Prevalence and patterns of anti-epileptic medication prescribing in the treatment of epilepsy in older adults with intellectual disabilities.

BACKGROUND: The prevalence of epilepsy is higher in people with intellectual disability (ID) and increases with the degree of ID. Although life expectancy for people with ID is increasing, people with ID coexisting with epilepsy have a higher mortality rate, particularly those who had recent seizures. There have been few observational studies of the prevalence and patterns of anti-epileptic prescribing among older people with ID and epilepsy. The aim of this study was to investigate prevalence and patterns of anti-epileptic prescribing in the treatment of epilepsy in a representative population of older people with ID and epilepsy. METHODS: This was an observational cross-sectional study from wave 1 (2009/2010) of Intellectual Disability Supplement to the Irish Longitudinal Study on Aging, a nationally representative sample of 753 persons with ID aged between 41 and 90 years. Participants and/or proxies recorded medicines used on a regular basis and reported doctor's diagnosis of epilepsy; medication data were available for 736 (98%). Prescribing of anti-epileptic drugs (AEDs) for epilepsy in those with a doctor's diagnosis of epilepsy (N = 205) was the primary exposure of interest for this study. Participant exposure to these AEDs was then categorised into AED monotherapy and polytherapy. Participants/carers reported seizure frequency, when epilepsy was last reviewed and which practitioner reviewed epilepsy. In addition, medications that may lower the seizure threshold that were listed in the Maudsley prescribing guidelines in psychiatry were examined. RESULTS: Of the 736 participants with reported medicines use, 38.9% (n = 287) were exposed to AEDs, and 30.6% (225) had a doctor's diagnosis of epilepsy. Of those with epilepsy (n = 225), 90.9% (n = 205) reported concurrent use of AEDs and epilepsy. Of these 205 participants, 50.3% (n = 103) were exposed to AED polytherapy, and 63 different polytherapy regimes were reported. The most frequently reported AEDs were valproic acid (n = 100, 48.7%), carbamazepine (n = 89, 46.3%) and lamotrigine (n = 57, 27.8%). In total, 13.7% had a concurrent psychotropic, which should be avoided in epilepsy, and 32.6% had a psychotropic where caution is required. Antipsychotics with potential epileptogenic potential accounted for 80% of these medications. Of those with AED polytherapy (n = 103), 29.5% (28) reported being seizure free for the previous 2 years. CONCLUSIONS: Prevalence of epilepsy was high among older people with ID, and half were exposed to two or more AEDs. Despite the use of AED therapy, over half had seizures in the previous 2 years. As the primary goals of optimal AED treatment are to achieve seizure freedom without unacceptable adverse effects, this was not achievable for many older patients with ID and epilepsy. Our findings indicated that people with ID and epilepsy were often exposed to psychotropic medications that may lower the seizure threshold. Regular review of epilepsy and medicines (including medicines that may interact with AEDs or lower the seizure threshold) by multidisciplinary teams working to agreed standards may improve quality of prescribing. Improved exchange of information and coordination of care between specialists and primary care practitioners in line with expert consensus recommendations could bring substantial benefit.

Prevalence, patterns and factors associated with psychotropic use in older adults with intellectual disabilities in Ireland.

