Applying a values-based decision process to facilitate comanagement of threatened species in Aotearoa New Zealand.

Ko koe ki tena, ko ahau ki tenai kiwai o te kete (you at that, and I at this handle of the basket). This Maori (New Zealanders of indigenous descent) saying conveys the principle of cooperation-we achieve more through working together, rather than separately. Despite decades of calls to rectify cultural imbalance in conservation, threatened species management still relies overwhelmingly on ideas from Western science and on top-down implementation. Values-based approaches to decision making can be used to integrate indigenous peoples' values into species conservation in a more meaningful way. We used such a values-based method, structured decision making, to develop comanagement of pekapeka (Mystacina tuberculata) (short-tailed bat) and tara iti (Sternula nereis davisae) (Fairy Tern) between Maori and Pakeha (New Zealanders of European descent). We implemented this framework in a series of workshops in which facilitated discussions were used to gather expert knowledge to predict outcomes and make management recommendations. For both species, stakeholders clearly stated their values as fundamental objectives from the start, which allowed alternative strategies to be devised that naturally addressed their diverse values, including matauranga Maori (Maori knowledge and perspectives). On this shared basis, all partners willingly engaged in the process, and decisions were largely agreed to by all. Most expectations of conflicts between values of Western science and Maori culture were unfounded. Where required, positive compromises were made by jointly developing alternative strategies. The values-based process successfully taha wairua taha tangata (brought both worlds together to achieve the objective) through codeveloped recovery strategies. This approach challenges the traditional model of scientists first preparing management plans focused on biological objectives, then consulting indigenous groups for approval. We recommend values-based approaches, such as structured decision making, as powerful methods for development of comanagement conservation plans between different peoples.

Aplicación de un Proceso de Decisiones Basadas en Valores para Facilitar el Comanejo de Especies Amenazadas en Aotearoa Nueva Zelanda Resumen Ko koe ki tena, ko ahau ki tenai kiwai o te kete (tú en ésa y yo en esta asa de la cesta). Este dicho Maori (neozelandeses con ascendencia indígena) expresa el principio de la cooperación - logramos más trabajando juntos que por separado. A pesar de las décadas de peticiones para rectificar el desbalance ambiental que existe en la conservación, el manejo de especies amenazadas todavía depende abrumadoramente de ideas tomadas de la ciencia occidental y en la implementación de arriba-abajo. Los enfoques para la toma de decisiones basados en valores pueden usarse para integrar de manera más significativa los valores de los pueblos indígenas dentro de la conservación de especies. Usamos un método basado en valores, la toma estructurada de decisiones, para desarrollar una estrategia de comanejo del pekapeka (Mystacina tuberculata) (murciélago de cola corta) y el tara iti (Sternula nereis davisae) (charrancito australiano) entre los Maori y los Pakeha (neozelandeses de ascendencia europea). Implementamos este marco de trabajo en una serie de talleres en los cuales se usaron discusiones facilitadas para recabar el conocimiento de los expertos para pronosticar los resultados y realizar recomendaciones de manejo. Para ambas especies, los actores sociales mencionaron claramente a sus valores como objetivos fundamentales desde el inicio, lo que permitió el diseño de estrategias alternativas que consideraran naturalmente estos diferentes valores, incluyendo el matauranga Maori (conocimiento y perspectivas Maori). Sobre esta base compartida, todos los colaboradores participaron voluntariamente en el proceso y la mayoría estuvo de acuerdo con las decisiones. La mayoría de los conflictos esperados entre la ciencia occidental y la cultura Maori no tuvieron fundamentos. En donde fueron requeridos, se realizaron concesiones positivas mediante el desarrollo conjunto de estrategias alternativas. El proceso basado en valores logró exitosamente taha wairua taha tangata (juntó a ambos mundos para conseguir el objetivo) por medio de estrategias de recuperación desarrolladas en conjunto. Esta estrategia desafía el modelo tradicional de los científicos preparando primero los planes de manejo enfocados en objetivos biológicos para después consultar a los grupos indígenas para que los aprueben. Recomendamos estos enfoques basados en valores, como la toma estructurada de decisiones, como métodos poderosos para el desarrollo de planes de conservación que incluyan el comanejo entre diferentes pueblos y personas.

