Adaptive ecological niche migration does not negate extinction susceptibility.

Extinction rates in the modern world are currently at their highest in 66 million years and are likely to increase with projections of future climate change. Our knowledge of modern-day extinction risk is largely limited to decadal-centennial terrestrial records, while data from the marine realm is typically applied to high-order (> 1 million year) timescales. At present, it is unclear whether fossil organisms with common ancestry and ecological niche exhibit consistent indicators of ecological stress prior to extinction. The marine microfossil record, specifically that of the planktonic foraminifera, allows for high-resolution analyses of large numbers of fossil individuals with incredibly well-established ecological and phylogenetic history. Here, analysis of the isochronous extinction of two members of the planktonic foraminiferal genus Dentoglobigerina shows disruptive selection differentially compounded by permanent ecological niche migration, "pre-extinction gigantism", and photosymbiont bleaching prior to extinction. Despite shared ecological and phylogenetic affinity, and timing of extinction, the marked discrepancies observed within the pre-extinction phenotypic responses are species-specific. These behaviours may provide insights into the nature of evolution and extinction in the open ocean and can potentially assist in the recognition and understanding of marine extinction risk in response to global climate change.

Retinopathy develops at similar glucose levels but higher HbA1c levels in people with black African ancestry compared to white European ancestry: evidence for the need to individualize HbA1c interpretation.

AIMS: To examine the association of HbA1c and glucose levels with incident diabetic retinopathy according to black African or white European ancestry. METHODS: In this retrospective cohort study of 202 500 US Veterans with diabetes (2000-2014), measures included HbA1c , outpatient random serum/plasma glucose, and incident retinopathy [conversion from negative to ≥2 positive evaluations (ICD-9 codes), without a subsequent negative]. RESULTS: At baseline, the study population had a mean age of 59.3 years, their mean BMI was 31.9 kg/m2 , HbA1c level was 57 mmol/mol (7.4%) and glucose level was 8.8 mmol/l, and 77% were of white European ancestry (white individuals) and 21% of black African ancestry (black individuals). HbA1c was 0.3% higher in black vs white individuals (P < 0.001), adjusting for baseline age, sex, BMI, estimated glomerular filtration rate (eGFR), haemoglobin, and average systolic blood pressure and glucose. Over 11 years, incident retinopathy occurred in 9% of black and 7% of white individuals, but black individuals had higher HbA1c , glucose, and systolic blood pressure (all P < 0.001); adjusted for these factors, incident retinopathy was reduced in black vs white individuals (P < 0.001). The population incidence of retinopathy (7%) was associated with higher mean baseline HbA1c in individuals with black vs white ancestry [63 mmol/mol (7.9%) vs 58 mmol/mol (7.5%); P < 0.001)], but with similar baseline glucose levels (9.0 vs 9.0 mmol/l; P = 0.660, all adjusted for baseline age, sex and BMI). CONCLUSIONS: Since retinopathy occurs at higher HbA1c levels in black people for a given level of average plasma glucose, strategies may be needed to individualize the interpretation of HbA1c measurements.

Organic Compounds in a Sub-Antarctic Ice Core: A Potential Suite of Sea Ice Markers.

Investigation of organic compounds in ice cores can potentially unlock a wealth of new information in these climate archives. We present results from the first ever ice core drilled on sub-Antarctic island Bouvet, representing a climatologically important but understudied region. We analyze a suite of novel and more familiar organic compounds in the ice core, alongside commonly measured ions. Methanesulfonic acid shows a significant, positive correlation to winter sea ice concentration, as does a fatty acid compound, oleic acid. Both may be sourced from spring phytoplankton blooms, which are larger following greater sea ice extent in the preceding winter. Oxalate, formate, and acetate are positively correlated to sea ice concentration in summer, but sources of these require further investigation. This study demonstrates the potential application of organic compounds from the marine biosphere in generating multiproxy sea ice records, which is critical in improving our understanding of past sea ice changes.

Racial differences in performance of HbA1c for the classification of diabetes and prediabetes among US adults of non-Hispanic black and white race.