BACKGROUND: People with intellectual disability (ID) are at increased risk of exposure to psychotropic drugs and psychotropic polypharmacy because of the higher prevalence of mental health conditions present and more controversially, the use of these agents to treat challenging behaviours. Despite the fact that many adults with ID are exposed to psychotropic polypharmacy, few studies to date have focused on the patterns of use of multiple psychotropics, or factors associated with psychotropic polypharmacy, particularly in the older population. This study aims to examine the prevalence, patterns and factors associated with psychotropic use in general and psychotropic polypharmacy in particular in a representative sample of ageing people with ID. METHODS: This was an observational cross-sectional study from Wave 1 of Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing; a nationally representative sample of 753 persons with ID aged between 41 and 90 years. Participants/proxy reported medicines (prescription and over the counter) taken on a regular basis; medication data were available for 736 participants (98%). Participants were divided into those with no psychotropic exposure, exposure to 1 psychotropic and psychotropic polypharmacy (2+ psychotropics). Patterns of psychotropic use were analysed. A multinomial logistic regression model identified factors associated with use of 1 psychotropic and psychotropic polypharmacy. RESULTS: Overall, 59.1% (436) of the sample was exposed to any psychotropic; of these, 66.2% reported psychotropic polypharmacy. Antipsychotics were the most frequently reported psychotropic class by 43% of the sample. Living in a residential institution and having a history of reporting a mental health condition or sleep problems were associated with psychotropic polypharmacy after adjusting for confounders, while those with epilepsy were less likely to experience exposure to polypharmacy, but age, gender had no significant effect. CONCLUSIONS: Psychotropic use and polypharmacy were commonplace for older adults with ID. Psychotropic use, particularly the use of psychotropic combinations, needs to be regularly reviewed for safety, efficacy and adverse effects, and rationale for use of multiple agents needs to be clear and documented.

A retrospective cohort analysis of hypoglycaemic and cardiovascular agent use in young adults in the Irish primary care setting.

AIM: The prevalence of type 2 diabetes in young adults is increasing, yet little is known about medication use in this population. This study aimed to describe hypoglycaemic and cardiovascular treatment patterns in young adults newly treated with oral hypoglycaemic agents. METHODS: A retrospective cohort study from 2008-2011 was conducted using the Irish national pharmacy claims database. Subjects aged 15-39 years were analysed for use of hypoglycaemic therapy, subsequent regimen changes, and any co-prescription of cardiovascular agents 1 year after treatment initiation. Cox-proportional-hazards regression and logistic regression were used to examine factors associated with non-persistence to initial hypoglycaemic therapy (in males only), insulin use as a regimen change, and use of cardiovascular agents. Hazard ratios (HR), odds ratios (OR), and 95 % confidence intervals (CI) are presented. RESULTS: There were 5284 individuals initiated on hypoglycaemic agents. Most were initiated on metformin (88 %); 13 % of subjects received a hypoglycaemic agent regimen change, with insulin being used in 26 % of these cases. A total of 38 % of males were non-persistent with their initial hypoglycaemic agent, with males aged 15-29 years and those on sulphonylureas significantly more likely to be non-persistent with therapy. Over 40 % of subjects were initiated on cardiovascular agents. Females were less likely to receive cardiovascular agents [OR 0.50 (95 % CI 0.42-0.83)]. CONCLUSIONS: Treatment patterns were found to be associated with high levels of non-persistence, substantial use of insulin, and a low use of cardiovascular agents. This may pose problems for the management of the long-term complications associated with type 2 diabetes.

The impact of initial antidiabetic agent and use of monitoring agents on prescription costs in newly treated type 2 diabetes: A retrospective cohort analysis.

AIMS: To measure the costs associated with the use of antidiabetic agents, monitoring materials and cardiovascular disease (CVD) agents in the management of newly treated type 2 diabetes, and to investigate the factors associated with these costs. METHODS: A population-based retrospective cohort study was conducted using the Irish national pharmacy claims database. Newly treated patients were identified for 2012 and followed for one year post treatment initiation. Factors associated with costs were assessed using a generalised linear model with gamma family and log-link function. Cost ratios (CR) and 95% CIs were used to determine the contributors of prescription costs. Adjusted odd ratios (OR) and 95% CIs were used to investigate factors associated with high frequency self-monitoring of blood glucose (SMBG). RESULTS: Mean prescription costs for the 12,941 subjects was €871, while total costs were €11 million. CVD agents accounted for 58% of total costs; 22% of costs were for SMBG; antidiabetic agents accounted for 17% of costs. SMBG resulted in costs that were 80% higher than those without, CR 1.80 (95% CI 1.76-1.84). No significant differences were observed between initiation on metformin or sulphonylureas and high frequency SMBG (OR 1.01 95% CI 0.97-1.04 vs reference). Initiation on newer antidiabetic agents was a significant positive predictors of prescription costs (CR 2.36 95% CI 2.21-2.51 vs metformin). CONCLUSIONS: Type of initial antidiabetic agent, and SMBG were significant predictors of prescription costs. SMBG represent a major proportion of total costs; however, its use in combination with antidiabetic agents that do not cause hypoglycaemia is questionable.