Glibenclamide and metfoRmin versus stAndard care in gEstational diabeteS (GRACES): a feasibility open label randomised trial.

BACKGROUND: Metformin is widely used to treat gestational diabetes (GDM), but many women remain hyperglycaemic and require additional therapy. We aimed to determine recruitment rate and participant throughput in a randomised trial of glibenclamide compared with standard therapy insulin (added to maximum tolerated metformin) for treatment of GDM. METHODS: We conducted an open label feasibility study in 5 UK antenatal clinics among pregnant women 16 to 36 weeks' gestation with metformin-treated GDM. Women failing to achieve adequate glycaemic control on metformin monotherapy were randomised to additional glibenclamide or insulin. The primary outcome was recruitment rate. We explored feasibility with uptake, retention, adherence, safety, glycaemic control, participant satisfaction and clinical outcomes. RESULTS: Records of 197 women were screened and 23 women randomised to metformin and glibenclamide (n = 13) or metformin and insulin (n = 10). Mean (SD) recruitment rate was 0.39 (0.62) women/centre/month. 9/13 (69.2%, 95%CI 38.6-90.9%) women adhered to glibenclamide and all provided outcome data (100% retention). There were no episodes of severe hypoglycaemia, but metformin and insulin gave superior glycaemic control to metformin and glibenclamide, with fewer blood glucose readings <3.5 mmol/l (median [IQR] difference/woman/week of treatment 0.58 [0.03-1.87]). CONCLUSIONS: A large randomised controlled trial comparing glibenclamide or insulin in combination with metformin for women with GDM would be feasible but is unlikely to be worthwhile, given the poorer glycaemic control with glibenclamide and metformin in this pilot study. The combination of metformin and glibenclamide should be reserved for women with GDM with true needle phobia or inability to use insulin therapy. TRIAL REGISTRATION: www.clinicaltrials.gov registration number:NCT02080377 February 11th 2014.

Development and early application of the Scottish Community Nursing Workload Measurement Tool.

This article describes the development and early application of the Scottish Community Nursing Workload Measurement Tool, part of a suite of tools aiming to ensure a consistent approach to measuring nursing workload across NHS Scotland. The tool, which enables community nurses to record and report their actual workload by collecting information on six categories of activity, is now being used by all NHS boards as part of a triangulated approach. Data being generated by the tool at national level include indications that approximately 50% of band 6 district nurses' time is spent in face-to-face and non-face-to-face contact and planned sessions with patients, and that over 60% of face-to-face contacts are at 'moderate' and 'complex' levels of intervention (2012 data). These data are providing hard evidence of key elements of community nursing activity and practice that will enable informed decisions about workforce planning to be taken forward locally and nationally. The article features an account of the early impact of the tool's implementation in an NHS board by an associate director of nursing. Positive effects from implementation include the generation of reliable data to inform planning decisions, identification of issues around nursing time spent on administrative tasks, clarification of school nursing roles, and information being fed back to teams on various aspects of performance.

Biobanking trends, challenges, and opportunities.

OBJECTIVES: To review the different interests and needs of industry and academic users of human biomaterials. METHODS: A review of the current literature and interviews with involved parties. Questionnaires were e-mailed to assess current attitudes towards biobanking and opinions of trends and implications for the future. The organisations included commercial biobanks, charitable foundations, academic biobanks, and hospital sites. RESULTS: Biobanks have the potential to have a critical impact across several industrial sectors, and their future success will depend on satisfying the differing needs of each group. There is a growing need for greater collaboration between researchers and biobanks, and if the involvement of industry is not sought by biobanks to create conditions that support the effective use of resources, there is a risk that samples will not be collected or used to the best advantage. CONCLUSIONS: It is evident that industry can play a vital role in the innovation process of biobanking, both in terms of the collecting and processing methods and the nature of the disease and sample types collected. With this feedback, biobanks can be utilised effectively to advance research to the benefits of all to the best advantage.

Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.

BACKGROUND: Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy. METHODS: In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581. FINDINGS: Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16, 95% CI 0.89-1.51). INTERPRETATION: Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy. FUNDING: Chief Scientist Office of the Scottish Government Health Directorate.

Study of progesterone for the prevention of preterm birth in twins (STOPPIT): findings from a trial-based cost-effectiveness analysis.