AIM: To characterize differences between black and white people in optimal HbA1c thresholds for diagnoses of diabetes and prediabetes. METHODS: Data were included from the National Health and Nutrition Examination Survey, 2005-2014. Black and white adults (age 18-70 years) who underwent an oral glucose tolerance test and had available fasting plasma glucose, 2-h plasma glucose and HbA1c measurements were eligible for inclusion. Diabetes or prediabetes status was defined by fasting plasma glucose and 2-h plasma glucose using American Diabetes Association criteria. Classification of diabetes, prediabetes and dysglycaemia by HbA1c was evaluated for a range of HbA1c thresholds, with optimal thresholds defined as those values that maximized the sum of sensitivity and specificity (Youden's index). RESULTS: In 5324 black (32.3%) and white (67.7%) individuals, Youden's index (optimal) thresholds for HbA1c were ≥42 mmol/mol (6.0%) and ≥39 mmol/mol (5.7%) for discriminating diabetes vs non-diabetes, ≥ 44 mmol/mol (6.2%) and ≥39 mmol/mol (5.7%) for discriminating diabetes vs prediabetes (excluding normoglycaemia), ≥39 mmol/mol (5.7%) and ≥37 mmol/mol (5.5%) for discriminating dysglycaemia vs normoglycaemia, and ≥39 mmol/mol (5.7%) and ≥37 mmol/mol (5.5%) for discriminating prediabetes vs normoglycaemia (excluding diabetes), in black and white people, respectively. CONCLUSIONS: Consistently higher optimal HbA1c thresholds in black people than in white people suggest a need to individualize HbA1c relative to glucose levels if HbA1c is used to diagnose diabetes and prediabetes.

Glucose challenge test screening for prediabetes and early diabetes.

AIMS: To test the hypothesis that a 50-g oral glucose challenge test with 1-h glucose measurement would have superior performance compared with other opportunistic screening methods. METHODS: In this prospective study in a Veterans Health Administration primary care clinic, the following test performances, measured by area under receiver-operating characteristic curves, were compared: 50-g oral glucose challenge test; random glucose; and HbA1c level, using a 75-g oral glucose tolerance test as the 'gold standard'. RESULTS: The study population was comprised of 1535 people (mean age 56 years, BMI 30.3 kg/m2 , 94% men, 74% black). By oral glucose tolerance test criteria, diabetes was present in 10% and high-risk prediabetes was present in 22% of participants. The plasma glucose challenge test provided area under receiver-operating characteristic curves of 0.85 (95% CI 0.78-0.91) to detect diabetes and 0.76 (95% CI 0.72-0.80) to detect high-risk dysglycaemia (diabetes or high-risk prediabetes), while area under receiver-operating characteristic curves for the capillary glucose challenge test were 0.82 (95% CI 0.75-0.89) and 0.73 (95% CI 0.69-0.77) for diabetes and high-risk dysglycaemia, respectively. Random glucose performed less well [plasma: 0.76 (95% CI 0.69-0.82) and 0.66 (95% CI 0.62-0.71), respectively; capillary: 0.72 (95% CI 0.65-0.80) and 0.64 (95% CI 0.59-0.68), respectively], and HbA1c performed even less well [0.67 (95% CI 0.57-0.76) and 0.63 (95% CI 0.58-0.68), respectively]. The cost of identifying one case of high-risk dysglycaemia with a plasma glucose challenge test would be $42 from a Veterans Health Administration perspective, and $55 from a US Medicare perspective. CONCLUSIONS: Glucose challenge test screening, followed, if abnormal, by an oral glucose tolerance test, would be convenient and more accurate than other opportunistic tests. Use of glucose challenge test screening could improve management by permitting earlier therapy.

Intervention fidelity for a complex behaviour change intervention in community pharmacy addressing cardiovascular disease risk.

