Quantification of Efavirenz Hydroxymetabolites in Human Plasma Using LC-HRMS/MS.

BACKGROUND: Efavirenz (EFV) is a drug used to treat HIV. Low plasma concentrations of EFV result in suboptimal viral suppression, whereas high concentrations can cause adverse neuropsychiatric side reactions. Some studies have identified a correlation between the plasma concentrations of EFV metabolites and neurotoxicity. To our knowledge, no studies have investigated the metabolism of EFV in young children and its effect on treatment outcomes. Therefore, the aim of this study was to develop and validate a method for quantifying EFV and its metabolites in human plasma derived from children. METHODS: Sample preparation was performed using protein precipitation of 100 µL plasma. Thereafter, an aliquot of the supernatant was used to quantify EFV, 7-hydroxyefavirenz (7-OH-EFV), 8-hydroxyefavirenz (8-OH-EFV), and a newly discovered metabolite ("EFAdeg") associated with 8-OH-EFV. A second aliquot of the supernatant was hydrolyzed using ß-glucuronidase/arylsulfatase and used with the first aliquot to quantify phase II metabolites. The analyses were performed using a Dionex Ultimate 3000RS LC-system coupled with a Q Exactive Orbitrap mass spectrometer. RESULTS: The method has a measuring range of 100-50,000 ng/mL (EFV, 8-OH-EFV), 125-25,000 ng/mL (7-OH-EFV), and 200-10,000 ng/mL ("EFAdeg"). All criteria of the European Medicines Agency guidelines regarding precision, accuracy, and selectivity were met. Of note, carryover must be considered for 8-OH-EFV. Overall, the validated method was successfully applied to plasma samples obtained from children and confirmed the presence of the newly discovered metabolite, "EFAdeg." CONCLUSIONS: An LC-HRMS/MS method for the quantification of EFV and its phase I and II metabolites was developed and validated. This method is suitable for analyzing plasma samples from children. Furthermore, studies using this method identified an additional metabolite that may influence the concentration of 8-OH-EFV in patient samples.

Homecare workers - an untapped resource in preventing emergency department visits among older individuals? A qualitative interview study from Sweden.

BACKGROUND: Older individuals with functional decline and homecare are frequent visitors to emergency departments (ED). Homecare workers (HCWs) interact regularly with their clients and may play a crucial role in their well-being. Therefore, this study explores if and how HCWs perceive they may contribute to the prevention of ED visits among their clients. METHODS: In this qualitative study, 12 semi-structured interviews were conducted with HCWs from Sweden between July and November 2022. Inductive thematic analysis was used to identify barriers and facilitators to prevent ED visits in older home-dwelling individuals. RESULTS: HCWs want to actively contribute to the prevention of ED visits among clients but observe many barriers that hinder them from doing so. Barriers refer to care organisation such as availability to primary care staff and information transfer; perceived attitudes towards HCWs as co-workers; and client-related factors. Participants suggest that improved communication and collaboration with primary care and discharge information from the ED to homecare services could overcome barriers. Furthermore, they ask for support and geriatric education from primary care nurses which may result in increased respect towards them as competent staff members. CONCLUSIONS: HCWs feel that they have an important role in the health management of older individuals living at home. Still, they feel as an untapped resource in the prevention of ED visits. They deem that improved coordination and communication between primary care, ED, and homecare organisations as well as proactive care would enable them to add significantly to the prevention of ED visits.

Proud but Powerless: A Qualitative Study of Homecare Workers´ Work Experiences and Their Suggestions for How Care for Homebound Older Adults Can Be Improved.

Many older adults with complex care needs live at home due to ageing-in-place policies. This study explored homecare workers' experiences and suggestions for improvements of care. Twelve semi-structured interviews were analyzed thematically, and revealed pride, capability, and satisfaction in their work, yet they feel undervalued and lack support. They advocate for integrated care models, recognition of their competence, flexible work approaches, and committed leadership. This would enhance patient care and address their own working conditions, addressing concerns from being relegated to the bottom of the hierarchy. They emphasize the need for comprehensive approaches, spanning from housekeeping to end-of-life palliative care.