OBJECTIVES: Preterm birth contributes to a range of healthcare problems amongst infants surmounting to sizeable healthcare costs. Twin pregnancies are at particular risk of preterm birth. The objective of this study was to assess the cost-effectiveness of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies. METHODS: An economic evaluation was conducted alongside a randomized placebo controlled trial (the STOPPIT trial) of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies. Five hundred women were recruited from nine maternity hospitals in the United Kingdom. The outcomes of the economic evaluation were presented in terms of net benefit statistics, cost-effectiveness acceptability curves, generated using the nonparametric bootstrap method, and the expected value of perfect information. RESULTS: Mean health service costs between the period of randomization and discharge for mother and infant were 28,031 pound sterling in the progesterone group and 25,972 pound sterling in the placebo group, generating a mean nonsignificant cost difference of 2,059 pound sterling (bootstrap mean cost difference 2,334 pound sterling; 95 percent confidence interval: -5,023 pound sterling, 9,142 pound sterling; p = .33). The probability of progesterone being cost-effective was 20 percent at a willingness to pay threshold of 30,000 pound sterling per preterm birth prevented. There is little economic justification for conducting further research into the use of vaginal progesterone gel in twin pregnancies for the prevention of preterm birth. CONCLUSIONS: Further studies of preventive interventions for preterm birth more generally are required given the scale of the clinical and economic burden of this condition. These studies should be sufficiently powered for economic endpoints and extend beyond hospital discharge.

Antimicrobial resistance profiles of Campylobacter from humans, retail chicken meat, and cattle feces.

We determined the antimicrobial resistance profiles of Campylobacter isolates from cases of sporadic human infection (n = 119), retail chicken meat (n = 105), and cattle feces (n = 105). Ampicillin and tetracycline resistance was highest in human isolates (32% and 29%, respectively) and retail chicken isolates (25% and 25%, respectively), whereas nalidixic acid resistance was highest in cattle fecal isolates (20%). We found that the antimicrobial resistance profiles were more similar in human and chicken meat isolates than those observed when comparing human and cattle fecal isolates. When we analyzed the distribution of minimum inhibitory concentrations for each antibiotic, in each host, the distribution was similar between human and chicken meat isolates, whereas cattle fecal isolates remained highly distinct from the other two hosts. This study suggests that chicken may be a major source of human Campylobacter infection and that the antimicrobial resistances found in the Campylobacter from this source will therefore also be prevalent in clinical isolates.

The effectiveness of drug round tabards in reducing incidence of medication errors.

BACKGROUND: A number of inpatients experience medication errors, which carry potential risks for patients and have cost implications for the NHS. These errors are often a result of interruptions during drug rounds. AIM: This audit study explored whether introducing drug round tabards reduced the number of interruptions during drug rounds and improved patient care and safety. METHOD: Red tabards, embroidered front and backwith "Drug round in progress please do not disturb", were introduced in three wards. A tick box questionnaire was used to collect information on interruptions during each drug round. NHS Grampian's Datix incident reporting system was reviewed for medication errors during the audit period and tabards were randomly swabbed to see if any cultures hadgrown. RESULTS AND DISCUSSION: The average number of interruptions was reduced significantly from six to five after drug round tabards were introduced and there was a slight reduction in the number of incidents reported over the five week audit period compared with the previous year. CONCLUSION: Further studies need to be conducted nationwide to provide a better understanding of the effectiveness of drug round tabards. Issues ofcost, laundering and infection control need to be further examined.

Rapid molecular testing for Staphylococcus aureus bacteraemia improves clinical management.

Introduction. Staphylococcus aureus bacteraemia (SAB) causes significant morbidity and mortality. Standard diagnostic methods require 24-48 h to provide results, during which time management is guideline-based and may be suboptimal.Aim. Evaluate the impact of rapid molecular detection of S. aureus in positive blood culture bottle fluid on patient management.Methodology. Samples were tested prospectively at two clinical centres. Positive blood cultures with Gram-positive cocci in clusters on microscopy were tested with the Xpert MRSA/SA blood culture assay (Cepheid), as well as standard culture-based identification and antimicrobial sensitivity tests. Results were passed to clinical microbiologists in real time and used for patient management.Results. Of 264 blood cultures tested (184 and 80 from each centre), S. aureus was grown from 39 (14.8 %) with one identified as methicillin-resistant S. aureus; all Xpert results agreed with culture results. Median turnaround time from culture flagging positive to result reporting for Xpert was 1.7 h, compared to 25.7 h for species identification by culture. Xpert results allowed early changes to management in 40 (16.8 %) patients, with Xpert positive patients starting specific therapy for SAB and Xpert negative patients stopping or avoiding empiric antimicrobials for SAB.Conclusion. Rapid and accurate detection of S. aureus with the Xpert MRSA/SA BC assay in positive blood culture bottles allowed earlier targeted patient management. Negative Xpert results are suggestive of coagulase negative staphylococci, allowing de-escalation of antimicrobial therapy if clinically appropriate.

