Treating the individual hypertensive patient: considerations on dose, sequential monotherapy and drug combinations.

For the general practitioner to be able to prescribe optimal therapy to his individual hypertensive patients, he needs accurate information on the therapeutic agents he is going to administer and practical treatment strategies. The information on drugs and drug combinations has to be applicable to the treatment of individual patients and not just patient study groups. A basic requirement is knowledge of the dose-response relationship for each compound in order to choose the optimal therapeutic dose. Contrary to general assumption, this key information is difficult to obtain and often not available to the physician for many years after marketing of a drug. As a consequence, excessive doses are often used. Furthermore, the physician needs comparative data on the various antihypertensive drugs that are applicable to the treatment of individual patients. In order to minimize potential side effects due to unnecessary combinations of compounds, the strategy of sequential monotherapy is proposed, with the goal of treating as many patients as possible with monotherapy at optimal doses. More drug trials of a crossover design and more individualized analyses of the results are badly needed to provide the physician with information that he can use in his daily practice. In this time of continuous intensive development of new antihypertensive agents, much could be gained in enhanced efficacy and reduced incidence of side effects by taking a closer look at the drugs already available and using them more appropriately in individual patients.

Review of the Iowa Department of Human Services Drug Testing Process for Drug Testing of a Person Responsible for the Care of a Child in Child Abuse Cases, December 1, 2008

This report outlines the current drug testing practices, guidelines, programs and initiatives as currently implemented by the Department regarding the process for drug testing of a person responsible for the care of a child in child abuse cases.

Iowa Drug Control Strategy, 2013

The Governor’s Office of Drug Policy Control offers the 2013 Drug Control Strategy pursuant to Iowa Code §80E.1. The purpose of the strategy is to describe the activities of the office and other state departments related to drug enforcement, substance abuse treatment and prevention. This report also highlights trends in respect to substance abuse within the state and sets out innovative approaches to reduce drug abuse and its associated damage to society. Finally, the Strategy shows the state funding levels for the various agencies working in this area, as divided among the three areas of emphasis: prevention, treatment and enforcement.

Antihypertensive drug treatment changes in the general population: the CoLaus study.

BACKGROUND: Changes in antihypertensive drug treatment are paramount in the adequate management of patients with hypertension, still, there is little information regarding changes in antihypertensive drug treatment in Switzerland. Our aim was to assess those changes and associated factors in a population-based, prospective study. METHODS: Data from the population-based, CoLaus study, conducted among subjects initially aged 35-75 years and living in Lausanne, Switzerland. 772 hypertensive subjects (371 women) were followed for a median of 5.4 years. Data Subjects were defined as continuers (no change), switchers (one antihypertensive class replaced by another), combiners (one antihypertensive class added) and discontinuers (stopped treatment). The distribution and the factors associated with changes in antihypertensive drug treatment were assessed. RESULTS: During the study period, the prescription of diuretics decreased and of ARBs increased: at baseline, diuretics were taken by 46.9% of patients; angiotensin receptor blockers (ARB) by 44.7%, angiotensin converting enzyme inhibitors (ACEI) by 28.8%, beta-blockers (BB) by 28.0%, calcium channel blockers (CCB) by 18.9% and other antihypertensive drugs by 0.3%. At follow-up (approximately 5 years later), their corresponding percentages were 42.8%, 51.7%, 25.5%, 33.0% 20.7% and 1.0%. Among all participants, 54.4% (95% confidence interval: 50.8-58.0) were continuers, 26.9% (23.8-30.2) combiners, 12.7% (10.4-15.3) switchers and 6.0% (4.4-7.9) discontinuers. Combiners had higher systolic blood pressure values at baseline than the other groups (p < 0.05). Almost one third (30.6%) of switchers and 29.3% of combiners improved their blood pressure status at follow-up, versus 18.8% of continuers and 8.7% of discontinuers (p < 0.001). Conversely, almost one third (28.3%) of discontinuers became hypertensive (systolic ≥140 mm Hg or diastolic ≥90 mm Hg), vs. 22.1% of continuers, 16.3% of switchers and 11.5% of combiners (p < 0.001). Multivariate analysis showed baseline uncontrolled hypertension, ARBs, drug regimen (monotherapy/polytherapy) and overweight/obesity to be associated with changes in antihypertensive therapy. CONCLUSION: In Switzerland, ARBs have replaced diuretics as the most commonly prescribed antihypertensive drug. Uncontrolled hypertension, ARBs, drug regimen (monotherapy or polytherapy) and overweight/obesity are associated with changes in antihypertensive treatment.

Risk perception by healthcare professionals related to drug use during pregnancy: a Swiss survey.