BACKGROUND: Delivery of cardiovascular disease (CVD) prevention programs by community pharmacists appears effective and enhances health service access. However, their capacity to implement complex behavioural change processes during patient counselling remains largely unexplored. This study aims to determine intervention fidelity by pharmacists for behavioural components of a complex educational intervention for CVD prevention. After receiving training to improve lifestyle and medicines adherence, pharmacists recruited 70 patients aged 50-74 years without established CVD, and taking antihypertensive or lipid lowering therapy. Patients received five counselling sessions, each at monthly intervals. Researchers assessed biomedical and behavioural risk factors at baseline and six months. Pharmacists documented key outcomes from counselling after each session. Most patients (86%) reported suboptimal cardiovascular diets, 41% reported suboptimal medicines adherence, and 39% were physically inactive. Of those advised to complete the intervention, 85% attended all five sessions. Pharmacists achieved patient agreement with most recommended goals for behaviour change, and overwhelmingly translated goals into practical behavioural strategies. Barriers to changing behaviours were regularly documented, and pharmacists reported most behavioural strategies as having had some success. Meaningful improvements to health behaviours were observed post-intervention. Findings support further exploration of pharmacists' potential roles for delivering interventions with complex behaviour change requirements.

A multifaceted pharmacist intervention to improve antihypertensive adherence: a cluster-randomized, controlled trial (HAPPy trial).

WHAT IS KNOWN AND OBJECTIVES: About half of all patients taking antihypertensives discontinue treatment by 12 months. There is potential for substantial health gains at both individual and population levels through improved treatment adherence. The objective was to evaluate a community pharmacist intervention to improve adherence with antihypertensive medicines with a view to improving blood pressure (BP) control. DESIGN: prospective, non-blinded, cluster-randomized, controlled trial. PARTICIPANTS: adults with primary hypertension who obtained antihypertensives in the previous 6 months. Patients with poor refill adherence were preferentially identified with the help of a purpose-built software application. INTERVENTION: package comprising BP monitor; training on BP self-monitoring; motivational interviewing; medication use review; prescription refill reminders. FOLLOW-UP: six months. PRIMARY OUTCOME: change in proportion self-reporting medication adherence. Secondary outcome: BP changes. RESULTS: Participants (n = 395; intervention - 207; control - 188) had a mean age of 66.7 years; 51.1% were males. The proportion of adherent participants increased in both groups but was not significantly different between groups [57·2% to 63·6% (control) vs. 60·0% to 73·5% (intervention), P = 0·23]. The mean reduction in systolic BP was significantly greater in the intervention group (10·0 mmHg vs. 4·6 mmHg; P = 0·05). The proportion of patients who were non-adherent at baseline and adherent at 6 months was 22·6% (95%CI 5·1-40·0%) higher in the intervention group (61·8% vs. 39·2%, P = 0·007). Among participants with baseline BP above target, reduction of systolic BP was significantly greater in the intervention group [by 7·2 mmHg (95%CI 1·6-12·8 mmHg); (P = 0·01)]. Among participants non-adherent at baseline and above target BP, the proportion reporting adherence at 6 months was significantly greater in the intervention group [56·8% vs. 35·9%, P = 0·039). WHAT IS NEW AND CONCLUSION: This community pharmacist intervention resulted in improved adherence to antihypertensive medication and reduced systolic BP.

Aging is associated with increased HbA1c levels, independently of glucose levels and insulin resistance, and also with decreased HbA1c diagnostic specificity.