Impact of COVID-19 on accident and emergency attendances and emergency and planned hospital admissions in Scotland: an interrupted time-series analysis.

OBJECTIVES: Following the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and the subsequent global spread of the 2019 novel coronavirus disease (COVID-19), health systems and the populations who use them have faced unprecedented challenges. We aimed to measure the impact of COVID-19 on the uptake of hospital-based care at a national level. DESIGN: The study period (weeks ending 5 January to 28 June 2020) encompassed the pandemic announcement by the World Health Organization and the initiation of the UK lockdown. We undertook an interrupted time-series analysis to evaluate the impact of these events on hospital services at a national level and across demographics, clinical specialties and National Health Service Health Boards. SETTING: Scotland, UK. PARTICIPANTS: Patients receiving hospital care from National Health Service Scotland. MAIN OUTCOME MEASURES: Accident and emergency (A&E) attendances, and emergency and planned hospital admissions measured using the relative change of weekly counts in 2020 to the averaged counts for equivalent weeks in 2018 and 2019. RESULTS: Before the pandemic announcement, the uptake of hospital care was largely consistent with historical levels. This was followed by sharp drops in all outcomes until UK lockdown, where activity began to steadily increase. This time-period saw an average reduction of -40.7% (95% confidence interval [CI]: -47.7 to -33.7) in A&E attendances, -25.8% (95% CI: -31.1 to -20.4) in emergency hospital admissions and -60.9% (95% CI: -66.1 to -55.7) in planned hospital admissions, in comparison to the 2018-2019 averages. All subgroup trends were broadly consistent within outcomes, but with notable variations across age groups, specialties and geography. CONCLUSIONS: COVID-19 has had a profoundly disruptive impact on hospital-based care across National Health Service Scotland. This has likely led to an adverse effect on non-COVID-19-related illnesses, increasing the possibility of potentially avoidable morbidity and mortality. Further research is required to elucidate these impacts.

Antibiotic stewardship and consumption: findings from a pan-European hospital study.

OBJECTIVES: Much has been written about antibiotic stewardship although less is known about the structure and content of antibiotic policies at hospital level. As part of the European Commission Concerted Action Antibiotic Resistance Prevention And Control (ARPAC) Project, data on antibiotic stewardship were collated and relationships investigated by antibiotic consumption in European hospitals. METHODS: A questionnaire survey on antibiotic stewardship factors was completed by 170 hospitals from 32 European countries. Data on committees, antibiotic formularies and policies addressing empirical therapy and prophylaxis were collated. Data on antibiotic use, expressed as defined daily doses per 100 occupied bed-days (DDD/100 BD), were provided by 139 hospitals from 30 countries, and 124 hospitals provided both data sets. Six key indicator stewardship variables were analysed by European region, case mix and antibiotic consumption. RESULTS: Hospitals from Northern and Western Europe were more likely to convene antibiotic committees or drugs and therapeutic committees compared with those from Southern and South-Eastern Europe (P < 0.001). One-fifth of hospitals had neither an antibiotic committee nor a policy. Hospital antibiotic policies commonly included recommendations on individual drugs, drug choices, dosage, duration and route but were less likely to contain information on side effects and cost. There were no significant differences by median total (J01) antibiotic consumption, although other antibiotic subgroups differed by stewardship indicators. CONCLUSIONS: Policies and practices relating to antibiotic stewardship varied considerably across European hospitals. These data provide a benchmark for newer European strategies tackling antibiotic resistance. More work is required to achieve harmonization of recommended practice, particularly in hospitals from Southern Europe.

Functionalized nanoparticles for nucleic acid sequence analysis using optical spectroscopies.