Collection and determination of nucleotide metabolites in neonatal and adult saliva by high performance liquid chromatography with tandem mass spectrometry.

Saliva contains a number of biochemical components which may be useful for diagnosis/monitoring of metabolic disorders, and as markers of cancer or heart disease. Saliva collection is attractive as a non-invasive sampling method for infants and elderly patients. We present a method suitable for saliva collection from neonates. We have applied this technique for the determination of salivary nucleotide metabolites. Saliva was collected from 10 healthy neonates using washed cotton swabs, and directly from 10 adults. Two methods for saliva extraction from oral swabs were evaluated. The analytes were then separated using high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS). The limits of detection for 14 purine/pyrimidine metabolites were variable, ranging from 0.01 to 1.0µM. Recovery of hydrophobic purine/pyrimidine metabolites from cotton tips was consistently high using water/acetonitrile extraction (92.7-111%) compared with water extraction alone. The concentrations of these metabolites were significantly higher in neonatal saliva than in adults. Preliminary ranges for nucleotide metabolites in neonatal and adult saliva are reported. Hypoxanthine and xanthine were grossly raised in neonates (49.3±25.4; 30.9±19.5µM respectively) compared to adults (4.3±3.3; 4.6±4.5µM); nucleosides were also markedly raised in neonates. This study focuses on three essential details: contamination of oral swabs during manufacturing and how to overcome this; weighing swabs to accurately measure small saliva volumes; and methods for extracting saliva metabolites of interest from cotton swabs. A method is described for determining nucleotide metabolites using HPLC with photodiode array or MS/MS. The advantages of utilising saliva are highlighted. Nucleotide metabolites were not simply in equilibrium with plasma, but may be actively secreted into saliva, and this process is more active in neonates than adults.

Associations of serum vitamin D concentrations with obstetric glucose metabolism in a subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study cohort.

AIMS: To assess associations between maternal serum vitamin D concentration and glucose metabolism in a cohort of pregnant women living in an Australian subtropical environment. METHODS: Cross-sectional assessment of 25-hydroxy vitamin D concentrations in 399 Hyperglycemia and Adverse Pregnancy Outcome ancillary study participants, treated at an obstetric teaching hospital in Brisbane, Australia. All patients underwent a blinded 75-g oral glucose tolerance test at 24-32 (target 28) weeks' gestation. RESULTS: The mean (± standard deviation) fasting plasma glucose was 4.5 ± 0.4 mmol/l. Mean (± standard deviation) serum 25-hydroxy vitamin D was 132.5 ± 44.0 nmol/l. A difference of one standard deviation in maternal 25-hydroxy vitamin D was inversely related to fasting glucose (fasting glucose lower by 0.047 mmol/l, P=0.012) when assessed with multiple linear regression after adjusting for confounders. Maternal 25-hydroxy vitamin D correlated with ß-cell function as estimated by the log-transformed homeostasis model assessment-ß-cell function equation (r=0.131, P=0.009), but not with the homeostasis model assessment of insulin resistance. CONCLUSIONS: An association between mid-gestational 25-hydroxy vitamin D and fasting glucose was confirmed in a largely normoglycaemic and vitamin D-replete pregnant population. The correlation between 25-hydroxy vitamin D and ß-cell function suggests that vitamin D may influence glucose metabolism through this mechanism. Intervention studies are required to determine causality and the role of vitamin D replacement in deficient individuals.

Lay constructions of decision-making in cancer.