AIM: To determine whether using HbA1c for screening and management could be confounded by age differences, whether age effects can be explained by unrecognized diabetes and prediabetes, insulin resistance or postprandial hyperglycaemia, and whether the effects of aging have an impact on diagnostic accuracy. METHODS: We conducted a cross-sectional analysis in adults without known diabetes in the Screening for Impaired Glucose Tolerance (SIGT) study 2005-2008 (n=1573) and the National Health and Nutrition Examination Survey (NHANES) 2005-2006 (n=1184). RESULTS: Both glucose intolerance and HbA(1c) levels increased with age. In univariate analyses including all subjects, HbA(1c) levels increased by 0.93 mmol/mol (0.085%) per 10 years of age in the SIGT study and by 1.03 mmol/mol (0.094%) per 10 years in the NHANES; in both datasets, the HbA(1c) increase was 0.87 mmol/mol (0.08%) per 10 years in subjects without diabetes, and 0.76 mmol/mol (0.07%) per 10 years in subjects with normal glucose tolerance, all P<0.001. In multivariate analyses of subjects with normal glucose tolerance, the relationship between age and HbA(1c) remained significant (P<0.001) after adjustment for covariates including race, BMI, waist circumference, sagittal abdominal diameter, triglyceride/HDL ratio, and fasting and 2-h plasma glucose and other glucose levels, as assessed by an oral glucose tolerance test. In both datasets, the HbA(1c) of an 80-year-old individual with normal glucose tolerance would be 3.82 mmol/mol (0.35%) greater than that of a 30-year-old with normal glucose tolerance, a difference that is clinically significant. Moreover, the specificity of HbA(1c) -based diagnostic criteria for prediabetes decreased substantially with increasing age (P<0.0001). CONCLUSIONS: In two large datasets, using different methods to measure HbA(1c), the association of age with higher HbA(1c) levels: was consistent and similar; was both statistically and clinically significant; was unexplained by features of aging; and reduced diagnostic specificity. Age should be taken into consideration when using HbA(1c) for the diagnosis and management of diabetes and prediabetes.

Vitamin B12 deficiency in Australian residential aged care facilities.

OBJECTIVE: To determine the prevalence of undiagnosed vitamin B12 deficiency among residential aged care facility residents in southern Tasmania, Australia, and to identify associated risk factors. DESIGN AND SETTING: Cross-sectional study of residents from five southern Tasmanian residential aged care facilities. PARTICIPANTS: Two hundred and fifty-nine residents without a prior diagnosis of vitamin B12 deficiency or recorded serum B12 level within the past 6 months were approached to have their serum B12 level tested. One hundred and sixty (61%) residents consented and their doctors were contacted for further consent. A total of 130 (50%) residents completed the study. MEASUREMENTS: Clinical and demographic characteristics, and serum B12 level. RESULTS: Of the 130 residents tested, 18 residents (14%) were considered vitamin B12 deficient (serum level <150 pmol/L), 47 (36%) were equivocal (150 pmol/L to 250 pmol/L) and 65 (50%) had normal serum B12 levels (>250 pmol/L). There was a weak negative correlation between age and serum B12 level in those residents not taking a multivitamin (n=120, r=-0.19, p<0.05). The use of a multivitamin or antipsychotic drug were associated with altered mean serum B12 levels (+137 pmol/L, p<0.001 and -70 pmol/L, p<0.001 respectively). CONCLUSION: As vitamin B12 deficiency can manifest in a range of symptoms that are frequently misdiagnosed, the finding of undetected deficiency in 14% of residents is a cause for concern. Oral multivitamin supplementation may help prevent deficiency, and potentially treat existing deficiencies in older institutionalised people.

Warfarin management after discharge from hospital: a qualitative analysis.

WHAT IS KNOWN AND OBJECTIVE: Warfarin is recognized as a high-risk medication for adverse events, and the risks are particularly heightened in the period immediately following a patient's discharge from hospital. This qualitative study aimed to explore the experiences of Australian patients and healthcare professionals of warfarin management in the post-discharge period and identify the benefits and deficiencies of existing systems, to inform the development of a model for a new collaborative post-discharge warfarin management service. METHODS: Healthcare professionals, professional organization representatives and patients recently discharged from hospital taking warfarin (consumers) were recruited via purposive, criterion-based sampling within two Australian states. Semi-structured telephone interviews were conducted between August and October 2008 using standard discussion guides. Data were manually analyzed to identify emergent themes using a phenomenological approach. RESULTS: Forty-seven participants were involved in the telephone interviews. Three major themes emerged: (i) appropriate warfarin education is integral to effective warfarin management, (ii) problems occur in communication along the continuum of care and (iii) home-delivered services are valuable to both patients and healthcare professionals. DISCUSSION: Although high-quality warfarin education and effective communication at the hospital-community interface were identified as important in post-discharge warfarin management, deficiencies were perceived within current systems. The role of home-delivered services in ensuring timely follow-up and promoting continuity of care was recognized. Previous studies exploring anticoagulation management in other settings have identified similar themes. Post-discharge management should therefore focus on providing patients with a solid foundation to minimize future problems. WHAT IS NEW AND CONCLUSION: Addressing the three identified facets of care within a new, collaborative post-discharge warfarin management service may address the perceived deficiencies in existing systems. Improvements may result in the short- and longer-term health outcomes of patients discharged from hospital taking warfarin, including a reduction in their risk of adverse events.