Parents' perspectives on dried blood spot self-sampling from children with epilepsy: A mixed-method study.

AIM: Children with epilepsy often have concomitant diagnoses. Dried blood spot samples for drug monitoring can be collected by parents at home as an alternative to traditional sampling. This mixed-method study aimed to understand the parents' perspectives on blood self-sampling from their children and to identify factors contributing to successful sampling. METHOD: Parents who had collected a sample from their child during a visit to the neuropediatric clinic were asked to fill in a questionnaire. To get in-depth information and individual perspectives, parents and nurses participated in semi-structured interviews and analysed with thematic analysis. RESULTS: The results from questionnaires (n = 64) and interviews (n = 9) were interpreted together. Watching an instruction video and practical training contributed to successful sampling. 97% of the parents managed to collect a sample, 72% thought it was easy to perform, and 80% found self-sampling at home desirable. Factors for success were as follows: high motivation, prepared parents with pre-understanding, a pragmatic attitude, flexible education, effective communication and willingness to take on the role as a performer. Risk factors were as follows: conflict, fear, unprepared parents, confused or worried children. CONCLUSION: Voluntary self-sampling at home for parents of children with epilepsy is feasible and can reduce stress factors in everyday life.

Pretreatment HIV drug resistance predicts accumulation of new mutations in ART-naïve Ugandan children.

AIM: To assess the prevalence of pretreatment drug resistance (PDR) and its association with virologic outcomes after 24 weeks of antiretroviral therapy (ART), within an urban cohort of Ugandan children. METHODS: Prospective observational study. Baseline and 24-week assessments of viral load (VL) and genotypic drug resistance to nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) were performed. RESULTS: Ninety-nine ART-naïve children (3-12 years) initiated efavirenz-based ART 2015-2016 and 18/90 (20%) had baseline NRTI/NNRTI associated drug resistance mutations (DRMs). By 24 weeks, 72/93 (77%) children had VL < 40 copies/mL and a total of 23 children had DRMs. Children with PDR accumulated new DRMs with a mean number (SD) of 1.4 (2.35) new mutations compared to 0.26 (0.98) in 67 children with wild-type virus (P = .003). High pretreatment VL and PDR (number of baseline DRMs) predicted viremia (P = .003; P = .023) as well as acquired drug resistance (P = .02; P = .04). CONCLUSION: Pretreatment drug resistance to NNRTI/NRTI was common among ART-naïve Ugandan children and predicted viremia and new resistance mutations after only 24 weeks of efavirenz-based therapy. PDR may compromise long-term ART outcomes-especially when access to resistance testing and VL monitoring is poor. The long-term importance of PDR for non-NNRTI-based regimens needs further evaluation.

Dried Blood Spot Self-Sampling by Guardians of Children With Epilepsy Is Feasible: Comparison With Plasma for Multiple Antiepileptic Drugs.

BACKGROUND: Dried blood spot (DBS) is an attractive matrix alternative to plasma for the measurement of antiepileptic drug concentrations with the possibility of self-sampling at home. The aim of this study was to evaluate whether DBS concentrations from a children population could be used as an alternative to plasma concentrations in a clinical routine laboratory. METHODS: Children with epilepsy using carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA) had capillary blood collected for routine plasma analysis. DBS samples were collected by guardians or nurses, and the quality of sampling was compared between the groups. DBS samples were analyzed with liquid chromatography-tandem mass spectrometry methods and plasma samples with immunochemical methods. In the comparison between DBS and plasma concentrations, previously analyzed sample data were pooled with data in this study and resulted in 190 comparison pairs. A bioanalytical cross-validation according to European Medicines Agency was performed. Clinicians evaluated the results to understand if a DBS concentration was linked to a different clinical dose recommendation for the patient in comparison with plasma concentrations. RESULTS: Comparison of DBS sample quality showed that 2.3% of the capillary DBS collected by guardians were rejected and 8.0% of the capillary DBS collected by nurses. For DBS, a conversion factor of 0.85 for CBZ and 1.65 for VPA was applied for the comparison with plasma. LTG and LEV results were directly comparable. In the cross-validation, 88% of CBZ, 75% of LTG, 74% of LEV, and 94% of VPA comparisons were within 20% of the difference of the mean, although LEV had a few major differences (+31% to -40%). In 4 of the 190 comparisons, the clinical evaluation indicated a risk of conflicting decisions regarding the need for dose adjustment when using DBS concentrations. However, the risk of negative patient outcomes was considered negligible. CONCLUSIONS: Our study demonstrates that a combination of bioanalytical cross-validation and clinical evaluation is an effective way to describe the applicability of DBS as an alternative to plasma, taking into account how therapeutic drug monitoring is used in specific patient groups. For LTG, converted CBZ and VPA, DBS is a feasible alternative for self-sampling at home. DBS for LEV can only be recommended for nonadherence queries due to the high variability of the plasma/DBS concentration ratios.