In recent years there has been increased emphasis on involving people in decision-making about their medical care. However, few studies have addressed the questions of why women with cancer want information, and what they believe to be the important factors influencing their decision-making. In order to examine these questions 20 women with cancer were interviewed via telephone 2 weeks after their first consultation with one of 6 medical oncologists. Recruitment continued until informational redundancy was achieved. While women cited the risk of recurrence, life expectancy, side-effects, and quality of life as influencing their decisions, they placed at least as much emphasis on their personal relationship with the specialist. These 'personal' factors included: feeling that the doctor cared for, understood and respected them; that they could trust and have confidence in the doctor; that the doctor would give them enough time; that they would be listened to; and that the doctor would be open and honest. If these factors were felt to be present, many women were happy to accept the doctor's recommendation, confident that they would receive the optimum treatment. However, many women felt there was no decision to be made: further treatment must be undertaken to reduce risk, and minor variations in the treatment protocol were of little significance. These results underline the importance of establishing patient priorities and concerns before embarking on discussions about treatment.

Improving the well-being of elderly patients via community pharmacy-based provision of pharmaceutical care: a multicentre study in seven European countries.

OBJECTIVE: This study aimed to measure the outcomes of a harmonised, structured pharmaceutical care programme provided to elderly patients (> or =65 years of age) by community pharmacists in a multicentre international study performed in 7 European countries. DESIGN AND SETTING: The study was a randomised, controlled, longitudinal, clinical trial with repeated measures performed over an 18-month period. A total of 104 intervention and 86 control pharmacy sites participated in the research and 1290 intervention patients and 1164 control patients were recruited into the study. MAIN OUTCOME MEASURES AND RESULTS: A general decline in health-related quality of life over time was observed in the pooled data; however, significant improvements were achieved in patients involved in the pharmaceutical care programme in some countries. Intervention patients reported better control of their medical conditions as a result of the study and cost savings associated with pharmaceutical care provision were observed in most countries. The new structured service was well accepted by intervention patients and patient satisfaction with the services improved during the study. The pharmacists involved in providing pharmaceutical care had a positive opinion on the new approach, as did the majority of general practitioners surveyed. The positive effects appear to have been achieved via social and psychosocial aspects of the intervention, such as the increased support provided by community pharmacists, rather than via biomedical mechanisms. CONCLUSIONS: This study is the first large-scale, multicentre study to investigate the effects of pharmaceutical care provision by community pharmacists to elderly patients. Future research methodology and implementation will be informed by the experience gained from this challenging trial.

Toxic effects of oxygen on human embryo development.

The toxic effects of oxygen on the embryos of various animal species are reviewed. Methodologies for assessing embryonic damage are discussed and possible ways of preventing the damage are explored. Three methods of potentially minimizing oxidative damage to human embryos were tested using gametes, zygotes, and embryos from a clinical IVF programme: (i) decreasing the oxygen tension in the gas phase used for culture during insemination, fertilization, and embryo growth; (ii) changing the formulation of culture media to include some components designed to protect against oxidative damage; and (iii) reducing the duration of insemination to minimize the effect of oxidative damage caused by spermatozoal metabolism. Fertilization, cleavage, embryo utilization, pregnancy, and embryo implantation rates were used to monitor these changes. Although all three methods gave an increase in success rates, there was still a dramatic decrease in success with patient age. It is suggested that, although the system of handling and culturing embryos can be optimized with respect to embryonic mitochondrial function, there are inherent age-related defects in oocytes and embryos that are still more fundamental than the environmental conditions of the embryo.

Molecular and phenotypic analysis of Candida dubliniensis: a recently identified species linked with oral candidosis in HIV-infected and AIDS patients.