Stroke risk assessment for atrial fibrillation: hospital-based stroke risk assessment and intervention program.

BACKGROUND: Despite the proven effectiveness of antithrombotic therapy for atrial fibrillation (AF), the treatment remains suboptimal. The aim of this study was to implement and evaluate a system to improve the appropriate use of antithrombotics for stroke prevention in AF utilizing a clinical pharmacist as a stroke risk assessor. METHOD: Hospital in-patients with AF were prospectively identified and they received a formal stroke risk assessment from a pharmacist. The patients' risk of stroke was assessed and documented according to Australian guidelines and a recommendation regarding antithrombotic therapy was made to the medical team on a specially designed stroke risk assessment form. RESULTS: One hundred and thirty-four stroke risk assessments were performed during the intervention period. For those patients at high risk of stroke and with no contraindication present (warfarin-eligible patients), 98% were receiving warfarin on discharge from hospital compared to 74% on admission (P < 0.001). Of the 50 (37%) assessments that recommended a change of therapy, 44 (88%) resulted in a change in the patient's current antithrombotic therapy compared to their admission therapy. Thirty (68%) of the assessments resulted in an 'upgrade' to more-effective treatment options for example from no therapy to any agent or from aspirin to warfarin. DISCUSSION AND CONCLUSION: The pharmacist-led stroke risk assessment program resulted in a significant increase in the proportion of patients receiving appropriate thromboprophylaxis for stroke prevention in AF. The methods used in this study should be evaluated in a larger trial, in multiple hospitals, with different pharmacists performing the intervention.

Public perceptions of the role of Australian pharmacists in cardiovascular disease.

BACKGROUND AND OBJECTIVE: To assess the public's perception of pharmacists' involvement and role in cardiovascular disease prevention and management. METHODS: A computer-assisted telephone interview of 505 households was conducted. The survey was administered to metropolitan, rural and remote residents over the age of 30 years. The interview had questions on the patient's general satisfaction with the quality of service provided by their regular community pharmacy, including factors such as location, professionalism, prices, product range and knowledge of the staff. The participants were asked if they thought pharmacists were capable of providing screening, testing and drug prescribing services for blood pressure and cholesterol, and how likely they would be to use these services through a pharmacy. The interview also included questions on how likely this person would be to seek advice on lifestyle changes and medications from various health professionals, including pharmacists. RESULTS: The majority (97%) were satisfied with the service provided at their regular pharmacy. Those surveyed agreed or strongly agreed that pharmacists are capable of providing screening or testing for raised blood pressure (52%) and diabetes (51%), with a minority (38%) agreeing that pharmacists are capable of testing for raised cholesterol. The pharmacist's role with perceived highest capability by those surveyed was in providing advice on how to take medicines properly, with 90% of respondents willing to seek this advice from their pharmacist. A limited role by pharmacists was seen in the diagnosis of CVD and prescribing medications. In relation to the prevention of CVD, even though 76% of respondents believed that pharmacists are capable of providing advice on lifestyle changes (e.g. weight loss, smoking and alcohol intake), only 8% of current or past smokers had sought assistance to give up smoking at their pharmacy and while 69% of all respondents had sought help with weight control, only 3% of these had looked towards their pharmacy for assistance. CONCLUSION: There was belief by those Australians surveyed that community pharmacists are capable of providing screening for hypertension and diabetes. Through these services and in conjunction with counselling on CVD risk reduction, pharmacists may play an important role in the reduction of CVD, ultimately improving public health and decreasing the burden on Australia's health care system. However, at present pharmacists are not being fully utilized to deliver health promotion advice and contribute to the prevention of CVD.

