology of contact allergy: an estimation of morbidity employing the clinical epidemiology and drug-utilization research (CE-DUR) approach.

    PubMed

    Schnuch, A; Uter, W; Geier, J; Gefeller, O

    2002-07-01

    Clinical epidemiology (CE) is considered unable to estimate morbidity concerning either contact sensitization (CS) or allergic contact dermatitis (ACD) at the population level. Drug-utilization research (DUR) methods estimate the morbidity of suitable diseases based on prescription data for disease-specific drugs. Our objective was to estimate population figures for incidence and prevalence of ACD and CS based on sales data for patch test material in Germany and on patient data from the Information Network of Departments of Dermatology (IVDK). Approximately 600000 standard series are sold per year in Germany, according to the 2 main manufacturers. This raw sales figure was corrected for certain effects (discarded preparations, proportion of formerly patch-tested patients, proportion of patients with ACD seeking medical advice) to obtain an estimate of the denominator of patients eligible for patch testing annually, and combined with patch test results from the Information Network of Departments of Dermatology (IVDK). In 17.8% (of 9266 IVDK patients) ACD was established. Extrapolated to the general population, an incidence of ACD of between 1.7 and 7 per 1000 per year was estimated, depending on whether conservative or more liberal assumptions concerning the above effects were made. Of 78067 IVDK patients tested between 1992 and 2000, 46.8% had at least 1 positive reaction (+ to + + +), and 22.7% had at least 1 stronger positive reaction (+ + or + + +). The 9-year prevalence of CS was estimated to lie between 4.0% and 16.6% for the first outcome, and between 2.0% and 8.1% for the second. Concerning single allergens, 1.9-4.5 million individuals are probably sensitized to nickel, and 1.4-3.4 million to fragrance mix among the German population of 82 million inhabitants. The morbidity data found in this study are in good accordance with data from population-based epidemiological studies. In comparison to these, the CE-DUR approach seems to be an economically feasible

  11. Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: a prospective study.

    PubMed

    Turner, S; Nunn, A J; Fielding, K; Choonara, I

    1999-09-01

    To determine the incidence of adverse drug reactions (ADRs) to unlicensed and off-label drugs used in paediatric inpatients, we carried out prospective surveillance on five different paediatric wards in a regional children's hospital for 13 wk. Comparison of the use of each drug with its summary of product characteristics was made to determine whether the drug was used in an unlicensed or off-label manner. The presence of an ADR was determined using previously defined criteria. In total, 4455 courses of drugs were administered to 936 patients in 1046 admissions. In 507 (48%) of the 1046 admissions, patients received one or more unlicensed or off-label drugs. ADRs occurred in 116 (11%) of the 1046 patient admissions. ADRs were associated with 112 (3.9%) of the 2881 licensed drug prescriptions and 95 (6%) of the 1574 unlicensed or off-label drug prescriptions. Use of drugs in an off-label or unlicensed manner to treat children is widespread. ADRs are a significant problem following unlicensed or off-label drug prescriptions. PMID:10519338

  12. Microbiologic Methods Utilized in the MAL-ED Cohort Study

    PubMed Central

    Houpt, Eric; Gratz, Jean; Kosek, Margaret; Zaidi, Anita K. M.; Qureshi, Shahida; Kang, Gagandeep; Babji, Sudhir; Mason, Carl; Bodhidatta, Ladaporn; Samie, Amidou; Bessong, Pascal; Barrett, Leah; Lima, Aldo; Havt, Alexandre; Haque, Rashidul; Mondal, Dinesh; Taniuchi, Mami; Stroup, Suzanne; McGrath, Monica; Lang, Dennis

    2014-01-01

    A central hypothesis of The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study is that enteropathogens contribute to growth faltering. To examine this question, the MAL-ED network of investigators set out to achieve 3 goals: (1) develop harmonized protocols to test for a diverse range of enteropathogens, (2) provide quality-assured and comparable results from 8 global sites, and (3) achieve maximum laboratory throughput and minimum cost. This paper describes the rationale for the microbiologic assays chosen and methodologies used to accomplish the 3 goals. PMID:25305291

  13. Microbiologic methods utilized in the MAL-ED cohort study.

    PubMed

    Houpt, Eric; Gratz, Jean; Kosek, Margaret; Zaidi, Anita K M; Qureshi, Shahida; Kang, Gagandeep; Babji, Sudhir; Mason, Carl; Bodhidatta, Ladaporn; Samie, Amidou; Bessong, Pascal; Barrett, Leah; Lima, Aldo; Havt, Alexandre; Haque, Rashidul; Mondal, Dinesh; Taniuchi, Mami; Stroup, Suzanne; McGrath, Monica; Lang, Dennis

    2014-11-01

    A central hypothesis of The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study is that enteropathogens contribute to growth faltering. To examine this question, the MAL-ED network of investigators set out to achieve 3 goals: (1) develop harmonized protocols to test for a diverse range of enteropathogens, (2) provide quality-assured and comparable results from 8 global sites, and (3) achieve maximum laboratory throughput and minimum cost. This paper describes the rationale for the microbiologic assays chosen and methodologies used to accomplish the 3 goals. PMID:25305291

  14. Screening hallucinogenic drugs: systematic study of three behavioral tests.

    PubMed

    Silva, M T; Calil, H M

    1975-05-28

    The effects of several hallucinogenic and non-hallucinogenic drugs have been studied on three behavioral tests proposed as useful indexes of hallucinogenic activity: "head-twitching" in mice, defecation in an open-field, and suppression of responding on a differential reinforcement of low rates (DRL) schedule of reinforcement. According to the original propositions, after administration of hallucinogenic agents the frequency of head-twitches would increase in mice, the defecation of rats in an open field would decrease without consistent change in ambulation, rearing and grooming, and the responding of rats on a DRL schedule would yield a typical cumulative record pattern. It was found that the head-twitch test was sensitive to mescaline and LSD-25, but not to delta9-THC or to myristicin and elemicin. Besides, the data on interobserver agreement suggested there is a high degree of subjectivity involved in assessing this response. In the open-field test, non-hallucinogenic drugs such as chlorpromazine and apomorphine fell into the hallucinogenic pattern proposed. In addition, the post-injection interval selected seemed to critically affect defecation scores. The DRL "hallucinogenic" pattern occurred nonspecifically after administration of hallucinogenic and non-hallucinogenic drugs. It was concluded that the three tests have limited value for screening purposes.

  15. [Ethical problems in utilization of specimens after laboratory examinations for clinical studies].

    PubMed

    Murakami, Masami

    2011-03-01

    Ethical Committee in Japanese Society of Laboratory Medicine published "Opinions of Japanese Society of Laboratory Medicine about utilization of specimens after laboratory examinations for laboratory work, education and clinical studies" in 2002. Ministry of Health, Labour and Welfare in Japan established "Ethical Guidelines for Clinical Studies" in 2003, and amended the document in 2008. According to the guidelines, Ethical Committee in Japanese Society of Laboratory Medicine revised the "Opinions of Japanese Society of Laboratory Medicine about utilization of specimens after laboratory examinations for laboratory work, education and clinical studies" in 2010. Ethical problems in utilization of specimens after laboratory examinations for clinical studies are discussed.

  16. Electric utility system planning studies for OTEC power integration

    NASA Astrophysics Data System (ADS)

    1980-11-01

    The integration of OTEC into the Florida Power Corporation (FTC) system was evaluated. Existing system planning procedures, assumptions, and corporate financial criteria for planning generating capacity were used without modification. A baseline configuration for an OTEC plant was developed for review with standard planning procedures. The OTEC plant characteristics and costs were incorporated in considerable detail. It was found that with the initial set of conditions, OTEC would not be economically viable. Using the same system planning procedures, a number of adjustments were made to the key study assumptions. It was found that two considerations dominate the analysis: the assumed rate of fuel cost escalation, and the projected capital cost of the OTEC plant. After corporate financial analysis, it was found that even if the cost competitive criterion were to be reached, the plan including OTEC could not be financed by FPC.

  17. Task 3 -- Bench-scale char upgrading and utilization study

    SciTech Connect

    Jha, M.C.; McCormick, R.L.

    1989-08-02

    This report describes the results of the bench-scale char upgrading study conducted as Task 3 of Development of an Advanced, Continuous Mild Gasification Process for the Production of Coproducts. A process where the char is gasified to produce methane in a first stage reactor was investigated. This methane is then decomposed to produce carbon and hydrogen for recycle in a second stage. The results indicate that both reaction steps are feasible using mild gasification char as the starting feedstock. Conditions for methanation are 700 to 800 C and 200 to 400 psig. Carbon formation conditions are 1,200 to 1,400 C at atmospheric pressure. The carbon produced has properties similar to those of carbons which are commercially marketed as carbon black.

  18. (Energy related studies utilizing K-feldspar thermochronology)

    SciTech Connect

    Not Available

    1992-01-01

    In our second year of current funding cycle, we have investigated the Ar diffusion properties and microstructures of K-feldspars and the application of domain theory to natural K-feldspars. We completed a combined TEM and argon diffusion study of the effect of laboratory heat treatment on the microstructure and kinetic properties of K-feldspar. We conclude in companion papers that, with one minor exception, no observable change in the diffusion behavior occurs during laboratory extraction procedures until significant fusion occurs at about 1100{degrees}C. The effect that is observed involves a correlation between the homogenization of cryptoperthite lamelle and the apparent increase in retentivity of about 5% of the argon in the K-feldspar under study. We can explain this effect of both as an artifact of the experiment or the loss of a diffusion boundary. Experiments are being considered to resolve this question. Refinements have been made to our experimental protocol that appears that greatly enhance the retrieval of multi-activation energies from K-feldspars. We have applied the multi-domain model to a variety of natural environments (Valles Caldera, Red River fault, Appalachian basin) with some surprising results. Detailed {sup 40}Ar/{sup 39} Ar coverage of the Red River shear zone, thought to be responsible for the accommodation of a significant fraction of the Indo-Asian convergence, strongly suggests that our technique can precisely date both the termination of ductile strike-slip motion and the initiation of normal faulting. Work has continued on improving our numerical codes for calculating thermal histories and the development of computer based graphing tools has significantly increased our productivity.

  19. Utility of imaging for nutritional intervention studies in Alzheimer's disease.

    PubMed

    de Wilde, Martijn C; Kamphuis, Patrick J G H; Sijben, John W C; Scheltens, Phillip

    2011-09-01

    Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder and the leading cause of dementia, wherein synapse loss is the strongest structural correlate with cognitive impairment. Basic research has shown that dietary supply of precursors and co-factors for synthesis of neuronal membranes enhances the formation of synapses. Daily intake of a medical food containing a mix of these nutrients for 12 weeks in humans improved memory, measured as immediate and delayed verbal recall by the Wechsler Memory Scale-revised, in patients with very mild AD (MMSE 24-26). An improvement of immediate verbal recall was noted following 24 weeks of intervention in an exploratory extension of the study. These data suggest that the intervention may improve synaptic formation and function in early AD. Here we review emerging technologies that help identify changes in pathological hallmarks in AD, including synaptic function and loss of connectivity in the early stages of AD, before cognitive and behavioural symptoms are observable. These techniques include the detection of specific biomarkers in the cerebrospinal fluid, as well as imaging procedures such as fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), amyloid PET, structural/functional magnetic resonance imaging, diffusion tensor imaging, magnetoencephalography (MEG) and electroencephalography (EEG). Such techniques can provide new insights into the functional and structural changes in the brain over time, and may therefore help to develop more effective AD therapies. In particular, nutritional intervention studies that target synapse formation and function may benefit from these techniques, especially FDG-PET and EEG/MEG employed in the preclinical or early stages of the disease. PMID:21816137

  20. 75 FR 51806 - Climate Change Vulnerability Assessment: Four Case Studies of Water Utility Practices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... AGENCY Climate Change Vulnerability Assessment: Four Case Studies of Water Utility Practices AGENCY...-day public comment period for the draft document titled, ``Climate Change Vulnerability Assessment... utilities to assess their vulnerability to future climate change. The report is intended to illustrate...

  1. Utilization of novel atom sources in studies of semiconductor surfaces

    NASA Astrophysics Data System (ADS)

    Wolan, John Thaddeus

    Nanometer-scale characterization of semiconductor surfaces is very important for precise control of the ultrafine structures necessary for the realization of devices using quantum confinement. The performance of these heterojunction devices is strongly dependent on interface quality. In the case of III-V semiconductors, the major problem is the presence of the native oxide layer and surface carbon contamination. This carbon is strongly bonded to the III-V surface even after ion-etching and high temperature annealing and induces a free-carrier depletion region at the substrate-epilayer interface. Furthermore, native oxides on GaAs and InP surfaces are detrimental to the formation of stable interfaces and can result in defective epitaxial growth, inducing undesirable electrical characteristics to the device so they must be removed without damaging the near-surface region. A surface characterization study using ion scattering spectroscopy (ISS) and X-ray photoelectron spectroscopy (XPS) has been performed on GaAs(001) and InP(111) substrates before and after cleaning by ion sputtering/annealing cycles and room temperature exposure to the flux produced by a novel atomic hydrogen source based on electron-stimulated desorption (ESD) to determine any treatment-induced alterations. In order to realize high performance III-V circuits, the preparation of a good quality passivating oxide interface is necessary. Device quality oxide-(III-V) interface fabrication will certainly depend on the composition of the oxide interface and any possible damage induced by the oxidation process. In the case of GaAs, thermal oxides and formation of thick oxides (which actually is diffusion-controlled and possibly close to thermal equilibrium) usually results in non-stoichiometric films of Gasb2Osb3 and Assb2Osb3 as well as a pile-up of elemental As at the GaAs-oxide interface. This structure is predicted by the Ga-O-As phase diagram, but it provides poor electrical isolation and surface

  2. Treatment Utility of Postpartum Antibiotics in Chorioamnionitis Study.

    PubMed

    Shanks, Anthony L; Mehra, Suwan; Gross, Gil; Colvin, Ryan; Harper, Lorie M; Tuuli, Methodius G

    2016-07-01

    Objective To determine if postpartum antibiotics are necessary for patients with chorioamnionitis after a cesarean delivery (CD). Study Design Multicenter randomized controlled trial. Laboring patients with singleton gestations and chorioamnionitis who underwent CD were eligible. Patients were treated with ampicillin and gentamicin per standard protocol, then given clindamycin prior to skin incision. Patients were randomized to either postpartum antibiotic prophylaxis or no treatment following delivery. The primary outcome was the rate of endometritis. Assuming a 30% risk of endometritis in patients with chorioamnionitis who undergo CD, 119 patients per arm would be required to detect a 50% decrease in endometritis. Results The trial was stopped for futility following a planned interim analysis after 80 patients were randomized. There was no difference in the rate of the primary outcome between the two groups (9.8 vs. 7.7%, relative risk [RR]: 1.27; 95% confidence interval [CI]: 0.30, 5.31). A meta-analysis comparing post-CD antibiotics versus no treatment did not find a statistically significant difference between the groups (16.7 vs. 12.0%, pooled RR: 1.43; 95% CI: 0.72, 2.84). Conclusion Additional postpartum antibiotics do not decrease the rate of endometritis in patients with chorioamnionitis who undergo CD. The current preoperative antibiotic regimen including clindamycin should remain the standard of care in these patients. PMID:26890440

  3. Coleman Highlands subsurface air utilization study. Final report

    SciTech Connect

    Shapiro, M.D.

    1982-11-15

    An investigation was conducted into the feasibility of using a 1 million square foot developed cave within the Downtown Industrial Park as a heating and cooling source for a proposed residential subdivision on an adjacent vacant tract of land. Both sites are located near the Coleman Highlands neighborhood in the Westport Community of Kansas City, Missouri. Characteristics of the cave and surface sites were studied, as well as potential heating and cooling sources and transfer media. BTU capacity of the cave and demand for the prototype houses was calculated. The preferred system included a water source in the cave, water transfer medium, and water-to-air heat pumps in the individual homes. Analysis of that system showed it would be marginally effective due to the limited heat valve available in the cave and substantial shortfalls of cooling capacity for summertime operation. Estimated system costs appeared to be in an affordable range, but it was felt that those capital costs could be better applied to other energy-conserving measures.

  4. Rapid and facile detection of four date rape drugs in different beverages utilizing proton transfer reaction mass spectrometry (PTR-MS).

    PubMed

    Jürschik, Simone; Agarwal, Bishu; Kassebacher, Thomas; Sulzer, Philipp; Mayhew, Christopher A; Märk, Tilmann D

    2012-09-01

    In this work, we illustrate the application of proton transfer reaction mass spectrometry (PTR-MS) in the field of food and drink safety. We present proof-of-principle measurements of four different drinks (water, tea, red wine and white wine) each spiked separately with four different date rape drugs (chloral hydrate, tricholorethanol, γ-butyrolactone and butanediol). At first, the ideal PTR-MS operating conditions (reduced electric field strength and monitoring the most abundant [fragment] ion) for detection of the drugs were determined utilizing a time-of-flight-based PTR-MS instrument. We then dissolved small quantities of the drugs (below the activation threshold for effects on humans) into the various types of drinks and detected them using a quadrupole-based PTR-MS instrument via two different sampling methods: (1) dynamic headspace sampling and (2) direct liquid injection. Both methods have their advantages and drawbacks. Only with dynamic headspace sampling can rape drug contaminations be detected within a timeframe of seconds, and therefore, this method is the most promising use of PTR-MS as a fast, sensitive and selective monitor for the detection of food and drink contamination. PMID:22972776

  5. A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis

    PubMed Central

    Mears, Emily Rose; Modabber, Farrokh; Don, Robert; Johnson, George E.

    2015-01-01

    The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host–parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major–C57BL/6 mice (or–vervet monkey, or–rhesus monkeys), L. tropica–CsS-16 mice, L. amazonensis–CBA mice, L. braziliensis–golden hamster (or–rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations. PMID:26334763

  6. A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis.

    PubMed

    Mears, Emily Rose; Modabber, Farrokh; Don, Robert; Johnson, George E

    2015-01-01

    The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host-parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major-C57BL/6 mice (or-vervet monkey, or-rhesus monkeys), L. tropica-CsS-16 mice, L. amazonensis-CBA mice, L. braziliensis-golden hamster (or-rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations. PMID:26334763

  7. 75 FR 45641 - Guidance for Industry on Label Comprehension Studies for Nonprescription Drug Products; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Label Comprehension Studies for Nonprescription Drug Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance for...

  8. 76 FR 58018 - Draft Guidance for Industry on Self-Selection Studies for Nonprescription Drug Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-19

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Self-Selection Studies for Nonprescription Drug Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for...

  9. Climate@Home: Utilizing Citizen Science for Climate Studies

    NASA Astrophysics Data System (ADS)

    Liu, K.; Yang, C.; Li, Z.; Sun, M.; Li, J.; Xu, C.

    2013-12-01

    Climate change has become a serious and urgent issue in the past decades (Stern N. 2007). It will influence many domains such as agriculture, economy, ecosystem, and others. To help scientists to simulate the climate change, NASA conducted a project, Climate@Home, to develop a cyberinfrastructure for running the modelE climate model. ModelE contains over 500 variables and needs many days to finish a 10 year analysis task. If scientists need to run 300 tasks, it may need about 3 years to complete the task using a single machine. As an exploratory study, an infrastructure was constructed to recruit citizen volunteers for harvesting computing resources from citizens based on the citizen science mechanism. However, there are challenges in order to build the infrastructure: 1) modelE is a Linux based model but volunteers may have different operating system platforms such as Windows, Apple OSX etc (Anderson et al. 2006); 2) modelE has big downloading file and generates big results file, how to download and upload files efficiently? 3) currently the task schedule uses first-come-fist-get mechanism, how to schedule task efficiently? We address these challenges with several designs: 1) virtual machines are used to package the modelE, an operating system and configured running environments; 2) Building FTPS based on users' spatiotemporal information for data downloading and uploading; 3) crafting the schedule system to grant tasks based on the volunteers spatiotemporal information and computing conditions such as CPU, memory and bandwidth. Key words: Volunteer Computing, Climate Change, Spatiotemporal, References: 1. Anderson, D. P., Christensen, C., & Allen, B. (2006, November). Designing a runtime system for volunteer computing. In SC 2006 Conference, Proceedings of the ACM/IEEE (pp. 33-33). IEEE. 2. Stern, N. N. H. (Ed.). (2007). The economics of climate change: the Stern review. Cambridge University Press.

  10. Turndown studies for utility fluidized-bed boilers. Final report

    SciTech Connect

    Divilio, R.J.; Reed, R.R.

    1984-01-01

    This report contains a series of analyses that evaluate the turndown potential of the EPRI 6 x 6 test facility and the TVA 20 MW FBC pilot plant by variation of the fluidization velocity. The basis of the analyses is a heat balance program that incorporates basic principles of thermodynamics and fluidization. The heat balance program is used to explain the interrelationship of operating variables of a fluidized-bed boiler and to predict the steady state operating conditions of the boilers over a range of loads. Turndown analyses were performed on two tube bundle designs for the EPRI 6 x 6 test unit including a nine drawer tube bundle designed for 8 ft/sec operation and a twelve drawer bundle for operation up to 12 ft/sec. This twelve drawer bundle was found to have reasonable turndown characteristics between 4 and 12 ft/sec. At a 20 inch static bed depth, for example, this bundle should operate between 1545 and 1620/sup 0/F at 3.2% O/sub 2/ for loads from 4 to 12 ft/sec. In addition to the two bundles studies, a tube bundle capable of a 3:1 turndown range with a minimum temperature variation was designed for the 6 x 6 test facility. The tube bundle for the TVA 20 MW pilot plant was found to have excellent turndown characteristics between 4 and 8 ft/sec. For example, a 21 inch static bed should allow operation between 1541 and 1575/sup 0/F bed temperature at 3% O/sub 2/.

  11. In vitro study of simultaneous infusion of incompatible drugs in multilumen catheters.

    PubMed

    Collins, J L; Lutz, R J

    1991-05-01

    Multilumen catheters are commonly used to simultaneously administer incompatible drugs to critically ill patients. Though there are no known documented reports that this practice has been responsible for harmful events in patients, likewise there are no published data to verify the safety and efficacy of this practice. This study utilized an in vitro model flow system to examine the physicochemical phenomena that occur when two incompatible drugs (phenytoin and total parenteral nutrition) are simultaneously administered through multilumen catheters. Flow conditions and drug infusions in the venous model were designed to mimic the in vivo clinical situation to evaluate two central venous catheter types, a double- and a triple-lumen catheter. Video recordings were made of drug interactions, and assays of phenytoin concentration were performed on samples of the circulating fluid. White clouds of phenytoin precipitation were observed near the tip of the double-lumen catheter but not the triple-lumen catheter. Infusion through the double-lumen catheter resulted in an average of 6% loss of phenytoin to precipitate, which, on microscopic examination, appeared as spindle-shaped crystals 25 to 50 microns in length and 5 to 10 microns wide. In some cases, millimeter-size fragments of phenytoin precipitate were seen to dislodge from the tip of the double-lumen catheter. The adjacent orifices at the tip of the end hole of the double-lumen catheter appeared to permit interaction of the two effusing streams of the incompatible drugs, whereas the staggered orifices of the triple-lumen catheter reduce this interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Dental care utilization: a study of 50- to 75-year-olds in southern Sweden.

    PubMed

    Bagewitz, Ingrid Collin; Söderfeldt, Björn; Palmqvist, Sigvard; Nilner, Krister

    2002-01-01

    This study investigates dental care utilization in an adult population in Southern Sweden in relation to dental and social conditions, attitudes to costs, and perceived need to obtain dental services. The study was based on responses to a questionnaire sent in 1998 to a random sample, 1974 persons, aged 56-75 years. The response rate was 66%. A significantly higher probability of dental care utilization less than once a year was found for men, for those with few remaining teeth, and for those with removable dentures. A higher probability of dental care utilization less than once a year was found for those who stated perceived need to obtain dental care with no possibility because of the cost and for those who stated that the cost had influenced their attendance for dental care. The results showed that there were differences for sex and dental conditions in dental care utilization and that dental care utilization was related to attitudes towards costs of dental care.

  13. Antihypertensive drugs for elderly patients: a cross- sectional study

    PubMed Central

    Lim, Ka Keat; Sivasampu, Sheamini; Khoo, Ee Ming

    2015-01-01

    INTRODUCTION As the population ages, the prevalence of hypertension also increases. Although primary care is usually the patient’s first point of contact for healthcare, little is known about the management of hypertension among elderly patients at the primary care level. This study aimed to determine the antihypertensive prescription trend for elderly patients, the predictors of antihypertensive use and any inappropriate prescribing practices in both public and private primary care settings. METHODS Data on patient demographics, diagnosis, prescription pattern, payment mode and follow-up was extracted from a cross-sectional study involving 122 public primary care clinics and 652 private primary care clinics in Malaysia. Encounters with hypertensive patients aged ≥ 60 years were included. RESULTS A total of 1,017 antihypertensive medications were prescribed – calcium channel blockers (27.1%), beta blockers (25.5%), diuretics (23.3%), angiotensin-converting enzyme inhibitors (14.9%) and angiotensin receptor blockers (6.3%). Out of the 614 patient encounters, 53.1% of the patients were prescribed monotherapy, 31.6% were prescribed dual therapy, 12.2% triple therapy, 2.8% quadruple therapy and 0.3% quintuple therapy. Type of primary care clinic and payment mode were significant predictors for the prescription of combination therapy and fixed-dose combination therapy, respectively. Four types of inappropriate prescriptions were identified. CONCLUSION Calcium channel blockers were the most common antihypertensive drug prescribed and more than half of the elderly patients were on monotherapy. Antihypertensive drug prescription was found to be associated with the type of primary care clinic and the payment mode, suggesting that prescription is influenced by the cost of the drug. PMID:25597751

  14. In Silico Augmentation of the Drug Development Pipeline: Examples from the study of Acute Inflammation

    PubMed Central

    An, Gary; Bartels, John; Vodovotz, Yoram

    2011-01-01

    The clinical translation of promising basic biomedical findings, whether derived from reductionist studies in academic laboratories or as the product of extensive high-throughput and –content screens in the biotechnology and pharmaceutical industries, has reached a period of stagnation in which ever higher research and development costs are yielding ever fewer new drugs. Systems biology and computational modeling have been touted as potential avenues by which to break through this logjam. However, few mechanistic computational approaches are utilized in a manner that is fully cognizant of the inherent clinical realities in which the drugs developed through this ostensibly rational process will be ultimately used. In this article, we present a Translational Systems Biology approach to inflammation. This approach is based on the use of mechanistic computational modeling centered on inherent clinical applicability, namely that a unified suite of models can be applied to generate in silico clinical trials, individualized computational models as tools for personalized medicine, and rational drug and device design based on disease mechanism. PMID:21552346

  15. Climate Change Vulnerability Assessments: Four Case Studies of Water Utility Practices (2011 Final)

    EPA Science Inventory

    EPA is releasing the final report titled, Climate Change Vulnerability Assessments: Four Case Studies of Water Utility Practices. This report was prepared by the National Center for Environmental Assessment's Global Climate Research Staff in the Office of Research and Developmen...

  16. Drug Education Based on a Knowledge, Attitude, and Experience Study

    ERIC Educational Resources Information Center

    Grant, John A.

