Message in a Bottle-Metabarcoding enables biodiversity comparisons across ecoregions.

BACKGROUND: Traditional biomonitoring approaches have delivered a basic understanding of biodiversity, but they cannot support the large-scale assessments required to manage and protect entire ecosystems. This study used DNA metabarcoding to assess spatial and temporal variation in species richness and diversity in arthropod communities from 52 protected areas spanning 3 Canadian ecoregions. RESULTS: This study revealed the presence of 26,263 arthropod species in the 3 ecoregions and indicated that at least another 3,000-5,000 await detection. Results further demonstrate that communities are more similar within than between ecoregions, even after controlling for geographical distance. Overall α-diversity declined from east to west, reflecting a gradient in habitat disturbance. Shifts in species composition were high at every site, with turnover greater than nestedness, suggesting the presence of many transient species. CONCLUSIONS: Differences in species composition among their arthropod communities confirm that ecoregions are a useful synoptic for biogeographic patterns and for structuring conservation efforts. The present results also demonstrate that metabarcoding enables large-scale monitoring of shifts in species composition, making it possible to move beyond the biomass measurements that have been the key metric used in prior efforts to track change in arthropod communities.

Development of the Manchester framework for the evaluation of emergency department pharmacy services.

BACKGROUND: Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as practitioners. They provide both traditional pharmaceutical care and novel practitioner care i.e. clinical examination, yet their impact on quality of care is unknown. AIM: To develop a framework of structures, processes and potential outcome indicators to support evaluation of the quality of ED pharmacy services in future studies. METHOD: Framework components (structures, processes and potential outcome indicators) were identified in three ways: from a narrative review of relevant international literature, and separate panel meetings with ED pharmacists and then other ED healthcare professionals. Structures and processes were collated into categories developed iteratively throughout data collection, with outcome indicators collated into six domains of quality as proposed by the Institute of Medicine. These raw data were then processed e.g. outcome indicators screened for clarity i.e. those which explicitly stated what would be measured were included in the framework. RESULTS: A total of 190 structures, 533 processes, and 503 outcome indicators were identified. Through data processing a total of 153 outcome indicators were included in the final framework divided into the domains safe (32), effective (50), patient centred (18), timely (24), efficient (20) and equitable (9). CONCLUSION: The first framework specific to the quality evaluation ED pharmacy services, service evaluators should validate potential outcome indicators prior to their use. The minimum expected of a high-quality service should also be defined to enable interpretation of relevant measurements.

The description and definition of Emergency Department Pharmacist Practitioners in the United Kingdom (the ENDPAPER study).

Background Due to a shortage of emergency department doctors and nurses, hospitals have started to employ pharmacists who have additional clinical skills, known as Emergency Department Pharmacist Practitioners, to help deliver services. Objective To describe, compare and define the Emergency Department Pharmacist Practitioner role. Setting UK emergency departments. Method Using a purpose developed questionnaire hosted on a tablet computer, Emergency Department Pharmacist Practitioners were asked to report their contribution to patient care and the wider emergency department over 10 work days. Main outcome measure Emergency Department Pharmacist Practitioners' work. Results Twenty Emergency Department Pharmacist Practitioners from 15 UK hospitals were recruited. Of 682 patients cared for, 4.8% (n=33) were of blue triage category (least urgent) and 4.1% (n=28) red (immediate need). Specific activities to inform patient diagnosis included clinical examinations (264/682 patients, 38.7%) and the review of investigation/test/procedure results (270, 39.6%). For treatment, EDPPs prescribed a total of 603 medicines (for administration in the ED) to 266 patients (39.0%) and performed procedures for 63 (9.2%). Eleven of the practitioners also took on the role of designated care provider (i.e. the healthcare professional with overall clinical responsibility) for at least some of their patients. From application of the care typology, all 20 practitioners carried out both 'traditional' and 'practitioner' activity and 9/20 of them sometimes provided more 'practitioner' than 'traditional' care to individual patients. Seven key role attributes were identified including how these pharmacists support patients with medical complaints and injuries of any severity and at any stage of their visit. Conclusion Emergency Department Pharmacist Practitioners combine traditional clinical pharmacy activities with more hands-on medical practise including being designated care provider. The role is versatile in that care and support provided to patients and the wider emergency department professional team is varied and therefore somewhat adaptable to situations which present.

Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records.

AIMS: To examine the risk of major cardiovascular events associated with second-line diabetes therapies, in patients with type 2 diabetes, after adjusting for known cardiovascular risk factors. METHODS: This was a retrospective cohort study of patients prescribed second-line regimens between 1998 and 2011 after first-line metformin. The UK Clinical Practice Research Datalink, with linked national hospitalization and mortality data, for the period up to December 2013, was used. Inverse probability of treatment-weighted time-varying Cox regression models was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a major cardiovascular event (cardiovascular death, myocardial infarction, stroke, acute coronary syndrome, unstable angina, or coronary revascularization) associated with second-line therapies. Analyses adjusted for patient demographic characteristics, comorbidities, glycated haemoglobin, socio-economic status, ethnicity, smoking status and concurrent medications. RESULTS: A total of 10 118 initiators of a second-line add-on to metformin of either a sulphonylurea (n = 6740), dipeptidyl peptidase-4 (DPP-4) inhibitor (n = 1030) or thiazolidinedione (n = 2348) were identified. After a mean (standard deviation) of 2.4 (1.9) years of follow-up, 386, 36 and 95 major cardiovascular events occurred in sulphonylurea-, DPP-4 inhibitor- and thiazolidinedione-initiators, respectively. In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen. CONCLUSIONS: Thiazolidinedione add-on treatments to metformin were associated with lower risks of major cardiovascular disease or cardiovascular death compared with sulphonylurea add-on treatment to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitor add-on therapies.

A comparison of medication adherence/persistence for asthma and chronic obstructive pulmonary disease in the United Kingdom.

AIM: To describe and compare adherence and persistence with maintenance therapies in patients with asthma or chronic obstructive pulmonary disease (COPD) in the United Kingdom (UK). METHODS: A retrospective prescribing database cohort was obtained from 44 general practitioner surgeries in National Health Service Forth Valley Scotland. Patients with physician-diagnosed asthma or COPD who received maintenance therapy between January 2008 and December 2009 were included. Five classes of therapy were assessed: inhaled corticosteroids, long-acting beta-agonists, combination therapy inhalers, theophyllines and long-acting muscarinic antagonists. Adherence was calculated using the medication possession ratio (MPR) and persistence was determined using Kaplan-Meier survival analysis for the time to discontinuation (TTD) over 1 year. Two step-wise logistic regressions were performed to assess the contribution of diagnosis to adherence/persistence. RESULTS: A total of 13,322 patients were included in the analysis: 10,521 patients with asthma and 2801 patients with COPD. 25.2% of medication episodes for asthma and 45.6% of medication episodes for COPD were classified as having an adequate medication supply (MPR of 80-120%). The overall median TTD was 92 days (IQR, interquartile range: 50-186 days) for patients with asthma and 116 days (IQR: 58-259 days, comparison p < 0.001) for patients with COPD. Patients with COPD were found to be more likely to achieve an MPR of at least 80% (OR: 1.27, 95% CI: 1.15-1.40), but had a similar likelihood of persistence at 1 year to patients with asthma. CONCLUSION: Adherence and persistence with respiratory therapies in the UK is relatively low. There is suggestion that patients with COPD may display more adherent behaviours than patients with asthma.

Comprehensive sampling reveals circumpolarity and sympatry in seven mitochondrial lineages of the Southern Ocean crinoid species Promachocrinus kerguelensis (Echinodermata).