PRINCIPLE: Healthcare professionals' (HCPs') perception of risk associated with drug use in pregnancy may have an impact on the pharmacological treatment of some women. The aim of this study was to examine this risk perception in a sample of Swiss HCPs with a special focus on their knowledge and use of available specialised information sources. METHOD: An online, French and German, questionnaire was e-mailed to 7,136 members of four Swiss professional societies (gynaecologists, paediatricians, midwives and pharmacists). The questionnaire was designed (a) to collect demographic characteristics, (b) to evaluate the frequency of use of several specialised sources of information on drugs in pregnancy in their daily practice, and (c) to examine the perception of risk associated with drug use during pregnancy. RESULTS: A total of 1,310 questionnaires were collected (response rate of 18.4%). More than 80% of the respondent HCPs use the Swiss Drug Reference Book (Compendium) to assess the risk associated with drugs during pregnancy and are not aware of available specialised information sources (books, websites or information centres). Despite some disparities between HPCs, the risk related to drug intake was overall highly misperceived. Blinded reading of three product monographs in the Compendium was associated with an overestimated perception of risk (e.g., after reading the "paracetamol" monograph, 38% of the participants stated they would probably not advise the use of this drug to a pregnant patient). CONCLUSION: Overall, an overestimation of the risk associated with drug use during pregnancy has been observed in our sample of HCPs, which might be related to the underuse of specialised information source among other factors. These findings evidenced the need for increased training for HCPs in order to optimise medication use during pregnancy. Further studies are needed to confirm these results and identify causes.

Drug-induced linear IgA bullous dermatosis probably induced by furosemide.

Linear IgA bullous dermatosis (LABD) is an autoimmune disease, characterized by linear deposition of IgA along the basement membrane zone. Drug-induced LABD is rare but increasing in frequency. A new case of drug-induced LABD associated with the administration of furosemide is described.

Drug price differentials caused by de-listing and price cap policies

This paper analyses the behaviour of pharmaceutical companies that face the threat of having their drugs excluded from reimbursement and the markets characterised also by price caps. We conclude that price elasticity of demand and cost differentials cause the price discounts which drug firms offer to health care organisations. Additionally, we conclude that price cap regulations affect the time path of prices, resulting in higher prices for new products and lower prices for old products.

Geographical determinants of the creation of manufacturing firms: The regions of Spain

La complexitat dels mecanismes que determinen l'entrada i la sortida de signatures augmenta quan diferències geogràfiques de l'estructura de producció, la capital humana i l'atur són considerades. Variacions interregionals en la tarifa de les noves de signatures dintre de cada activitat industrial persisteixen durant els períodes llargs de temps, una circumstància que indica que hi ha determinants no-conjunturals en la capacitat de regions per a crear nous projectes industrials. Aquest estudi està preocupat amb l'establiment d'influència variables geogràfiques sobre la fundació de nous establiments de la fabricació. Les indústries (NEIX la R 25) en les regions espanyoles (el BOIG 2) han estat preses com les unitats d'anàlisis per al període 1980-1992

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Introduction: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on measurement of blood concentrations. Maintaining concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. In the last decades computer programs have been developed to assist clinicians in this assignment. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Method: Literature and Internet search was performed to identify software. All programs were tested on common personal computer. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software's characteristics. Numbers of drugs handled vary widely and 8 programs offer the ability to the user to add its own drug model. 10 computer programs are able to compute Bayesian dosage adaptation based on a blood concentration (a posteriori adjustment) while 9 are also able to suggest a priori dosage regimen (prior to any blood concentration measurement), based on individual patient covariates, such as age, gender, weight. Among those applying Bayesian analysis, one uses the non-parametric approach. The top 2 software emerging from this benchmark are MwPharm and TCIWorks. Other programs evaluated have also a good potential but are less sophisticated (e.g. in terms of storage or report generation) or less user-friendly.¦Conclusion: Whereas 2 integrated programs are at the top of the ranked listed, such complex tools would possibly not fit all institutions, and each software tool must be regarded with respect to individual needs of hospitals or clinicians. Interest in computing tool to support therapeutic monitoring is still growing. Although developers put efforts into it the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capacity of data storage and report generation.

Combination of carbon isotope ratio with hydrogen isotope ratio determinations in sports drug testing.