Combined Recirculatory-compartmental Population Pharmacokinetic Modeling of Arterial and Venous Plasma S(+) and R(-) Ketamine Concentrations.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: The pharmacokinetics of infused drugs have been modeled without regard for recirculatory or mixing kinetics. We used a unique ketamine dataset with simultaneous arterial and venous blood sampling, during and after separate S(+) and R(-) ketamine infusions, to develop a simplified recirculatory model of arterial and venous plasma drug concentrations. METHODS: S(+) or R(-) ketamine was infused over 30 min on two occasions to 10 healthy male volunteers. Frequent, simultaneous arterial and forearm venous blood samples were obtained for up to 11 h. A multicompartmental pharmacokinetic model with front-end arterial mixing and venous blood components was developed using nonlinear mixed effects analyses. RESULTS: A three-compartment base pharmacokinetic model with additional arterial mixing and arm venous compartments and with shared S(+)/R(-) distribution kinetics proved superior to standard compartmental modeling approaches. Total pharmacokinetic flow was estimated to be 7.59 ± 0.36 l/min (mean ± standard error of the estimate), and S(+) and R(-) elimination clearances were 1.23 ± 0.04 and 1.06 ± 0.03 l/min, respectively. The arm-tissue link rate constant was 0.18 ± 0.01 min, and the fraction of arm blood flow estimated to exchange with arm tissue was 0.04 ± 0.01. CONCLUSIONS: Arterial drug concentrations measured during drug infusion have two kinetically distinct components: partially or lung-mixed drug and fully mixed-recirculated drug. Front-end kinetics suggest the partially mixed concentration is proportional to the ratio of infusion rate and total pharmacokinetic flow. This simplified modeling approach could lead to more generalizable models for target-controlled infusions and improved methods for analyzing pharmacokinetic-pharmacodynamic data.

Primary care physicians report high trust in and usefulness of the Stockholm drug and therapeutic committee's list of recommended essential medicines (the 'Wise List').

PURPOSE: Inappropriate use of medicines causes increased morbidity, mortality, adverse drug reactions, therapeutic failures and drug resistance as well as wastes valuable resources. Evidence-based cost-effective treatment recommendations of essential medicines are a way of avoiding these. We assessed primary care prescribers' knowledge about and perceptions of an essential medicines formulary, as well as the reasons for adhering to the recommendations. METHODS: We conducted a web based questionnaire survey targeting all physicians working in the primary healthcare of the Stockholm healthcare region (2.3 million inhabitants), regarding the knowledge of, attitudes to and usefulness of the essential medicines formulary of the Stockholm Drug and Therapeutics Committee, the so-called Wise List. RESULTS: Of the 1862 physicians reached by our e-mail invitations, 526 (28%) participated in the survey. All but one respondent knew of the formulary, and 72% used it at least once a week when prescribing. The main reason for using the formulary was evidence-based prescribing; 97% trusted the guidelines, and almost all (98%) found the content easy to understand. At the same time, many prescribers thought that the annual changes of some recommendations were too frequent, and some felt that a national formulary would increase its trustworthiness. CONCLUSIONS: We found that the essential medicines formulary was widely used and trusted by the prescribers. The high uptake of the treatment recommendations could be due to the Stockholm Drug and Therapeutics Committee's transparent process for developing recommendations involving respected experts and clinicians using strict criteria for handling potential conflicts of interest, feedback to prescribers, continuous medical education and minor financial incentives.