SERRS (surface-enhanced resonance Raman scattering) is a vibrational spectroscopy which allows extremely sensitive and selective detection of labelled DNA sequences with detection limits which rival, and in most cases surpass, that of fluorescence. SERRS relies on a visible chromophore adsorbing on to an enhancing surface. DNA itself is not SERRS-active, as it lacks a suitable visible chromophore and has poor adsorption properties on to the surfaces used for enhancement. The surface normally used for enhancement in these sorts of studies are metallic nanoparticles and, through modification of DNA probes by the addition of suitable SERRS labels, signals can be obtained that are highly sensitive and very selective. The aggregation state of the nanoparticles is critical to the sensitivity, and, in the present paper, we show how straightforward detection of labelled DNA probes can be achieved using SERRS in a quantitative manner and with a variety of different commercially available labels. In a second approach, we show how the properties of aggregation to turn on the SERRS effect can be exploited through DNA hybridization to give identification of a particular DNA sequence. This approach lends itself to closed-tube formats and is a promising way forward for molecular diagnostics using SERRS.

"A Lot of People Are Struggling Privately. They Don't Know Where to Go or They're Not Sure of What to Do": Frontline Service Provider Perspectives of the Nature of Household Food Insecurity in Scotland.

This qualitative study explored frontline service providers' perceptions of the nature of food insecurity in Scotland in 2015 to inform national policy and the provision of locally-based support for 'at risk' groups. A country-wide in-depth interview study was undertaken with informants from 25 health, social care, and third sector organisations. The study investigated informants' perspectives associated with how food insecurity was manifesting itself locally, and what was happening at the local level in response to the existence of food insecurity. Data analysis revealed three key themes. First, the multiple faces and factors of food insecurity involving not only increased concern for previously recognised 'at risk of food insecurity' groups, but also similar concern held about newly food insecure groups including working families, young people and women. Secondly, respondents witnessed stoicism and struggle, but also resistance amongst some food insecure individuals to external offers of help. The final theme identified community participation yet pessimism associated with addressing current and future needs of food insecure groups. These findings have important implications for the design and delivery of health and social policy in Scotland and other countries facing similar challenges.

Genetic variation affecting DNA methylation and the human imprinting disorder, Beckwith-Wiedemann syndrome.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder with a population frequency of approximately 1 in 10,000. The most common epigenetic defect in BWS is a loss of methylation (LOM) at the 11p15.5 imprinting centre, KCNQ1OT1 TSS-DMR, and affects 50% of cases. We hypothesised that genetic factors linked to folate metabolism may play a role in BWS predisposition via effects on methylation maintenance at KCNQ1OT1 TSS-DMR. RESULTS: Single nucleotide variants (SNVs) in the folate pathway affecting methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR), cystathionine beta-synthase (CBS) and methionine adenosyltransferase (MAT1A) were examined in 55 BWS patients with KCNQ1OT1 TSS-DMR LOM and in 100 unaffected cases. MTHFR rs1801133: C>T was more prevalent in BWS with KCNQ1OT1 TSS-DMR LOM (p < 0.017); however, the relationship was not significant when the Bonferroni correction for multiple testing was applied (significance, p = 0.0036). None of the remaining 13 SNVs were significantly different in the two populations tested. The DNMT1 locus was screened in 53 BWS cases, and three rare missense variants were identified in each of three patients: rs138841970: C>T, rs150331990: A>G and rs757460628: G>A encoding NP_001124295 p.Arg136Cys, p.His1118Arg and p.Arg1223His, respectively. These variants have population frequencies of less than 1 in 1000 and were absent from 100 control cases. Functional characterization using a hemimethylated DNA trapping assay revealed a reduced methyltransferase activity relative to wild-type DNMT1 for each variant ranging from 40 to 70% reduction in activity. CONCLUSIONS: This study is the first to examine folate pathway genetics in BWS and to identify rare DNMT1 missense variants in affected individuals. Our data suggests that reduced DNMT1 activity could affect maintenance of methylation at KCNQ1OT1 TSS-DMR in some cases of BWS, possibly via a maternal effect in the early embryo. Larger cohort studies are warranted to further interrogate the relationship between impaired MTHFR enzymatic activity attributable to MTHFR rs1801133: C>T, dietary folate intake and BWS.