The discovery and characterisation of a novel species of Candida, termed Candida dubliniensis, associated with oral candidosis in HIV-infected individuals is described. These organisms share several phenotypic characteristics in common with Candida albicans and Candida stellatoidea, including the ability to produce germ tubes and chlamydospores. However, in contrast to these latter two species, C. dubliniensis isolates produce abundant chlamydospores, which are often arranged in contiguous pairs, triplets and other multiples suspended from a single suspensor cell. They belong to C. albicans serotype A and exhibit atypical substrate assimilation profiles. Genomic DNA fingerprinting analysis with the C. albicans-specific probe 27A and five different oligonucleotide probes consisting of short repeat sequence-containing motifs, demonstrated that C. dubliniensis has a distinct genomic organisation relative to C. albicans and C. stellatoidea. This was confirmed by karyotype analysis and random amplified polymorphic DNA (RAPD) analysis. Comparison of 500 bp of the V3 variable region of the large ribosomal subunit genes from 14 separate C. dubliniensis isolates and the corresponding sequences from C. albicans, C. stellatoidea, C. tropicalis, C. glabrata, C. parapsilosis, C. kefyr and C. krusei demonstrated that the C. dubliniensis isolates formed a homogenous cluster (100% similarity), representing a discrete taxon within the genus Candida that was significantly different from the other species analysed.

Widespread geographic distribution of oral Candida dubliniensis strains in human immunodeficiency virus-infected individuals.

Candida dubliniensis is a recently identified chlamydospore-positive yeast species associated with oral candidiasis in human immunodeficiency virus (HIV)-infected (HIV+) patients and is closely related to Candida albicans. Several recent reports have described atypical oral Candida isolates with phenotypic and genetic properties similar to those of C. dubliniensis. In this study 10 atypical chlamydospore-positive oral isolates from HIV+ patients in Switzerland, the United Kingdom, and Argentina and 1 isolate from an HIV-negative Irish subject were compared to reference strains of C. albicans and Candida stellatoidea and reference strains of C. dubliniensis recovered from Irish and Australian HIV+ individuals. All 11 isolates were phenotypically and genetically similar to and phylogenetically identical to C. dubliniensis. These findings demonstrate that the geographical distribution of C. dubliniensis is widespread, and it is likely that it is a significant constituent of the normal oral flora with the potential to cause oral candidiasis, particularly in immunocompromised patients.

Antifungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole-resistant derivatives in vitro.

Candida dubliniensis is a recently described species of Candida associated with oral candidiasis in human immunodeficiency virus (HIV)-infected individuals. Nineteen oral isolates of C. dubliniensis recovered from 10 HIV-positive and 4 HIV-negative individuals and one vaginal isolate from an additional HIV-negative subject were assessed for fluconazole susceptibility by broth microdilution (BMD), hyphal elongation assessment, and Etest. The susceptibilities of these 20 isolates to itraconazole and amphotericin B and of 10 isolates to ketoconazole were also determined by BMD only. Sixteen of the C. dubliniensis isolates were susceptible to fluconazole (MIC range, 0.125 to 1.0 microgram ml-1), and four (recovered from two AIDS patients) were fluconazole resistant (MIC range, 8 to 32 micrograms ml-1). Fluconazole susceptibility data obtained by hyphal elongation assessment correlated well with results obtained by BMD, but the corresponding Etest MIC results were one to four times higher. All of the isolates tested were found to be sensitive to itraconazole, ketoconazole, and amphotericin B. Sequential exposure of two fluconazole-sensitive (MIC, 0.5 microgram ml-1) C. dubliniensis isolates to increasing concentrations of fluconazole in agar medium resulted in the recovery of derivatives which expressed a stable fluconazole-resistant phenotype (BMD-determined MIC range, 16 to 64 micrograms ml-1), even after a minimum of 10 consecutive subcultures on drug-free medium and following prolonged storage at -70 degrees C. The clonal relationship between the parental isolates and their respective fluconazole-resistant derivatives was confirmed by genomic DNA fingerprinting and karyotype analysis. The results of this study demonstrate that C. dubliniensis is inherently susceptible to commonly used antifungal drugs, that fluconazole resistance does occur in clinical isolates, and that stable fluconazole resistance can be readily induced in vitro following exposure to the drug.

Molecular genetic approaches to identification, epidemiology and taxonomy of non-albicans Candida species.