    1971-01-01

    Results of a questionnaire concerning factual knowledge of attitudes toward, and experience with a variety of drugs are reported. It was concluded that marihuana and other drugs are readily available to secondary school students, and widespread experimentation exists; however, a strict dichotomy exists between marihuana and other drugs. (Author/BY)

  17. Drug-Induced Liver Injury Network (DILIN) Prospective Study

    PubMed Central

    Fontana, Robert J.; Watkins, Paul B.; Bonkovsky, Herbert L.; Chalasani, Naga; Davern, Timothy; Serrano, Jose; Rochon, James

    2013-01-01

    Background Drug-induced liver injury (DILI) is an uncommon adverse drug reaction of increasing importance to the medical community, pharmaceutical industry, regulatory agencies and the general public. Objectives The Drug-Induced Liver Injury Network (DILIN) was established to advance understanding and research into DILI by initiating a prospective registry of patients with bona fide DILI for future studies of host clinical, genetic, environmental and immunological risk factors. The DILIN was also charged with developing standardized nomenclature, terminology and causality assessment instruments. Methods Five clinical sites, a data coordinating centre and senior scientists from the National Institute of Diabetes and Digestive and Kidney Diseases initiated the DILIN prospective study in September 2004. Eligible patients are required to meet minimal laboratory or histological criteria within 6 months of DILI onset and have other competing causes of liver injury excluded. Patients in the general community setting with pre-existing HIV, hepatitis B virus or hepatitis C virus infections and/or abnormal baseline liver biochemistries are eligible for enrolment. In addition, subjects with liver injury due to herbal products are eligible to participate. Control patients without DILI are also to be recruited in the future. Results All referred subjects undergo an extensive review of available laboratory, pathology and imaging studies. Subjects who meet pre-defined eligibility criteria at the 6-month study visit are followed for 2 years to better define the natural history of chronic DILI. Causality assessment is determined by a panel of three hepatologists who independently assign a causality score ranging from 1 (definite) to 5 (unlikely) as well as a severity score ranging from 1 (mild) to 5 (fatal). During the first 3 years, 367 subjects were enrolled into the DILIN prospective study. Conclusion DILIN is a multicentre research network charged with improving our

  18. Open Source Drug Discovery in Practice: A Case Study

    PubMed Central

    Årdal, Christine; Røttingen, John-Arne

    2012-01-01

    Background Open source drug discovery offers potential for developing new and inexpensive drugs to combat diseases that disproportionally affect the poor. The concept borrows two principle aspects from open source computing (i.e., collaboration and open access) and applies them to pharmaceutical innovation. By opening a project to external contributors, its research capacity may increase significantly. To date there are only a handful of open source R&D projects focusing on neglected diseases. We wanted to learn from these first movers, their successes and failures, in order to generate a better understanding of how a much-discussed theoretical concept works in practice and may be implemented. Methodology/Principal Findings A descriptive case study was performed, evaluating two specific R&D projects focused on neglected diseases. CSIR Team India Consortium's Open Source Drug Discovery project (CSIR OSDD) and The Synaptic Leap's Schistosomiasis project (TSLS). Data were gathered from four sources: interviews of participating members (n = 14), a survey of potential members (n = 61), an analysis of the websites and a literature review. Both cases have made significant achievements; however, they have done so in very different ways. CSIR OSDD encourages international collaboration, but its process facilitates contributions from mostly Indian researchers and students. Its processes are formal with each task being reviewed by a mentor (almost always offline) before a result is made public. TSLS, on the other hand, has attracted contributors internationally, albeit significantly fewer than CSIR OSDD. Both have obtained funding used to pay for access to facilities, physical resources and, at times, labor costs. TSLS releases its results into the public domain, whereas CSIR OSDD asserts ownership over its results. Conclusions/Significance Technically TSLS is an open source project, whereas CSIR OSDD is a crowdsourced project. However, both have enabled high quality

  19. Directional reflectance analysis for identifying counterfeit drugs: Preliminary study.

    PubMed

    Wilczyński, Sławomir; Koprowski, Robert; Błońska-Fajfrowska, Barbara

    2016-05-30

    The WHO estimates that up to 10% of drugs on the market may be counterfeit. In order to prevent intensification of the phenomenon of drug counterfeiting, the methods for distinguishing genuine medicines from fake ones need to be developed. The aim of this study was to try to develop simple, reproducible and inexpensive method for distinguishing between original and counterfeit medicines based on the measurement of directional reflectance. The directional reflectance of 6 original Viagra(®) tablets (Pfizer) and 24 (4 different batches) counterfeit tablets (imitating Viagra(®)) was examined in six spectral bands: from 0.9 to 1.1 μm, from 1.9 to 2.6 μm, from 3.0 to 4.0 μm, from 3.0 to 5.0 μm, from 4.0 to 5.0 μm, from 8.0 to 12.0 μm, and for two angles of incidence, 20° and 60°. Directional hemispherical reflectometer was applied to measure directional reflectance. Significant statistical differences between the directional reflectance of the original Viagra(®) and counterfeit tablets were registered. Any difference in the value of directional reflectance for any spectral band or angle of incidence identifies the drug as a fake one. The proposed method of directional reflectance analysis enables to differentiate between the real Viagra(®) and fake tablets. Directional reflectance analysis is a fast (measurement time under 5s), cheap and reproducible method which does not require expensive equipment or specialized laboratory staff. It also seems to be an effective method, however, the effectiveness will be assessed after the extension of research. PMID:26977587

  20. From Abstinence to Relapse: A Preliminary Qualitative Study of Drug Users in a Compulsory Drug Rehabilitation Center in Changsha, China

    PubMed Central

    Yang, Mei; Mamy, Jules; Gao, Pengcheng; Xiao, Shuiyuan

    2015-01-01

    Background Relapse among abstinent drug users is normal. Several factors are related to relapse, but it remains unclear what individuals’ actual life circumstances are during periods of abstinence, and how these circumstances facilitate or prevent relapse. Objective To illuminate drug users’ experiences during abstinence periods and explore the real-life catalysts and inhibitors contributing to drug use relapse. Method Qualitative in-depth interviews were conducted with 20 drug users recruited from a compulsory isolated drug rehabilitation center in Changsha. The interviews were guided by open-ended questions on individuals’ experiences in drug use initiation, getting addicted, treatment history, social environment, abstinence, and relapse. Participants were also encouraged to share their own stories. Interviews were digitally recorded and fully transcribed. The data of 18 participants who reported abstinence experiences before admission were included in the analyses. The data were analyzed using a thematic analysis with inductive hand coding to derive themes. Results Most drug users were able to successfully abstain from drugs. During abstinence, their lives were congested with challenges, such as adverse socioeconomic conditions, poor family/social support, interpersonal conflicts, and stigma and discrimination, all of which kept them excluded from mainstream society. Furthermore, the police’s system of ID card registration, which identifies individuals as drug users, worsened already grave situations. Relapse triggers reported by the participants focused mainly on negative feelings, interpersonal conflicts, and stressful events. Craving was experienced but not perceived as a relapse trigger by most participants. Conclusions This study of in-depth interview with drug users found evidence of situations and environments they live during abstinence appear rather disadvantaged, making it extremely difficult for them to remain abstinent. Comprehensive programs

  1. Epoetin alfa and darbepoetin alfa for the treatment of chemotherapy-related anemia in cancer patients in Sweden: comparative analysis of drug utilization, costs, and hematologic response.

    PubMed

    Persson, Ulf; Borg, Sixten; Jansson, Sandra; Ekman, Tor; Franksson, Lars; Friesland, Signe; Larsson, Anna-Maria

    2005-01-01

    A retrospective chart review was performed at 3 Swedish hospitals to evaluate the utilization, outcomes, and cost of using epoetin alfa or darbepoetin alfa to treat cancer patients with chemotherapy-related anemia. Data on dosage, duration of treatment, hematologic response, red blood cell transfusions, and healthcare resource consumption were collected and analyzed at various time points following the initiation of drug therapy. A significantly faster hematologic response and increase in hemoglobin were observed in patients treated with epoetin alfa. Dosages used in clinical practice appeared to be lower than those recommended by Swedish treatment guidelines. There were no significant differences in resource utilization or healthcare costs between the 2 treatment groups. By day 112, the mean treatment cost per patient, in Swedish kronors (SEK), was SEK74,701 (approximately US$9800 or approximately 8300) with epoetin alfa and SEK85,285 (approximately US$11,000 or approximately 9500) with darbepoetin alfa. Drug acquisition and administration accounted for 81% and 67% of the total cost of epoetin alfa and darbepoetin alfa therapy, respectively; the remainder of the total cost was for hospitalization and transfusions.

  2. Functionalized mesoporous materials for adsorption and release of different drug molecules: A comparative study

    SciTech Connect

    Wang Gang; Otuonye, Amy N.; Blair, Elizabeth A.; Denton, Kelley; Tao Zhimin; Asefa, Tewodros

    2009-07-15

    The adsorption capacity and release properties of mesoporous materials for drug molecules can be improved by functionalizing their surfaces with judiciously chosen organic groups. Functionalized ordered mesoporous materials containing various types of organic groups via a co-condensation synthetic method from 15% organosilane and by post-grafting organosilanes onto a pre-made mesoporous silica were synthesized. Comparative studies of their adsorption and release properties for various model drug molecules were then conducted. Functional groups including 3-aminopropyl, 3-mercaptopropyl, vinyl, and secondary amine groups were used to functionalize the mesoporous materials while rhodamine 6G and ibuprofen were utilized to investigate the materials' relative adsorption and release properties. The self-assembly of the mesoporous materials was carried out in the presence of cetyltrimethylammonium bromide (CTAB) surfactant, which produced MCM-41 type materials with pore diameters of {approx}2.7-3.3 nm and moderate to high surface areas up to {approx}1000 m{sup 2}/g. The different functional groups introduced into the materials dictated their adsorption capacity and release properties. While mercaptopropyl and vinyl functionalized samples showed high adsorption capacity for rhodamine 6G, amine functionalized samples exhibited higher adsorption capacity for ibuprofen. While the diffusional release of ibuprofen was fitted on the Fickian diffusion model, the release of rhodamine 6G followed Super Case-II transport model. - Graphical abstract: The adsorption capacity and release properties of mesoporous materials for various drug molecules are tuned by functionalizing the surfaces of the materials with judiciously chosen organic groups. This work reports comparative studies of the adsorption and release properties of functionalized ordered mesoporous materials containing different hydrophobic and hydrophilic groups that are synthesized via a co-condensation and post

  3. Utility of a thematic network in primary health care: a controlled interventional study in a rural area

    PubMed Central

    Coma del Corral, Maria Jesús; Abaigar Luquín, Pedro; Cordero Guevara, José; Olea Movilla, Angel; Torres Torres, Gerardo; Lozano Garcia, Javier

    2005-01-01

    Background UniNet is an Internet-based thematic network for a virtual community of users (VCU). It supports a virtual multidisciplinary community for physicians, focused on the improvement of clinical practice. This is a study of the effects of a thematic network such as UniNet on primary care medicine in a rural area, specifically as a platform of communication between specialists at the hospital and doctors in the rural area. Methods In order to study the effects of a thematic network such as UniNet on primary care medicine in a rural area, we designed an interventional study that included a control group. The measurements included the number of patient displacements due to disease, number of patient hospital stays and the number of prescriptions of drugs of low therapeutic utility and generic drug prescriptions by doctors. These data were analysed and compared with those of the control center. Results Our study showed positive changes in medical practice, reflected in the improvement of the evaluated parameters in the rural health area where the interventional study was carried out, compared with the control area. We discuss the strengths and weaknesses of UniNet as a potential medium to improve the quality of medical care in rural areas. Conclusion The rural doctors had an effective, useful, user-friendly and cheap source of medical information that may have contributed to the improvement observed in the medical quality indices. PMID:16042778

  4. Determination of Critical Parameters of Drug Substance Influencing Dissolution: A Case Study

    PubMed Central

    Bojnanska, Erika; Kalina, Michal; Bartonickova, Eva; Opravil, Tomas; Vesely, Michal; Pekar, Miloslav

    2014-01-01

    The purpose of this study was to specify critical parameters (physicochemical characteristics) of drug substance that can affect dissolution profile/dissolution rate of the final drug product manufactured by validated procedure from various batches of the same drug substance received from different suppliers. The target was to design a sufficiently robust drug substance specification allowing to obtain a satisfactory drug product. For this reason, five batches of the drug substance and five samples of the final peroral drug products were analysed with the use of solid state analysis methods on the bulk level. Besides polymorphism, particle size distribution, surface area, zeta potential, and water content were identified as important parameters, and the zeta potential and the particle size distribution of the drug substance seem to be critical quality attributes affecting the dissolution rate of the drug substance released from the final peroral drug formulation. PMID:25317424

  5. The Michigan regulatory incentives study for electric utilities. Phase 1, Final report

    SciTech Connect

    Reid, M.W.; Weaver, E.M.

    1991-06-17

    This is the final report of Phase I of the Michigan Regulatory Incentives Study for Electric Utilities, a three-phase review of Michigan`s regulatory system and its effects on resource selection by electric utilities. The goal of Phase I is to identify and analyze financial incentive mechanisms that encourage selection of resources in accord with the principles of integrated resource planning (IRP) or least-cost planning (LCP). Subsequent study phases will involve further analysis of options and possibly a collaborative formal effort to propose regulatory changes. The Phase I analysis proceeded in three steps: (1) identification and review of existing regulatory practices that affect utilities; selection of resources, particularly DSM; (2) preliminary analysis of ten financial mechanisms, and selection of three for further study; (3) detailed analysis of the three mechanisms, including consideration of how they could be implemented in Michigan and financial modeling of their likely impacts on utilities and ratepayers.

  6. A New Screen for Tuberculosis Drug Candidates Utilizing a Luciferase-Expressing Recombinant Mycobacterium bovis Bacillus Calmette-Guéren

    PubMed Central

    Igarashi, Masayuki; Doe, Matsumi; Tamaru, Aki; Kinoshita, Naoko; Ogura, Yoshitoshi; Iwamoto, Tomotada; Sawa, Ryuichi; Umekita, Maya; Enany, Shymaa; Nishiuchi, Yukiko; Osada-Oka, Mayuko; Hayashi, Tetsuya; Niki, Mamiko; Tateishi, Yoshitaka; Hatano, Masaki

    2015-01-01

    Tuberculosis (TB) is a serious infectious disease caused by a bacterial pathogen. Mortality from tuberculosis was estimated at 1.5 million deaths worldwide in 2013. Development of new TB drugs is needed to not only to shorten the medication period but also to treat multi-drug resistant and extensively drug-resistant TB. Mycobacterium tuberculosis (Mtb) grows slowly and only multiplies once or twice per day. Therefore, conventional drug screening takes more than 3 weeks. Additionally, a biosafety level-3 (BSL-3) facility is required. Thus, we developed a new screening method to identify TB drug candidates by utilizing luciferase-expressing recombinant Mycobacterium bovis bacillus Calmette-Guéren (rBCG). Using this method, we identified several candidates in 4 days in a non-BSL-3 facility. We screened 10,080 individual crude extracts derived from Actinomyces and Streptomyces and identified 137 extracts which possessed suppressive activity to the luciferase of rBCG. Among them, 41 compounds inhibited the growth of both Mtb H37Rv and the extensively drug-resistant Mtb (XDR-Mtb) strains. We purified the active substance of the 1904–1 extract, which possessed strong activity toward rBCG, Mtb H37Rv, and XDR-Mtb but was harmless to the host eukaryotic cells. The MIC of this substance was 0.13 μg/ml, 0.5 μg/ml, and 2.0–7.5 μg/ml against rBCG, H37Rv, and 2 XDR-strains, respectively. Its efficacy was specific to acid-fast bacterium except for the Mycobacterium avium intracellular complex. Mass spectrometry and nuclear magnetic resonance analyses revealed that the active substance of 1904–1 was cyclomarin A. To confirm the mode of action of the 1904-1-derived compound, resistant BCG clones were used. Whole genome DNA sequence analysis showed that these clones contained a mutation in the clpc gene which encodes caseinolytic protein, an essential component of an ATP-dependent proteinase, and the likely target of the active substance of 1904–1. Our method provides a

  7. Assessment of Social Media Utilization and Study Habit of Students of Tertiary Institutions in Katsina State

    ERIC Educational Resources Information Center

    Olutola, Adekunle Thomas; Olatoye, Olufunke Omotoke; Olatoye, Rafiu Ademola

    2016-01-01

    This study investigated assessment of social media utilization and study habits of students of tertiary institutions in Katsina State. The descriptive survey design was adopted for this study. Three hundred and eighty-one (381) students' of tertiary institutions in Katsina State were randomly selected for the study. Researchers'-designed…

  8. Predicting Heavy Drug Use. Results of a Longitudinal Study, Youth Characteristics Describing and Predicting Heavy Drug Use by Adults

    ERIC Educational Resources Information Center

    Schildhaus, Sam; Shaw-Taylor, Yoku; Pedlow, Steven; Pergamit, Michael R.

    2004-01-01

    The primary aim of this study was to describe the movement of adolescents and young adults into and out of drug use and to predict heavy drug use. The data source is the Department of Labor's National Longitudinal Survey of Youth, which began in 1979 with a sample of 12,686 adolescents aged 14-21. After 17 rounds and 19 years, the response rate in…

  9. Interpreting the clinical utility of a pharmacogenomic marker based on observational association studies.

    PubMed

    Sorich, M J; Coory, M

    2014-02-01

    It is increasingly recognized that the clinical utility of a pharmacogenomic marker is a fundamental characteristic influencing the likelihood of successful clinical translation. Although appropriately designed and executed randomized controlled trials generally provide the most valid evidence for the clinical utility of a pharmacogenomic marker, such evidence may not always be available. Observational pharmacogenomic association studies are a common form of evidence available, but the assessment of clinical utility based on such evidence is often not straightforward. This paper aims to provide insight into this issue using a range of illustrative examples.

  10. Leadership skills for the California electric utility industry: A qualitative study

    NASA Astrophysics Data System (ADS)

    Hubbell, Michael

    The purpose of this qualitative study was to determine the skills and knowledge necessary for leaders in the California electric utility industry in 2020. With rapid industry changes, skills to effectively lead and stay competitive are undetermined. Leaders must manage an increasingly hostile social and political environment, incorporate new technology, and deal with an aging workforce and infrastructure. Methodology. This study utilized a qualitative case study design to determine the factors that influence the skills leaders will require in 2020. It incorporated the perspectives of current electric utility leaders while looking with a future lens. Findings. Interviews were conducted with transmission and distribution (T&D) directors at 3 investor-owned public electric utilities headquartered in California. The questions followed an open-ended format to gather responses as perceived by electric utility leaders for each research question category: overall skills, aging workforce, regulation, technology, and leading younger generations. The research resulted in 18 major themes: 5 for overall skills, 3 for aging workforce, 4 for regulation, 3 for technology, and 3 for leading younger generations. Conclusions. The study identified leadership skills including the ability to embrace, leverage, and stay current with technology; understand and provide a clear vision for the future; increase creativity; manage the next set of workers; motivate during a time of great change; prepare for knowledge transfer and change in workforce culture; manage regulatory expectations; expand potential utility opportunities; leverage "big data"; allow worker collaboration; and understand what drives younger generations. Recommendations. California-based electric utility leaders can remain effective by implementing key strategies identified herein. Further research could examine perspectives of additional utility leaders who lead in organizational units outside of T&D, expand the research to

  11. Transdermal film-loaded finasteride microplates to enhance drug skin permeation: Two-step optimization study.

    PubMed

    Ahmed, Tarek A; El-Say, Khalid M

    2016-06-10

    The goal was to develop an optimized transdermal finasteride (FNS) film loaded with drug microplates (MIC), utilizing two-step optimization, to decrease the dosing schedule and inconsistency in gastrointestinal absorption. First; 3-level factorial design was implemented to prepare optimized FNS-MIC of minimum particle size. Second; Box-Behnken design matrix was used to develop optimized transdermal FNS-MIC film. Interaction among MIC components was studied using physicochemical characterization tools. Film components namely; hydroxypropyl methyl cellulose (X1), dimethyl sulfoxide (X2) and propylene glycol (X3) were optimized for their effects on the film thickness (Y1) and elongation percent (Y2), and for FNS steady state flux (Y3), permeability coefficient (Y4), and diffusion coefficient (Y5) following ex-vivo permeation through the rat skin. Morphological study of the optimized MIC and transdermal film was also investigated. Results revealed that stabilizer concentration and anti-solvent percent were significantly affecting MIC formulation. Optimized FNS-MIC of particle size 0.93μm was successfully prepared in which there was no interaction observed among their components. An enhancement in the aqueous solubility of FNS-MIC by more than 23% was achieved. All the studied variables, most of their interaction and quadratic effects were significantly affecting the studied variables (Y1-Y5). Morphological observation illustrated non-spherical, short rods, flakes like small plates that were homogeneously distributed in the optimized transdermal film. Ex-vivo study showed enhanced FNS permeation from film loaded MIC when compared to that contains pure drug. So, MIC is a successful technique to enhance aqueous solubility and skin permeation of poor water soluble drug especially when loaded into transdermal films.

  12. Husbands' involvement in delivery care utilization in rural Bangladesh: A qualitative study

    PubMed Central

    2012-01-01

    Background A primary cause of high maternal mortality in Bangladesh is lack of access to professional delivery care. Examining the role of the family, particularly the husband, during pregnancy and childbirth is important to understanding women's access to and utilization of professional maternal health services that can prevent maternal mortality. This qualitative study examines husbands' involvement during childbirth and professional delivery care utilization in a rural sub-district of Netrokona district, Bangladesh. Methods Using purposive sampling, ten households utilizing a skilled attendant during the birth of the youngest child were selected and matched with ten households utilizing an untrained traditional birth attendant, or dhatri. Households were selected based on a set of inclusion criteria, such as approximate household income, ethnicity, and distance to the nearest hospital. Twenty semi-structured interviews were conducted in Bangla with husbands in these households in June 2010. Interviews were transcribed, translated into English, and analyzed using NVivo 9.0. Results By purposefully selecting households that differed on the type of provider utilized during delivery, common themes--high costs, poor transportation, and long distances to health facilities--were eliminated as sufficient barriers to the utilization of professional delivery care. Divergent themes, namely husbands' social support and perceived social norms, were identified as underlying factors associated with delivery care utilization. We found that husbands whose wives utilized professional delivery care provided emotional, instrumental and informational support to their wives during delivery and believed that medical intervention was necessary. By contrast, husbands whose wives utilized an untrained dhatri at home were uninvolved during delivery and believed childbirth should take place at home according to local traditions. Conclusions This study provides novel evidence about male

  13. Study the efficacy of neuroprotective drugs on brain physiological properties during focal head injury using optical spectroscopy data analysis

    NASA Astrophysics Data System (ADS)

    Abookasis, David; Shochat, Ariel

    2016-03-01

    We present a comparative evaluation of five different neuroprotective drugs in the early phase following focal traumatic brain injury (TBI) in mouse intact head. The effectiveness of these drugs in terms of changes in brain tissue morphology and hemodynamic properties was experimentally evaluated through analysis of the optical absorption coefficient and spectral reduced scattering parameters in the range of 650-1000 nm. Anesthetized male mice (n=50 and n=10 control) were subjected to weight drop model mimics real life focal head trauma. Monitoring the effect of injury and neuroprotective drugs was obtained by using a diffuse reflectance spectroscopy system utilizing independent source-detector separation and location. Result indicates that administration of minocycline improve hemodynamic and reduced the level of tissue injury at an early phase post-injury while hypertonic saline treatment decrease brain water content. These findings highlight the heterogeneity between neuroprotective drugs and the ongoing controversy among researchers regarding which drug therapy is preferred for treatment of TBI. On the other hand, our results show the capability of optical spectroscopy technique to noninvasively study brain function following injury and drug therapy.

  14. Research influence on antimalarial drug policy change in Tanzania: case study of replacing chloroquine with sulfadoxine-pyrimethamine as the first-line drug

    PubMed Central

    Mubyazi, Godfrey M; Gonzalez-Block, Miguel A

    2005-01-01

    , the need for a more effective drug was indispensable but for an interim 5–10 year period it was justifiable to recommend SP that was relatively more cost-effective than CQ and AQ. The government launched the policy change considering that studies (ethically approved by the Ministry of Health) on therapeutic efficacy and cost-effectiveness of artemisinin drug combination therapies were underway. Nevertheless, the process of communicating research results and recommendations to policy-making authorities involved critical debates between policy makers and researchers, among the researchers themselves and between the researchers and general practitioners, the speculative media reports on SP side-effects and reservations by the general public concerning the rationale for policy change, when to change, and to which drug of choice. Conclusion Changing national drug policy will remain a sensitive issue that cannot be done overnight. However, to ensure that research findings are recognised and the recommendations emanating from such findings are effectively utilized, a systematic involvement of all the key stakeholders (including policy-makers, drug manufacturers, media, practitioners and the general public) at all stages of research is crucial. It also matters how and when research information is communicated to the stakeholders. Professional organizations such as the East African Network on Malaria Treatment have potential to bring together malaria researchers, policy-makers and other stakeholders in the research-to-drug policy change interface. PMID:16242017

  15. Online Availability and Safety of Drugs in Shortage: A Descriptive Study of Internet Vendor Characteristics

    PubMed Central

    Mackey, Tim K

    2012-01-01

    Background Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. Objective To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. Methods We performed a descriptive study of the prevalence of online marketing for shortage drugs—that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Results Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. Conclusions FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing. PMID:22321731

  16. Stem cell models for drug discovery and toxicology studies.

    PubMed

    Liu, Wenwei; Deng, Yaguang; Liu, Ying; Gong, Wenrong; Deng, Wenbin

    2013-01-01

    Human stem cells and their derivatives could provide virtually unlimited sources of tissue for a wide range of toxicity models that could complement conventional animal models with more relevant, humanized versions. Human embryonic stem cells (hESCs) have already been proven valuable for drug/toxicity screens and mechanistic studies including analysis of disease pathway and developmental toxicity. Human-induced pluripotent stem cells (iPSCs), which are generated by reprogramming somatic cells back to become hESC-like cells, allow assays to be designed where the contribution of an individual's genetic background or environmental exposure history to toxicity response can be determined. Comprehensive profiling of hESC/iPSCs via genomics, proteomics, transcriptomics, and metabolomics could be used to elucidate pathway perturbations that underlie toxicity and disease, enabling the development of predictive assays for toxicity. While technological hurdles still exist for widespread use and implementation, incorporation of human stem cell based assays into drug discovery and toxicity testing offers the potential for safer, more customized medicines and more accurate risk assessment for environmental toxicants, as well as reduced costs and decreased use of animal models. We examine limitations and deficiencies of current toxicology approaches and how human stem cell based in vitro assays may overcome them. We describe how human stem cells are used for predictive toxicology. We also identify technological limitations that prevent stem cells from being integrated into standard practice, as well as new tools and technologies that may overcome them. We discuss research priorities that are most useful for transforming cell-based toxicology models into reality, and research areas in which stem cell technology could make substantial contributions to the development and implementation of stem cell based models for toxicity testing. Increased use of human in vitro models of

  17. [Multicenter study on the use of drugs during pregnancy in Spain (II). Drugs used during pregnancy. Spain DUP workshop].

    PubMed

    1991-01-12

    A structured questionnaire administered to the 1,371 participating women was used for data collection on drug use in the multicentric study on Drug Use during Pregnancy in Spain. This paper describes and discusses the pattern of the use of medicines during pregnancy. Only 104 women (7%) stated that they had not taken any drug during their pregnancy, while 627 (45%) had taken 3 or more medicines; 39% of all medicines used were fixed-dose combinations of two or more drugs, the mean number of these taken by the participating women being 8.9. The most frequent reason for taking medicines during pregnancy was vitamin supplementation (823 women, 60%), and out of the 1,119 medicines taken to this end, 443 (30%) contained vitamin A. Other reasons for using medicines were the treatment of anaemia (497, 36%), dispepsia (235, 17%), nausea and/or vomiting (204, 14%), colds, pain, urinary tract infections, headache, and genital infections.