Attitudes of Australian pharmacists towards practice-based research.

BACKGROUND AND OBJECTIVE: The aim was to conduct a national cross-sectional survey of randomly selected Australian pharmacists to determine their attitudes towards and involvement in pharmacy practice research. This included the canvassing of perceived barriers and potential solutions to promote research activity in pharmacy practice. METHODS: A questionnaire was developed around those used in UK and Australasian studies of general practitioners' attitudes towards research. Questions assessed attitudes to research, involvement in research, barriers and facilitators to involvement, self-assessed understanding of research terminology, and access to and use of electronic bibliographic databases. One thousand pharmacists were randomly and proportionately selected from the State and Territory Pharmacy Board registers to receive the anonymous questionnaire by mail. Non-respondents were sent a follow-up reminder and second copy of the questionnaire after 3 weeks. RESULTS: A response rate of 37% was achieved. Approximately, one-third of responding pharmacists were presently, or had been, involved in research activities, and generally reported positive experiences. Lack of time and never being approached or not being aware of the opportunities were major barriers to pharmacist participation in research. Approximately, one-third of the pharmacists were not interested in participating in research. There was low usage of publicly available electronic bibliographic databases and of scientific journals. Although there was overwhelming recognition of the value of research to the profession, few pharmacists possessed a good understanding of key terms related to research and evidence-based practice (e.g. P-value or number needed to treat). CONCLUSION: There was overwhelming recognition of the value of research to the pharmacy profession. Important factors encouraging individual pharmacists to participate in research were a desire to improve the profession, the opportunity to learn more about disease management and to provide enhanced services to patients, and personal interest.

A comparison of planar, laser-induced fluorescence, and high-sensitivity interferometry techniques for gas-puff nozzle density measurements.

The distribution of argon gas injected by a 12-cm-diameter triple-shell nozzle was characterized using both planar, laser-induced fluorescence (PLIF) and high-sensitivity interferometry. PLIF is used to measure the density distribution at a given time by detecting fluorescence from an acetone tracer added to the gas. Interferometry involves making time-dependent, line-integrated gas density measurements at a series of chordal locations that are then Abel inverted to obtain the gas density distribution. Measurements were made on nominally identical nozzles later used for gas-puff Z-pinch experiments on the Saturn pulsed-power generator. Significant differences in the mass distributions obtained by the two techniques are presented and discussed, along with the strengths and weaknesses of each method.

Harm minimization strategies: opinions of health professionals in rural and remote Australia.

BACKGROUND AND OBJECTIVE: There is some evidence that the problem of illicit drug use (IDU) is increasing in rural areas of Australia. Lack of access to harm minimization (HM) strategies is potentially exacerbated by a shortage of health care facilities and health care professionals in rural areas. This study was conducted to determine barriers to implementation, access to, and success of HM strategies, as seen by health professionals presently working in rural Australia. METHODS: Four hundred rural pharmacists Australia-wide and 425 doctors in rural Victoria and Tasmania were sent postal surveys to assess their opinions on the level of IDU in their area, the types of drugs commonly used, the adequacy of HM strategies and facilities, and the barriers faced by doctors, pharmacists and clients. RESULTS: The overall response rate was almost 50%. Slightly less than half of surveyed health professionals felt that IDU was increasing in their area, with heroin perceived to be the most prevalent drug used in all States except Tasmania and the Northern Territory. Both methadone prescribers and dispensers believed the methadone maintenance programmes were highly valuable to the community, but not without problems (e.g. risk of overdose). A lack of time or staff was the greatest influence on doctors not participating in the methadone programmes, whereas safety concerns were prominent with pharmacists. The majority of doctors felt HM facilities were inadequate, with needle-syringe exchange being the most frequently nominated HM strategy lacking. CONCLUSION: Despite best intentions, there are still problems with HM strategies in these areas. Improving the number and expertise of health professionals in rural areas, and providing adequate support for them, would address some of these problems.