Carbon isotope ratio (CIR) analysis has been routinely and successfully applied to doping control analysis for many years to uncover the misuse of endogenous steroids such as testosterone. Over the years, several challenges and limitations of this approach became apparent, e.g., the influence of inadequate chromatographic separation on CIR values or the emergence of steroid preparations comprising identical CIRs as endogenous steroids. While the latter has been addressed recently by the implementation of hydrogen isotope ratios (HIR), an improved sample preparation for CIR avoiding co-eluting compounds is presented herein together with newly established reference values of those endogenous steroids being relevant for doping controls. From the fraction of glucuronidated steroids 5β-pregnane-3α,20α-diol, 5α-androst-16-en-3α-ol, 3α-Hydroxy-5β-androstane-11,17-dione, 3α-hydroxy-5α-androstan-17-one (ANDRO), 3α-hydroxy-5β-androstan-17-one (ETIO), 3β-hydroxy-androst-5-en-17-one (DHEA), 5α- and 5β-androstane-3α,17β-diol (5aDIOL and 5bDIOL), 17β-hydroxy-androst-4-en-3-one and 17α-hydroxy-androst-4-en-3-one were included. In addition, sulfate conjugates of ANDRO, ETIO, DHEA, 3β-hydroxy-5α-androstan-17-one plus 17α- and androst-5-ene-3β,17β-diol were considered and analyzed after acidic solvolysis. The results obtained for the reference population encompassing n = 67 males and females confirmed earlier findings regarding factors influencing endogenous CIR. Variations in sample preparation influenced CIR measurements especially for 5aDIOL and 5bDIOL, the most valuable steroidal analytes for the detection of testosterone misuse. Earlier investigations on the HIR of the same reference population enabled the evaluation of combined measurements of CIR and HIR and its usefulness regarding both steroid metabolism studies and doping control analysis. The combination of both stable isotopes would allow for lower reference limits providing the same statistical power and certainty to distinguish between the endo- or exogenous origin of a urinary steroid.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

Implementation of raltegravir in routine clinical practice: selection criteria for choosing this drug, virologic response rates, and characteristics of failures.

BACKGROUND: Raltegravir (RAL) achieved remarkable virologic suppression rates in randomized-clinical trials, but today efficacy data and factors for treatment failures in a routine clinical care setting are limited. METHODS: First, factors associated with a switch to RAL were identified with a logistic regression including patients from the Swiss HIV Cohort Study with a history of 3 class failure (n = 423). Second, predictors for virologic outcome were identified in an intent-to-treat analysis including all patients who received RAL. Last observation carried forward imputation was used to determine week 24 response rate (HIV-1 RNA >or= 50 copies/mL). RESULTS: The predominant factor associated with a switch to RAL in patients with suppressed baseline RNA was a regimen containing enfuvirtide [odds ratio 41.9 (95% confidence interval: 11.6-151.6)]. Efficacy analysis showed an overall response rate of 80.9% (152/188), whereas 71.8% (84/117) and 95.8% (68/71) showed viral suppression when stratified for detectable and undetectable RNA at baseline, respectively. Overall CD4 cell counts increased significantly by 42 cells/microL (P < 0.001). Characteristics of failures were a genotypic sensitivity score of the background regimen <or=1, very low RAL plasma concentrations, poor adherence, and high viral load at baseline. CONCLUSIONS: Virologic suppression rates in our routine clinical care setting were promising and comparable with data from previously published randomized-controlled trials.

Distinct Roles of Candida albicans Drug Resistance Transcription Factors TAC1, MRR1, and UPC2 in Virulence.

Azoles are widely used in antifungal therapy in medicine. Resistance to azoles can occur in Candida albicans principally by overexpression of multidrug transporter gene CDR1, CDR2, or MDR1 or by overexpression of ERG11, which encodes the azole target. The expression of these genes is controlled by the transcription factors (TFs) TAC1 (involved in the control of CDR1 and CDR2), MRR1 (involved in the control of MDR1), and UPC2 (involved in the control of ERG11). Several gain-of-function (GOF) mutations are present in hyperactive alleles of these TFs, resulting in the overexpression of target genes. While these mutations are beneficial to C. albicans survival in the presence of the antifungal drugs, their effects could potentially alter the fitness and virulence of C. albicans in the absence of the selective drug pressure. In this work, the effect of GOF mutations on C. albicans virulence was addressed in a systemic model of intravenous infection by mouse survival and kidney fungal burden assays. We engineered a set of strains with identical genetic backgrounds in which hyperactive alleles were reintroduced in one or two copies at their genomic loci. The results obtained showed that neither TAC1 nor MRR1 GOF mutations had a significant effect on C. albicans virulence. In contrast, the presence of two hyperactive UPC2 alleles in C. albicans resulted in a significant decrease in virulence, correlating with diminished kidney colonization compared to that by the wild type. In agreement with the effect on virulence, the decreased fitness of an isolate with UPC2 hyperactive alleles was observed in competition experiments with the wild type in vivo but not in vitro. Interestingly, UPC2 hyperactivity delayed filamentation of C. albicans after phagocytosis by murine macrophages, which may at least partially explain the virulence defects. Combining the UPC2 GOF mutation with another hyperactive TF did not compensate for the negative effect of UPC2 on virulence. In conclusion, among the major TFs involved in azole resistance, only UPC2 had a negative impact on virulence and fitness, which may therefore have consequences for the epidemiology of antifungal resistance.