  18. Financial Analysis of Incentive Mechanisms to Promote Energy Efficiency: Case Study of a Prototypical Southwest Utility

    SciTech Connect

    Cappers, Peter; Goldman, Charles; Chait, Michele; Edgar, George; Schlegel, Jeff; Shirley, Wayne

    2009-03-04

    Many state regulatory commissions and policymakers want utilities to aggressively pursue energy efficiency as a strategy to mitigate demand and energy growth, diversify the resource mix, and provide an alternative to building new, costly generation. However, as the National Action Plan for Energy Efficiency (NAPEE 2007) points out, many utilities continue to shy away from aggressively expanding their energy efficiency efforts when their shareholder's fundamental financial interests are placed at risk by doing so. Thus, there is increased interest in developing effective ratemaking and policy approaches that address utility disincentives to pursue energy efficiency or lack of incentives for more aggressive energy efficiency efforts. New regulatory initiatives to promote increased utility energy efficiency efforts also affect the interests of consumers. Ratepayers and their advocates are concerned with issues of fairness, impacts on rates, and total consumer costs. From the perspective of energy efficiency advocates, the quid pro quo for utility shareholder incentives is the obligation to acquire all, or nearly all, achievable cost-effective energy efficiency. A key issue for state regulators and policymakers is how to maximize the cost-effective energy efficiency savings attained while achieving an equitable sharing of benefits, costs and risks among the various stakeholders. In this study, we modeled a prototypical vertically-integrated electric investor-owned utility in the southwestern US that is considering implementing several energy efficiency portfolios. We analyze the impact of these energy efficiency portfolios on utility shareholders and ratepayers as well as the incremental effect on each party when lost fixed cost recovery and/or utility shareholder incentive mechanisms are implemented. A primary goal of our quantitative modeling is to provide regulators and policymakers with an analytic framework and tools that assess the financial impacts of

  19. Taste Masked Orally Disintegrating Pellets of Antihistaminic and Mucolytic Drug: Formulation, Characterization, and In Vivo Studies in Human.

    PubMed

    Taj, Yasmeen; Pai, Roopa S; Kusum Devi, V; Singh, Gurinder

    2014-01-01

    The main aim of the present study was to evaluate the potential of orally disintegrating pellets (ODPs) as an approach for taste masking of bitter drugs, namely, Ambroxol hydrochloride (A-HCl) and Cetirizine dihydrochloride (C-DHCl). Pellets were prepared by extrusion/spheronization with Eudragit EPO, kyron T-134, Kyron T-314, mannitol, sorbitol, MCC (Avicel PH-101), sucralose, chocolate flavor, and 5% xanthum gum. The prepared pellets were characterized for percentage yield, drug content, particle size, in vitro drug release, and in vivo evaluation on humans for taste, mouth feel, and in vivo disintegration time. The results revealed that the average size of pellets was influenced greatly by the percentage of binder and extrusion speed. The optimized ODPs disintegrated in less than 20 s and showed more than 98% of drugs in ODPs dissolved within 15 min. Taste perception study was carried out on human volunteers to evaluate the taste masking ability of ODPs for taste, mouth feel, and in vivo disintegration time. Crystalline state evaluation of drugs in the optimized ODPs was conducted for X-ray powder diffraction. In conclusion, the study confirmed that ODPs can be utilized as an alternative approach for effective taste masking and rapid disintegration in the oral cavity.

  20. Taste Masked Orally Disintegrating Pellets of Antihistaminic and Mucolytic Drug: Formulation, Characterization, and In Vivo Studies in Human

    PubMed Central

    Taj, Yasmeen; Pai, Roopa S.; Kusum Devi, V.; Singh, Gurinder

    2014-01-01

    The main aim of the present study was to evaluate the potential of orally disintegrating pellets (ODPs) as an approach for taste masking of bitter drugs, namely, Ambroxol hydrochloride (A-HCl) and Cetirizine dihydrochloride (C-DHCl). Pellets were prepared by extrusion/spheronization with Eudragit EPO, kyron T-134, Kyron T-314, mannitol, sorbitol, MCC (Avicel PH-101), sucralose, chocolate flavor, and 5% xanthum gum. The prepared pellets were characterized for percentage yield, drug content, particle size, in vitro drug release, and in vivo evaluation on humans for taste, mouth feel, and in vivo disintegration time. The results revealed that the average size of pellets was influenced greatly by the percentage of binder and extrusion speed. The optimized ODPs disintegrated in less than 20 s and showed more than 98% of drugs in ODPs dissolved within 15 min. Taste perception study was carried out on human volunteers to evaluate the taste masking ability of ODPs for taste, mouth feel, and in vivo disintegration time. Crystalline state evaluation of drugs in the optimized ODPs was conducted for X-ray powder diffraction. In conclusion, the study confirmed that ODPs can be utilized as an alternative approach for effective taste masking and rapid disintegration in the oral cavity. PMID:27379290

  1. Taste Masked Orally Disintegrating Pellets of Antihistaminic and Mucolytic Drug: Formulation, Characterization, and In Vivo Studies in Human.

    PubMed

    Taj, Yasmeen; Pai, Roopa S; Kusum Devi, V; Singh, Gurinder

    2014-01-01

    The main aim of the present study was to evaluate the potential of orally disintegrating pellets (ODPs) as an approach for taste masking of bitter drugs, namely, Ambroxol hydrochloride (A-HCl) and Cetirizine dihydrochloride (C-DHCl). Pellets were prepared by extrusion/spheronization with Eudragit EPO, kyron T-134, Kyron T-314, mannitol, sorbitol, MCC (Avicel PH-101), sucralose, chocolate flavor, and 5% xanthum gum. The prepared pellets were characterized for percentage yield, drug content, particle size, in vitro drug release, and in vivo evaluation on humans for taste, mouth feel, and in vivo disintegration time. The results revealed that the average size of pellets was influenced greatly by the percentage of binder and extrusion speed. The optimized ODPs disintegrated in less than 20 s and showed more than 98% of drugs in ODPs dissolved within 15 min. Taste perception study was carried out on human volunteers to evaluate the taste masking ability of ODPs for taste, mouth feel, and in vivo disintegration time. Crystalline state evaluation of drugs in the optimized ODPs was conducted for X-ray powder diffraction. In conclusion, the study confirmed that ODPs can be utilized as an alternative approach for effective taste masking and rapid disintegration in the oral cavity. PMID:27379290

  2. A Study of Thermal Analyses and Fundamental Combustion Characteristics for Thermal Utility with Biomass Volatile Matter

    NASA Astrophysics Data System (ADS)

    Ida, Tamio; Namba, Kunihiko; Sano, Hiroshi

    Based on un-use biomass utilities, Carbonized technology is noticed as material utilities and solid fuel. Therefore, this technology is tackling by national project as large-scale utilities. But, this technology is dehydrated volatiles matter during carbonized from biomass. Especially, Woody tar into one of volatile matter has vicious handling to get into trouble in carbonized equipment. In this study, we propose to get fundamental knowledge for effective thermal utility through thermal decompositions and fundamental combustion properties on experimental results. Woody tar has high caloric value (approximately 30MJ/kg) and high carbon ration. On the other hand, a woody vinegar liquid has thermal decomposition property close to water property with heat absorption as evaporation latent heat of water. In fundamental combustion experimental result, a woody tar has fl ammable combustion and surface combustion. Especially, a total combustion and ignition time properties has hyperbola relation to environment temperatures in furnace.

  3. Vehicle Systems and Excipients Used in Minipig Drug Development Studies.

    PubMed

    Weaver, Margaret L; Grossi, Anette Blak; Schützsack, Jorgen; Parish, Joanna; Løgsted, Jeanet; Bøgh, Ingrid Brück; Cameron, David; Harvey, Warren; Festag, Matthias; Downes, Noel; Venturella, Silvana; Schlichtiger, Julia; Mhedhbi, Sofiene; Ross, Vanessa; Kissner, Thomas; Stark, Claudia; Milano, Stephane; Heining, Peter; Sanchez-Felix, Manual

    2016-04-01

    Minipigs have been used for dermal drug development studies for decades, and they are currently more frequently considered as the second nonrodent species for pivotal nonclinical studies, in lieu of the dog or nonhuman primate, for compounds delivered via standard systemic routes of administration. Little is known about the tolerability of different excipients in minipigs; sharing knowledge of excipient tolerability and compositions previously used in nonclinical studies may avoid testing of inadequate formulations, thereby contributing to reduced animal usage. This article reviews vehicles employed in the Göttingen(®)minipig based on the combined experience from a number of pharmaceutical companies and contract research organizations. The review includes vehicles tolerated for single or multiple dosing by the Göttingen minipig, some of which are not appropriate for administration to other common nonrodent species (e.g., dogs). By presenting these data for dermal, oral, subcutaneous, and intravenous routes of administration, studies to qualify these vehicles in minipigs can be minimized or avoided. Additionally, investigators may more frequently consider using the minipig in place of higher species if the tolerability of a vehicle in the minipig is known. PMID:26674803

  4. A case-comparison study of automatic document classification utilizing both serial and parallel approaches

    NASA Astrophysics Data System (ADS)

    Wilges, B.; Bastos, R. C.; Mateus, G. P.; Dantas, M. A. R.

    2014-10-01

    A well-known problem faced by any organization nowadays is the high volume of data that is available and the required process to transform this volume into differential information. In this study, a case-comparison study of automatic document classification (ADC) approach is presented, utilizing both serial and parallel paradigms. The serial approach was implemented by adopting the RapidMiner software tool, which is recognized as the worldleading open-source system for data mining. On the other hand, considering the MapReduce programming model, the Hadoop software environment has been used. The main goal of this case-comparison study is to exploit differences between these two paradigms, especially when large volumes of data such as Web text documents are utilized to build a category database. In the literature, many studies point out that distributed processing in unstructured documents have been yielding efficient results in utilizing Hadoop. Results from our research indicate a threshold to such efficiency.

  5. Experimental Pilot Study of a Novel Endobronchial Drug Delivery Catheter

    PubMed Central

    Tsukada, Hisashi; Seward, Kirk P.; Rafeq, Samaan; Kocher, Olivier; Ernst, Armin

    2015-01-01

    Background An endobronchial infusion catheter introduced through a flexible bronchoscope channel has not been previously described. The aim of this study was to evaluate the technical feasibility of a new device. Methods Four porcine models underwent bronchoscopy with the infusion catheter. In the first experiment, Methylene blue was injected into airway in volumes of 0.1 ml, 0.3 ml or 1.0 ml into two animals. One animal was sacrificed at 1 hour and one at 24 hours after the procedure and gross dye diffusion was visually assessed. In the second experiment, a mixture of 80% sterile normal saline and 20% contrast media was injected into the airway in volumes of 0.3 ml, 1.0 ml and 3.0 ml into two animals. One animal was sacrificed at 7 days and one at 20 days. Histological evaluations were performed according to a bronchial damage scoring system. Results There was no perioperative morbidity. In the first experiment, infusion volumes of 0.1ml, 0.3ml and 1.0ml resulted in dye surrounding 67±29%, 55±17% and 80±20% of the infusion site circumference, and longitudinal distribution of 4.0±1.7mm, 8.1±4.1mm and 18.0±3.0mm, each respectively. In the second experiment, infusion of 0.3 to 3.0 ml resulted in mild injury, inflammation and hemorrhage/fibrin/thrombus at 7 and 20 days after surgery. Conclusion Endobronchial infusion of dye and contrast media by the Endobronchial Drug Delivery Catheter [EDDC] showed dose dependent fashion spread media macroscopically and histologically. Further investigation will be required to assess the catheter as a new tool for localized drug delivery into the airway. PMID:26492604

  6. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  7. Drugs: A Pilot Study of Minneapolis Secondary School Students.

    ERIC Educational Resources Information Center

    Faunce, R. W.; Johnson, Larry

    The results of a survey of over 1800 junior high and senior high school students are presented. Purposes of the survey were: (1) to obtain information about the extent of drug use and experimentation; (2) to obtain suggestions for improving Minneapolis Public Schools' health education curriculum; and (3) to pretest the drug education questionnaire…

  8. Drug-DNA Interaction Studies of Acridone-Based Derivatives.

    PubMed

    Thimmaiah, Kuntebomanahalli; Ugarkar, Apoorva G; Martis, Elvis F; Shaikh, Mushtaque S; Coutinho, Evans C; Yergeri, Mayur C

    2015-01-01

    N10-alkylated 2-bromoacridones are a novel series of potent antitumor compounds. DNA binding studies of these compounds were carried out using spectrophotometric titrations, Circular dichroism (CD) measurements using Calf Thymus DNA (CT DNA). The binding constants were identified at a range of K=0.3 to 3.9×10(5) M(-1) and the percentage of hypochromism from the spectral titrations at 28-54%. This study has identified a compound 9 with the good binding affinity of K=0.39768×10(5) M(-1) with CT DNA. Molecular dynamics (MD) simulations have investigated the changes in structural and dynamic features of native DNA on binding to the active compound 9. All the synthesized compounds have increased the uptake of Vinblastine in MDR KBChR-8-5 cells to an extent of 1.25- to1.9-fold than standard modulator Verapamil of similar concentration. These findings allowed us to draw preliminary conclusions about the structural features of 2-bromoacridones and further chemical enhancement will improve the binding affinity of the acridone derivatives to CT-DNA for better drug-DNA interaction. The molecular modeling studies have shown mechanism of action and the binding modes of the acridones to DNA.

  9. Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study

    PubMed Central

    Basak, Silpi; Singh, Priyanka; Rajurkar, Monali

    2016-01-01

    Background and Objective. Antimicrobial resistance is now a major challenge to clinicians for treating patients. Hence, this short term study was undertaken to detect the incidence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacterial isolates in a tertiary care hospital. Material and Methods. The clinical samples were cultured and bacterial strains were identified in the department of microbiology. The antibiotic susceptibility profile of different bacterial isolates was studied to detect MDR, XDR, and PDR bacteria. Results. The antibiotic susceptibility profile of 1060 bacterial strains was studied. 393 (37.1%) bacterial strains were MDR, 146 (13.8%) strains were XDR, and no PDR was isolated. All (100%) Gram negative bacterial strains were sensitive to colistin whereas all (100%) Gram positive bacterial strains were sensitive to vancomycin. Conclusion. Close monitoring of MDR, XDR, or even PDR must be done by all clinical microbiology laboratories to implement effective measures to reduce the menace of antimicrobial resistance. PMID:26942013

  10. Breast cancer resistance protein (ABCG2) in clinical pharmacokinetics and drug interactions: practical recommendations for clinical victim and perpetrator drug-drug interaction study design.

    PubMed

    Lee, Caroline A; O'Connor, Meeghan A; Ritchie, Tasha K; Galetin, Aleksandra; Cook, Jack A; Ragueneau-Majlessi, Isabelle; Ellens, Harma; Feng, Bo; Taub, Mitchell E; Paine, Mary F; Polli, Joseph W; Ware, Joseph A; Zamek-Gliszczynski, Maciej J

    2015-04-01

    Breast cancer resistance protein (BCRP; ABCG2) limits intestinal absorption of low-permeability substrate drugs and mediates biliary excretion of drugs and metabolites. Based on clinical evidence of BCRP-mediated drug-drug interactions (DDIs) and the c.421C>A functional polymorphism affecting drug efficacy and safety, both the US Food and Drug Administration and European Medicines Agency recommend preclinical evaluation and, when appropriate, clinical assessment of BCRP-mediated DDIs. Although many BCRP substrates and inhibitors have been identified in vitro, clinical translation has been confounded by overlap with other transporters and metabolic enzymes. Regulatory recommendations for BCRP-mediated clinical DDI studies are challenging, as consensus is lacking on the choice of the most robust and specific human BCRP substrates and inhibitors and optimal study design. This review proposes a path forward based on a comprehensive analysis of available data. Oral sulfasalazine (1000 mg, immediate-release tablet) is the best available clinical substrate for intestinal BCRP, oral rosuvastatin (20 mg) for both intestinal and hepatic BCRP, and intravenous rosuvastatin (4 mg) for hepatic BCRP. Oral curcumin (2000 mg) and lapatinib (250 mg) are the best available clinical BCRP inhibitors. To interrogate the worst-case clinical BCRP DDI scenario, study subjects harboring the BCRP c.421C/C reference genotype are recommended. In addition, if sulfasalazine is selected as the substrate, subjects having the rapid acetylator phenotype are recommended. In the case of rosuvastatin, subjects with the organic anion-transporting polypeptide 1B1 c.521T/T genotype are recommended, together with monitoring of rosuvastatin's cholesterol-lowering effect at baseline and DDI phase. A proof-of-concept clinical study is being planned by a collaborative consortium to evaluate the proposed BCRP DDI study design.

  11. Biomarker assay translation from discovery to clinical studies in cancer drug development: quantification of emerging protein biomarkers.

    PubMed

    Lee, Jean W; Figeys, Daniel; Vasilescu, Julian

    2007-01-01

    Many candidate biomarkers emerging from genomics and proteomics research have the potential to serve as predictive indexes for guiding the development of safer and more efficacious drugs. Research and development of biomarker discovery, selection, and clinical qualification, however, is still a relatively new field for the pharmaceutical industry. Advances in technology provide a plethora of analytical tools to discover and analyze mechanism-and-disease-specific biomarkers for drug development. In the discovery phase, differential proteomic analysis using mass spectrometry enables the identification of candidate biomarkers that are associated with a specific mechanism relevant to disease progression and affected by drug treatment. Reliable bioanalytical methods are then developed and implemented to select promising biomarkers for further studies in animals and humans. Quantitative analytical methods capable of generating reliable data constitute a solid basis for statistical assessment of the predictive utility of biomarkers. Biomarker method validation is diverse and for purposes that are very different from those of drug bioanalysis or diagnostic use. Besides being flexible, it should sufficiently demonstrate the method's ability to meet the study intent and the attendant regulatory requirements. Several papers have been published outlining specific requirements for successful biomarker method development and validation using a "Fit-for-Purpose" approach. Many of the challenges faced during biomarker discovery as well as during technology and process translation are discussed in this chapter, including preanalytical planning, assay development, and preclinical and clinical validation. Specific references to protein biomarkers for cancer drug development are also discussed.

  12. Novel Drug Targets for Food-Borne Pathogen Campylobacter jejuni: An Integrated Subtractive Genomics and Comparative Metabolic Pathway Study

    PubMed Central

    Mehla, Kusum

    2015-01-01

    Abstract Campylobacters are a major global health burden and a cause of food-borne diarrheal illness and economic loss worldwide. In developing countries, Campylobacter infections are frequent in children under age two and may be associated with mortality. In developed countries, they are a common cause of bacterial diarrhea in early adulthood. In the United States, antibiotic resistance against Campylobacter is notably increased from 13% in 1997 to nearly 25% in 2011. Novel drug targets are urgently needed but remain a daunting task to accomplish. We suggest that omics-guided drug discovery is timely and worth considering in this context. The present study employed an integrated subtractive genomics and comparative metabolic pathway analysis approach. We identified 16 unique pathways from Campylobacter when compared against H. sapiens with 326 non-redundant proteins; 115 of these were found to be essential in the Database of Essential Genes. Sixty-six proteins among these were non-homologous to the human proteome. Six membrane proteins, of which four are transporters, have been proposed as potential vaccine candidates. Screening of 66 essential non-homologous proteins against DrugBank resulted in identification of 34 proteins with drug-ability potential, many of which play critical roles in bacterial growth and survival. Out of these, eight proteins had approved drug targets available in DrugBank, the majority serving crucial roles in cell wall synthesis and energy metabolism and therefore having the potential to be utilized as drug targets. We conclude by underscoring that screening against these proteins with inhibitors may aid in future discovery of novel therapeutics against campylobacteriosis in ways that will be pathogen specific, and thus have minimal toxic effect on host. Omics-guided drug discovery and bioinformatics analyses offer the broad potential for veritable advances in global health relevant novel therapeutics. PMID:26061459

  13. In silico study on the effects of matrix structure in controlled drug release

    NASA Astrophysics Data System (ADS)

    Villalobos, Rafael; Cordero, Salomón; Maria Vidales, Ana; Domínguez, Armando

    2006-07-01

    Purpose: To study the effects of drug concentration and spatial distribution of the medicament, in porous solid dosage forms, on the kinetics and total yield of drug release. Methods: Cubic networks are used as models of drug release systems. They were constructed by means of the dual site-bond model framework, which allows a substrate to have adequate geometrical and topological distribution of its pore elements. Drug particles can move inside the networks by following a random walk model with excluded volume interactions between the particles. The drug release time evolution for different drug concentration and different initial drug spatial distribution has been monitored. Results: The numerical results show that in all the studied cases, drug release presents an anomalous behavior, and the consequences of the matrix structural properties, i.e., drug spatial distribution and drug concentration, on the drug release profile have been quantified. Conclusions: The Weibull function provides a simple connection between the model parameters and the microstructure of the drug release device. A critical modeling of drug release from matrix-type delivery systems is important in order to understand the transport mechanisms that are implicated, and to predict the effect of the device design parameters on the release rate.

  14. 21 CFR 201.200 - Disclosure of drug efficacy study evaluations in labeling and advertising.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Commissioner of Food and Drugs from the National Academy of Sciences (1969).” As the report notes, this review... or submission or existence of adequate data), such qualification is not necessary. When the Food and... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Disclosure of drug efficacy study evaluations...

  15. 21 CFR 201.200 - Disclosure of drug efficacy study evaluations in labeling and advertising.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Commissioner of Food and Drugs from the National Academy of Sciences (1969).” As the report notes, this review... or submission or existence of adequate data), such qualification is not necessary. When the Food and... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Disclosure of drug efficacy study evaluations...

  16. Methodological Issues in Controlled Studies on Effects of Prenatal Exposure to Drug Abuse. Research Monograph 114.

    ERIC Educational Resources Information Center

    Kilbey, M. Marlyne, Ed.; Asghar, Khursheed, Ed.

    This monograph presents the proceedings of the first National Institute on Drug Abuse technical review related to the conduct of controlled studies on prenatal exposure to drugs of abuse. Papers in the monograph are categorized by session. The first session (two papers) focused on the detection and quantification of prenatal drug exposure in…

  17. Self-Reported Utilization of Eye Care among Latinos: The Los Angeles Latino Eye Study (LALES)

    PubMed Central

    Morales, Leo S.; Varma, Rohit; Paz, Sylvia H.; Lai, Mei Ying; Mazhar, Kashif; Andersen, Ronald M.; Azen, Stanley P.

    2009-01-01

    Purpose To identify the prevalence and determinants of self-reported eye care utilization in Latinos. Design Population-based ocular epidemiological study in Latinos age 40+ living in La Puente, California. Participants 5,455 participants. Methods Univariate, multivariable and stepwise logistic regression analyses were conducted to identify predisposing, enabling and need variables associated with self-reported eye care utilization. Main Outcome Measures Prevalence of self-reported utilization: eye care visit, having had a dilated examination in the past 12 months, ever having had a dilated examination, and odds ratios for factors associated with self-reported utilization. Results Overall, 36% of participants reported an eye care visit and 19% reported having a dilated examination in the past year. Fifty-seven percent reported ever having had a dilated eye examination. Greater eye care utilization was associated with older age, female gender, bilingual language proficiency (English and Spanish), more education, having health insurance, having a usual place for care, having a regular provider of care, greater number of co-morbidities, visual impairment, and lower vision-specific quality of life scores. Conclusions Increasing utilization and access to eye care for Latinos should be a priority because visual impairment has significant impacts on well-being and mortality. PMID:20018380

  18. Utilization of optical polarization microscopy in the study of sorption characteristics of wound dressing host materials.

    PubMed

    Devetak, Miha; Peršin, Zdenka; Stana-Kleinschek, Karin; Maver, Uroš

    2014-04-01

    Polarization microscopy was used for evaluation of kinetics of diclofenac sorption in three different wound dressing materials. The sorption kinetics can be evaluated by radii change and intensity of the light traveling through the fiber. The most frequently used host materials for drugs in wound dressings are alginate, polyesters such as polyethylene terephthalate, and viscose. We studied sorption of diclofenac as an example drug. Effective, but rather simple in vitro simulation of diclofenac sorption gives insight into the applicability of the mentioned materials for development of wound healing materials.

  19. Development of a simple system for screening anti-hepatitis C virus drugs utilizing mutants capable of vigorous replication.

    PubMed

    Yu, Lijuan; Aoki, Chie; Shimizu, Yohko; Shimizu, Kazufumi; Hou, Wei; Yagyu, Fumihiro; Wen, Xianzi; Oshima, Masamichi; Iwamoto, Aikichi; Gao, Bin; Liu, Wenjun; Gao, George Fu; Kitamura, Yoshihiro

    2010-11-01

    Replication of infectious hepatitis C virus in Huh7 cells, a human hepatocyte cell line, has become possible due to the unique properties of the JFH1 isolate. Developing reporter virus systems for a simple titration has been attempted by integrating heterologous reporter genes into the JFH1 genome, resulting in a big infectivity reduction that limits the usefulness of such reporter systems. To overcome this problem, JFH1-infected Huh7 cells were cultured continuously for 2 years to obtain Huh7-adapted JFH1 variants capable of yielding up to 1000-fold higher titers. Sequence analysis of variant genome RNA suggested that this adapted population consisted mainly of two variants. By joining the 5'-half of the obtained representative viral complementary DNA (cDNA) fragments of the variants with the 3'-half of the wild-type's, two prototype clones, A/WT and B/WT, were constructed. Replication of A/WT and B/WT viruses in Huh7 cells showed up to 100-1000-fold higher titers than the wild-type. A Renilla luciferase cDNA was inserted into the Nonstructural Protein 5A region of the A/WT and B/WT cDNA to generate A/WT-Rluc and B/WT-Rluc, respectively. Transfection of Huh7 cells with in vitro-transcribed A/WT-Rluc and B/WT-Rluc RNA resulted in production of infectious viruses with approximately 15- and 25-fold higher titers, respectively, than the wild-type RNA. The replication of A/WT-Rluc and B/WT-Rluc viruses was more vigorous than the wild-type even with insertion of the luciferase cDNA showing a good correlation of luciferase activities with infectious titers. Furthermore, interferon-alpha inhibited the replication of A/WT-Rluc and B/WT-Rluc viruses in a dose-dependent manner as determined by a luciferase assay. These results imply that our system is potentially a tool useful for screening anti-hepatitis C virus drugs in a simple and time/cost-saving manner.

  20. Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans.

    PubMed

    Holden-Dye, Lindy; Walker, Robert J

    2014-01-01

    Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for agriculture. As such, these nematodes place a major burden on human health, on livestock production, on the welfare of companion animals and on crop production. In the 21st century there are two major challenges posed by the wide-spread prevalence of parasitic nematodes. First, many anthelmintic drugs are losing their effectiveness because nematode strains with resistance are emerging. Second, serious concerns regarding the environmental impact of the nematicides used for crop protection have prompted legislation to remove them from use, leaving agriculture at increased risk from nematode pests. There is clearly a need for a concerted effort to address these challenges. Over the last few decades the free-living nematode Caenorhabditis elegans has provided the opportunity to use molecular genetic techniques for mode of action studies for anthelmintics and nematicides. These approaches continue to be of considerable value. Less fruitful so far, but nonetheless potentially very useful, has been the direct use of C. elegans for anthelmintic and nematicide discovery programmes. Here we provide an introduction to the use of C. elegans as a 'model' parasitic nematode, briefly review the study of nematode control using C. elegans and highlight approaches that have been of particular value with a view to facilitating wider-use of C. elegans as a platform for anthelmintic and nematicide discovery and development. PMID:25517625

  1. Human hepatoma cell lines on gas foaming templated alginate scaffolds for in vitro drug-drug interaction and metabolism studies.