Sampling at appropriate spatial scales in the Southern Ocean is logistically challenging and may influence estimates of diversity by missing intermediate representatives. With the assistance of sampling efforts especially influenced by the International Polar Year 2007-2008, we gathered nearly 1500 specimens of the crinoid species Promachocrinus kerguelensis from around Antarctica. We used phylogeographic and phylogenetic tools to assess its genetic diversity, demographic history and evolutionary relationships. Six phylogroups (A-F) identified in an earlier study are corroborated here, with the addition of one new phylogroup (E2). All phylogroups are circumpolar, sympatric and eurybathic. The phylogeny of Promachocrinus phylogroups reveals two principal clades that may represent two different cryptic species with contrasting demographic histories. Genetic diversity indices vary dramatically within phylogroups, and within populations, suggesting multiple glacial refugia in the Southern Ocean: on the Kerguelen Plateau, in the East Weddell Sea and the South Shetland Islands (Atlantic sector), and on the East Antarctic continental shelf in the Dumont d'Urville Sea and Ross Sea. The inferences of gene flow vary among the phylogroups, showing discordant spatial patterns. Phylogroup A is the only one found in the Sub-Antarctic region, although without evident connectivity between Bouvet and Kerguelen populations. The Scotia Arc region shows high levels of connectivity between populations in most of the phylogroups, and barriers to gene flow are evident in East Antarctica.

DNA barcoding highlights a cryptic species of grenadier Macrourus in the Southern Ocean.

Although three species of the genus Macrourus are recognized in the Southern Ocean, DNA sequencing of the mitochondrial COI gene revealed four well-supported clades. These barcode data suggest the presence of an undescribed species, a conclusion supported by meristic and morphometric examination of specimens.

Molecular and morphological evidence supports the species status of the Mahachai fighter Betta sp. Mahachai and reveals new species of Betta from Thailand.

Two regions of mitochondrial (mt) DNA, cytochrome c oxidase subunit 1 (COI) and 16S rRNA, were sequenced in nine species of Betta from Thailand and Indonesia. Most species showed little intraspecific COI variation (adjusted mean = 0.48%) including the putative species Betta sp. Mahachai, but one species (Betta smaragdina) included three lineages showing much greater divergence (7.03-13.48%) that probably represent overlooked species. These findings were confirmed by maximum likelihood analysis and Bayesian inference, which revealed well-supported corresponding monophyletic clades. Based on these results and morphological differences, the putative species Betta sp. Mahachai from central Thailand is a species distinct from other members of the B. splendens group and represents a new and hitherto undescribed species. Furthermore, this study also demonstrated the probable existence of two overlooked Betta species found in the Khorat plateau basin, illustrating the utility of mitochondrial genetic markers in the revelation of overlooked diversity.

Chelation of molybdenum in Medicago sativa (alfalfa) grown on reclaimed mine tailings.

Extraction and analytical procedures were developed from 1999 to 2005 for the chemical investigation of molybdenum (Mo) in aerial portions of alfalfa ( Medicago sativa L.) grown on a reclaimed mine tailings site at the Highland Valley Copper Mine in British Columbia, Canada. The purification procedures were guided by colorimetric analyses specific for Mo. The Mo levels in freeze-dried plant samples exceeded 100 ppm, which is more than 20 times the maximum level recommended for livestock feed. In contrast to previous work, which detected the inorganic molybdate anion (MoO4(2-)) in alfalfa from the site, the present study identified the major pool of Mo as a chelate bound to malic acid in five sources of plant material. However, the inorganic form of Mo was characterized in aqueous tailings samples, but once imbibed by vegetation, the anion was chelated to the alpha-hydroxy organic acid. Synthetic chelates were synthesized to differentiate the Mo-malate complex from the Mo-citrate by 95Mo NMR. Crystal structure of the synthetic Mo-malate determined that the Mo was bound to two malato ligands as Na 2[MoO2(malate) 2] x 5H2O, which confirmed the structure of the isolates deduced by 95Mo NMR. The chelation of Mo at the site may well explain the apparent lack of long-term clinical effects in cattle grazing the site.

Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data.