Patients' knowledge and attitudes to the Wise List - a drug formulary from the Stockholm Drug and Therapeutic committee.

BACKGROUND: Involving patients in decisions about their pharmacotherapy is crucial for a satisfactory treatment outcome. Information and opinions about medicines are available from a variety of sources. The Wise List is the drug formulary of recommended essential medicines for the Stockholm healthcare region and is issued by the Drug and Therapeutics Committee (DTC). To inform the public about treatment for common diseases and the concept of recommended medicines, a patient edition of the Wise List was developed. The aim of this study was to explore patients' knowledge, needs and attitudes to the Wise List, DTC and information about medicines in general. METHODS: To examine patient knowledge about recommended medicines a survey (n = 312) was carried out at four large primary healthcare centres in Stockholm, Sweden. To further elucidate the patients' needs of the information on recommended medicines and medicines in general, three focus group discussions (FGDs) were performed. RESULTS: Of the respondents 57% did not recognise the Wise List, 26% recognised but did not use it and 17% used it. A total of 63% reported that they search for information about medicines. The most common information source was "asking their doctor" (36%) followed by searching the internet (31%). The FGDs revealed that the patients were not interested in medicines in general, only in the medicines they use themselves. They did not understand the aim of the Wise List or how they could benefit from information about recommended medicines. The patients expressed a wish to access all information they need about their own care as well as public healthcare information at one location. CONCLUSION: The intended aim of the DTC with providing information to the public was not achieved as the patients have difficulties to understand the information and how they should use it. The patients were not interested in medicines in general, they wanted information tailored to their specific needs. The findings highlight the importance of creating tools for patients in collaboration with them and evaluate the concept continuously.

High Rate of Treatment Failures in Nonimmune Travelers Treated With Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum Malaria in Sweden: Retrospective Comparative Analysis of Effectiveness and Case Series.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment of Plasmodium falciparum malaria. Since the introduction of artemether-lumefantrine (AL) for treatment of uncomplicated malaria in Sweden, treatment failures have been reported in adults. METHODS: A retrospective comparative analysis of treatment regimen for P. falciparum malaria in adults in Stockholm during 2000-2015 was performed to evaluate the effectiveness of AL. Parasite genotyping and drug concentrations were investigated in the AL treatment failures. RESULTS: Among the total 397 P. falciparum episodes, 310 were treated with oral regimen only (95 AL, 162 mefloquine, 36 atovaquone-proguanil [AP], and 17 others), and 87 were administered initial intravenous therapy (38 artesunate and 49 quinine) followed by oral treatments. Five late treatment failures were detected after AL and one slow response to AP. The effectiveness of AL alone was 94.7% (95% confidence interval [CI], 88.1%-98.3%), compared with 99.5% for other oral regimens (P = .003). All AL failures occurred in European men and the effectiveness in this group was only 73.7% (95% CI, 48.8%-90.0%). Genotyping confirmed recrudescence of the initial parasite populations and drug resistance markers revealed no clinically significant resistance patterns. Lumefantrine concentrations suggested subtherapeutic concentrations in at least 2 cases. CONCLUSIONS: Our findings indicate a high rate of symptomatic late treatment failures after 6-dose AL regime in nonimmune adults, especially in men. Our report warrants the need to establish optimal dosing of AL in adults and to alert clinicians about the importance of informing patients regarding the risk of parasites reappearing weeks after AL treatment.

Quantification of valproic acid in dried blood spots.