Topical antimicrobials in combination with admission screening and barrier precautions to control endemic methicillin-resistant Staphylococcus aureus in an Intensive Care Unit.

We aimed to establish whether screening for methicillin-resistant Staphylococcus aureus (MRSA) and body decontamination upon admission to an Intensive Care Unit (ICU), in combination with barrier precautions, reduced rates of MRSA infection acquired on the unit. This was an interrupted time series study employing segmented regression analysis of data collected for all patients admitted to a 16-bed adult ICU over 48 months. Before the intervention (24 months; 1232 patients (44% female)), MRSA was sought from clinical cultures only and positive patients were barrier nursed in isolation. During the intervention (24 months; 1421 patients (54% female)), all ICU patients were screened for MRSA on admission and were barrier nursed in single rooms when established as MRSA-positive; all were given topical nasal anti-MRSA preparations and daily bed baths with 4% chlorhexidine throughout their stay. Changes in the proportion of patients colonised or infected with MRSA in the ICU were assessed. Before the intervention, 193 new MRSA cases (16%) were identified from 1232 ICU admissions; during the intervention, this was reduced to 92 cases (6%) of 1421 admissions. By time series regression analysis, the proportion of patients with MRSA decreased by 11.38% from ca. 15% to ca. 5% (ca. three-fold reduction) (95% confidence interval 3.5-19.3%; P=0.005). Thus, treatment of 11 patients prevented 1 clinical case of MRSA. Mean length of stay decreased significantly (P<0.001). Although MRSA and methicillin-susceptible S. aureus bacteraemia rates dropped, the changes detected were not statistically significant. The proportion of patients with coagulase-negative staphylococcal bacteraemia decreased significantly (P<0.001) and the trend changed from increasing to decreasing (P<0.001), as did the trend in glycopeptide use (P=0.014). An inexpensive and easy to implement intervention to control MRSA in the ICU was highly successful without compromising antimicrobial susceptibility.

The role of microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals.

This observational, cross-sectional study describes the role played by clinical microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals. A total of 170 acute care hospitals from 32 European countries returned a questionnaire on antibiotic policies and practices implemented in 2001. Data on antibiotic use, expressed as Defined Daily Doses per 100 occupied bed-days (DDD/100 BD) were provided by 139 hospitals from 30 countries. A total of 124 hospitals provided both datasets. 121 (71%) of Clinical Microbiology departments and 66 (41%) of Pharmacy departments provided out of hours clinical advice. 70 (41%) of microbiology/infectious disease specialists and 28 (16%) of pharmacists visited wards on a daily basis. The majority of laboratories provided monitoring of blood cultures more than once per day and summary data of antibiotic susceptibility testing (AST) for empiric prescribing (86% and 73% respectively). Most of the key laboratory and pharmacy-led initiatives examined did not vary significantly by geographical location. Hospitals from the North and West of Europe were more likely to examine blood cultures more than once daily compared with other regions (p < 0.01). Hospitals in the North were least likely routinely to report susceptibility results for restricted antibiotics compared to those in the South-East and Central/Eastern Europe (p < 0.01). Hospital wards in the North were more likely to hold antibiotic stocks (100%) compared with hospitals in the South-East which were least likely (39%) (p < 0.001). Conversely, hospital pharmacies in the North were least likely to dispense antibiotics on an individual patient basis (16%) compared with hospital pharmacies from Southern Europe (60%) (p = 0.01). Hospitals that routinely reported susceptibility results for restricted antibiotics had significantly lower median total antibiotic use in 2001 (p < 0.01). Hospitals that provided prescribing advice outside normal working hours had significantly higher antibiotic use compared with institutions that did not provide this service (p = 0.01). A wide range of antibiotic stewardship measures was practised in the participating hospitals in 2001, although there remains great scope for expansion of those overseen by pharmacy departments. Most hospitals had active antibiotic stewardship programmes led by specialists in infection, although there is no evidence that these were associated with reduced antibiotic consumption. There was also no evidence that pharmacy services reduced the amount of antibiotics prescribed.

Use of the bacteriology laboratory to decrease general practitioners' antibiotic prescribing.