The reported incidence of fungal infections associated with non-albicans species from the Candida genus is increasing. Most of these infections occur in immunocompromised patients, particularly those infected with HIV. The role of molecular genetic techniques alongside the existing techniques for the identification and typing of these organisms is discussed. Species-specific genomic DNA fragments cloned from C. tropicalis and C. krusei have been developed for identification and strain typing. Analysis of tRNA profiles has been shown to be effective for the identification of C. glabrata, C. guilliermondii, C. parapsilosis and C. tropicalis. A PCR method employing primers complimentary to large ribosomal subunit genes and the lanosterol-alpha-demethylase gene has been applied for several species, including C. glabrata, C. krusei and C. tropicalis. Strain typing by comparison of genomic DNA fingerprints has been demonstrated for C. tropicalis and C. krusei following hybridisation analysis with species-specific probes. Synthetic oligonucleotide probes--which do not have to be species-specific and which can detect minor polymorphisms--have also been used for strain typing of isolates of several non-albicans species. Random amplification of polymorphic DNA (RAPD) has also been used for analysis of C. glabrata, C. lusitaniae and C. tropicalis isolates. The potential for the application of these and other techniques to Candida spp. taxonomy--and the example of a recently discovered novel species, C. dubliniensis--is discussed.

Oligonucleotide fingerprinting of isolates of Candida species other than C. albicans and of atypical Candida species from human immunodeficiency virus-positive and AIDS patients.

Oligonucleotide fingerprinting of genomic DNA from oral isolates of four different Candida species other than C. albicans and atypical chlamydospore-positive isolates from human immunodeficiency virus (HIV)-positive individuals and AIDS patients was investigated as a means for differentiating between isolates within individual species. Oligonucleotides composed of simple repetitive sequence motifs, including (GACA)4, (GATA)4, (GGAT)4, (GTG)5, and (GT)8, all yielded fingerprints suitable for strain segregation of 8 C. tropicalis isolates, 12 Torulopsis (Candida) glabrata isolates, 8 atypical Candida isolates, and, except for (GATA)4, 2 C. krusei probe in turn and so generate several distinct DNA fingerprints of the same DNA sample. However, none of the probes yielded fingerprints suitable for strain segregation with three C. parapsilosis isolates. The (GATA)4 probe was also used to detect restriction fragment length polymorphisms among a genetically closely related group of atypical Candida isolates on primary isolation from an additional HIV-infected patient. These chlamydospore-positive atypical Candida isolates were sucrose positive, were of C. albicans serotype A, hybridized weakly with the C. albicans-specific mid-repeat sequence probe 27A, and yielded fingerprint profiles by random polymorphic DNA analysis that were distinct from those derived from C. albicans isolates. The C. stellatoidea ex-type strain NCPF 3108 was indistinguishable from the atypical Candida isolates in all these tests and also yielded an identical carbohydrate and nitrogen source assimilation profile by using the ID 32C yeast identification system.

Oral Candida in HIV infection and AIDS: new perspectives/new approaches.

Oral candidosis has become an increasingly important problem in HIV-infected individuals. At present, the small body of published literature on the characterization of the Candida strains and species found in HIV+ patients is full of confusion and contradictions. Some of these difficulties are the result of the methodological shortcomings of a number of the techniques that have been used. Examples of the problems that may be encountered on primary isolation and subculture are described and the drawbacks associated with the systems used to date for phenotyping Candida are quoted. While molecular characterization techniques would appear to offer a reliable and objective alternative, they too have their strengths and weaknesses. An attempt is made to summarize the progress that has been made recently in the detection and identification of Candida albicans and also the non-albicans species from HIV-infected individuals. What emerges is that the commensal Candida species that inhabit the oral cavities of HIV+ patients are subjected to a number of significant pressures that probably promote the selection of organisms with unusual phenotypes and genotypes. These Candida are more difficult to characterize and behave differently compared to their counterparts in HIV- individuals. It is clear that uncovering the factors that are important for the selection of treatment regimens and will be predictive of outcome will not be easy. Candida organisms are neither as benign nor as simple as once thought.

Reduced azole susceptibility of oral isolates of Candida albicans from HIV-positive patients and a derivative exhibiting colony morphology variation.