    PubMed

    Stampella, A; Rizzitelli, G; Donati, F; Mazzarino, M; de la Torre, X; Botrè, F; Giardi, M F; Dentini, M; Barbetta, A; Massimi, M

    2015-12-25

    Liver in vitro systems that allow reliable prediction of major human in vivo metabolic pathways have a significant impact in drug screening and drug metabolism research. In the present study, a novel porous scaffold composed of alginate was prepared by employing a gas-in-liquid foaming approach. Galactose residues were introduced on scaffold surfaces to promote cell adhesion and to enhance liver specific functions of the entrapped HepG2/C3A cells. Hepatoma cells in the gal-alginate scaffold showed higher levels of liver specific products (albumin and urea) and were more responsive to specific inducers (e.g. dexamethasone) and inhibitors (e.g. ketoconazole) of the CYP3A4 system than in conventional monolayer culture. HepG2/C3A cells were also more efficient in terms of rapid elimination of testosterone, used as a model substance, at rates comparable to those of in vivo excretion. In addition, an improvement in metabolism of testosterone, in terms of phase II metabolite formation, was also observed when the more differentiated HepaRG cells were used. Together the data suggest that hepatocyte/gas templated alginate-systems provide an innovative high throughput platform for in vitro drug metabolism and drug-drug interaction studies, with broad fields of application, and might provide a valid tool for minimizing animal use in preclinical testing of human relevance.

  2. The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs

    PubMed Central

    2016-01-01

    Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand–receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure–activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3. PMID:25587888

  3. The 3-metros study of drugs and crime in South Africa: findings and policy implications.

    PubMed

    Parry, Charles D; Plüddemann, Andreas; Louw, Antoinette; Leggett, Ted

    2004-01-01

    This study examined the drug-crime nexus by investigating the prevalence of recent drug use among persons arrested by the police. Data were gathered during August/September 2000 from 1050 adult arrestees in eight police stations in Cape Town, Durban, and Johannesburg (South Africa). Measures included urinalysis results for cannabis, methaqualone (Mandrax), opiates, cocaine, amphetamines, and benzodizepines, and a questionnaire designed to assess socioeconomic and demographic backgrounds of arrestees, history of prior arrests and imprisonment, current arrest information, profile of substance use, etc. Results of the study show high levels of drug use among arrestees, with 45% testing positive for at least one drug (mainly cannabis and Mandrax). A greater proportion of arrestees in Cape Town tested positive for drugs than in the other sites. Data were also analyzed in terms of gender, age, race, location (site and police station), and offense category. Persons arrested on charges of housebreaking or for drugs/alcohol offenses were particularly likely to test positive for drugs. Drug positive arrestees were more likely to have had a prior arrest. Among the conclusions of the study are that 1) strategies to reduce drug use and drug related crime must be area specific, 2) particular attention needs to focus on young offenders, 3) police need to be trained to recognize particular symptoms and to establish protocols on handling arrestees under the influence of drugs, and 4) diversion to treatment of drug using offenders deserves more consideration.

  4. Individual response to drug therapy: bases and study approaches.

    PubMed

    León-Cachón, Rafael Baltazar Reyes; Ascacio-Martínez, Jorge Angel; Barrera-Saldaña, Hugo Alberto

    2012-01-01

    Genomic variation largely explains the differences in an individual's response to drug treatments. A field of genomic medicine focuses on the identification of genetic polymorphisms and gene mutations involved in the development and progression of disease. Another part focuses on the development of genetic tests to accompany medical prescriptions, to predict how certain patients respond to therapy with a given pharmacological agent. The field of predicting responses to drugs has different strategies and methods, among which we find: the use of liver microsomes, cell models, monitoring of probe drugs, assays with recombinant proteins and recently the use of microarray platforms or DNAchips.

  5. Studies in Multifunctional Drug Development: Preparation and Evaluation of 11beta-Substituted Estradiol-Drug Conjugates, Cell Membrane Targeting Imaging Agents, and Target Multifunctional Nanoparticles

    NASA Astrophysics Data System (ADS)

    Dao, KinhLuan Lenny D.

    with an azido-tetraethylene glycol moiety that could be coupled to a complementary doxorubicin benzoyl hydrazone, functionalized with a propargyl tetraethylene glycol moiety. Huisgen [3+2] cycloaddition chemistry gave the final hybrid which was evaluated for receptor binding to demonstrate ER-affinity and for cytotoxicity in ER(+)-MCF-7 and ER(-)-MDA-MB-231 breast cancer cell lines. The anti-estrogen-doxorubicin hybrid demonstrated enhanced (>70-fold) selectivity for ER(+)-cells versus ER(-)-cells and enhanced efficacy compared to doxorubicin alone. The reversal of these effects by co-administration of estradiol demonstrated that the presence of the anti-estrogenic component was critical for selectivity and cytotoxicity in ER(+)-MCF-7 human breast cancer cells. The results suggest that this approach the basis for developing selective therapeutic agents for ER(+)-cancer cells with reduced effects on non-target tissues.1,2 The second study describes our use of 11beta-AE for targeting ER membrane targeting in hormone-dependent breast cancer, and of a urea-based prostate specific membrane antigen (PSMA) inhibitor for targeting PSMA membrane receptors in androgen-independent of prostate cancer. These derivatives were used to prepare a series of molecular imaging probes. We have successfully established our model compound, 11beta-AE radiolabeled with 18F-fluoro-OEG-azide, for in vivo imaging.3 The third study describes a strategy based on the design and synthesis of a multifunctional gold nanoparticulate (mfAuNPs) drug delivery system that can be used for prostate cancer therapy. We have utilized a convergent modular assembly approach to prepare individual components such as a) prostate specific membrane antigen (PSMA) ligands for targeting; b) pH-sensitive doxorubicin; and c) Re/99Tc chelating complex for radioimaging. The components can be assembled with a terminal lipoic acid or thiolated ethylene glycol oligomer for attachment to the Au surface. Initial in vitro studies

  6. Antiretroviral Therapy and Health Care Utilization: A Study of Privately Insured Men and Women with HIV Disease

    PubMed Central

    Hellinger, Fred J; Encinosa, William E

    2004-01-01

    Objective To compare the use of antiretroviral therapy and other health care resources by women and men with HIV disease who are privately insured. Data Sources Data were obtained from the MarketScan Commercial Claims and Encounter Database produced by the Medstat Group, Inc., of Ann Arbor, Michigan. This database includes eligibility files as well as claims data for inpatient care, outpatient care, physician services, and prescription drugs for enrollees in employer-sponsored benefit plans for 24 large employers around the nation. Study Design Examine utilization by 2,026 privately insured persons (1,494 men and 532 women) with HIV disease in calendar year 2000 under the age of 65. Principal Findings Using a simple comparison, we found that 71 percent of men (68.7 to 73.3 percent is 95 percent confidence interval) and 39 percent of women (35.1 to 43.5 percent is 95 percent confidence interval) with HIV disease received antiretroviral therapy. We also found that the average annual drug cost was $9,037 for a man ($8,372 to $9,702 is 95 percent confidence interval) and $3,893 for a woman ($3,476 to $4,490 is 95 percent confidence interval). Furthermore, we found that the out-of-pocket expenses comprised 10 percent of total expenses for men ($1,617 out of $16,405) and 4 percent for women ($405 out of $10,397). Conclusion There are major differences in the utilization and cost of health care between privately insured men and women with HIV disease. PMID:15230936

  7. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    PubMed Central

    Jacob, Joe Antony; Salmani, Jumah Masoud Mohammad; Chen, Baoan

    2016-01-01

    Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia. PMID:27382259

  8. An ex vivo approach to botanical-drug interactions: A proof of concept study

    PubMed Central

    Wang, Xinwen; Zhu, Hao-Jie; Munoz, Juliana; Gurley, Bill J.; Markowitz, John S.

    2015-01-01

    Ethnopharmacological relevance Botanical medicines are frequently used in combination with therapeutic drugs, imposing a risk for harmful botanical-drug interactions (BDIs). Among the existing BDI evaluation methods, clinical studies are the most desirable, but due to their expense and protracted time-line for completion, conventional in vitro methodologies remain the most frequently used BDI assessment tools. However, many predictions generated from in vitro studies are inconsistent with clinical findings. Accordingly, the present study aimed to develop a novel ex vivo approach for BDI assessment and expand the safety evaluation methodoloy in applied ethnopharmacological research. Materials and Methods This approach differs from conventional in vitro methods in that rather than botanical extracts or individual phytochemicals being prepared in artificial buffers, human plasma/serum collected from a limited number of subjects administered botanical supplements was utilized to assess BDIs. To validate the methodology, human plasma/serum samples collected from healthy subjects administered either milk thistle or goldenseal extracts were utilized in incubation studies to determine their potential inhibitory effects on CYP2C9 and CYP3A4/5, respectively. Silybin A and B, two principal milk thistle phytochemicals, and hydrastine and berberine, the purported active constituents in goldenseal, were evaluated in both phosphate buffer and human plasma based in vitro incubation systems. Results Ex vivo study results were consistent with formal clinical study findings for the effect of milk thistle on the disposition of tolbutamide, a CYP2C9 substrate, and for goldenseal’s influence on the pharmacokinetics of midazolam, a widely accepted CYP3A4/5 substrate. Compared to conventional in vitro BDI methodologies of assessment, the introduction of human plasma into the in vitro study model changed the observed inhibitory effect of silybinA, silybin B and hydrastine and berberine

  9. A Qualitative Study of Underutilization of the AIDS Drug Assistance Program

    PubMed Central

    Olson, Kristin M.; Godwin, Noah C.; Wilkins, Sara Anne; Mugavero, Michael J.; Moneyham, Linda D.; Slater, Larry Z.; Raper, James L.

    2014-01-01

    In our previous work, we demonstrated underutilization of the AIDS Drug Assistance Program (ADAP) at an HIV clinic in Alabama. In order to understand barriers and facilitators to utilization of ADAP, we conducted focus groups of ADAP enrollees. Focus groups were stratified by sex, race, and historical medication possession ratio as a measure of program utilization. We grouped factors according to the social-ecological model. We found that multiple levels of influence, including patient and clinic-related factors, influenced utilization of antiretroviral medications. Patients introduced issues that illustrated high-priority needs for ADAP policy and implementation, suggesting that in order to improve ADAP utilization, the following issues must be addressed: patient transportation, ADAP medication refill schedules and procedures, mailing of medications, and the ADAP recertification process. These findings can inform a strategy of approaches to improve ADAP utilization, which may have widespread implications for ADAP programs across the United States. PMID:24503498

  10. Impact of potential pregabalin or duloxetine drug–drug interactions on health care costs and utilization among Medicare members with fibromyalgia

    PubMed Central

    Ellis, Jeffrey J; Sadosky, Alesia B; Ten Eyck, Laura L; Cappelleri, Joseph C; Brown, Courtney R; Suehs, Brandon T; Parsons, Bruce

    2014-01-01

    Purpose To examine the impact of newly initiated pregabalin or duloxetine treatment on fibromyalgia (FM) patients’ encounters with potential drug–drug interactions (DDIs), the health care cost and utilization consequences of those interactions, and the impact of treatment on opioid utilization. Patients and methods Subjects included those with an FM diagnosis, a pregabalin or duloxetine prescription claim (index event), ≥1 inpatient or ≥2 outpatient medical claims, and ≥12 months preindex and ≥6 postindex enrollment. Propensity score matching was used to help balance the pregabalin and duloxetine cohorts on baseline demographics and comorbidities. Potential DDIs were defined based on Micromedex 2.0 software and were identified by prescription claims. Results No significant differences in baseline characteristics were found between matched pregabalin (n=794) and duloxetine cohorts (n=794). Potential DDI prevalence was significantly greater (P<0.0001) among duloxetine subjects (71.9%) than among pregabalin subjects (4.0%). There were no significant differences in all-cause health care utilization or costs between pregabalin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($9,373 versus $7,228; P<0.0001) and higher mean number of outpatient visits/member (16.0 versus 13.0; P=0.0009) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a statistically significant difference between pregabalin and duloxetine subjects in their respective pre- versus post-differences in use of ≥1 long-acting opioids (1.6% and 3.4%, respectively; P=0.077). Conclusion The significantly higher prevalence of potential DDIs and potential cost impact found in FM duloxetine subjects, relative to pregabalin subjects, underscore the importance of considering DDIs when selecting a treatment. PMID:25339847

  11. Driving Under the Influence of Non-Alcohol Drugs--An Update Part I: Epidemiological Studies.

    PubMed

    Gjerde, H; Strand, M C; Mørland, J

    2015-07-01

    Epidemiological studies of the association between drug use and involvement in road traffic crashes (RTCs) published from January 1998 to February 2015 have been reviewed. Cohort andpopulation studies compared RTC involvement among drug users and non-drug users, case-control studies compared drug use among RTC-involved and non-RTC-involved drivers, and responsibility studies and case-crossover studies were performed for RTC-involved drivers. Difficulties associated with the types of studies are discussed with a special focus on case-control studies. Statistically significant associations between drug use and RTC involvement were found for benzodiazepines and z-hypnotics in 25 out of 28 studies, for cannabis in 23 out of 36 studies, for opioids in 17 out of 25 studies, for amphetamines in 8 out of 10 studies, for cocaine in 5 out of 9 studies, and for antidepressants in 9 out of 13 studies. It was a general trend among studies that did not report significant associations between the use of these drugs and increased RTC risk that they often had either poor statistical power or poor study design compared to studies that found an association. Simultaneous use of two or more psychoactive drugs was associated with higher RTC risk. Studies on the combination of alcohol and drugs have not been reviewed in this article even though this combination is known to be associated with the highest RTC risk. PMID:26227253

  12. Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine-A Study with Felodipine as a Model Drug.

    PubMed

    Lindfors, Lennart; Jonsson, Malin; Weibull, Emelie; Brasseur, James G; Abrahamsson, Bertil

    2015-09-01

    The aim of this study was to understand and predict the influence of hydrodynamic effects in the small intestine on dissolution of primary and aggregated drug particles. Dissolution tests of suspensions with a low-solubility drug, felodipine, were performed in a Couette cell under hydrodynamic test conditions corresponding to the fed small intestine. Dissolution was also performed in the USP II apparatus at two paddle speeds of 25 and 200 rpm and at different surfactant concentrations below critical micelle concentration. The experimental dissolution rates were compared with theoretical calculations. The different levels of shear stress in the in vitro tests did not influence the dissolution of primary or aggregated particles and experimental dissolution rates corresponded very well to calculations. The dissolution rate for the aggregated drug particles increased after addition of surfactant because of deaggregation, but there were still no effect of hydrodynamics. In conclusion, hydrodynamics do not influence dissolution and deaggregation of micronized drug particles in the small intestine of this model drug. Surface tension has a strong effect on the deaggregation and subsequent dissolution. Addition of surfactants at in vivo relevant surface tension levels is thus critical for in vivo predictive in vitro dissolution testing. PMID:25980801

  13. Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine-A Study with Felodipine as a Model Drug.

    PubMed

    Lindfors, Lennart; Jonsson, Malin; Weibull, Emelie; Brasseur, James G; Abrahamsson, Bertil

    2015-09-01

    The aim of this study was to understand and predict the influence of hydrodynamic effects in the small intestine on dissolution of primary and aggregated drug particles. Dissolution tests of suspensions with a low-solubility drug, felodipine, were performed in a Couette cell under hydrodynamic test conditions corresponding to the fed small intestine. Dissolution was also performed in the USP II apparatus at two paddle speeds of 25 and 200 rpm and at different surfactant concentrations below critical micelle concentration. The experimental dissolution rates were compared with theoretical calculations. The different levels of shear stress in the in vitro tests did not influence the dissolution of primary or aggregated particles and experimental dissolution rates corresponded very well to calculations. The dissolution rate for the aggregated drug particles increased after addition of surfactant because of deaggregation, but there were still no effect of hydrodynamics. In conclusion, hydrodynamics do not influence dissolution and deaggregation of micronized drug particles in the small intestine of this model drug. Surface tension has a strong effect on the deaggregation and subsequent dissolution. Addition of surfactants at in vivo relevant surface tension levels is thus critical for in vivo predictive in vitro dissolution testing.

  14. A comparative study on the nanoparticles for improved drug delivery systems.

    PubMed

    Mahmoodi, Nosrat O; Ghavidast, Atefeh; Amirmahani, Najmeh

    2016-09-01

    Nanoparticles have attracted considerable recent interest for diverse biomedical applications because of the unique properties of the nanomaterials. It is already known that one of the major advances in the relative application of nanoparticles is the recognition of the steric stabilization which can increase the particle stability in the biological environment and provide the opportunities of the application of nanoparticles in the development of drug delivery systems (DDSs) for achieving drug targeting and controlled drug release. To facilitate their use in such applications, the appropriate design of surface ligands on these nanoparticles is necessary. In view of these, functionalized nanoparticles through surface modification can be utilized to specifically interact with the target molecules on the cell membrane or intracellular ones. This review briefly presents self-assembled nanoparticles with molecules of therapeutic significance with two strategies. The first strategy attempts to improve the placement of the drugs using conjugating the appropriate ligands or adding targeting moieties to the DDS. The second strategy utilizes trigger-controlled drug-release, which restricts drug release at the targeted site to kill cancer cells by externally controlled mechanisms. Among external stimulations, conveniently light has attracted much interest because it, as an orthogonal external stimulus, gives spatiotemporal control of payload release. PMID:27498233

  15. Sea truth and environmental characterization studies of Mobile Bay, Alabama, utilizing ERTS-1, data collection platforms

    NASA Technical Reports Server (NTRS)

    Schroeder, W. W.

    1977-01-01

    The paper reports on the scientific results obtained during a feasibility study that evaluated the potential of using ERTS data collection platforms (DCPs) in the coastal environment of Mobile Bay, Alabama. The utility of instrumented buoys operated in a coastal marine environment as ERTS DCPs is demonstrated. It is shown that these platforms are capable of providing both sea-truth data for ERTS imagery studies and time-series data for event monitoring and/or environmental characterization studies.

  16. Factorial design studies of antiretroviral drug-loaded stealth liposomal injectable: PEGylation, lyophilization and pharmacokinetic studies

    NASA Astrophysics Data System (ADS)

    Sudhakar, Beeravelli; Krishna, Mylangam Chaitanya; Murthy, Kolapalli Venkata Ramana

    2016-01-01

    The aim of the present study was to formulate and evaluate the ritonavir-loaded stealth liposomes by using 32 factorial design and intended to delivered by parenteral delivery. Liposomes were prepared by ethanol injection method using 32 factorial designs and characterized for various physicochemical parameters such as drug content, size, zeta potential, entrapment efficiency and in vitro drug release. The optimization process was carried out using desirability and overlay plots. The selected formulation was subjected to PEGylation using 10 % PEG-10000 solution. Stealth liposomes were characterized for the above-mentioned parameters along with surface morphology, Fourier transform infrared spectrophotometer, differential scanning calorimeter, stability and in vivo pharmacokinetic studies in rats. Stealth liposomes showed better result compared to conventional liposomes due to effect of PEG-10000. The in vivo studies revealed that stealth liposomes showed better residence time compared to conventional liposomes and pure drug solution. The conventional liposomes and pure drug showed dose-dependent pharmacokinetics, whereas stealth liposomes showed long circulation half-life compared to conventional liposomes and pure ritonavir solution. The results of statistical analysis showed significance difference as the p value is (<0.05) by one-way ANOVA. The result of the present study revealed that stealth liposomes are promising tool in antiretroviral therapy.

  17. Pitavastatin as an in vivo probe for studying hepatic organic anion transporting polypeptide-mediated drug-drug interactions in cynomolgus monkeys.

    PubMed

    Takahashi, Tsuyoshi; Ohtsuka, Tatsuyuki; Yoshikawa, Takahiro; Tatekawa, Ichiro; Uno, Yasuhiro; Utoh, Masahiro; Yamazaki, Hiroshi; Kume, Toshiyuki

    2013-10-01

    Drug-drug interactions (DDIs) caused by the inhibition of hepatic uptake transporters such as organic anion transporting polypeptide (OATP) can affect therapeutic efficacy and cause adverse reactions. We investigated the potential utility of pitavastatin as an in vivo probe substrate for preclinically studying OATP-mediated DDIs using cynomolgus monkeys. Cyclosporine A (CsA) and rifampicin (RIF), typical OATP inhibitors, inhibited active uptake of pitavastatin into monkey hepatocytes with half-maximal inhibitory concentration values comparable with those in human hepatocytes. CsA and RIF increased the area under the plasma concentration-time curve (AUC) of intravenously administered pitavastatin in cynomolgus monkeys by 3.2- and 3.6-fold, respectively. In addition, there was no apparent prolongation of the elimination half-life of pitavastatin due to the decrease in both hepatic clearance and volume of distribution. These findings suggest that DDIs were caused by the inhibition of hepatic uptake of pitavastatin. CsA and RIF increased the AUC of orally administered pitavastatin by 10.6- and 14.8-fold, respectively, which was additionally caused by the effect of the CsA and RIF in the gastrointestinal tract. Hepatic contribution to the overall DDI for oral pitavastatin with CsA was calculated from the changes in hepatic availability and clearance, and it was shown that the magnitude of hepatic DDI was comparable between the present study and the clinical study. In conclusion, pharmacokinetic studies using pitavastatin as a probe in combination with drug candidates in cynomolgus monkeys are useful to support the assessment of potential clinical DDIs involving hepatic uptake transporters.

  18. Drug therapy and adverse drug reactions to terbutaline in obstetric patients: a prospective cohort study in hospitalized women.

    PubMed

    Hernández-Hernández, Dulce; Vargas-Rivera, María; Nava-Ocampo, Alejandro A; Palma-Aguirre, José; Sumano-López, Héctor

    2002-04-01

    BACKGROUND: Adverse drug reactions (ADR's) could be expected more frequently in pregnant women. This study was performed in order to identify ADR's to tocolytic drugs in hospitalised pregnant women. METHODS: A prospective cohort study was performed in two General Hospitals of the Instituto Mexicano del Seguro Social (IMSS) in Mexico City. Two hundred and seven women undergoing labor, premature labor, threatened abortion or suffering any obstetric related disease were included. Drug prescription and signs and symptoms of any potential ADR were registered daily during the hospital stay. Any potential ADR to tocolytic drugs was evaluated and classified by three of the authors using the Kramer's algorithm. RESULTS: Of the 207 patients, an ADR was positively classified in 25 cases (12.1%, CI95% 8.1 to 17.5%). All ADR's were classified as minor reactions. Grouping patients with diagnosis of threatened abortion, premature labor or under labor (n= 114), 24 ADR's were related to terbutaline, accounting for a rate of 21.1 ADR's per 100 obstetric patients. Obstetric patients suffering an ADR were older than obstetric patients without any ADR. However, the former received less drugs/day x patient-1 and had a shorter hospital stay (p < 0.05) whereas the dose of terbutaline was similar between the two groups. Terbutaline inhibited uterine motility in women with and without any ADR at a similar rate, 70 and 76% respectively (x2 = 0.07; p = 0.8). CONCLUSION: Terbutaline, used as a tocolytic drug, was related to a high frequency of minor ADRs and to a high rate of effcicacy. PMID:11934352

  19. Biomarker Utility Analysis Using an Exposure-PBPK/PD Model: A Carbaryl Case Study

    EPA Science Inventory

    There are two common biomarkers: markers of exposure and markers of health effects. The strength of the correlation between exposure or effect and a biomarker measurement determines the utility of a biomarker for assessing exposures or risks. In the current study, a linked expo...

  20. Utility of Hospital Emergency Department Data for Studying Intimate Partner Violence

    ERIC Educational Resources Information Center

    Saltzman, Linda E.; Mahendra, Reshma R.; Ikeda, Robin M.; Ingram, Eben M.

    2005-01-01

    The authors examine 12 months of emergency department visit data (N = 2,521) from the National Electronic Injury Surveillance System All Injury Program and explore its utility for measuring and studying intimate partner violence. Given the dearth of national data on intimate partner violence-related injury and its potential value for public health…

  1. Classroom Utilization of Ancillary Personnel: Delivery Systems for Mainstreaming in Elementary Social Studies.

    ERIC Educational Resources Information Center

    Rockoff, Edward

    1979-01-01

    Proposes in-service training on the utilization of ancillary personnel (special education teacher, school nurse, hearing and speech clinician, guidance counselor) in assisting the social studies teacher with the mainstreamed student. Outlines how ancillary personnel may aid in preparing students for entrance into the regular classroom, developing…

  2. Study of the Validity and Reliability of a Self-Efficacy Scale of Teaching Material Utilization

    ERIC Educational Resources Information Center

    Korkmaz, Ozgen

    2011-01-01

    The main purpose of this study is to develop a scale in order to detect the level of pre-service teachers' utilization from teaching materials based on their perception of self-efficacy. The sample group is composed of 439 students for the first application and 215 students for the second. In order to detect the validity of the scale, exploratory…

  3. Creating Critical Conversations: Investigating the Utility of Socratic Dialogues in Elementary Social Studies Methods

    ERIC Educational Resources Information Center

    Buchanan, Lisa Brown

    2012-01-01

    This article explores the utility of Socratic dialogues in the elementary social studies methods course. Findings include preservice teachers' behaviors during dialogues, perceived strengths and challenges of using Socratic dialogues in teacher education, and the impact on student learning. Challenges and apprehensions encountered by the teacher…

  4. Linking Resource Allocation to Student Achievement: A Study of Title 1 and Title 1 Stimulus Utilization

    ERIC Educational Resources Information Center

    Krumpe, Kati P.

    2012-01-01

    With the emphasis on high standards and fiscal accountability, there is a heightened need to inform the research linking student achievement to the allocation of resources. This mixed methods inquiry sought to study how schools utilized Title 1 and Title 1 stimulus funding from 2009-2011 to determine if correlations existed between areas of…

  5. A Study on Polypharmacy and Potential Drug-Drug Interactions among Elderly Patients Admitted in Department of Medicine of a Tertiary Care Hospital in Puducherry

    PubMed Central

    Kalyansundaram, Dharani; Bahurupi, Yogesh

    2016-01-01

    Introduction The proportion of elderly population has been constantly increasing over last few years. Polypharmacy is unavoidable in the elderly as they often suffer from multiple co-morbidities. Potential drug-drug interaction due to polypharmacy and potential inappropriate medication among the elderly must be carefully assessed. Aim To find out polypharmacy and potential drug-drug interactions among elderly patients admitted and discharged in Department of Medicine. Materials and Methods This study was carried out on 100 patients above 65 years of age both males and females. Data was collected through review of case sheets. Polypharmacy was observed based on admission and discharge prescriptions. Frequently occurring drug-drug interactions were assessed using online checks. Results Mean number of drugs prescribed to patients on admission (7.61 ± 3.37) was more than that on discharge (5.48±2.46). More than half of these patients received 5 to 9 number of drugs. On admission 52.69% potential drug-drug interactions were observed and on discharge 52.91%. Most common drug interactions observed in both the groups were of moderate grade. Conclusion From the present study we can conclude that polypharmacy leads to more potential drug-drug interactions. To improve drug safety in this high-risk population, appropriate prescribing is very important. PMID:27042480

  6. Embracing Uncertainty: A Case Study Examination of How Climate Change is Shifting Water Utility Planning

    NASA Astrophysics Data System (ADS)

    Kaatz, L.