OBJECTIVE: Use of the bacteriology laboratory to guide antibiotic prescribing in primary care is often considered inappropriate due to difficulties of access in a relevant time scale. The overnight analysis offered to general practitioners in the Grampian area of Scotland for the past 6 years (ABLE), and which had previously been shown to reduce antibiotic prescribing by two-thirds in a randomized controlled trial, was audited to see if it was being used correctly in general practice, that is to reduce unnecessary antibiotic prescribing. METHODS: 699 consultations were audited. Of these, 357 were ABLE patients. The other 342 were chosen because an antibiotic had been prescribed. RESULTS: Only 36.7% (140) of the ABLE patients were prescribed an antibiotic, 65.7% being given a delayed action script. All but 10 were culture positive. ABLE patients had a greater proportion of urinary tract infections than the non-ABLE patients, but less lower-respiratory and skin or soft-tissue infection. The antibiotics prescribed reflected the differences in infection type. The repeat visit rate and repeat antibiotic prescription rate were almost identical between the two groups. CONCLUSION: While the overall use of ABLE in Grampian is low, its use seems to be appropriate in that it is successfully being used to identify bacterial infection and reduce unnecessary antibiotic prescribing.

The "PRIM" study: a randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety profile of prostaglandin E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term. STUDY DESIGN: Primigravid women were assigned randomly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostaglandin E2. Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery. Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening. RESULTS: Prostaglandin E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score. Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostaglandin E2. There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment. However, in the prostaglandin E2 group, 7% of the pregnancies had abnormal fetal heart rate patterns (P = .0002). Maternal satisfaction was significantly higher in the isosorbide mononitrate group. CONCLUSION: Although isosorbide mononitrate was less effective, maternal satisfaction was significantly greater. The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate, but not prostaglandin E2, on an outpatient basis.

The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family.

Ibudilast is widely used in Japan to treat ischemic stroke and bronchial asthma. Its mode of action is through the inhibition of cyclic nucleotide phosphodiesterases (PDEs). Growing evidence suggests this compound has utility in a range of neurological conditions linked to its ability to elevate cellular cyclic nucleotide concentrations, however limited data exists on Ibudilast's action on individual PDE families. We therefore used an extensive panel of human PDE enzymes to define the PDE inhibitory profile of this compound. Ibudilast preferentially inhibits PDE3A, PDE4, PDE10 and PDE11 with lesser inhibition of a number of other families. The significance of these findings is discussed in relation to Ibudilast's observed effects on certain disease states.

IMOP: randomised placebo controlled trial of outpatient cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour - clinical trial with analyses of efficacy, cost effectiveness and acceptability.

BACKGROUND: There is increasing interest in carrying out pre-induction cervical ripening on an outpatient basis. However, there are concerns about the use of prostaglandins, the agents commonly used in hospital settings for this indication, because prostaglandins induce uterine contractions that may lead to fetal hypoxia. Indeed, in a recent study we demonstrated abnormalities in 9% of fetal heart rate tracings performed following prostaglandin induced cervical ripening at term. In contrast, we confirmed in the same study that isosorbide mononitrate (IMN) (administered on an inpatient basis) was both effective in inducing cervical ripening at term, and was associated with no associated fetal heart rate abnormalities. METHODS/DESIGN: The aim of this study is to determine whether IMN self administered by women on an outpatient basis improves the process of induction of labour. Specifically, we hypothesise that the use of outpatient IMN will result in a shorter inpatient stay before delivery, decreased costs to the health service and greater maternal satisfaction with ripening and induction of labour, compared with placebo treatment. In the study described here (the "IMOP" study), women scheduled for induction of labour at term, and who require pre-induction cervical ripening will be randomised to self-administer at home either IMN 40 mg, or a placebo, each vaginally, at 48 hours, 32 hours and 16 hours before scheduled hospital admission. After admission to hospital, treatment will revert to the usual induction of labour protocol. We will compare the primary outcomes of the elapsed time interval from hospital admission to vaginal delivery, the costs to the health service of induction of labour, and women's experience of induction of labour in the two groups. DISCUSSION: This trial will provide evidence on the efficacy of outpatient IMN for pre-induction cervical ripening at term. We will study a formulation of IMN which is cheap and widely available. If the treatment is effective, acceptable to women, and cost effective, it could be implemented into obstetric practice worldwide. TRIAL REGISTRATION: The trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRTN39772441.