Approximately 50% (15/28) of a selection of oral isolates of Candida albicans from separate individuals infected with the human immunodeficiency virus (HIV) exhibited low susceptibility to ketoconazole as determined by hyphal elongation assessment. Nine of these isolates exhibited colony morphology variation or switching at 37 degrees C, of which six expressed low ketoconazole susceptibility. To determine whether colony morphology variation could give rise to derivatives with reduced azole susceptibility, several high-frequency switching variants of three HIV-patient isolates were recovered and assessed. All but one of the variants expressed similar azole susceptibility profiles to their respective parental strains. However, the C. albicans derivative 132ACR expressed significantly reduced susceptibility to ketoconazole in comparison to its parental strain 132A. In whole cells, on the basis of total growth the switched derivative 132ACR was markedly less susceptible than its parental isolate 132A to ketoconazole at 10 microM. A much smaller difference was observed with fluconazole at 10 microM, with the switched derivative 132ACR exhibiting a threefold lower susceptibility compared with the parental isolate 132A. The incorporation of [14C]acetate in control and azole-treated cells of both organisms was higher for the parental strain. When cell lysates of strain 132A and its derivative 132ACR were incubated with [14C]mevalonic acid and ketoconazole, the IC50 for 14C-label incorporation into C-4 demethyl sterols was fivefold higher for lysates of the switched derivative 132ACR compared with those of the parental strain 132A. With fluconazole the IC50 value for the derivative 132ACR was 25-fold higher than for strain 132A. The 14-sterol demethylase of the switched derivative 132ACR was possibly less sensitive to azole inhibition than that of the enzyme of strain 132A. These studies indicated that colony morphology variation in vitro can generate derivatives with stable, reduced azole susceptibility without prior exposure to azoles.

Impact of a nationwide limited prescribing list: preliminary findings.

In the Republic of Ireland, the state pays the cost of medical care for around 40 percent of the population through the General Medical Services (GMS). Doctors treating GMS patients are entitled to prescribe from an approved list of drugs. In October 1982, many antacids, cough and cold preparations, antihistamines, and mild analgesics were removed from the GMS prescribing list. The visiting rate and the amount of prescribing fell in the GMS during 1982-83. Drug utilization within the GMS was measured using prescription numbers and in the total population using data obtained from pharmaceutical wholesalers expressed as defined daily doses. These results showed substantial changes in GMS prescribing in the utilization of mefenamic acid, carbocysteine, and H2-receptor antagonists associated with the introduction of the limited list, suggesting a switch to these agents from delisted preparations. The therapeutic and economic implications of this policy are discussed.

A survey of drug and therapeutics committees operating in Ireland.

A survey of the number and characteristics of Drug and Therapeutics Committees (DTCs) operating in hospitals in Ireland was conducted in 1984. Just under half of the hospitals surveyed had a DTC and half of those had been formed after 1981. Pharmacists and consultant medical staff were present on every DTC and the latter also chaired most DTCs. Formularies or limited lists had been drawn up by half the DTCs identified and the most frequently discussed topics at DTC meetings were concerned with expenditure control. These findings are discussed and compared with the experience of DTC formation and operation in other countries.

Comparison of bioassay methods for the estimation of wound-released prostaglandin-like activity.

Methods of bioassay of prostaglandin-like activity (PGLA) released from wounds applied to isolated rat tail skin strips were compared. Administration of multiple bolus doses of PGE2 was used to simulate the response to wound-released PGLA. Estimates of the multiple dose administered were prepared by measuring the peak heights of single bolus and infused doses of PGE2 and also of peak response area measurements of single bolus doses in a three point assay procedure. Comparison of these three methods of measurement demonstrated that peak response height estimates underestimated the simulated wound response value. The mean difference between the bolus dose area estimate and the simulated wound response value was 1.4 +/- 1.2 ng PGE2, and there was a highly significant correlation between the bolus dose area estimates and the simulated wound response values over the range 2.0-12.15 ng PGE2. Data from additional studies using this assay method show that arachidonic acid increased and indomethacin decreased the release of PGLA from wounds and further that wound PGLA release from the skin of diabetic rats was also decreased.