BACKGROUND: Therapeutic drug monitoring (TDM) of the antiepileptic drug valproic acid (VPA) is recommended in patients with multiple drug therapy or with concomitant disabilities to ensure treatment efficacy and avoid adverse reactions in both adults and children. The use of sampling techniques compatible with home sampling, such as dried blood spot sampling could potentially facilitate this for patients. AIM. To assess the usefulness of a bioanalytical method for quantification of VPA in dried blood spots. MATERIALS AND METHODS: Quantification was based on liquid chromatography-mass spectrometry (LC-MS), both for the DBS method and the plasma-based reference method. RESULTS: The method was validated in the range 10-1200 µmol/L. Total imprecision ranged from 4.9-8.9 (%CV) and accuracy was within ± 14%. CONCLUSION: The validated method has potential for evaluation in therapeutic drug monitoring in combination with home sampling of DBS. The impact of spot size can be controlled through acceptance criteria and hematocrit in the range 30-60% can be accepted in sampling. Comparison of VPA levels between plasma and whole blood cannot be done without considering the blood-plasma ratio.

A cross-sectional pilot study assessing needs and attitudes to implementation of Information and Communication Technology for rational use of medicines among healthcare staff in rural Tanzania.

BACKGROUND: In resource-poor countries access to essential medicines, suboptimal prescribing and use of medicines are major problems. Health workers lack updated medical information and treatment support. Information and Communication Technology (ICT) could help tackle this. The impact of ICT on health systems in resource-poor countries is likely to be significant and transform the practice of medicine just as in high-income countries. However, research for finding the best way of doing this is needed. We aimed to assess current approaches to and use of ICT among health workers in two rural districts of Tanzania in relation to the current drug distribution practices, drug stock and continuing medical information (CME), as well as assessing the feasibility of using ICT to improve ordering and use of medicines. METHODS: This pilot study was conducted in 2010-2011, mapping the drug distribution chain in Tanzania, including problems and barriers. The study was conducted in Bunda and Serengeti districts, both part of the ICT4RD (ICT for rural development) project. Health workers involved in drug procurement and use at 13 health facilities were interviewed on use and knowledge of ICT, and their attitudes to its use in their daily work. They were also shown and interviewed about their thoughts on an android tablet application prototype for drug stock inventory and drug ordering, based on the Tanzanian Medical Stores Department (MSD) current paper forms. RESULTS: The main challenge was a stable supply of essential medicines. Drug supplies were often delayed and incomplete, resulting in stock-outs. All 20 interviewed health workers used mobile phones, 8 of them Smartphones with Internet connection. The Health workers were very positive to the tablet application and saw its potential in reducing drug stock-outs. They also expressed a great need and wish for CME by distance. CONCLUSION: The tablet application was easily used and appreciated by health workers, and thus has the potential to save time and effort, reduce transportation costs and minimise drug stock-outs. Furthermore, the android tablet could be used to reach out with CME programs to health care workers at remote health facilities, as well as those in towns.

Personalizing health care: feasibility and future implications.

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer's perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.

Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study.

BACKGROUND: HIV infection, anti-tuberculosis and efavirenz therapy are associated with neuropsychological effects. We evaluated the influence of rifampicin cotreatment, efavirenz pharmacokinetics and pharmacogenetics on neuropsychiatric disorders in Ugandan HIV patients with or without tuberculosis coinfection. METHODS: 197 treatment naïve Ugandan HIV patients, of whom 138 were TB co-infected, enrolled prospectively and received efavirenz based HAART. TB-HIV confected patients received concomitant rifampicin based anti-TB therapy. Genotypes for CYP2B6 (*6, *11), CYP3A5 (*3, *6, *7), ABCB1 (c.3435C>T and c.4036 A/G rs3842), CYP2A6 (*9, *17) and NR1I3 rs3003596 T/C were determined. Efavirenz plasma concentrations were serially quantified at 3rd day, 1st, 2nd, 4th, 6th, 8th and 12th weeks during therapy. Efavirenz neuropsychiatric symptoms were evaluated in terms of sleep disorders, hallucinations and cognitive effects at baseline, at two and twelve weeks of efavirenz treatment using a modified Mini Mental State Examination (MMSE) score. RESULTS: During the first twelve weeks of ART, 73.6% of the patients experienced at least one efavirenz related neuropsychiatric symptom. Commonest symptoms experienced were sleep disorders 60.5% (n=124) and hallucination 30.7% (n=63). Neuropsychiatric symptoms during HAART were significantly predicted by efavirenz plasma concentrations consistently. Rifampicin cotreatment reduced plasma efavirenz concentrations significantly only during the first week but not afterwards. There was no significant difference in the incidence of neuropsychiatric symptoms between patients receiving efavirenz with or without rifampicin cotreatment. CYP2B6*6 and ABCB1 c.4036 A/G genotype significantly predicted efavirenz concentrations. The tendency of CYP2B6*6 genotype association with higher incidence of having vivid dream (p=0.05), insomnia (p=0.19) and tactile hallucination (p=0.09) was observed mainly at week-2. CONCLUSIONS: Efavirenz related neuropsychiatric symptoms are common among Ugandan HIV patients receiving ART and is mainly predicted by higher efavirenz plasma concentrations and CYP2B6 genotype but not by rifampicin based anti-TB co-treatment.