OBJECTIVE: To look for evidence of a relation between antibiotic resistance and prescribing by general practitioners by analysis of prescribing at both practice and individual patient level. DESIGN: Repeated cross-sectional study in 1995 and 1996. SETTING: 28 general practices in the Ninewells Hospital laboratory catchment area, Tayside, Scotland. SUBJECTS REVIEWED: 8833 patients registered with the 28 practices who submitted urine samples for analysis. MAIN OUTCOME MEASURES: Resistance to trimethoprim in bacteria isolated from urine samples at practice and individual level simultaneously in a multilevel model. RESULTS: Practices showed considerable variation in both the prevalence of trimethoprim resistance (26-50% of bacteria isolated) and trimethoprim prescribing (67-357 prescriptions per 100 practice patients). Although variation in prescribing showed no association with resistance at the practice level after adjustment for other factors (P = 0.101), in the multilevel model resistance to trimethoprim was significantly associated with age, sex, and individual-level exposure to trimethoprim (P < 0.001) or to other antibiotics (P = 0.002). The association with trimethoprim resistance was strongest for people recently exposed to trimethoprim, and there was no association for people with trimethoprim exposure more than six months before the date of the urine sample. DISCUSSION: Analysis of practice level data obscured important associations between antibiotic prescribing and resistance. The results support efforts to reduce unnecessary prescribing of antibiotics in the community and show the added value of individual patient data for research on the outcomes of prescribing.

Eight years' experience of gastrostomy tube management.

BACKGROUND AND STUDY AIMS: Increasingly, patients fed by gastrostomy tube are surviving the lifespan of the device. Data are scarce concerning the factors affecting the longevity and failure of gastrostomy tubes or the criteria for selection of replacement devices which leads to cost-effective patient management. The aims of the study were: to set criteria for selection of replacement gastrostomy tubes; to determine the causes of gastrostomy tube failure, and the factors affecting device longevity; and to examine the effect of initiating an educational programme for caregivers on resource utilization in long-term enteral nutrition patients. MATERIALS AND METHODS: We analyzed the clinical gastrostomy tube database compiled prospectively over 8 years by the nutrition team at Ninewells Hospital, Dundee. RESULTS: For 363 gastrostomy tubes inserted in 304 patients (160 women; median age 71), the median duration of gastrostomy tube use was 138 days. The total follow-up was 294 patient-years. Death occurred before the first gastrostomy tube replacement in 48 % of patients, but 20 % resumed oral nutrition. Tube failure mechanisms were: dislodgment, 28 %; perishing of tube material, 25 %; tube-related Candida albicans infection, 16 %; leakage, 7 %; and unspecified, 7 %. Of the balloon tubes and gastrostomy buttons, 8 % needed early replacement due to dislodgment and/or leakage. The cost per day for replacement percutaneous endoscopic gastrostomy (PEG) was Euro 2.12, for balloon tubes it was Euro 0.62, and for gastrostomy buttons Euro 1.80. Despite an increasing PEG insertion rate throughout the study period, yearly referrals for PEG-related problems dropped by 30 % between 1997 to 1999, coinciding with the initiation of an educational programme for caregivers. CONCLUSION: Tube longevity is mainly limited by the patient's diagnosis and prognosis. The choice of replacement device should be based on clinical factors. The use of more durable materials in the manufacture of gastrostomy tubes may prolong tube life and reduce cost. Education of patients and caregivers by a multidisciplinary nutrition support team promotes independence and limits demand on the service.

Changes in treatment after the start of oral hypoglycaemic therapy in Type 2 diabetes: a population-based study.

AIMS: To determine the changes in oral hypoglycaemic therapy and the time to incidence of insulin therapy in people with Type 2 diabetes. METHODS: A retrospective incidence cohort was constructed of 1305 subjects with Type 2 diabetes, who obtained a first prescription for oral hypoglycaemic medication between 1 July 1993 and 31 December 1994 in Tayside, Scotland. The primary endpoint of changes in oral hypoglycaemic therapy and time to insulin was determined up to the end of the follow-up, on 31 December 1995. RESULTS: Overall, 9.4% of subjects switched to insulin, while 11% of those initially on sulphonylurea, and 6% of those initially on metformin switched to insulin therapy. Approximately three-quarters (72%) remained on the same class of drug throughout the study period (median follow-up 588 days). Only 9% died during the follow-up and this did not differ appreciably by drug group. Males were more likely to switch to insulin compared with females (10.3% vs. 8.5%), and those who switched were slightly younger with a mean age of 58 years compared with a mean age of 60 years of those who did not switch. The median time of switching to insulin was 186 days or approximately 6 months for this cohort, giving a rate of switching to insulin of 5.84% per year. Poorer glycaemic control (HBA1c) and low body mass index (BMI) were associated with switching to insulin. CONCLUSIONS: Following initial therapy with oral hypoglycaemic medication in the population, switching to insulin occurred at a rate of 5.84% per year. Switching to insulin was associated with being younger, male, having low BMI and higher HbA1c.