    2015-12-01

    Climate change has emerged as one of the greatest challenges facing water utilities' planning for the future, adding a new source and level of complexity that is forcing many agencies to re-examine their decision-making processes. A significant barrier for many agencies is figuring out how to consider highly uncertain climate information and move away from deterministic thinking to make climate-informed decisions. To provide water professionals with practical and relevant information, the Water Utility Climate Alliance teamed up with the American Water Works Association, in coordination with the Water Research Foundation and Association of Metropolitan Water Agencies, to develop a white paper sharing insights into how and why water agencies are modifying planning and decision-making processes. The 13 case studies presented illustrate the variety of ways in which utilities are incorporating climate change into planning, from immediate operational decisions, to capital planning and asset management, to long-term supply planning.

  7. Consistency of self-reported drug use events in a mixed methods study of people who inject drugs

    PubMed Central

    Dyal, Stephanie R.; Kral, Alex H.; Gonzalez, Karina Dominguez; Wenger, Lynn; Bluthenthal, Ricky N.

    2015-01-01

    Background Little is known about the consistency of information provided by people who inject drugs (PWID) during quantitative and qualitative interviews in mixed methods studies. Objectives We illustrate the use of the intraclass correlation coefficient, descriptive statistics, and regression to assess the consistency of information provided during a mixed methods study of PWID living in Los Angeles and San Francisco, California, USA. Methods Age of first use of heroin, methamphetamine, marijuana, powder cocaine, and crack cocaine and first injection of heroin, methamphetamine, and powder cocaine were collected during an interviewer administered computer-assisted personal interview followed by an in-depth qualitative interview (N=102). Results Participants were 63% male, racially/ethnically diverse. 80.4% between the ages of 40 and 60 years old, 89% US-born, and 57% homeless. Consistency of self-reported data was adequate for most drug use events. Exact concordance between quantitative and qualitative measures of age of onset ranged from 18.2% to 50%. Event ordering was consistent across qualitative and quantitative results for 90.2% of participants. Analyses indicated that age of onset for heroin use, heroin injection, and injection of any drug was significantly lower when assessed by qualitative methods as compared to quantitative methods. Conclusion While inconsistency will emerge during mixed method studies, confidence in the timing and ordering of major types of events such as drug initiation episodes appear to be warranted. PMID:25970020

  8. A 2013 workshop: vaccine and drug ontology studies (VDOS 2013)

    PubMed Central

    2014-01-01

    The 2013 “Vaccine and Drug Ontology Studies” (VDOS 2013) international workshop series focuses on vaccine- and drug-related ontology modeling and applications. Drugs and vaccines have contributed to dramatic improvements in public health worldwide. Over the last decade, tremendous efforts have been made in the biomedical ontology community to ontologically represent various areas associated with vaccines and drugs – extending existing clinical terminology systems such as SNOMED, RxNorm, NDF-RT, and MedDRA, as well as developing new models such as Vaccine Ontology. The VDOS workshop series provides a platform for discussing innovative solutions as well as the challenges in the development and applications of biomedical ontologies for representing and analyzing drugs and vaccines, their administration, host immune responses, adverse events, and other related topics. The six full-length papers included in this thematic issue focuses on three main areas: (i) ontology development and representation, (ii) ontology mapping, maintaining and auditing, and (iii) ontology applications. PMID:24650607

  9. The Role of Drug-Drug Interactions in Hydrogel Delivery Systems: Experimental and Model Study.

    PubMed

    Rossi, Filippo; Castiglione, Franca; Ferro, Monica; Moioli, Marta; Mele, Andrea; Masi, Maurizio

    2016-06-01

    To address the increasing need for improved tissue substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from polymeric materials able to incorporate cells and drugs. The interpretation of transport phenomena is a key step, but comprehensive theoretical data is still missing and many issues related to these systems are still unsolved. In particular, the contribution of solute-solute interactions is not yet completely understood. Here, we investigate a promising agar-carbomer (AC) hydrogel loaded with sodium fluorescein (SF), a commonly used drug mimetic. The self-diffusion coefficient of SF in AC formulations was measured by using high resolution magic angle spinning NMR spectroscopy (HR-MAS NMR). Starting from experimental data, a complete overview on SF transport properties is provided, in particular a mathematical model that describes and rationalizes the differences between gel and water environments is developed and presented. The hydrogel molecular environment is able to prevent SF aggregation, owing to the adsorption mechanism that reduces the number of monomers available for oligomer formation at low solute concentration. Then, when all adsorption sites are saturated free SF molecules are able to aggregate and form oligomers. The model predictions satisfactorily match with experimental data obtained in water and the gel environment, thus indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing device behavior and could be used to rationalize experimental activity. PMID:26919298

  10. Analytical methodologies for metallomics studies of antitumor Pt-containing drugs.

    PubMed

    Esteban-Fernández, Diego; Moreno-Gordaliza, Estefanía; Cañas, Benito; Palacios, María Antonia; Gómez-Gómez, María Milagros

    2010-01-01

    Pt-containing drugs are nowadays essential components in cancer chemotherapy. However, drug resistance and side effects limit the efficiency of the treatments. In order to improve the response to Pt-based drugs, different administration strategies or new Pt-compounds have been developed with little success. The reason for this failure could be that the mechanism of action of these drugs is not completely understood. In this way, metallomics studies may contribute to clarify the interactions of Pt-containing drugs within the organism. This review is mainly focused on the role of Analytical Chemistry on the study of the interactions between Pt-based drugs and biomolecules. A summary of the analytical techniques and the most common sample treatment procedures currently used in metallomics studies of these drugs is presented. Both are of paramount importance to study these complex samples preserving the drug-biomolecule interaction. Separation and detection techniques must be carefully selected in order to achieve the intended goals. The use of multidimensional hyphenated techniques is usually necessary for a better understanding of the Pt-based drugs interactions in the organism. An overview of Pt-drugs biological interactions is presented, considering the different sample matrices and the drugs course through the organism. Samples analysed in the included studies are blood, urine, cell cytosol, DNA as well as the drugs themselves and their derivatives. However, most of these works are based on in vitro experiments or incubations of standards, leading in some cases to contradictory results depending on the experimental conditions used. Though in vivo experiments represent a great challenge due to the high complexity and the low concentrations of the Pt-adducts in real samples, these studies must be undertaken to get a deeper understanding of the real interactions concerning Pt-containing drugs.

  11. Decellularized skeletal muscle as an in vitro model for studying drug-extracellular matrix interactions

    PubMed Central

    Wassenaar, Jean W.; Boss, Gerry R.; Christman, Karen L.

    2015-01-01

    Several factors can affect drug absorption after intramuscular (IM) injection: drug solubility, drug transport across cell membranes, and drug metabolism at the injection site. We found that potential interactions between the drug and the extracellular matrix (ECM) at the injection site can also affect the rate of absorption post-injection. Using decellularized skeletal muscle, we developed a simple method to model drug absorption after IM injection, and showed that the nature of the drug-ECM interaction could be investigated by adding compounds that alter binding. We validated the model using the vitamin B12 analog cobinamide with different bound ligands. Cobinamide is being developed as an IM injectable treatment for cyanide poisoning, and we found that the in vitro binding data correlated with previously published in vivo drug absorption in animals. Commercially available ECM products, such as collagen and GelTrex, did not recapitulate drug binding behavior. While decellularized ECM has been widely studied in fields such as tissue engineering, this work establishes a novel use of skeletal muscle ECM as a potential in vitro model to study drug-ECM interactions during drug development. PMID:26125502

  12. Study on microvisualizing assay of delivered drug infiltration using 2-color optical coherence dosigraphy

    NASA Astrophysics Data System (ADS)

    Nakamichi, Yu; Saeki, Souichi; Saito, Takashi; Hiro, Takafumi; Matsuzaki, Masunori

    2009-02-01

    Recently, clinical treatments applying drug delivery system (DDS) have been being developed. However, it is quite difficult to in vivo diagnose spatiotemporal distribution of drug infiltration, so the validation study should be too insufficient to progress the DDS development. In this study, we propose a visualizing assay of DDS, namely 2-Color Optical Coherence Dosigraphy (2C-OCD). 2C-OCD is based on optical coherence tomography using two waveband "2-Color" light sources having different optical absorbance of drug. This can simultaneously provide microscale tomographic images of scatterer density and drug concentration. In order to evaluate the efficacy of this technique, this was applied to drug-diffusion phenomena in microchannel and lipidrich plaques of rabbit with drug administration, respectively. As a result of diffusion experiment, it was confirmed that 2C-OCD can visualize a cross-sectional map of drug concentration, with spatial resolution 5 micro m × 10 μm and accuracy plus-minus 13.0 μM. In ex vivo animal experiment, the enhancement of absorptivity could be observed inside lipidrich plaques, in which DDS drug could be therein uptaken by drug administration. The absorption maps corresponding to drug concentration were calculated, comparing with their histological images. Consequently, they had good coincidence with histological examinations, therefore, it was concluded that 2C-OCD could visualize drug infiltration in biological tissue with almost the same spatial resolution as OCT system.

  13. Antibiotic-loaded chitosan-Laponite films for local drug delivery by titanium implants: cell proliferation and drug release studies.

    PubMed

    Ordikhani, Farideh; Dehghani, Mehdi; Simchi, Arash

    2015-12-01

    In this study, chitosan-Laponite nanocomposite coatings with bone regenerative potential and controlled drug-release capacity are prepared by electrophoretic deposition technique. The controlled release of a glycopeptide drug, i.e. vancomycin, is attained by the intercalation of the polymer and drug macromolecules into silicate galleries. Fourier-transform infrared spectrometry reveals electrostatic interactions between the charged structure of clay and the amine and hydroxyl groups of chitosan and vancomycin, leading to a complex positively-charged system with high electrophoretic mobility. By applying electric field the charged particles are deposited on the surface of titanium foils and uniform chitosan films containing 25-55 wt% Laponite and 937-1655 µg/cm(2) vancomycin are obtained. Nanocomposite films exhibit improved cell attachment with higher cell viability. Alkaline phosphatase assay reveals enhanced cell proliferation due the gradual dissolution of Laponite particles into the culture medium. In-vitro drug-release studies show lower release rate through a longer period for the nanocomposite compared to pristine chitosan. PMID:26507202

  14. Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina

    NASA Astrophysics Data System (ADS)

    Geng, Shengyong; Yang, Bin; Wang, Guowu; Qin, Geng; Wada, Satoshi; Wang, Jin-Ye

    2014-07-01

    In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4‧-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4‧-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes’ stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats’ retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.

  15. Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

    NASA Astrophysics Data System (ADS)

    Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

    2016-04-01

    Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

  16. A Statistical Perspective on the Design of Drug-Court Studies

    ERIC Educational Resources Information Center

    Merrall, Elizabeth L. C.; Bird, Sheila M.

    2009-01-01

    Recent meta-analyses of drug-court studies recognized the poor methodological quality of the evaluations, with only a few being randomized. This article critiques the design of the randomized studies from a statistical perspective. Learning points are identified for future drug-court studies and are applicable to evaluations both of other…

  17. QSPR studies on aqueous solubilities of drug-like compounds.

    PubMed

    Duchowicz, Pablo R; Castro, Eduardo A

    2009-06-01

    A rapidly growing area of modern pharmaceutical research is the prediction of aqueous solubility of drug-sized compounds from their molecular structures. There exist many different reasons for considering this physico-chemical property as a key parameter: the design of novel entities with adequate aqueous solubility brings many advantages to preclinical and clinical research and development, allowing improvement of the Absorption, Distribution, Metabolization, and Elimination/Toxicity profile and "screenability" of drug candidates in High Throughput Screening techniques. This work compiles recent QSPR linear models established by our research group devoted to the quantification of aqueous solubilities and their comparison to previous research on the topic. PMID:19582218

  18. QSPR studies on aqueous solubilities of drug-like compounds.

    PubMed

    Duchowicz, Pablo R; Castro, Eduardo A

    2009-06-03

    A rapidly growing area of modern pharmaceutical research is the prediction of aqueous solubility of drug-sized compounds from their molecular structures. There exist many different reasons for considering this physico-chemical property as a key parameter: the design of novel entities with adequate aqueous solubility brings many advantages to preclinical and clinical research and development, allowing improvement of the Absorption, Distribution, Metabolization, and Elimination/Toxicity profile and "screenability" of drug candidates in High Throughput Screening techniques. This work compiles recent QSPR linear models established by our research group devoted to the quantification of aqueous solubilities and their comparison to previous research on the topic.

  19. Primary care appointment availability and preventive care utilization: evidence from an audit study.

    PubMed

    Saloner, Brendan; Polsky, Daniel; Friedman, Ari; Rhodes, Karin

    2015-04-01

    Insurance expansions under the Affordable Care Act raise concerns about primary care access in communities with large numbers of newly insured. We linked individual-level, cross-sectional data on adult preventive care utilization from the 2011-2012 Behavioral Risk Factor Surveillance System to novel county-level measures of primary care appointment availability collected from an experimental audit study conducted in 10 states in 2012 to 2013 and other county-level health service and demographic measures. In multivariate regressions, we found higher county-level appointment availability for privately insured adults was associated with significantly lower preventive care utilization among adults likely to have private insurance. Estimates were attenuated after controlling for county-level uninsurance, poverty, and unemployment. By contrast, greater availability of Medicaid appointments was associated with higher, but not statistically significant, preventive care utilization for likely Medicaid enrollees. Our study highlights that the relationship between preventive care utilization and primary care access in small areas likely differs by insurance status. PMID:25637580

  20. Public Utility Regulatory Policies Act of 1978: Natural Gas Rate Design Study

    SciTech Connect

    1980-05-01

    First, the comments on May 3, 1979 Notice of Inquiry of DOE relating to the Gas Utility Rate Design Study Required by Section 306 of PURPA are presented. Then, comments on the following are included: (1) ICF Gas Utility Model, Gas Utility Model Data Outputs, Scenario Design; (2) Interim Model Development Report with Example Case Illustrations; (3) Interim Report on Simulation of Seven Rate Forms; (4) Methodology for Assessing the Impacts of Alternative Rate Designs on Industrial Energy Use; (5) Simulation of Marginal-Cost-Based Natural Gas Rates; and (6) Preliminary Discussion Draft of the Gas Rate Design Study. Among the most frequent comments expressed were the following: (a) the public should be given the opportunity to review the final report prior to its submission to Congress; (b) results based on a single computer model of only four hypothetical utility situations cannot be used for policy-making purposes for individual companies or the entire gas industry; (c) there has been an unobjective treatment of traditional and economic cost rate structures; the practical difficulties and potential detrimental consequences of economic cost rates are not fully disclosed; and (d) it is erroneous to assume that end users, particularly residential customers, are influenced by price signals in the rate structure, as opposed to the total bill.

  1. Adverse drug reactions to self-medication: a study in a pharmacovigilance database.

    PubMed

    Berreni, Aurélia; Montastruc, François; Bondon-Guitton, Emmanuelle; Rousseau, Vanessa; Abadie, Delphine; Durrieu, Geneviève; Chebane, Leila; Giroud, Jean-Paul; Bagheri, Haleh; Montastruc, Jean-Louis

    2015-10-01

    Although self-medication is widely developed, there are few detailed data about its adverse drug reactions (ADRs). This study investigated the main characteristics of ADRs with self-medication recorded in the Midi-Pyrénées PharmacoVigilance between 2008 and 2014. Self-medication included first OTC drugs and second formerly prescribed drugs later used without medical advice (reuse of previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%) were related to SM with 186 drugs. Around three-forth of the ADRs were 'serious'. Mean age was 48.8 years with 56.3% females. The most frequent ADRs were gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs, analgesics, and benzodiazepines. Phytotherapy-homeopathy accounted for 9.1% of drugs.

  2. Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing.

    PubMed

    Liang, Chen; Sun, Jingchun; Tao, Cui

    2016-01-01

    Despite ongoing progress towards treating mental illness, there remain significant difficulties in selecting probable candidate drugs from the existing database. We describe an ontology - oriented approach aims to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. Along with this approach, we report a case study in which we attempted to explore the candidate drugs that effective for both bipolar disorder and epilepsy. We constructed an ontology that incorporates the knowledge between the two diseases and performed semantic reasoning task on the ontology. The reasoning results suggested 48 candidate drugs that hold promise for a further breakthrough. The evaluation was performed and demonstrated the validity of the proposed ontology. The overarching goal of this research is to build a framework of ontology - based data integration underpinning psychiatric drug repurposing. This approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders. PMID:27570661

  3. Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing.

    PubMed

    Liang, Chen; Sun, Jingchun; Tao, Cui

    2016-01-01

    Despite ongoing progress towards treating mental illness, there remain significant difficulties in selecting probable candidate drugs from the existing database. We describe an ontology - oriented approach aims to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. Along with this approach, we report a case study in which we attempted to explore the candidate drugs that effective for both bipolar disorder and epilepsy. We constructed an ontology that incorporates the knowledge between the two diseases and performed semantic reasoning task on the ontology. The reasoning results suggested 48 candidate drugs that hold promise for a further breakthrough. The evaluation was performed and demonstrated the validity of the proposed ontology. The overarching goal of this research is to build a framework of ontology - based data integration underpinning psychiatric drug repurposing. This approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders.

  4. EPR studies of intermolecular interactions and competitive binding of drugs in a drug-BSA binding model.

    PubMed

    Akdogan, Y; Emrullahoglu, M; Tatlidil, D; Ucuncu, M; Cakan-Akdogan, G

    2016-08-10

    Understanding intermolecular interactions between drugs and proteins is very important in drug delivery studies. Here, we studied different binding interactions between salicylic acid and bovine serum albumin (BSA) using electron paramagnetic resonance (EPR) spectroscopy. Salicylic acid was labeled with a stable radical (spin label) in order to monitor its mobilized (free) or immobilized (bound to BSA) states. In addition to spin labeled salicylic acid (SL-salicylic acid), its derivatives including SL-benzoic acid, SL-phenol, SL-benzene, SL-cyclohexane and SL-hexane were synthesized to reveal the effects of various drug binding interactions. EPR results of these SL-molecules showed that hydrophobic interaction is the main driving force. Whereas each of the two functional groups (-COOH and -OH) on the benzene ring has a minute but detectable effect on the drug-protein complex formation. In order to investigate the effect of electrostatic interaction on drug binding, cationic BSA (cBSA) was synthesized, altering the negative net charge of BSA to positive. The salicylic acid loading capacity of cBSA is significantly higher compared to that of BSA, indicating the importance of electrostatic interaction in drug binding. Moreover, the competitive binding properties of salicylic acid, ibuprofen and aspirin to BSA were studied. The combined EPR results of SL-salicylic acid/ibuprofen and SL-ibuprofen/salicylic acid showed that ibuprofen is able to replace up to ∼83% of bound SL-salicylic acid, and salicylic acid can replace only ∼14% of the bound SL-ibuprofen. This indicates that ∼97% of all salicylic acid and ibuprofen binding sites are shared. On the other hand, aspirin replaces only ∼23% of bound SL-salicylic acid, and salicylic acid replaces ∼50% of bound SL-aspirin, indicating that ∼73% of all salicylic acid and aspirin binding sites are shared. These results show that EPR spectroscopy in combination with the spin labeling technique is a very powerful

  5. EPR studies of intermolecular interactions and competitive binding of drugs in a drug-BSA binding model.

    PubMed

    Akdogan, Y; Emrullahoglu, M; Tatlidil, D; Ucuncu, M; Cakan-Akdogan, G

    2016-08-10

    Understanding intermolecular interactions between drugs and proteins is very important in drug delivery studies. Here, we studied different binding interactions between salicylic acid and bovine serum albumin (BSA) using electron paramagnetic resonance (EPR) spectroscopy. Salicylic acid was labeled with a stable radical (spin label) in order to monitor its mobilized (free) or immobilized (bound to BSA) states. In addition to spin labeled salicylic acid (SL-salicylic acid), its derivatives including SL-benzoic acid, SL-phenol, SL-benzene, SL-cyclohexane and SL-hexane were synthesized to reveal the effects of various drug binding interactions. EPR results of these SL-molecules showed that hydrophobic interaction is the main driving force. Whereas each of the two functional groups (-COOH and -OH) on the benzene ring has a minute but detectable effect on the drug-protein complex formation. In order to investigate the effect of electrostatic interaction on drug binding, cationic BSA (cBSA) was synthesized, altering the negative net charge of BSA to positive. The salicylic acid loading capacity of cBSA is significantly higher compared to that of BSA, indicating the importance of electrostatic interaction in drug binding. Moreover, the competitive binding properties of salicylic acid, ibuprofen and aspirin to BSA were studied. The combined EPR results of SL-salicylic acid/ibuprofen and SL-ibuprofen/salicylic acid showed that ibuprofen is able to replace up to ∼83% of bound SL-salicylic acid, and salicylic acid can replace only ∼14% of the bound SL-ibuprofen. This indicates that ∼97% of all salicylic acid and ibuprofen binding sites are shared. On the other hand, aspirin replaces only ∼23% of bound SL-salicylic acid, and salicylic acid replaces ∼50% of bound SL-aspirin, indicating that ∼73% of all salicylic acid and aspirin binding sites are shared. These results show that EPR spectroscopy in combination with the spin labeling technique is a very powerful

  6. Magnetic Drug Targeting: Preclinical in Vivo Studies, Mathematical Modeling, and Extrapolation to Humans.

    PubMed

    Al-Jamal, Khuloud T; Bai, Jie; Wang, Julie Tzu-Wen; Protti, Andrea; Southern, Paul; Bogart, Lara; Heidari, Hamed; Li, Xinjia; Cakebread, Andrew; Asker, Dan; Al-Jamal, Wafa T; Shah, Ajay; Bals, Sara; Sosabowski, Jane; Pankhurst, Quentin A

    2016-09-14

    A sound theoretical rationale for the design of a magnetic nanocarrier capable of magnetic capture in vivo after intravenous administration could help elucidate the parameters necessary for in vivo magnetic tumor targeting. In this work, we utilized our long-circulating polymeric magnetic nanocarriers, encapsulating increasing amounts of superparamagnetic iron oxide nanoparticles (SPIONs) in a biocompatible oil carrier, to study the effects of SPION loading and of applied magnetic field strength on magnetic tumor targeting in CT26 tumor-bearing mice. Under controlled conditions, the in vivo magnetic targeting was quantified and found to be directly proportional to SPION loading and magnetic field strength. Highest SPION loading, however, resulted in a reduced blood circulation time and a plateauing of the magnetic targeting. Mathematical modeling was undertaken to compute the in vivo magnetic, viscoelastic, convective, and diffusive forces acting on the nanocapsules (NCs) in accordance with the Nacev-Shapiro construct, and this was then used to extrapolate to the expected behavior in humans. The model predicted that in the latter case, the NCs and magnetic forces applied here would have been sufficient to achieve successful targeting in humans. Lastly, an in vivo murine tumor growth delay study was performed using docetaxel (DTX)-encapsulated NCs. Magnetic targeting was found to offer enhanced therapeutic efficacy and improve mice survival compared to passive targeting at drug doses of ca. 5-8 mg of DTX/kg. This is, to our knowledge, the first study that truly bridges the gap between preclinical experiments and clinical translation in the field of magnetic drug targeting. PMID:27541372

  7. An Anthropological Paradigm for the Study of Youth and Drugs

    ERIC Educational Resources Information Center

    Soloway, Irving H.; And Others

    1977-01-01

    Authors note that the focus of their current research is substantive. They have begun to analyze and explicate the native defined views of an age-stratified set of peer groups with respect to numerous variables such as their concepts of health and sickness and their definitions of drugs. (Author/AM)

  8. Area-Specific Marginal Costing for Electric Utilities: a Case Study of Transmission and Distribution Costs

    NASA Astrophysics Data System (ADS)

    Orans, Ren

    1990-10-01

    utility distribution investment. The study makes use of data from an actual distribution planning area, located within PGandE's service territory, to demonstrate the important characteristics of this new costing approach. The most significant result of this empirical work is that geographic differences in the cost of capacity in distribution systems can be as much as four times larger than the current system average utility estimates. Furthermore, lumpy capital investment patterns can lead to significant cost differences over time.

  9. Brief strategic family therapy for adolescent drug abusers: a multi-site effectiveness study.

    PubMed

    Robbins, Michael S; Szapocznik, José; Horigian, Viviana E; Feaster, Daniel J; Puccinelli, Marc; Jacobs, Petra; Burlew, Kathy; Werstlein, Robert; Bachrach, Ken; Brigham, Greg

    2009-05-01

    Brief strategic family therapy (BSFT) is a manualized treatment designed to address aspects of family functioning associated with adolescent drug use and behavior problems (J. Szapocznik, U. Hervis, S. Schwartz, (2003). Brief strategic family therapy for adolescent drug abuse. (NIH Publication No. 03-4751). Bethesda, MD: National Institute on Drug Abuse). Within the National Institute on Drug Abuse's (NIDA's) Clinical Trials Network, BSFT is being compared to treatment as usual (TAU) in a multisite, prospective randomized clinical trial for drug using adolescents and their families in outpatient settings. The effectiveness of BSFT is being compared to TAU in reducing adolescent drug use, conduct problems, and sexually risky behaviors as well as in improving family functioning and adolescent prosocial behaviors. This paper describes the following aspects of the study: specific aims, research design and study organization, assessment of primary and secondary outcomes, study treatments, data analysis plan, and data monitoring and safety reporting.

  10. How innovative are new drugs launched in the UK? A retrospective study of new drugs listed in the British National Formulary (BNF) 2001–2012

    PubMed Central

    Ward, Derek J; Slade, Angharad; Genus, Tracey; Martino, Orsolina I; Stevens, Andrew J

    2014-01-01

    Objectives Innovative new drugs offer potential benefits to patients, healthcare systems, governments and the pharmaceutical industry. Recent data suggest annual numbers of new drugs launched in the UK have increased in recent years, and we sought to understand whether this represents increasing numbers of highly innovative drugs being made available or the introduction of increasing numbers of drugs with limited additional therapeutic value. Design and setting Retrospective observational study of new drug entries in the British National Formulary (BNF). Primary and secondary outcome measures Number of new drugs launched in the UK each year (based on first appearance in the BNF) from 2001 to 2012, including new chemical entities and new biological drugs, categorised by degree of innovativeness according to published criteria that incorporate both clinical usefulness and the nature of the innovation. Results Highly innovative, moderately innovative and slightly innovative drugs made up 26%, 18% and 56% of all newly launched drugs, respectively, for the study period (n=290). There was an upward trend in annual numbers of slightly innovative drugs from 2004 onwards (R2=0.44), which aligned closely with the recovery in total numbers of new drugs launched each year since that time. There were no discernible time trends in the highly or moderately innovative categories. New drugs for malignancy and skin disease were most likely to be characterised as highly innovative (44% and 57%, respectively). Conclusions Highly innovative new drugs comprise only around a quarter of all new drug launches in the UK. In contrast, drugs categorised as only slightly innovative comprised well over half of all new drugs and annual numbers in this category are increasing. Current policy initiatives that seek to increase the supply of innovative new drugs have long-lead times to impact, and will need careful assessment to ensure they deliver their aims without unintended consequences. PMID

  11. Implicit and Explicit Drug-Related Cognitions during Detoxification Treatment Are Associated with Drug Relapse: An Ecological Momentary Assessment Study

    ERIC Educational Resources Information Center

    Marhe, Reshmi; Waters, Andrew J.; van de Wetering, Ben J. M.; Franken, Ingmar H. A.