Drugs and Birth Defects: a knowledge database providing risk assessments based on national health registers.

PURPOSE: To present concept, methods and use of a knowledge database providing assessments of potential fetal risks for all drugs on the Swedish market. METHODS: Assessments of fetal risks are made primarily by analyzing prospective epidemiological data from the Swedish Medical Birth Register on drug intake in relation to birth outcome. This is complemented by evaluation of the scientific literature. Following standardized working procedures, a statement is compiled for each substance, which is also classified into one of three categories depending on the estimated risk level. The final documents include drug product names on the market, via linkage to a medicinal products register. The information is free and published on the website www.janusinfo.se . It can also be used as an integrated part of electronic health records. RESULTS: The database covers assessments of fetal risks for close to 1,250 medicinal drug substances on the Swedish market. Each year, 96,000 searches are made, which might be compared to the around 100,000 children born in Sweden yearly. Apart from the Swedish Physicians' Desk Reference (Fass), the database is the most commonly used resource among specialists within gynaecology and perinatal medicine for information on drugs during pregnancy. CONCLUSIONS: A non-commercial knowledge base with assessments of fetal risk of different drugs is valued by health care professionals and is used extensively in Sweden. Based on analyses of national health registers, the database provides unique information on teratogenic drug risks.

The continuing challenge of providing drug information services to diminish the knowledge--practice gap in medical practice.

Information must be collected, evaluated and utilized to support every qualified activity. Medicine, with a written scientific tradition stretching back more than 2,000 years, is no exception. Here, we discuss a number of important items associated with the establishment of a drug information centre run by clinical pharmacologists and information pharmacists, serving a broad demand, mainly among clinical specialists. The working methods include a professional literature search, critical evaluation of the material, writing a structured answer, quality control, feedback to the inquirer and storage in a database which is publicly available. One can foresee even more complex systems wherein a number of active and specialized databases communicate to provide relevant advice and support at the point of care, supplying information on drug recommendations, reimbursement, environmental aspects, antimicrobial resistance, pharmacogenetics and adverse effects, and linked to a list of prescribed drugs for the individual patient. This will be possible in both rich and poor countries through the application of modern and developing information technology. However, research on the best and safest methods of such decision support systems will be needed to ensure that they really do improve the quality of drug prescribing and use.

Interface management of pharmacotherapy. Joint hospital and primary care drug recommendations.

PURPOSE: In September 2012 an interactive course on the "Interface Management of Pharmacotherapy" was organized by the Stockholm Drug and Therapeutics Committee in cooperation with Department of Clinical Pharmacology at Karolinska Institutet and at Karolinska University Hospital in Stockholm, Sweden, in collaboration with the WHO. The basis for the course was the "Stockholm model" for the rational use of medicines but also contained presentations about successful models in interface management of pharmacotherapy in other European countries. METHODS: The "Stockholm model" consists of 8 components: 1) Independent Drug and Therapeutics Committee with key role for respected drug experts with policy for "interest of conflicts", 2) The "Wise List", recommendations of medicines jointly for primary and hospital care, 3) Communication strategy with continuous medical education, 4) Systematic introduction of new expensive medicines, 5) E-pharmacological support at "point of care", 6) Methods and tools for follow-up of medicines use, 7) Medicines policy strategy and 8) Operative resources. RESULTS: The course highlighted the importance of efficient and targeted communication of drug recommendations building on trust among prescribers and patients for the guidelines to achieve high adherence. Trust is achieved by independent Drug and Therapeutics Committees with a key role for respected experts and a strict policy for "conflicts of interest". Representations of GPs are also crucial for successful implementation, being the link between evidence based medicine and practice. CONCLUSION: The successful models in Scotland and in Stockholm as well as the ongoing work in Catalonia were considered as examples of multifaceted approaches to improve the quality of medicine use across primary and hospital care.