Epidemiology and economic burden of viral hepatitis: an observational population based study.

OBJECTIVE: To describe the epidemiology and estimate the health resource use of patients with viral hepatitis in Tayside, Scotland, using record linkage techniques. DESIGN: A retrospective observational study. SETTING: Liver disease database, Tayside, Scotland. PATIENTS: All subjects resident in Tayside in the study period 1989-1999 and registered on the Epidemiology of Liver Disease in Tayside (ELDIT) database. MAIN OUTCOME MEASURES: Incidence and prevalence of known viral hepatitis in Tayside, survival of subjects diagnosed with viral hepatitis, and the health resource use with respect to hospital admissions compared with the general population. RESULTS: There were 4992 patients identified with viral hepatitis in the study period 1989-1999; 86 were IgM positive anti-hepatitis A, 187 patients were hepatitis B surface antigen (HBsAg) positive, and 469 were anti-hepatitis C (HCV) positive. HCV and HBsAg seropositive patients were more likely to be hospitalised and stay in hospital longer, less likely to survive after six years, and used more drugs of potential abuse than the general population. There was an increase in cost per admission and per patient as a consequence of liver disease. CONCLUSIONS: A record linkage population based study of viral hepatitis allows outcomes to be identified and costed. Those at risk of viral hepatitis infection in the Tayside population should be informed about the future implication to their health and costs to society. The health service should investigate the cost effectiveness of vaccination and opportunity costs to the health service of viral hepatitis taking into consideration the increasing incidence and prevalence of disease.

Association between antibiotic resistance and community prescribing: a critical review of bias and confounding in published studies.

The reported association between antibiotic prescribing and resistance may be subject to bias or confounding. Bias describes any effect at any stage of investigation or inference tending to produce results that depart systematically from the true value. A confounding variable is one that is associated independently with both exposure and outcome. Confounding variables may create an apparent association or mask a real association. Pharmacoepidemiology is the study of the use and the effects of drugs in large numbers of people. We have used standard pharmacoepidemiological methods to investigate sources of bias and confounding in the association between prescribing and resistance. We conclude that the association is statistically valid and that the consistency of evidence supports a cause-effect relationship. Nonetheless, several important sources of bias and confounding must be taken into account in future studies that analyze the impact of prescribing policies on resistance.

The multiple propensity score for analysis of dose-response relationships in drug safety studies.

In order to detect adverse drug reactions, large observational drug safety studies are necessary as randomized clinical trials rarely have enough power. However, in order to obtain reliable results the issue of confounding, especially confounding by indication, should be addressed. We proposed a multiple propensity score, which is an extension of the propensity score, to reduce the bias in a dose-response analysis in a drug safety study. The multiple propensity score has similar properties to the propensity score in Rosenbaum and Rubin.(1) Using the propensity score for bias reduction of the risk ratio was considered. We used the multiple propensity score in a study of the dose-response relationship between diclofenac prescriptions and hospitalization for gastrointestinal bleeding and perforation using a record linkage database. We found that the unadjusted risk ratios were biased downwards due to confounders and that this bias was reduced by using stratification based on the multiple propensity score.

Prior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors.