    2013-01-01

    Objective: Relapse is a major problem in drug addiction treatment. Both drug craving and drug-related cognitions (e.g., attentional bias and implicit attitudes to drugs) may contribute to relapse. Using ecological momentary assessments, we examined whether craving and cognitions assessed during drug detoxification treatment were associated with…

  12. A retrospective study to assess resource utilization in patients with cervical dystonia in the United Kingdom

    PubMed Central

    Raluy-Callado, Mireia; Gabriel, Sylvie; Dinet, Jérôme; Wang, Meng; Wasiak, Radek

    2015-01-01

    Purpose Cervical dystonia (CD) is a hypertonic condition caused by damage to the central nervous system. Very few studies have assessed the overall economic burden of the disease. The objective of this study was to describe the utilization of health care resources of patients with CD in the UK primary care setting, using a large population-based database. Patients and methods Adults with a first diagnosis of CD between January 1, 2007 and January 31, 2011, who were registered to a general practitioner (GP) practice contributing to The Health Improvement Network (THIN), were included. Sociodemographic and clinical characteristics were assessed at the time of diagnosis. Health care resource utilization and pharmacological treatment were investigated at the end of the first and second year after diagnosis. Results Overall, 4,024 newly diagnosed patients with CD were identified, with average age at diagnosis of 45 years old; 65.3% were female. Depression in the year prior to diagnosis was the most common comorbidity. Primary care utilization was high in the first year, with 99.2% of patients visiting their GP (on average 6.2 times), and 43% visiting a nurse (on average 2.5 times). Patients were most commonly referred to an orthopedic surgeon, and 15.9% reported at least one physiotherapy visit. In the second year, utilization was similar. Prescriptions of at least one of the investigated treatments were found in 82.0% and 45.3%, in the first and second year, respectively. Conclusion Findings suggest a high number of new CD cases are being identified in primary care, but not all will be referred to secondary care. Health care resource utilization was compared with that of all patients registered in THIN, which is representative of the UK, and the adjusted usage of primary care resources was found to be similar to that of the THIN population. PMID:25834443

  13. Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders.

    PubMed

    Barral, Serena; Kurian, Manju A

    2016-01-01

    The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders. PMID:27656126

  14. Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders

    PubMed Central

    Barral, Serena; Kurian, Manju A.

    2016-01-01

    The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders. PMID:27656126

  15. Healthcare utilization and costs in patients beginning pharmacotherapy for generalized anxiety disorder: a retrospective cohort study

    PubMed Central

    2011-01-01

    Background Patterns of healthcare utilization and costs in patients beginning pharmacotherapy for generalized anxiety disorder (GAD) have not been well characterized. Methods Using a large US health insurance database, we identified all patients with evidence of GAD (ICD-9-CM diagnosis code 300.02) who initiated pharmacotherapy with medications commonly used to treat GAD (eg, selective serotonin reuptake inhibitors [SSRIs], venlafaxine, benzodiazepines) between 1/1/2003 and 12/31/2007. We examined healthcare utilization and costs over the 12-month periods preceding and following date of initial receipt of such therapy ("pretreatment" and "follow-up", respectively). Patients with incomplete data were excluded. Results A total of 10,275 patients met all study inclusion criteria. Forty-eight percent of patients received SSRIs; 34%, benzodiazepines; and 6%, venlafaxine. SSRIs and venlafaxine were about three times more likely to be used on a long-term basis (> 90 days) than benzodiazepines (p < 0.01). In general, levels of healthcare utilization were higher during follow-up than pretreatment. Mean (SD) total healthcare costs increased from $4812 ($10,006) during pretreatment to $7182 ($22,041) during follow-up (p < 0.01); costs of GAD-related pharmacotherapy during follow-up were $420 ($485). Conclusions More than one-half of patients initiating pharmacotherapy for GAD receive either SSRIs or venlafaxine. Levels of healthcare utilization and costs are greater in the year following initiation of therapy than in the immediately preceding one. PMID:22151689

  16. Investigation of parameters highlighting drug induced small changes of the T-wave's morphology for drug safety studies.

    PubMed

    Baas, Tobias; Gräfe, Ksenija; Khawaja, Antoun; Dössel, Olaf

    2011-01-01

    In guideline E14, the American Food and Drug Administration (FDA) requests for clinical studies to investigate the prolongation of the heart rate corrected QT-interval (QTc) of the ECG. As drug induced QT-prolongation can be caused by changes in the repolarisation of the ventricles, it is so far a thorough ECG biomarker of risk for ventricular tachyarrhythmias and Torsade de Pointes (TdP). Ventricular repolarisation changes not only change QT but also influence the morphology of the T-wave. In a (400 mg single dose) Moxifloxacin positive control study both, QTc and several descriptors describing the T-wave morphology have been measured. Moxifloxacin is changing two shape dependent descriptors significantly (P<0.05) about 3 to 4 hours after a 400 mg oral single dose of Moxifloxacin.

  17. Evaluating Drugs and Food Additives for Public Use: A Case Studies Approach.

    ERIC Educational Resources Information Center

    Merritt, Sheridan V.

    1980-01-01

    Described is a case study used in an introductory college biology course that provides a basis for generating debate on an issue concerning the regulation of controversial food additives and prescription drugs. The case study contained within this article deals with drug screening, specifically with information related to thalidomide. (CS)

  18. A food waste utilization study for removing lead(II) from drinks.

    PubMed

    Kaplan Ince, Olcay; Ince, Muharrem; Yonten, Vahap; Goksu, Ali

    2017-01-01

    This is the first study about removal of lead (Pb(II)) from energy drinks. In this paper, food waste, namely eggshell (hydroxyapatite) utilization, was used to remove Pb(II) from mineral water and energy drinks. Mineral water and energy drinks were chosen for removal of lead since the latter is severely hazardous to human health even in small amounts. Response Surface Methodology (RSM) was performed to optimize the application process by practice of the quadratic model united with the Central Composite Design (CCD) and quadratic combined program was utilized to study the most effective parameters on aforementioned liquids. Through the application of variance analysis (ANOVA) factors critical to removing of lead were identified for each experimental design response. Maximum adsorption capacity of eggshell was achieved as 923mgg(-1) for Pb(II). The obtained optimum conditions were applied to drinks. Results showed that used adsorbent was quite effective in removing Pb(II) from drinks. PMID:27507520

  19. A food waste utilization study for removing lead(II) from drinks.

    PubMed

    Kaplan Ince, Olcay; Ince, Muharrem; Yonten, Vahap; Goksu, Ali

    2017-01-01

    This is the first study about removal of lead (Pb(II)) from energy drinks. In this paper, food waste, namely eggshell (hydroxyapatite) utilization, was used to remove Pb(II) from mineral water and energy drinks. Mineral water and energy drinks were chosen for removal of lead since the latter is severely hazardous to human health even in small amounts. Response Surface Methodology (RSM) was performed to optimize the application process by practice of the quadratic model united with the Central Composite Design (CCD) and quadratic combined program was utilized to study the most effective parameters on aforementioned liquids. Through the application of variance analysis (ANOVA) factors critical to removing of lead were identified for each experimental design response. Maximum adsorption capacity of eggshell was achieved as 923mgg(-1) for Pb(II). The obtained optimum conditions were applied to drinks. Results showed that used adsorbent was quite effective in removing Pb(II) from drinks.

  20. Veterans Affairs databases are accurate for gout-related health care utilization: a validation study

    PubMed Central

    2013-01-01

    Introduction The aim of this study was to assess the accuracy of Veterans Affairs (VA) databases for gout-related health care utilization. Methods This retrospective study utilized VA administrative and clinical databases. A random sample of gout patients with visits (outpatient, inpatient or emergent/urgent care) with or without the diagnosis of gout (International Classification of Diseases, ninth revision, common modification ICD-9-CM code of 274.x or 274.xx) at the Birmingham VA hospital was selected. A blinded abstractor performed a review of VA electronic health records for the documentation of gout or gout-related terms (gouty arthritis, tophaceous gout, tophus/tophi, acute gout, chronic gout, podagra, urate stones, urate or uric acid crystals and so on) in the chief complaint, history of present illness or assessment and plan for the visit; this constituted the gold standard for gout-related utilization. The accuracy of database-derived gout-related claims was assessed by calculating sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Results Of 108 potential visits, 85 outpatient, inpatient or urgent care/emergency room visits to a health care provider (85 patients: 84 men and 1 woman with a mean age of 63 years) and retrievable data from medical records constituted the analyzed dataset. Administrative claims for gout-related utilization with ICD-9 code for gout were accurate with a PPV of 86%, specificity of 95%, sensitivity of 86% and NPV of 95%. Conclusions VA databases are accurate for gout-related visits. These findings support their use for studies of health services and outcome studies. It remains to be seen if these findings are generalizable to other settings and databases. PMID:24377421

  1. Toward a European definition for a drug shortage: a qualitative study

    PubMed Central

    De Weerdt, Elfi; Simoens, Steven; Casteels, Minne; Huys, Isabelle

    2015-01-01

    Background: Drug shortages are currently on the rise. In-depth investigation of the problem is necessary, however, a variety of definitions for ‘drug shortages’ are formulated in legislations, by different organizations, authorities, and other initiatives. For international comparison, the underlying definition for drug shortages is important to allow appropriate interpretation of national databases and the results of scientific studies. The objective is to identify the different elements which should be considered in a uniform definition for drug shortages in the European Union (EU) and to detect the different conditions for reporting drug shortages. Materials and Methods: Definitions of drug shortages were searched in the scientific databases as well as in the gray literature. Similar topics were identified and organizations were contacted to formulate the reasoning underlying the definitions. Results: Over 20 different definitions for drug shortages were identified. A distinction is made between general definitions of drug shortages and definitions used for the reporting of drug shortages. Differences and similarities are observed in the elements within the definitions, e.g., when does a supply problem become a drug shortage, permanent and/or temporally shortages, the typology and time frame of a drug shortage. The moment a supply problem is considered as a shortage, can be defined at four levels: (i) demand side, (ii) supply side, (iii) delivery of a drug, and (iv) availability of a drug. Permanent discontinuations of drugs are not always covered in definitions for drug shortages. Some definitions only consider those drugs used for the treatment of serious diseases or drugs for which no alternative is available. Different time frames were observed, varying between 1 day and 20 days. Conclusion: Obtaining a uniform definition for drug shortages is important as well as identifying which conditions are preferable to report drug shortages in order to facilitate

  2. Middle and High School Drug Testing and Student Illicit Drug Use: A National Study 1998–2011

    PubMed Central

    O’Malley, Patrick M.; Johnston, Lloyd D.

    2013-01-01

    Purpose This study uses 14 years of data from nationally representative samples of US middle and high school students in the Monitoring the Future study to examine associations between school student drug testing (SDT), substance use, and participation in extracurricular activities. Methods Analyses use questionnaire data collected from 1998–2011 from 89,575 students in 883 middle schools and 157,400 students in 1,463 high schools to examine: (1) the current prevalence of SDT; (2) SDT trends over time; (3) associations between substance use and SDT type, volume, or duration among the general student population or students participating in activities subject to testing; (4) associations between students’ beliefs/attitudes about marijuana use and SDT; and (5) associations between extracurricular participation rates and SDT. Results Moderately lower marijuana use was associated with any random testing of the general high school student population and for SDT of middle and high school sub-populations specifically subject to testing (athletes or participants in non-athletic extracurricular activities). However, SDT generally was associated with increased use of illicit drugs other than marijuana. Conclusions Because the study design is observational and the data are cross-sectional, no strong causal conclusions can be drawn. However, there is evidence of lower marijuana use in the presence of SDT, and evidence of higher use of illicit drugs other than marijuana. Until further research can clarify the apparent opposing associations, schools should approach SDT with caution. PMID:23406889

  3. Best practices for the use of itraconazole as a replacement for ketoconazole in drug-drug interaction studies.

    PubMed

    Liu, Lichuan; Bello, Akintunde; Dresser, Mark J; Heald, Donald; Komjathy, Steven Ferenc; O'Mara, Edward; Rogge, Mark; Stoch, S Aubrey; Robertson, Sarah M

    2016-02-01

    Ketoconazole has been widely used as a strong cytochrome P450 (CYP) 3A (CYP3A) inhibitor in drug-drug interaction (DDI) studies. However, the US Food and Drug Administration has recommended limiting the use of ketoconazole to cases in which no alternative therapies exist, and the European Medicines Agency has recommended the suspension of its marketing authorizations because of the potential for serious safety concerns. In this review, the Innovation and Quality in Pharmaceutical Development's Clinical Pharmacology Leadership Group (CPLG) provides a compelling rationale for the use of itraconazole as a replacement for ketoconazole in clinical DDI studies and provides recommendations on the best practices for the use of itraconazole in such studies. Various factors considered in the recommendations include the choice of itraconazole dosage form, administration in the fasted or fed state, the dose and duration of itraconazole administration, the timing of substrate and itraconazole coadministration, and measurement of itraconazole and metabolite plasma concentrations, among others. The CPLG's recommendations are based on careful review of available literature and internal industry experiences.

  4. Inequality and inequity in healthcare utilization in urban Nepal: a cross-sectional observational study

    PubMed Central

    Saito, Eiko; Gilmour, Stuart; Yoneoka, Daisuke; Gautam, Ghan Shyam; Rahman, Md Mizanur; Shrestha, Pradeep Krishna; Shibuya, Kenji

    2016-01-01

    Inequality in access to quality healthcare is a major health policy challenge in many low- and middle-income countries. This study aimed to identify the major sources of inequity in healthcare utilization using a population-based household survey from urban Nepal. A cross-sectional survey was conducted covering 9177 individuals residing in 1997 households in five municipalities of Kathmandu valley between 2011 and 2012. The concentration index was calculated and a decomposition method was used to measure inequality in healthcare utilization, along with a horizontal inequity index (HI) to estimate socioeconomic inequalities in healthcare utilization. Results showed a significant pro-rich distribution of general healthcare utilization in all service providers (Concentration Index: 0.062, P < 0.001; HI: 0.029, P < 0.05) and private service providers (Concentration Index: 0.070, P < 0.001; HI: 0.030, P < 0.05). The pro-rich distribution of probability in general healthcare utilization was attributable to inequalities in the level of household economic status (percentage contribution: 67.8%) and in the self-reported prevalence of non-communicable diseases such as hypertension (36.7%) and diabetes (14.4%). Despite the provision of free services by public healthcare providers, our analysis found no evidence of the poor making more use of public health services (Concentration Index: 0.041, P = 0.094). Interventions to reduce the household economic burden of major illnesses, coupled with improvement in the management of public health facilities, warrant further attention by policy-makers. PMID:26856362

  5. Inequality and inequity in healthcare utilization in urban Nepal: a cross-sectional observational study.

    PubMed

    Saito, Eiko; Gilmour, Stuart; Yoneoka, Daisuke; Gautam, Ghan Shyam; Rahman, Md Mizanur; Shrestha, Pradeep Krishna; Shibuya, Kenji

    2016-09-01

    Inequality in access to quality healthcare is a major health policy challenge in many low- and middle-income countries. This study aimed to identify the major sources of inequity in healthcare utilization using a population-based household survey from urban Nepal. A cross-sectional survey was conducted covering 9177 individuals residing in 1997 households in five municipalities of Kathmandu valley between 2011 and 2012. The concentration index was calculated and a decomposition method was used to measure inequality in healthcare utilization, along with a horizontal inequity index (HI) to estimate socioeconomic inequalities in healthcare utilization. Results showed a significant pro-rich distribution of general healthcare utilization in all service providers (Concentration Index: 0.062, P < 0.001; HI: 0.029, P < 0.05) and private service providers (Concentration Index: 0.070, P < 0.001; HI: 0.030, P < 0.05). The pro-rich distribution of probability in general healthcare utilization was attributable to inequalities in the level of household economic status (percentage contribution: 67.8%) and in the self-reported prevalence of non-communicable diseases such as hypertension (36.7%) and diabetes (14.4%). Despite the provision of free services by public healthcare providers, our analysis found no evidence of the poor making more use of public health services (Concentration Index: 0.041, P = 0.094). Interventions to reduce the household economic burden of major illnesses, coupled with improvement in the management of public health facilities, warrant further attention by policy-makers. PMID:26856362

  6. Kinetic study on the reactions of platinum drugs with glutathione.

    PubMed

    Hagrman, Douglas; Goodisman, Jerry; Souid, Abdul-Kader

    2004-02-01

    The binding of platinum (Pt) drugs (oxaliplatin, carboplatin, and cisplatin) to glutathione (GSH, 6.75 mM) was investigated at 37 degrees C in Hepes (100 mM, pH approximately 7.4) or Tris-NO(3) (60 mM, pH 7.4) buffer and NaCl (4.62, 6.63, or 7.82 mM). The conditions were chosen to mimic passage of clinical concentrations of the drugs (135 microM) through the cytosol. The reactions were monitored by UV-absorption spectroscopy, high-performance liquid chromatography (HPLC), and atomic absorption spectroscopy. The initial rates, detected by UV absorbance, were similar for oxaliplatin and cisplatin reacting with GSH and were more than 5-fold faster than for carboplatin reacting with GSH. The Pt contents in HPLC eluates corresponding to unbound drug decreased exponentially with time, confirming that the reactions were first order in [Pt drug] and allowing determination of the pseudo first-order rate constants (k(1)). The second-order rate constants (k(2)) were calculated as k(1) divided by [GSH]. The k(2) value for oxaliplatin reacting with GSH was approximately 3.8 x 10(-2) M(-1) s(-1), for cisplatin reacting with GSH approximately 2.7 x 10(-2) M(-1) s(-1), and for carboplatin reacting with GSH approximately 1.2 x 10(-3) M(-1) s(-1) (approximately 32-fold slower than that of oxaliplatin and approximately 23-fold slower than that of cisplatin). These results demonstrate an influence of ligands surrounding the Pt coordination sphere on the reactivity of Pt(2+) with GSH.

  7. Use of illicit stimulant drugs in Finland: a wastewater study in ten major cities.

    PubMed

    Kankaanpää, Aino; Ariniemi, Kari; Heinonen, Mari; Kuoppasalmi, Kimmo; Gunnar, Teemu

    2014-07-15

    Estimations of drug use at the national level are generally based on various sources of information, such as drug seizures, socio-scientific studies, toxicological data and hospital records. Nevertheless, all of these approaches have limitations that cannot be overcome, even if conclusions are drawn from combined data retrieved from different sources. Drug epidemiology through wastewater analysis has the potential to provide unique perspectives, internationally comparable data, and up-to-date information on the use of both traditional illicit drugs and new psychoactive substances (NPSs). In Finland, no large-scale studies on regional illicit drug consumption, based on a wastewater approach, have been reported. In this study, 24-h influent composite samples were collected during two 1-week study periods from ten different wastewater treatment plants in May and November-December 2012. The cities included in the study represent the geographical areas throughout Finland and cover 40% of the Finnish population. The samples were analyzed with an in-house validated, ultra high-performance liquid-chromatography mass spectrometric (UHPLC-MS/MS) method for various common illicit drugs and some NPS type stimulant drugs. The results were also compared with available statistics, information on drug seizures and laboratory-confirmed toxicological data, as well as other studies available based on wastewater analysis. The data show that illicit stimulant drug use is more common in the larger cities of Southern Finland. Amphetamine was the most commonly used drug in all 10 cities during both collection periods (excluding the collection period in May in Lappeenranta). Cocaine consumption remains very low in Finland in comparison to other European countries; it was concentrated in the biggest cities in Southern Finland. This study shows interesting temporal and spatial differences in drug use in Finland, as well as the possibilities of using wastewater analytics to reveal local

  8. Prodrug/Enzyme based acceleration of absorption of hydrophobic drugs: an in vitro study.

    PubMed

    Kapoor, Mamta; Siegel, Ronald A

    2013-09-01

    Poor water solubility of APIs is a key challenge in drug discovery and development as it results in low drug bioavailability upon local or systemic administration. The prodrug approach is commonly utilized to enhance solubility of hydrophobic drugs. However, for accelerated drug absorption, supersaturated solutions need to be employed. In this work, a novel prodrug/enzyme based system was developed wherein prodrug and enzyme are coadministered at the point of absorption (e.g., nasal cavity) to form in situ supersaturated drug solutions for enhanced bioavailability. A combination of fosphenytoin/alkaline phosphatase was used as a model system. Prodrug conversion kinetics were evaluated with various prodrug/enzyme ratios at pH 7.4 and 32 °C. Phenytoin permeation rates were determined at various degrees of supersaturation (S = 0.8-6.1), across confluent Madin Darby canine kidney II-wild type monolayers (a nasal epithelium model), with prodrug and enzyme spiked into the apical chamber. Membrane intactness was confirmed by measuring transepithelial electrical resistance and inulin permeability. Fosphenytoin and phenytoin concentrations were analyzed using HPLC. Results indicated that a supersaturated solution could be formed using such prodrug/enzyme systems. Drug absorption increased proportionately with increasing degrees of supersaturation; this flux was 1.5-6 fold greater than that for the saturated phenytoin solution. The experimental data fitted reasonably well to a two compartment pharmacokinetic (PK) model with first order conversion of prodrug to drug. This prodrug/enzyme system markedly enhances drug transport across the model membrane. Applied in vivo, this strategy could be used to facilitate drug absorption through mucosal membranes when absorption is limited by solubility.

  9. An evaluation of tandem mass spectrometry in drug metabolism studies.

    PubMed

    Naylor, S; Kajbaf, M; Lamb, J H; Jahanshahi, M; Gorrod, J W

    1993-07-01

    The use of precursor ion and constant neutral loss scanning as a means of rapidly detecting drug metabolites is evaluated. Four clinically useful drugs, namely (i) cyclophosphamide, (ii) mifentidine, (iii) cimetropium bromide and (iv) haloperidol, were subjected to microsomal incubations to afford phase I metabolites. Aside from a minor clean-up procedure involving zinc sulfate precipitation of microsomal proteins and solid-phase extraction of metabolites using a Sep-pak C-18 cartridge, the mixtures were analysed directly by fast atom bombardment tandem mass spectrometry. It is demonstrated that such screening strategies are important in detecting novel metabolites. However, there are some problems associated with only using such methods, including (i) the possibility of not detecting metabolites that undergo unusual collision-induced dissociation fragmentation pathways, (ii) the non-detection of metabolites that have undergone metabolic change at unusual sites of reactivity, and (iii) production of artifacts derived from the parent drug by the primary ionization process. Examples are discussed that highlight both the strengths and weaknesses of such an approach.

  10. Molecular modeling study of chiral drug crystals: lattice energy calculations.

    PubMed

    Li, Z J; Ojala, W H; Grant, D J

    2001-10-01

    The lattice energies of a number of chiral drugs with known crystal structures were calculated using Dreiding II force field. The lattice energies, including van der Waals, Coulombic, and hydrogen-bonding energies, of homochiral and racemic crystals of some ephedrine derivatives and of several other chiral drugs, are compared. The calculated energies are correlated with experimental data to probe the underlying intermolecular forces responsible for the formation of racemic species, racemic conglomerates, or racemic compounds, termed chiral discrimination. Comparison of the calculated energies among ephedrine derivatives reveals that a greater Coulombic energy corresponds to a higher melting temperature, while a greater van der Waals energy corresponds to a larger enthalpy of fusion. For seven pairs of homochiral and racemic compounds, correlation of the differences between the two forms in the calculated energies and experimental enthalpy of fusion suggests that the van der Waals interactions play a key role in the chiral discrimination in the crystalline state. For salts of the chiral drugs, the counter ions diminish chiral discrimination by increasing the Coulombic interactions. This result may explain why salt forms favor the formation of racemic conglomerates, thereby facilitating the resolution of racemates.

  11. A study on the utilization of advanced composites in commercial aircraft wing structure: Executive summary

    NASA Technical Reports Server (NTRS)

    Watts, D. J.

    1978-01-01

    The overall wing study objectives are to study and plan the effort by commercial transport aircraft manufacturers to accomplish the transition from current conventional materials and practices to extensive use of advanced composites in wings of aircraft that will enter service in the 1985-1990 time period. Specific wing study objectives are to define the technology and data needed to support an aircraft manufacturer's commitment to utilize composites primary wing structure in future production aircraft and to develop plans for a composite wing technology program which will provide the needed technology and data.

  12. The utility of human challenge studies in vaccine development: lessons learned from cholera.

    PubMed

    Shirley, Debbie-Ann T; McArthur, Monica A

    2011-10-01

    Experiments in which virulent infectious organisms are administered to healthy adult volunteers with the intent to deliberately induce infection have been practiced for centuries. Many useful applications have developed from these experiments such as the provision of evidence of microbial pathogenicity and the identification of key virulence factors. Challenge studies have also played an important role in the evaluation of preliminary efficacy of potential vaccine candidates. Over the past 40 years, these experimental human challenge studies have found particular utility with regards to the development of both living and nonliving attenuated cholera vaccines. This review highlights some of the important contributions made by these challenge studies to cholera vaccine research. PMID:24482781

  13. PARTICIPANT FOLLOWUP STUDY--THE PERT LECTURES, A CASE STUDY IN KNOWLEDGE DISSEMINATION AND UTILIZATION, VOLUME 2.

    ERIC Educational Resources Information Center

    COOK, DESMOND L.

    A FOLLOWUP STUDY WAS CONDUCTED OF THE PERT (PROGRAM EVALUATION AND REVIEW TECHNIQUE) LECTURES, CONDUCTED IN 1965 TO INFORM THE EDUCATIONAL COMMUNITY OF PERT AND TO ENCOURAGE ITS USE. QUESTIONNAIRES WERE SENT TO 397 LECTURE PARTICIPANTS TO DETERMINE THE DEGREE OF UTILIZATION OF THE INFORMATION PRESENTED AND TO SEEK INFORMATION ON THE DISSEMINATION…

  14. Toledo Public Schools School Utilization Study, 1980-81 School Year. 2nd Year Study. Elementary School Buildings.

    ERIC Educational Resources Information Center

    Toledo Public Schools, OH.

    In response to declining student enrollment, the Toledo, Ohio public school system conducted a school utilization study involving the evaluation of eight categories of achievement. These categories were: (1) educational adequacy as determined by the ability of the facility to meet the requirements of a good instructional program; (2) an overview…

  15. Psychomotor developmental effects of prenatal exposure to psychotropic drugs: a study in EFEMERIS database.

    PubMed

    Hurault-Delarue, Caroline; Damase-Michel, Christine; Finotto, Laurent; Guitard, Claudine; Vayssière, Christophe; Montastruc, Jean-Louis; Montastruc, François; Lacroix, Isabelle

    2016-10-01

    Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics. PMID:27324073

  16. Knowledge, perceptions and use of generic drugs: a cross sectional study

    PubMed Central

    de Lira, Claudio Andre Barbosa; Oliveira, Jéssica Nathalia Soares; Andrade, Marília dos Santos; Vancini-Campanharo, Cássia Regina; Vancini, Rodrigo Luiz

    2014-01-01

    Objective To assess the level of knowledge, perceptions and usage profile for generic drugs among laypersons. Methods A cross-sectional study was conducted with 278 volunteers (180 women and 98 men, aged 37.1±15.8 years). A questionnaire was drawn up with questions on their use, perceptions and knowledge of generic drugs. Results Most respondents (99.6%) knew that generic drugs exist, but only 48.6% were able to define them correctly, while 78.8% of the respondents had some information about generics. This information was obtained mainly through television (49.3%). In terms of generic drug characteristics, 79.1% stated that they were confident about their efficacy, 74.8% believed that generic drugs have the same effect as branded medications, 88.8% said that generics were priced lower than branded medications, and 80.2% stated that they bought generic drugs because of price. With regard to drugs prescribed by medical practitioners, 17.6% of the participants said that their doctors never prescribed generics and only 7.5% confirmed that their doctors always prescribed generics. Conclusion For the lay public, the sample in this study has sufficient knowledge of generic drugs in terms of definition, efficacy and cost. Consequently, the volunteers interviewed are very likely to use generics. Furthermore, the results of this study indicate that programs should be implemented in order to boost generic drug prescriptions by medical practitioners. PMID:25295444

  17. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    NASA Astrophysics Data System (ADS)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  18. Collagen as a delivery system for hydrophobic drugs: studies with cyclosporine.