"Quality of prenatal and maternal care: bridging the know-do gap" (QUALMAT study): an electronic clinical decision support system for rural Sub-Saharan Africa.

BACKGROUND: Despite strong efforts to improve maternal care, its quality remains deficient in many countries of Sub-Saharan Africa as persistently high maternal mortality rates testify. The QUALMAT study seeks to improve the performance and motivation of rural health workers and ultimately quality of primary maternal health care services in three African countries Burkina Faso, Ghana, and Tanzania. One major intervention is the introduction of a computerized Clinical Decision Support System (CDSS) for rural primary health care centers to be used by health care workers of different educational levels. METHODS: A stand-alone, java-based software, able to run on any standard hardware, was developed based on assessment of the health care situation in the involved countries. The software scope was defined and the final software was programmed under consideration of test experiences. Knowledge for the decision support derived from the World Health Organization (WHO) guideline "Pregnancy, Childbirth, Postpartum and Newborn Care; A Guide for Essential Practice". RESULTS: The QUALMAT CDSS provides computerized guidance and clinical decision support for antenatal care, and care during delivery and up to 24 hours post delivery. The decision support is based on WHO guidelines and designed using three principles: (1) Guidance through routine actions in maternal and perinatal care, (2) integration of clinical data to detect situations of concern by algorithms, and (3) electronic tracking of peri- and postnatal activities. In addition, the tool facilitates patient management and is a source of training material. The implementation of the software, which is embedded in a set of interventions comprising the QUALMAT study, is subject to various research projects assessing and quantifying the impact of the CDSS on quality of care, the motivation of health care staff (users) and its health economic aspects. The software will also be assessed for its usability and acceptance, as well as for its influence on workflows in the rural setting of primary health care in the three countries involved. CONCLUSION: The development and implementation of a CDSS in rural primary health care centres presents challenges, which may be overcome with careful planning and involvement of future users at an early stage. A tailored software with stable functionality should offer perspectives to improve maternal care in resource-poor settings.

Are prescribing initiatives readily transferable across classes: the case of generic losartan in Scotland?

BACKGROUND: There are on-going initiatives in Scotland to improve the quality and efficiency of prescribing in primary care. Activities to enhance prescribing of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin receptor blockers (ARBs) include prescribing guidance, guidelines, benchmarking, prescribing targets and financial incentives. These measures stabilised reimbursed expenditure for renin-angiotensin inhibitor drugs between 2001 and 2007 despite a 159% increase in volumes. Generic losartan was included in the Drug Tariff from July 2010. As there is no appreciable difference between ARBs, and the prices of generic losartan are falling, health boards should be actively encouraging its prescribing. AIM: To primarily assess changes in utilisation patterns of losartan versus other ARBs after July 2010. Second, to assess the utilisation of generic versus originator losartan. METHOD: We used an interrupted time series analysis of ARB utilisation, measured in defined daily doses (DDDs) before and after July 2010. Utilisation data were obtained from the NHS National Services Scotland Corporate Warehouse. RESULTS: There was no significant change in the utilisation pattern of losartan or other ARBs combined before or after the introduction of generic losartan. Losartan accounted for 32% of total ARBs 12 months after listing. Between 98 and 99% of losartan was prescribed generically. In March 2012, the price of losartan was 88% below prepatent prices with potential savings of ?8m per year. CONCLUSION: Specific measures are needed to change prescribing habits especially with complex messages. The cost of deriving savings must be weighed against other quality initiatives and other ARBs losing or shortly losing their patents.