Trimethoprim resistance is increasingly prevalent in community-acquired urinary infections. The objective of this study was to evaluate the association between exposure to community-prescribed trimethoprim and other risk factors in subjects and subsequent trimethoprim-resistant urinary tract infection. The design was a nested case-control study using a record-linkage database. Study subjects submitted a urine sample to the Ninewells Hospital Laboratory between July 1993 and December 1995. Antibiotic exposure in subjects with trimethoprim-resistant isolates (cases) was compared with antibiotic exposure in subjects with trimethoprim-susceptible isolates (controls). Study subjects were drawn from the catchment area of a large teaching hospital in Tayside, Scotland. There were 13765 males and females aged 1-106 years who submitted their first urine sample for culture during the study period. After adjustment for significant risk factors and confounding variables, logistic regression analysis showed exposure to trimethoprim [odds ratio (OR) 4.35] or any antibiotic other than trimethoprim (OR 1.32) to be predictive of resistance. The growth of Proteus spp. (OR 115.14) and bacterial growth other than Escherichia coli and Proteus spp. (OR 2.83) were also predictor variables. Hospitalization in the previous 6 months was not independently associated with trimethoprim resistance. In conclusion, trimethoprim resistance was independently associated with exposure to trimethoprim and to antibiotics other than trimethoprim. Reduction in trimethoprim prescribing alone may not reduce the prevalence of trimethoprim resistance.

CT angiography for the detection and characterization of carotid artery bifurcation disease.

BACKGROUND AND PURPOSE: Computed tomographic angiography (CTA) is a relatively new and minimally invasive method of imaging intracranial and extracranial blood vessels. The main purpose of this study was to compare CTA to the current gold standard of arterial imaging, digital subtraction angiography (DSA), for the detection and quantification of carotid artery bifurcation stenosis. We also compared Doppler ultrasound (US) with these 2 techniques. METHODS: In a prospective study, 40 patients (80 carotid arteries) underwent CTA, US, and DSA. Patients chosen for inclusion were symptomatic with TIAs or stroke and had initial US screening that indicated >50% carotid stenosis on the side appropriate for the symptoms. Source axial, maximum intensity projection (MIP), and shaded-surface display (SSD) images were produced for each CTA study. The US, CTA, and DSA images were reviewed, with the degree of stenosis quantified and presence of ulcers determined; each type of imaging was reviewed by a separate investigator blinded to the results of the other 2 modalities. The results of CTA and US imaging were compared with the DSA images for degrees of carotid stenosis. RESULTS: CTA source axial images correlated with DSA more closely than MIP or SSD images for all degrees of stenosis. The correlation between US and DSA (0.808) was poorer than that between CTA and DSA (0.892 to 0.922). CTA performed well in the detection of mild (0% to 29%) carotid stenosis, as well as carotid occlusion, with values for sensitivity, specificity, and accuracy near 100%. In determining that a stenosis was >50% by DSA measurement, CTA was again useful, with a sensitivity, specificity, and accuracy of 89%, 91%, and 90%, respectively. While CTA was quite specific and accurate in identifying degrees of stenoses in either the 50% to 69% or the 70% to 99% ranges, in this task it was much less sensitive: 65% for 50%-69% stenosis and 73% for 70%-99% stenosis. These results did not change significantly when only the data from the most clinically relevant symptomatic arteries were analyzed. CTA was found to correlate quite well with DSA in the detection of ulcers associated with the carotid stenosis. CONCLUSIONS: CTA was found to be an excellent examination for the detection of carotid occlusion and categorization of stenosis in either the 0%-29% or >50% ranges. However, CTA was unable to reliably distinguish between moderate (50%-69%) and severe (70%-99%) stenosis, which is an important limitation in the investigation and treatment of carotid stenosis.

Practice factors that influence antibiotic prescribing in general practice in Tayside.

A cohort design was used to evaluate antibiotic prescribing in relation to patient and general practice characteristics. The study included prescribing to all subjects resident in Tayside, from January to December 1994 and found 215217 antibiotic prescriptions dispensed to 118596 people. Training status of general practitioners (GPs) was found to be the characteristic most associated with prescribing. Adjusting for other GP characteristics had little effect on these results. Training practice status was the dominant factor associated with significant differences in rates of antibiotic prescribing, in class of antibiotic prescribed and in performance indicators of antibiotic prescribing.