    PubMed

    Gebhardt, B M; Kaufman, H E

    1995-01-01

    The time-honored approach to delivering drugs to the ocular surface is through the use of liquid drops and semisolid ointments. Such delivery systems, however, are not efficient at delivering therapeutic concentrations of drugs to the cornea and intraocularly. Over the past several years, we tested the biopolymer, collagen, as a means of delivering both hydrophilic and hydrophobic drugs to the ocular surface. This study summarizes results obtained using the hydrophobic drug, cyclosporine, incorporated into collagen shields and collagen particles. Corn oil drops containing cyclosporine were used as the control. Groups of anesthetized rabbits were fitted with collagen shields containing cyclosporine, treated topically with collagen particles containing cyclosporine suspended in an ocular surface lubricant, or given topical drops of corn oil containing cyclosporine. At intervals after a single treatment with one of the drug formulations, corneas, aqueous humor, and blood were collected for analysis of cyclosporine concentration. With either of the two collagen vehicles, peak concentrations of the drug were found in the cornea 4 hours after application. The corn oil vehicle yielded a significantly lower and earlier peak concentration (1 hour after application). By 8 hours, significant amounts of the drug were still present in the corneas of the collagen-treated animals, whereas drug levels in the corn oil treatment group had returned to baseline. Drug delivery profiles in the aqueous humor were similar, except that the amounts of drug were five times lower. No cyclosporine was detected in the blood from any of the treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Reasons for illicit drug use in people with schizophrenia: Qualitative study

    PubMed Central

    2010-01-01

    Background Drug misuse is an important clinical problem associated with a poorer outcome in patients who have a diagnosis of schizophrenia. Qualitative studies have rarely been used to elicit reasons for drug use in psychosis, but not in schizophrenia. Methods Seventeen people with a diagnosis of schizophrenia and who had used street drugs were interviewed and asked to describe, in narrative form, their street drug use from their early experiences to the present day. Grounded theory was used to analyse the transcripts. Results We identified five reasons for continuing street drug use. The reasons were: as an 'identity defining vocation', 'to belong to a peer group', due to 'hopelessness', because of 'beliefs about symptoms and how street drugs influence them' and viewing drugs as 'equivalent to taking psychotropic medication'. Street drugs were often used to reduce anxiety aroused by voice hearing. Some participants reported street drugs to focus their attention more on persecutory voices in the hope of outwitting their perceived persecutors. Conclusions It would be clinically useful to examine for the presence of the five factors in patients who have a diagnosis of schizophrenia and use street drugs, as this is likely to help the clinician to tailor management of substance misuse to the individual patient's beliefs. PMID:21092168

  20. Driving under the influence of non-alcohol drugs--An update. Part II: Experimental studies.

    PubMed

    Strand, M C; Gjerde, H; Mørland, J

    2016-07-01

    Experimental studies on the impairing effects of drugs of relevance to driving-related performance published between 1998 and 2015 were reviewed. Studies with on-the-road driving, driving simulators, and performance tests were included for benzodiazepines and related drugs, cannabis, opioids, stimulants, GHB, ketamine, antihistamines, and antidepressants. The findings in these experimental studies were briefly discussed in relation to a review of epidemiological studies published recently. The studies mainly concluded that there may be a significant psychomotor impairment after using benzodiazepines or related drugs, cannabis, opioids, GHB, or ketamine. Low doses of central stimulants did not seem to cause impairment of driving behavior. PMID:27257716

  1. Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

    SciTech Connect

    Cosgrove, Benjamin D.; King, Bracken M.; Hasan, Maya A.; Alexopoulos, Leonidas G.; Farazi, Paraskevi A.; Hendriks, Bart S.; Griffith, Linda G.; Sorger, Peter K.; Tidor, Bruce; Xu, Jinghai J.

    2009-06-15

    Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFN{gamma}, IL-1{alpha}, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1{alpha}, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.

  2. Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging.

    PubMed

    Kim, Hyuncheol; Lizak, Martin J; Tansey, Ginger; Csaky, Karl G; Robinson, Michael R; Yuan, Peng; Wang, Nam Sun; Lutz, Robert J

    2005-02-01

    Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA (Magnevist) released from a polymer-based implant in rabbit vitreous using T1-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10(-6) cm2 s(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane (representing the retina-choroidsclera membrane) of 6.0 x 10(-8) cm2 s(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10(-6) cm s(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system.

  3. Integration of heterogeneous clinical decision support systems and their knowledge sets: feasibility study with Drug-Drug Interaction alerts.

    PubMed

    Kam, Hye Jin; Kim, Jeong Ah; Cho, InSook; Kim, Yoon; Park, Rae Woong

    2011-01-01

    There exist limitations in both commercial and in-house clinical decision support systems (CDSSs) and issues related to the integration of different knowledge sources and CDSSs. We chose Standard-based Shareable Active Guideline Environment (SAGE) as a new architecture with knowledge integration and a centralized knowledge base which includes authoring/management functions and independent CDSS, and applied it to Drug-Drug Interaction (DDI) CDSS. The aim of this study was to evaluate the feasibility of the newly integrated DDI alerting CDSS into a real world hospital information system involving construction of an integrated CDSS derived from two heterogeneous systems and their knowledge sets. The proposed CDSS was successfully implemented and compensated for the weaknesses of the old CDSS from knowledge integration and management, and its applicability in actual situations was verified. Although the DDI CDSS was constructed as an example case, the new CDS architecture might prove applicable to areas of CDSSs.

  4. A Comparative Study of the Attitudes of College Students and Drug Treatment Center Residents Toward Drugs, Other Drug Users and Themselves.

    ERIC Educational Resources Information Center

    Page, Richard C.; Mitchell, Sam

    1986-01-01

    Assessed the attitudes of college students and drug treatment center residents with histories of using marijuana and amphetamines. The drug treatment center residents tended to devalue themselves, drugs, and peers in the drug culture to a greater extent than the students. (Author/BL)

  5. Study of phenanthrene utilizing bacterial consortia associated with cowpea (Vigna unguiculata) root nodules.

    PubMed

    Sun, Ran; Crowley, David E; Wei, Gehong

    2015-02-01

    Many legumes have been selected as model plants to degrade organic contaminants with their special associated rhizosphere microbes in soil. However, the function of root nodules during microbe-assisted phytoremediation is not clear. A pot study was conducted to examine phenanthrene (PHE) utilizing bacteria associated with root nodules and the effects of cowpea root nodules on phytoremediation in two different types of soils (freshly contaminated soil and aged contaminated soil). Cowpea nodules in freshly-contaminated soil showed less damage in comparison to the aged-contaminated soil, both morphologically and ultra-structurally by scanning electron microscopy. The study of polycyclic aromatic hydrocarbon (PAH) attenuation conducted by high performance liquid chromatography revealed that more PAH was eliminated from liquid culture around nodulated roots than nodule-free roots. PAH sublimation and denaturation gradient gel electrophoresis were applied to analyze the capability and diversity of PAH degrading bacteria from the following four parts of rhizo-microzone: bulk soil, root surface, nodule surface and nodule inside. The results indicated that the surface and inside of cowpea root nodules were colonized with bacterial consortia that utilized PHE. Our results demonstrated that root nodules not only fixed nitrogen, but also enriched PAH-utilizing microorganisms both inside and outside of the nodules. Legume nodules may have biotechnological values for PAH degradation. PMID:25601371

  6. Study of phenanthrene utilizing bacterial consortia associated with cowpea (Vigna unguiculata) root nodules.

    PubMed

    Sun, Ran; Crowley, David E; Wei, Gehong

    2015-02-01

    Many legumes have been selected as model plants to degrade organic contaminants with their special associated rhizosphere microbes in soil. However, the function of root nodules during microbe-assisted phytoremediation is not clear. A pot study was conducted to examine phenanthrene (PHE) utilizing bacteria associated with root nodules and the effects of cowpea root nodules on phytoremediation in two different types of soils (freshly contaminated soil and aged contaminated soil). Cowpea nodules in freshly-contaminated soil showed less damage in comparison to the aged-contaminated soil, both morphologically and ultra-structurally by scanning electron microscopy. The study of polycyclic aromatic hydrocarbon (PAH) attenuation conducted by high performance liquid chromatography revealed that more PAH was eliminated from liquid culture around nodulated roots than nodule-free roots. PAH sublimation and denaturation gradient gel electrophoresis were applied to analyze the capability and diversity of PAH degrading bacteria from the following four parts of rhizo-microzone: bulk soil, root surface, nodule surface and nodule inside. The results indicated that the surface and inside of cowpea root nodules were colonized with bacterial consortia that utilized PHE. Our results demonstrated that root nodules not only fixed nitrogen, but also enriched PAH-utilizing microorganisms both inside and outside of the nodules. Legume nodules may have biotechnological values for PAH degradation.

  7. In Vivo Studies Evaluating the Use of Contact Lenses for Drug Delivery.

    PubMed

    Hui, Alex; Willcox, Mark

    2016-04-01

    This review highlights the current state of knowledge of in vivo testing of drug-delivering contact lenses. There has been a significant increase in interest in alternative means to deliver ocular pharmaceuticals, and within the past few decades, contact lenses have emerged as a vehicle of interest because of their biocompatibility and acceptance by both eye care professionals and the public. Using techniques such as molecular imprinting, vitamin E diffusion barriers, ionic reservoirs, and drug-impregnated films, significantly improved drug release kinetics have been observed in vitro. Extension of these results into in vivo studies has thus far been limited but has led to evidence of the viability of this drug delivery platform by demonstrating improved drug residence time, drug penetration, and clinical outcomes when compared with conventional therapy such as eye drops. The evidence supporting these improvements has occurred in both animal models and small human trials and is presented within this review.

  8. In Vivo Studies Evaluating the Use of Contact Lenses for Drug Delivery.

    PubMed

    Hui, Alex; Willcox, Mark

    2016-04-01

    This review highlights the current state of knowledge of in vivo testing of drug-delivering contact lenses. There has been a significant increase in interest in alternative means to deliver ocular pharmaceuticals, and within the past few decades, contact lenses have emerged as a vehicle of interest because of their biocompatibility and acceptance by both eye care professionals and the public. Using techniques such as molecular imprinting, vitamin E diffusion barriers, ionic reservoirs, and drug-impregnated films, significantly improved drug release kinetics have been observed in vitro. Extension of these results into in vivo studies has thus far been limited but has led to evidence of the viability of this drug delivery platform by demonstrating improved drug residence time, drug penetration, and clinical outcomes when compared with conventional therapy such as eye drops. The evidence supporting these improvements has occurred in both animal models and small human trials and is presented within this review. PMID:26784709

  9. Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing.

    PubMed

    Liang, Chen; Sun, Jingchun; Tao, Cui

    2015-01-01

    There remain significant difficulties selecting probable candidate drugs from existing databases. We describe an ontology-oriented approach to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. We also report a case study in which we attempted to explore candidate drugs effective for bipolar disorder and epilepsy. We constructed an ontology incorporating knowledge between the two diseases and performed semantic reasoning tasks with the ontology. The results suggested 48 candidate drugs that hold promise for further breakthrough. The evaluation demonstrated the validity our approach. Our approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders.

  10. Incorporation of tramadol drug into Li-fluorohectorite clay: A preliminary study of a medical nanofluid

    NASA Astrophysics Data System (ADS)

    Valdés, L.; Hernández, D.; de Ménorval, L. Ch.; Pérez, I.; Altshuler, E.; Fossum, J. O.; Rivera, A.

    2016-07-01

    During the last years, clays have been increasingly explored as hosts for drugs. In the present paper, we have been able to host the non-steroidal anti-inflammatory drug, Tramadol, into the clay Li-fluorohectorite (Li-Fh). We preliminary evaluate its incorporation by means of UV spectroscopy and X ray diffraction. Our results indicate that the clay hosts the drug molecule in its interlayer space. We suggest a set of parameters to guarantee an efficient incorporation process. Future studies will concentrate on the release of the drug from the clay nanofluid.

  11. Utilizing Drumming for American Indians/Alaska Natives with Substance Use Disorders: A Focus Group Study

    PubMed Central

    Dickerson, Daniel; Robichaud, Francis; Teruya, Cheryl; Nagaran, Kathleen; Hser, Yih-Ing

    2013-01-01

    Background Drumming has been utilized among American Indian/Alaska Native (AI/AN) tribes for centuries to promote healing and self-expression. Drum-Assisted Recovery Therapy for Native Americans (DARTNA), currently under development, is a substance abuse treatment utilizing drumming as a core component. Objectives Focus groups were conducted to assist in the development of the DARTNA protocol. Feedback obtained from these focus groups will inform a subsequent pretest of DARTNA and an empirical study analyzing its effectiveness. Methods Three focus groups were conducted among AIs/ANs with substance use disorders (n = 6), substance abuse treatment providers (n = 8), and a community advisory board (n = 4) to solicit feedback prior to a pretest of the DARTNA protocol. Results Overall, participants indicated that DARTNA could be beneficial for AIs/ANs with substance use disorders. Four overarching conceptual themes emerged across the focus groups: (1) benefits of drumming, (2) importance of a culture-based focus, (3) addressing gender roles in drumming activities, and (4) providing a foundation of common AI/AN traditions. Conclusions The DARTNA protocol is a potentially beneficial and culturally appropriate substance abuse treatment strategy for AIs/ANs. In order to optimize the potential benefits of a substance abuse treatment protocol utilizing drumming for AIs/ANs, adequate attention to tribal diversity and gender roles is needed. Scientific Significance Due to the shortage of substance abuse treatments utilizing traditional healing activities for AIs/ANs, including drumming, results from this study provide an opportunity to develop an intervention that may meet the unique treatment needs of AIs/ANs. PMID:22931086

  12. Tyramine studies and the safety of MAOI drugs.

    PubMed

    Simpson, G M; White, K

    1984-07-01

    A major source of concern in using MAOIs is the risk of hypertensive crises, often called the "cheese effect" and thought to represent a drug-induced enhancement of the tyramine pressor effect. Several approaches to reduction of this risk are being explored, including use of inhibitors specific for the B vs. the A type of the enzyme, coadministration of tricyclic with MAOI, and development of reversible inhibitors which might be competitively displaced by tyramine. Such approaches require assessment of sensitivity to tyramine, usually given by the intravenous route. The oral tyramine pressor test, while cumbersome and in need of technical refinement, represents a significantly closer laboratory analogue to the clinical situation.

  13. A study on the utilization of advanced composites in commercial aircraft wing structure

    NASA Technical Reports Server (NTRS)

    Watts, D. J.

    1978-01-01

    A study was conducted to define the technology and data needed to support the introduction of advanced composite materials in the wing structure of future production aircraft. The study accomplished the following: (1) definition of acceptance factors, (2) identification of technology issues, (3) evaluation of six candidate wing structures, (4) evaluation of five program options, (5) definition of a composite wing technology development plan, (6) identification of full-scale tests, (7) estimation of program costs for the total development plan, (8) forecast of future utilization of composites in commercial transport aircraft and (9) identification of critical technologies for timely program planning.

  14. Drugs usage of drivers suspected of driving under the influence of alcohol and/or drugs. A study of one week's samples in 1979 and 1993 in Finland.

    PubMed

    Lillsunde, P; Korte, T; Michelson, L; Portman, M; Pikkarainen, J; Seppälä, T

    1996-01-12

    The extent of drug use among drivers suspected of driving under the influence of alcohol and/or drugs in Finland was studied. All blood samples submitted to the laboratory during 1 week in two study periods, in 1979 (n = 298) and 1993 (n = 332), were analyzed for alcohol and psychotropic drugs. Drugs classified as hazardous to traffic safety were detected in 7.0% of the samples in 1979 and 26.8% in 1993. Benzodiazepines were the most frequently found drugs in both years: 6.0% of the cases in 1979 and 22.9% in 1993. Illegal drugs were found in 4% of the cases in 1993. Of the samples tested, 296 in 1979 and 317 in 1993 were from drivers suspected of driving under the influence of alcohol only. In 1979 every fourteenth and in 1993 every fourth of these suspected drunken drivers had drugs in their blood. Drugs, other than alcohol, were found six times more often than expected by the police. The results indicate that the trend of drug use, multidrug use and drug abuse is increasing among cases suspected of driving under the influence of alcohol/drugs.

  15. Binge Drinkers, Illicit Drug Users, and Polydrug Users: An Epidemiological Study of American Collegians.

    ERIC Educational Resources Information Center

    Feigelman, William; Gorman, Bernard S.; Lee, Julia A.

    1998-01-01

    Compares four subgroups of young adult drug users based on secondary analysis of data originally collected in 1993. Consistent with results from clinical studies, polydrug users were far more likely to engage in risk-taking behaviors. Findings demonstrate the need to offer a full complement of drug rehabilitation and education services to…

  16. Beyond the Theoretical Rhetoric: A Proposal to Study the Consequences of Drug Legalization.

    ERIC Educational Resources Information Center

    Yacoubian, George S., Jr.

    2001-01-01

    In this study, the arguments surrounding the drug legalization debate are synthesized into a proposal for future research. Such a proposal illustrates that the core elements surrounding drug legalization are not only testable, but that the time may be right to consider such an empirical effort. (Author)

  17. Longitudinal HIV Risk Behavior among the Drug Abuse Treatment Outcome Studies (DATOS) Adult Sample

    ERIC Educational Resources Information Center

    Murphy, Debra A.; Brecht, Mary-Lynn; Herbeck, Diane; Evans, Elizabeth; Huang, David; Hser, Yih-Ing

    2008-01-01

    Longitudinal trajectories for HIV risk were examined over 5 years following treatment among 1,393 patients who participated in the nationwide Drug Abuse Treatment Outcome Studies. Both injection drug use and sexual risk behavior declined over time, with most of the decline occurring between intake and the first-year follow-up. However, results of…

  18. Healthcare Service Utilization for Practicing Physicians: A Population-Based Study

    PubMed Central

    Kao, Senyong; Lin, Herng-Ching; Lee, Cha-Ze

    2016-01-01

    Background Physicians are considered to be the most informed consumers in the use of medical services since they have more information about diseases or medical technology. However, although plenty of researchers have suggested that different medical seeking behavior exists among physicians, very few empirical studies have been conducted to investigate differences in medical utilization between physicians and the general population. Objective We explored differences in the utilization of healthcare services between physicians and the general population using a population-based dataset. Design A cross-sectional study. Participants Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included 1426 physicians and 1426 sex- and age-matched comparison subjects. Methods We used Wilcoxon-Mann-Whitney tests to explore differences in variables of healthcare resource utilization between physicians and comparison subjects. We further used Kruskal-Wallis tests to examine differences in variables of healthcare resource utilization between physician practice location and comparison subjects. Results We found that physicians had significantly fewer outpatient visits (13.2 vs. 15.7, p<0.001) and significantly lower outpatient costs (US$477 vs. US$680, p<0.001) than comparison subjects. Furthermore, physicians had lower total health service costs than comparison subjects (US$643 vs. US$1066, p<0.001). This indicates that the mean total health service costs in the year 2010 was 1.66-fold greater for comparison subjects than for physicians. We also found that there were significant differences in the mean number of outpatient services (p<0.001), outpatient costs (p = 0.001), inpatients costs (p = 0.018), and total costs (p = 0.001) among office-based physicians, hospital-based physicians, and comparison subjects. Specifically, Scheffe contrast tests showed that office-based physicians had significantly more outpatient visits (19.3 vs.10

  19. Pharmacy utilization and the Medicare Modernization Act.

    PubMed

    Maio, Vittorio; Pizzi, Laura; Roumm, Adam R; Clarke, Janice; Goldfarb, Neil I; Nash, David B; Chess, David

    2005-01-01

    To control expenditures and use medications appropriately, the Medicare drug coverage program has established pharmacy utilization management (PUM) measures. This article assesses the effects of these strategies on the care of seniors. The literature suggests that although caps on drug benefits lower pharmaceutical costs, they may also increase the use of other health care services and hurt health outcomes. Our review raises concerns regarding the potential unintended effects of the Medicare drug program's PUM policies for beneficiaries. Therefore, the economic and clinical impact of PUM measures on seniors should be studied further to help policymakers design better drug benefit plans. PMID:15787955

  20. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  1. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: II. In vitro transport study.

    PubMed

    Rao, Sripriya Venkata Ramana; Agarwal, Payal; Shao, Jun

    2008-10-01

    To develop a self-nanoemulsifying drug delivery system (SNEDDS) for protein drugs, and particularly, to test the in vitro transport of beta-lactamase (BLM) by SNEDDS across the cell monolayer. Fluorescently labeled BLM (FITC-BLM), a model protein, formulated into 16 SNEDDS preparations through a solid dispersion technique were studied for transport across MDCK monolayer. All the SNEDDS nanoemulsions resulted in higher transport rate than the free solution. The transport rate by SNEDDS depends on the SNEDDS composition. SNEDDS NE-12-7 (oil: Lauroglycol FCC, surfactant: Cremophor EL and a cosurfactant: Transcutol HP) at the ratio of 5:4:3, rendered the highest transportation rate, 33% as compared to negligible transport by the free solution. FITC-BLM solution mixed with the surfactant and the cosurfactant of SNEDDS NE-12-7 or with blank SNEDDS NE-12-7 increased the transport only by 3.3 and 1.5 folds, respectively, compared to free solution alone. It was found that the monolayer integrity was not compromised in the presence of SNEDDS NE-12-7 or its surfactant/cosurfactant. The SNEDDS significantly increased the transport of FITC-BLM across MDCK monolayer in vitro. SNEDDS may be a potential effective delivery system for non-invasive protein drug delivery.

  2. Artificial lightweight aggregates as utilization for future ashes - A case study.

    PubMed

    Sarabèr, Angelo; Overhof, Robert; Green, Terry; Pels, Jan

    2012-01-01

    In the future, more electricity in the Netherlands will be produced using coal with co-combustion. Due to this, the generated annual ash volume will increase and the chemical composition will be influenced. One of the options for utilization if present markets are saturated and for use of fly ashes with different compositions, is as raw material for lightweight aggregates. This was selected as one of the best utilizations options regarding potential ash volume to be applied, environmental aspects and status of technology. Because of this, a study has been performed to assess the potential utilization of fly ash for the production of lightweight aggregate. Lightweight aggregate has been produced in a laboratory scale rotary kiln. The raw material consisted of class F fly ash with high free lime content. An addition of 8% clay was necessary to get green pellets with sufficient green strength. The basic properties of the produced lightweight aggregate and its behaviour in concrete have been investigated. The concrete has a good compressive strength and its leaching behaviour meets the most stringent requirements of Dutch environmental regulations. The carbon foot print of concrete will be negatively influenced if only the concrete itself is taken into account, but the reduction of the volume weight has advantages regarding design, transport emissions and isolation properties which may counteract this. In the Dutch situation the operational costs are higher than expected potential selling price for the LWA, which implies that the gate fee for the fly ash is negative.

  3. Artificial lightweight aggregates as utilization for future ashes - A case study.

    PubMed

    Sarabèr, Angelo; Overhof, Robert; Green, Terry; Pels, Jan

    2012-01-01

    In the future, more electricity in the Netherlands will be produced using coal with co-combustion. Due to this, the generated annual ash volume will increase and the chemical composition will be influenced. One of the options for utilization if present markets are saturated and for use of fly ashes with different compositions, is as raw material for lightweight aggregates. This was selected as one of the best utilizations options regarding potential ash volume to be applied, environmental aspects and status of technology. Because of this, a study has been performed to assess the potential utilization of fly ash for the production of lightweight aggregate. Lightweight aggregate has been produced in a laboratory scale rotary kiln. The raw material consisted of class F fly ash with high free lime content. An addition of 8% clay was necessary to get green pellets with sufficient green strength. The basic properties of the produced lightweight aggregate and its behaviour in concrete have been investigated. The concrete has a good compressive strength and its leaching behaviour meets the most stringent requirements of Dutch environmental regulations. The carbon foot print of concrete will be negatively influenced if only the concrete itself is taken into account, but the reduction of the volume weight has advantages regarding design, transport emissions and isolation properties which may counteract this. In the Dutch situation the operational costs are higher than expected potential selling price for the LWA, which implies that the gate fee for the fly ash is negative. PMID:21963657

  4. Studies in Multifunctional Drug Development: Preparation and Evaluation of 11beta-Substituted Estradiol-Drug Conjugates, Cell Membrane Targeting Imaging Agents, and Target Multifunctional Nanoparticles

    NASA Astrophysics Data System (ADS)

    Dao, KinhLuan Lenny D.

    with an azido-tetraethylene glycol moiety that could be coupled to a complementary doxorubicin benzoyl hydrazone, functionalized with a propargyl tetraethylene glycol moiety. Huisgen [3+2] cycloaddition chemistry gave the final hybrid which was evaluated for receptor binding to demonstrate ER-affinity and for cytotoxicity in ER(+)-MCF-7 and ER(-)-MDA-MB-231 breast cancer cell lines. The anti-estrogen-doxorubicin hybrid demonstrated enhanced (>70-fold) selectivity for ER(+)-cells versus ER(-)-cells and enhanced efficacy compared to doxorubicin alone. The reversal of these effects by co-administration of estradiol demonstrated that the presence of the anti-estrogenic component was critical for selectivity and cytotoxicity in ER(+)-MCF-7 human breast cancer cells. The results suggest that this approach the basis for developing selective therapeutic agents for ER(+)-cancer cells with reduced effects on non-target tissues.1,2 The second study describes our use of 11beta-AE for targeting ER membrane targeting in hormone-dependent breast cancer, and of a urea-based prostate specific membrane antigen (PSMA) inhibitor for targeting PSMA membrane receptors in androgen-independent of prostate cancer. These derivatives were used to prepare a series of molecular imaging probes. We have successfully established our model compound, 11beta-AE radiolabeled with 18F-fluoro-OEG-azide, for in vivo imaging.3 The third study describes a strategy based on the design and synthesis of a multifunctional gold nanoparticulate (mfAuNPs) drug delivery system that can be used for prostate cancer therapy. We have utilized a convergent modular assembly approach to prepare individual components such as a) prostate specific membrane antigen (PSMA) ligands for targeting; b) pH-sensitive doxorubicin; and c) Re/99Tc chelating complex for radioimaging. The components can be assembled with a terminal lipoic acid or thiolated ethylene glycol oligomer for attachment to the Au surface. Initial in vitro studies

  5. Analysis of risk factors in human bioequivalence study that incur bioinequivalence of oral drug products.

    PubMed

    Yamashita, Shinji; Tachiki, Hidehisa

    2009-01-01

    In the study of human bioequivalence (BE), newly developed oral products sometimes fail to prove BE with a reference product due to the high variability in pharmacokinetic (PK) parameters after oral absorption. In this study, risk factors that incur bioinequivalence in BE study were analyzed by applying the Biopharmaceutics Classification System (BCS). Forty-four generic products were selected from a database of BE studies in the past 10 years at Towa Pharmaceutical Co., Ltd. (Osaka, Japan), and 90% confidence interval (CI) of AUC and C(max) in human BE study for all products were converted into coefficient of variation (CV(90)). Then, the required number of subjects to confirm BE was estimated from the 90% CI in human BE study of new products. It was found that both the permeability of drugs to human intestinal membrane (P(eff)) and the dose number calculated from their water solubility did not correlate well to CV(90) and the estimated subject number in human BE study, suggesting the contribution of other factors to cause the variability in oral drug absorption. As the PK parameter of drugs, the value of AUC/dose was calculated and plotted against CV(90) and the estimated subject number by classifying drugs into 4 BCS classes. For drugs in classes 1 and 3, AUC/dose gave a clear criterion to distinguish the drugs with a high risk of bioinequivalence, where drugs with low AUC/dose showed high CV(90) and large number of subjects. It was suggested that the high metabolic clearance (for class 1 drug) and low oral absorption (for class 3 drug) could be significant factors to incur bioinequivalence in human BE study, although for drugs in classes 2 and 4, clear factors were not defined. Consequently, for drugs in BCS classes 1 and 3, risks in human BE study to incur bioinequivalence could be predicted by calculating the AUC/dose. In the case of generic drugs, since the parameter of AUC/dose is available before initiating human BE study, this finding is expected to

  6. Pathways of colicin import: utilization of BtuB, OmpF porin and the TolC drug-export protein.

    PubMed

    Zakharov, Stanislav D; Sharma, Onkar; Zhalnina, Mariya; Yamashita, Eiki; Cramer, William A

    2012-12-01

    Pathway I. Group A nuclease colicins parasitize and bind tightly (Kd ≤ 10(-9) M) to the vitamin B12 receptor on which they diffuse laterally in the OM (outer membrane) and use their long (≥100 Å; 1 Å=0.1 nm) receptor-binding domain as a 'fishing pole' to locate the OmpF porin channel for translocation. Crystal structures of OmpF imply that a disordered N-terminal segment of the colicin T-domain initiates insertion. Pathway II. Colicin N does not possess a 'fishing pole' receptor-binding domain. Instead, it uses OmpF as the Omp (outer membrane protein) for reception and translocation, processes in which LPS (lipopolysaccharide) may also serve. Keio collection experiments defined the LPS core that is used. Pathway III. Colicin E1 utilizes the drug-export protein TolC for import. CD spectra and thermal-melting analysis predict: (i) N-terminal translocation (T) and central receptor (BtuB) -binding (R) domains are predominantly α-helical; and (ii) helical coiled-coil conformation of the R-domain is similar to that of colicins E3 and Ia. Recombinant colicin peptides spanning the N-terminal translocation domain defined TolC-binding site(s). The N-terminal 40-residue segment lacks the ordered secondary structure. Peptide 41-190 is helical (78%), co-elutes with TolC and occluded TolC channels. Driven by a trans-negative potential, peptides 82-140 and 141-190 occluded TolC channels. The use of TolC for colicin E1 import implies that the interaction of this colicin with the other Tol proteins does not occur in the periplasmic space, but rather through Tol domains in the cytoplasmic membrane, thus explaining colicin E1 cytotoxicity towards a strain in which a 234 residue periplasmic TolA segment is deleted.

  7. Studying synaptic plasticity in the human brain and opportunities for drug discovery.

    PubMed

    Nathan, Pradeep J; Cobb, Stuart R; Lu, Bai; Bullmore, Edward T; Davies, Ceri H

    2011-10-01

    Synaptic plasticity is the ability of synaptic connections between neurons to be strengthened or weakened; a process that is central to the information processing within the brain and which plays a particularly important role in enabling higher cognitive processes [1,2]. Its role in disease is becoming increasingly clear across a wide spectrum of CNS disorders. Thus, for example, dysfunctional synaptic plasticity has been reported in neurodegenerative disorders such as Alzheimer's Disease (AD) as well as in schizophrenia and in a range of disorders associated with learning disabilities [3]. Moreover, maladaptive plasticity processes in response to specific external challenges are believed to underlie disorders such as addiction and post-traumatic stress disorder (PTSD). The molecular basis of normal and disease plasticity is rapidly being unravelled such that synaptic plasticity now provides a unique platform from which to launch the hunt for highly innovative drugs to treat CNS disease by either, firstly, rectifying identifiable abnormalities in these processes, or secondly, utilizing these processes as a vehicle to rectify, or bypass, other mechanisms underlying disease. In this respect, recent advances have been made in studying synaptic plasticity in humans at the molecular through to clinical level and these approaches now provide a real opportunity to test synaptic plasticity as a treatment paradigm for a wide variety of CNS disorders.

  8. Studies on pectins as potential hydrogel matrices for controlled-release drug delivery.

    PubMed

    Sungthongjeen, S; Pitaksuteepong, T; Somsiri, A; Sriamornsak, P

    1999-12-01

    Polymeric hydrogels are widely used as controlled-release matrix tablets. In the present study, we investigated high-methoxy pectins for their potential value in controlled-release matrix formulations. The effects of compression force, ratio of drug to pectin, and type of pectin on drug release from matrix tablets were also investigated. The results of the in vitro release studies show that the drug release from compressed matrix tablets prepared from pectin can be modified by changing the amount and the type of pectin in the matrix tablets. However, compression force did not significantly affect the drug release. The mechanisms controlling release rate were discussed with respect to drug diffusion through the polymer matrices, but may be more complex.

  9. Adaptive Interventions May Optimize Outcomes in Drug Courts: A Pilot Study

    PubMed Central

    Marlowe, Douglas B.; Festinger, David S.; Arabia, Patricia L.; Dugosh, Karen L.; Benasutti, Kathleen M.; Croft, Jason R.

    2009-01-01

    Adaptive interventions apply a priori decision rules for adjusting treatment services in response to participants’ clinical presentation or performance in treatment. This pilot study (N = 30) experimentally examined an adaptive intervention in a misdemeanor drug court. The participants were primarily charged with possession of marijuana (73%) or possession of drug paraphernalia (23%). Results revealed that participants in the adaptive condition had relatively higher graduation rates and required significantly less time to graduate from the program and achieve a final resolution of the case. It took an average of nearly 4 fewer months for participants in the adaptive intervention to resolve their cases as compared to drug court as-usual. Participants in the adaptive condition also reported equivalent satisfaction with the program and therapeutic alliances with their counselors. These data suggest that adaptive interventions may enhance the efficiency and effectiveness of drug courts, and justify examining adaptive interventions in large-scale drug court studies. PMID:19785978

  10. A Parametric Geometry Computational Fluid Dynamics (CFD) Study Utilizing Design of Experiments (DOE)

    NASA Technical Reports Server (NTRS)

    Rhew, Ray D.; Parker, Peter A.

    2007-01-01

    Design of Experiments (DOE) techniques were applied to the Launch Abort System (LAS) of the NASA Crew Exploration Vehicle (CEV) parametric geometry Computational Fluid Dynamics (CFD) study to efficiently identify and rank the primary contributors to the integrated drag over the vehicles ascent trajectory. Typical approaches to these types of activities involve developing all possible combinations of geometries changing one variable at a time, analyzing them with CFD, and predicting the main effects on an aerodynamic parameter, which in this application is integrated drag. The original plan for the LAS study team was to generate and analyze more than1000 geometry configurations to study 7 geometric parameters. By utilizing DOE techniques the number of geometries was strategically reduced to 84. In addition, critical information on interaction effects among the geometric factors were identified that would not have been possible with the traditional technique. Therefore, the study was performed in less time and provided more information on the geometric main effects and interactions impacting drag generated by the LAS. This paper discusses the methods utilized to develop the experimental design, execution, and data analysis.

  11. The Methylene Alkoxy Carbamate Self-Immolative Unit: Utilization for the Targeted Delivery of Alcohol-Containing Payloads with Antibody-Drug Conjugates.

    PubMed

    Kolakowski, Robert V; Haelsig, Karl T; Emmerton, Kim K; Leiske, Chris I; Miyamoto, Jamie B; Cochran, Julia H; Lyon, Robert P; Senter, Peter D; Jeffrey, Scott C

    2016-07-01

    A strategy for the conjugation of alcohol-containing payloads to antibodies has been developed and involves the methylene alkoxy carbamate (MAC) self-immolative unit. A series of MAC β-glucuronide model constructs were prepared to evaluate stability and enzymatic release, and the results demonstrated high stability at physiological pH in a substitution-dependent manner. All the MAC model compounds efficiently released alcohol drug surrogates under the action of β-glucuronidase. To assess the MAC technology for ADCs, the potent microtubule-disrupting agent auristatin E (AE) was incorporated through the norephedrine alcohol. Conjugation of the MAC β-glucuronide AE drug linker to the anti-CD30 antibody cAC10, and an IgG control antibody, gave potent and immunologically specific activities in vitro and in vivo. These studies validate the MAC self-immolative unit for alcohol-containing payloads within ADCs, a class that has not been widely exploited. PMID:27198854

  12. Minimally Invasive Swine Experimental Model for the In Vivo Study of Liver Metabolism of Drugs

    PubMed Central

    Piazza, O; Romano, R; Scarpati, G; Esposito, C; Cavaglià, E; Corona, M

    2012-01-01

    Purpose To develop a clinically relevant porcine model for the study of hepatic metabolism of drugs by means of hepatic vein catheterization. Materials and Methods: review of literature and elaboration of a hypothesis, design of an experimental method. Results: recent clinical studies were conducted by withdrawing cirrhotic patients’ blood from right hepatic vein during hepatic vein pressure gradient measurements. Basing on our personal clinical experience and evaluation of research needs, an experimental model is proposed. Conclusions: contemporary measurement of peripheral and hepatic concentration of drugs by peripheral vein and hepatic vein catheterization can be used to create a reliable and reproducible porcine model to study liver metabolism of drugs in vivo. PMID:23905064

  13. A 2012 Workshop: Vaccine and Drug Ontology in the Study of Mechanism and Effect (VDOSME 2012).

    PubMed

    He, Yongqun; Toldo, Luca; Burns, Gully; Tao, Cui; Abernethy, Darrell R

    2012-01-01

    Vaccines and drugs have contributed to dramatic improvements in public health worldwide. Over the last decade, there have been efforts in developing biomedical ontologies that represent various areas associated with vaccines and drugs. These ontologies combined with existing health and clinical terminology systems (e.g., SNOMED, RxNorm, NDF-RT, MedDRA, VO, OAE, and AERO) could play significant roles on clinical and translational research. The first "Vaccine and Drug Ontology in the Study of Mechanism and Effect" workshop (VDOSME 2012) provided a platform for discussing problems and solutions in the development and application of biomedical ontologies in representing and analyzing vaccines/drugs, vaccine/drug administrations, vaccine/drug-induced immune responses (including positive host responses and adverse events), and similar topics. The workshop covered two main areas: (i) ontologies of vaccines, of drugs, and of studies thereof; and (ii) analysis of administration, mechanism and effect in terms of representations based on such ontologies. Six full-length papers included in this thematic issue focus on ontology representation and time analysis of vaccine/drug administration and host responses (including positive immune responses and adverse events), vaccine and drug adverse event text mining, and ontology-based Semantic Web applications. The workshop, together with the follow-up activities and personal meetings, provided a wonderful platform for the researchers and scientists in the vaccine and drug communities to demonstrate research progresses, share ideas, address questions, and promote collaborations for better representation and analysis of vaccine and drug-related terminologies and clinical and research data.

  14. [Circadian rhythm study from anticipatory behavior to drug treatment].

    PubMed

    Shibata, Shigenobu

    2005-10-01

    Precise, rhythmic, daily change of the internal milieu is a conspicuous feature of all living organisms. It affects temporal patterns of all kinds of behaviors during a day and deeply influences both the social structure and daily life of individual human beings. These daily variations arise from the internal circadian mechanisms. Three functions of the endogenous clock are discriminated as rhythm generation, entrainment to light-dark cycle and output from the clock. The endogenous clock is localized in the suprachiasmatic nucleus (SCN) in mammals. Recent papers demonstrated strong expression of clock genes such as Per1, Per2 and Per3 in the SCN. Circadian oscillation is basically regulated by the transcription/translation feedback system of the Per gene in mammals. As serotonin/antidepressant and GABA/benzodiazepine drugs affect the light and non-light-induced entrainment, these drugs can regulate the circadian oscillation of clock genes and environmental stimuli-induced change of Per gene expression in the SCN. There are two main stimuli that entrain circadian rhythm, the light-dark cycle (LD) and restricted feeding. Light resets the circadian clock with induction of Per1 and Per2 gene in the SCN, the locus of a main oscillator. Mice were allowed access to food for 4 h during daytime (7 h in advance of feeding time) under LD or constant darkness. The peaks of mPer1 and mPer2 mRNA in the cerebral cortex and liver were advanced 6-12 h after 6 days of RF, whereas those in SCN were unaffected. The increase of mPer expression by RF treatment was observed in SCN-lesioned mice. The present results suggest that RF strongly entrained the expression of mPer and clock-controlled genes in the cerebral cortex and liver without affecting light-dependent SCN clock function.

  15. Cancer incidence among population utilizing geothermal hot water: a census-based cohort study.

    PubMed

    Kristbjornsdottir, Adalbjorg; Rafnsson, Vilhjalmur

    2013-12-15

    The aim of the study was to assess whether utilization of geothermal hot-water is associated with risk of cancer. The cohort from census was followed from 1981 to 2010 in nation-wide death and cancer registries. The moving apart of American-Eurasian tectonic plates, observed in Iceland, results in high volcanic activity. The definition of the study populations was based on geological information. The target population was inhabitants of communities located on bedrock younger than 3.3 million years, utilizing hot-water supply generated from geothermal wells since 1972. The two reference populations were inhabitants of communities without this hot-water supply located on areas with less volcanic/geothermal activity, and bedrock older than 3.3 million years. Hazard ratio (HR), and 95% confidence intervals (CI) were adjusted for age, gender, education, housing, reproductive factors and smoking. HR in the geothermal hot-water supply areas for all cancer was 1.15 (95% CI 1.05-1.25) as compared with nongeothermal areas. The HR for breast cancer was 1.40 (1.12-1.75), prostate cancer 1.61 (1.29-2.00), kidney cancer 1.64 (1.11-2.41), lymphatic and haematopoietic tissue cancers 1.45 (1.08-1.95), and for basal cell carcinoma (BCC) of the skin 1.46 (1.16-1.82). Positive exposure-response relations were observed between the risk of these cancers and the degree of volcanic/geothermal activity in the reference areas. Increased incidence of all cancers, breast, prostate, kidney cancer and BCC of the skin was found among the population utilizing geothermal hot-water for decades. More precise information on exposure is needed in future studies. PMID:23733434

  16. Cancer incidence among population utilizing geothermal hot water: a census-based cohort study.

    PubMed

    Kristbjornsdottir, Adalbjorg; Rafnsson, Vilhjalmur

    2013-12-15

    The aim of the study was to assess whether utilization of geothermal hot-water is associated with risk of cancer. The cohort from census was followed from 1981 to 2010 in nation-wide death and cancer registries. The moving apart of American-Eurasian tectonic plates, observed in Iceland, results in high volcanic activity. The definition of the study populations was based on geological information. The target population was inhabitants of communities located on bedrock younger than 3.3 million years, utilizing hot-water supply generated from geothermal wells since 1972. The two reference populations were inhabitants of communities without this hot-water supply located on areas with less volcanic/geothermal activity, and bedrock older than 3.3 million years. Hazard ratio (HR), and 95% confidence intervals (CI) were adjusted for age, gender, education, housing, reproductive factors and smoking. HR in the geothermal hot-water supply areas for all cancer was 1.15 (95% CI 1.05-1.25) as compared with nongeothermal areas. The HR for breast cancer was 1.40 (1.12-1.75), prostate cancer 1.61 (1.29-2.00), kidney cancer 1.64 (1.11-2.41), lymphatic and haematopoietic tissue cancers 1.45 (1.08-1.95), and for basal cell carcinoma (BCC) of the skin 1.46 (1.16-1.82). Positive exposure-response relations were observed between the risk of these cancers and the degree of volcanic/geothermal activity in the reference areas. Increased incidence of all cancers, breast, prostate, kidney cancer and BCC of the skin was found among the population utilizing geothermal hot-water for decades. More precise information on exposure is needed in future studies.

  17. Pharmacokinetic drug-drug interaction study of ranolazine and metformin in subjects with type 2 diabetes mellitus.

    PubMed

    Zack, Julia; Berg, Jolene; Juan, Axel; Pannacciulli, Nicola; Allard, Martine; Gottwald, Mildred; Zhang, Heather; Shao, Yongwu; Ben-Yehuda, Ori; Jochelson, Phil

    2015-03-01

    Ranolazine and metformin may be frequently co-administered in subjects with chronic angina and co-morbid type 2 diabetes mellitus (T2DM). The potential for a drug-drug interaction was explored in two phase 1 clinical studies in subjects with T2DM to evaluate the pharmacokinetics and safety of metformin 1000 mg BID when administered with ranolazine 1000 mg BID (Study 1, N = 28) or ranolazine 500 mg BID (Study 2, N = 25) as compared to metformin alone. Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively. Co-administration of ranolazine and metformin was well tolerated in these T2DM subjects, with no serious adverse events or drug-related adverse events leading to discontinuation. The most common adverse events were nausea, diarrhea, and dizziness. These findings are consistent with a dose-related interaction between ranolazine and metformin, and suggest that a dose adjustment of metformin may not be required with ranolazine 500 mg BID; whereas, the metformin dose should not exceed 1700 mg of total daily dose when using ranolazine 1000 mg BID. PMID:27128216

  18. Using standardized methods for research on HIV and injecting drug use in developing/transitional countries: case study from the WHO Drug Injection Study Phase II

    PubMed Central

    Des Jarlais, Don C; Perlis, Theresa E; Stimson, Gerry V; Poznyak, Vladimir

    2006-01-01

    Background Successful cross-national research requires methods that are both standardized across sites and adaptable to local conditions. We report on the development and implementation of the methodology underlying the survey component of the WHO Drug Injection Study Phase II – a multi-site study of risk behavior and HIV seroprevalence among Injecting Drug Users (IDUs). Methods Standardized operational guidelines were developed by the Survey Coordinating Center in collaboration with the WHO Project Officer and participating site Investigators. Throughout the duration of the study, survey implementation at the local level was monitored by the Coordinating Center. Surveys were conducted in 12 different cities. Prior rapid assessment conducted in 10 cities provided insight into local context and guided survey implementation. Where possible, subjects were recruited both from drug abuse treatment centers and via street outreach. While emphasis was on IDUs, non-injectors were also recruited in cities with substantial non-injecting use of injectable drugs. A structured interview and HIV counseling/testing were administered. Results Over 5,000 subjects were recruited. Subjects were recruited from both drug treatment and street outreach in 10 cities. Non-injectors were recruited in nine cities. Prior rapid assessment identified suitable recruitment areas, reduced drug users' distrust of survey staff, and revealed site-specific risk behaviors. Centralized survey coordination facilitated local questionnaire modification within a core structure, standardized data collection protocols, uniform database structure, and cross-site analyses. Major site-specific problems included: questionnaire translation difficulties; locating affordable HIV-testing facilities; recruitment from drug treatment due to limited/selective treatment infrastructure; access to specific sub-groups of drug users in the community, particularly females or higher income groups; security problems for users

  19. Study of Utilization of Automotive Diesel Glow Plug as AN IR Source

    NASA Astrophysics Data System (ADS)

    White, Allen R.

    2013-06-01

    Glow plugs are used in commercially available Diesel engines to assist in cold weather starting. These devices are an Infrared source that are consistent in their function and inexpensive. The operational temperature of a glow plug is in the lower range of globar operational temperatures (1100 C) but is still potentially spectroscopically useful. This study seeks to characterize these devices with respect to their utility as an infrared emission source. The spectral response of the glow plug to input current variation was measured as was the temporal stability of the emission spectrum. Finally, comparisions are made between the emission spectra of glow plugs and globars.

  20. A Checklist for Reporting Valuation Studies of Multi-Attribute Utility-Based Instruments (CREATE).

    PubMed

    Xie, Feng; Pickard, A Simon; Krabbe, Paul F M; Revicki, Dennis; Viney, Rosalie; Devlin, Nancy; Feeny, David

    2015-08-01

    Multi-attribute utility-based instruments (MAUIs) assess health status and provide an index score on the full health-dead scale, and are widely used to support reimbursement decisions for new healthcare interventions worldwide. A valuation study is a key part of the development of MAUIs, with the primary goal of developing a scoring algorithm through eliciting societal preferences. We developed the 21-item Checklist for REporting VAluaTion StudiEs (CREATE) by following a modified two-round Delphi panel approach plus an email survey. CREATE is intended to promote good reporting practice as well as guiding developers to thoroughly and carefully think through key methodological elements in designing valuation studies.

  1. Sociodemographic characteristics and drug abuse patterns of treatment-seeking illicit drug abusers in Finland, 1997-2008: the Huuti study.

    PubMed

    Onyeka, Ifeoma N; Uosukainen, Hanna; Korhonen, Maarit Jaana; Beynon, Caryl; Bell, J Simon; Ronkainen, Kimmo; Föhr, Jaana; Tiihonen, Jari; Kauhanen, Jussi

    2012-01-01

    The epidemiological part of the Huume tietokanta (HUUTI) consortium research project is the first large-scale longitudinal study of treatment-seeking illicit drug abusers in Finland. The objective of this report was to describe the sociodemographic characteristics and drug abuse patterns of treatment-seeking clients at their first visit. This study analysed baseline data of 4817 clients (3365 men and 1452 women) aged 11-65 years who sought treatment for drug abuse between 1997 and 2008 at Helsinki Deaconess Institute. Data were collected using a structured questionnaire. The majority (56%) of clients were between 15 and 24 years, educated at elementary school level (75%), and unemployed (57%). Opiates (30%) were the primary drugs of abuse. The primary drugs were mostly injected (45%) and were abused daily during the past month (44%). Cannabis was the most common secondary drug of abuse (34%). The secondary drugs were predominantly smoked (39%) or taken orally (38%) and were abused once per week or less frequently during the past month (33%). Age at initiation of illicit drug abuse ranged from 5 to 49 years. Polydrug abuse was common, with a mean consumption of 3.5 concurrent polydrug use, which were combined from 3 or more drug classes. The prevalence of lifetime/ever intravenous drug abuse was 64% and past month intravenous drug abuse was 64%, respectively, and 13% reported sharing injecting equipment during the past month. Early initiation, polydrug abuse, and risky consumption of illicit drugs were major areas of concern among the study population. Injecting drug use could place considerable burden on health services in view of complications and transmission of infectious diseases.

  2. Current Situation, Determinants, and Solutions to Drug Shortages in Shaanxi Province, China: A Qualitative Study

    PubMed Central

    Yang, Caijun; Wu, Lina; Cai, Wenfang; Zhu, Wenwen; Shen, Qian; Li, Zongjie; Fang, Yu

    2016-01-01

    Objective Drug shortages were a complex global problem. The aim of this study was to analyze, characterize, and assess the drug shortages, and identify possible solutions in Shaanxi Province, western China. Methods A qualitative methodological approach was conducted during May–June 2015 and December 2015–January 2016. Semi-structured interviews were performed to gather information from representatives of hospital pharmacists, wholesalers, pharmaceutical producers, and local health authorities. Results Thirty participants took part in the study. Eight traditional Chinese medicines and 87 types of biologicals and chemicals were reported to be in short supply. Most were essential medicines. Five main determinants of drug shortages were detected: too low prices, too low market demands, Good Manufacturing Practice (GMP) issues, materials issues, and approval issues for imported drugs. Five different solutions were proposed by the participants: 1) let the market decide the drug price; 2) establish an information platform; 3) establish a reserve system; 4) enhance the communication among the three parties in the supply chain; and 5) improve hospital inventory management. Conclusions Western China was currently experiencing a serious drug shortage. Numerous reasons for the shortage were identified. Most drug shortages in China were currently because of “too low prices.” To solve this problem, all of the stakeholders, especially the government, needed to participate in managing the drug shortages. PMID:27780218

  3. Poly(alkylcyanoacrylate) colloidal particles as vehicles for antitumour drug delivery: a comparative study.

    PubMed

    Arias, José L; Ruiz, M A Adolfina; López-Viota, Margarita; Delgado, Angel V

    2008-03-15

    Because of the fundamental importance of new therapeutic routes for cancer treatment, a number of systems based on colloidal particles as vehicles for the delivery of chemotherapeutic agents have been devised. The target is always to provide the proper dose of the antitumour agent only at the desired locus of action, thus reducing the unwanted side effects. The systems studied in this work are nanospheres of the biodegradable polymers poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate) and poly(octylcyanoacrylate), all suitable for parenteral administration, as vehicles for 5-fluorouracil, a well studied drug used for the treatment of solid tumours. Two loading methods have been analyzed: the first one is based on drug addition during the process of generation of the particles, by an anionic emulsion/polymerization procedure, and the subsequent drug trapping in the polymeric network. The second method is based on surface adsorption in already formed nanoparticles, after incubation in the drug solution. A detailed investigation of the capabilities of the polymer particles to load this drug is described. The main factors determining the drug incorporation to the polymer network were the type of monomer, the pH and the drug concentration. The release kinetics of 5-fluorouracil is found to be controlled by the pH of the release medium, the type of drug incorporation and the type of polymer.

  4. Approaches to Recording Drug Allergies in Electronic Health Records: Qualitative Study

    PubMed Central

    Fernando, Bernard; Morrison, Zoe; Kalra, Dipak; Cresswell, Kathrin; Sheikh, Aziz

    2014-01-01

    Background Drug allergy represent an important subset of adverse drug reactions that is worthy of attention because many of these reactions are potentially preventable with use of computerised decision support systems. This is however dependent on the accurate and comprehensive recording of these reactions in the electronic health record. The objectives of this study were to understand approaches to the recording of drug allergies in electronic health record systems. Materials and Methods We undertook a case study comprising of 21 in-depth interviews with a purposefully selected group of primary and secondary care clinicians, academics, and members of the informatics and drug regulatory communities, observations in four General Practices and an expert group discussion with 15 participants from the Allergy and Respiratory Expert Resource Group of the Royal College of General Practitioners. Results There was widespread acceptance among healthcare professionals of the need for accurate recording of drug allergies and adverse drug reactions. Most drug reactions were however likely to go unreported to and/or unrecognised by healthcare professionals and, even when recognised and reported, not all reactions were accurately recorded. The process of recording these reactions was not standardised. Conclusions There is considerable variation in the way drug allergies are recorded in electronic health records. This limits the potential of computerised decision support systems to help alert clinicians to the risk of further reactions. Inaccurate recording of information may in some instances introduce new problems as patients are denied treatments that they are erroneously believed to be allergic to. PMID:24740090

  5. Could Education Contribute to Reduce Prevalence of HIV among Injecting Drug Users? A Case Study of IDUs from the Rehabilitation Center for Drugs Users

    ERIC Educational Resources Information Center

    Rajbhandari, Mani Man Singh

    2008-01-01

    This study primarily focuses on Injecting Drug Users (IDUs) from the Narconon Nepal for drugs rehabilitation and prevention center. The study attempt to explore the changing behavior of IDUs from the education received from the rehabilitation center which contributes to reduce the prevalence of HIV among IDUs. The data were collected through semi…

  6. Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease.

    PubMed

    Sanders, Angela; Hemmelgarn, Harmony; Melrose, Heather L; Hein, Leanne; Fuller, Maria; Clarke, Lorne A

    2013-08-01

    Gaucher disease is an autosomal recessively inherited storage disorder caused by deficiency of the lysosomal hydrolase, acid β-glucosidase. The disease manifestations seen in Gaucher patients are highly heterogeneous as is the responsiveness to therapy. The elucidation of the precise factors responsible for this heterogeneity has been challenging as the development of clinically relevant animal models of Gaucher disease has been problematic. Although numerous murine models for Gaucher disease have been described each has limitations in their specific utility. We describe here, transgenic murine models of Gaucher disease that will be particularly useful for the study of pharmacological chaperones. We have produced stable transgenic mouse strains that individually express wild type, N370S and L444P containing human acid β-gluco