Development of an intelligent decision support system for medication review.

BACKGROUND AND OBJECTIVE: The aim was to develop and evaluate a pilot version of a knowledge-based system that can identify existing and potential medication-related problems from patient information. This intelligent system could directly support pharmacists and other health professionals providing medication reviews. METHODS: Rather than being based on static rules to trigger alerts, this system utilizes a multiple classification ripple-down rules approach, which allows the user to build rules incrementally and improve the accuracy of the knowledge base in identifying medication-related problems while the system is in use, with no outside assistance or training. The system contextualizes the potential drug therapy problems by taking into consideration the patient's demographics, and other medical condition and drugs. The system is capable of both being instructed in the domain of medication review through its routine use by an expert, and acting similarly to the expert when analysing genuine medication review cases. The system was handed over to an experienced clinical pharmacist (expert), with no knowledge or conclusions preloaded into the system. The expert was then able to add the case details and generate the rules required for 126 actual medication review cases. RESULTS: Over 250 rules were generated from the review cases, incorporating demographics, medical history, symptoms, medications and pathology results from these cases. At the completion of the cases, more than 80% of the potential medication-related problems identified by the expert were also detected by the system. The false positive rate, or number of incorrect medication-related problems identified by the system, was <10% overall and was zero for the last 15 cases analysed. The system found significantly more potential medication-related problems than the expert, with the system consistently remaining at least one finding ahead. There was a high incidence of missed potential medication-related problems by the expert, which were automatically repaired by the system. CONCLUSIONS: The knowledge-based system has already demonstrated that the technique employed is well suited to a domain of this nature and has furthermore demonstrated that it is capable of improving the quality of service that the medication reviewer can provide. The system will be further enhanced and tested prior to use in the field. It should help pharmacists in the provision of medication reviews, improving their clinical and time management capabilities, and enhancing their ability to contribute to the quality use of medications.

Mucor rouxii ultrastructure: cyclic AMP and actin cytoskeleton.

A comparative analysis of the effect of two compounds, dibutyryl-cyclic-AMP (dbcAMP) and latrunculin B, on the morphology and ultrastructure of the dimorphic fungus Mucor rouxii under aerobic growth conditions is presented. dbcAMP acts through the sustained activation of protein kinase A, and latrunculin B through the disruption of the actin cytoskeleton. Upon addition of these compounds to the growth medium at any stage of the germination process, cells lost polarised growth and switched to isodiametric growth. The effect was reversible. The morphologies, visualised by light microscopy or scanning electron microscopy (SEM), were alike. A switch from a rough to a smooth surface was observed by SEM when cells were repolarised by removal of the added compound. Ultrastructural changes under both conditions, as observed by transmission electron microscopy, were similar, the main feature being the enlargement of the cell wall, with irregular depositions, and detachment from the cell membrane. dbcAMP-treated cells showed a decrease in the number of glycogen granules compared with control and latrunculin B-treated cells. F-actin staining with fluorescein isothiocyanate-phalloidin showed that both dbcAMP- and latrunculin B-treated cells displayed a much lower fluorescence than control cells, with only a few pale plaques. The results suggest that the sustained activation of protein kinase A, which impairs polarised growth, might exert its effect through a modification of actin cytoskeleton organisation, very probably also involving an integrinlike pathway, as judged by the cell wall detachment and loss of cell adhesiveness of the dbcAMP-treated isodiametric cells.

Improving the outcomes of anticoagulation in rural Australia: an evaluation of pharmacist-assisted monitoring of warfarin therapy.

OBJECTIVE: The aim of this project was to assess whether rural pharmacist involvement in the management of patients receiving warfarin has the potential to lead to safer and more effective anticoagulation, and is valued and welcomed by patients and their general practitioners (GPs). METHODS: A convenience sample of rural pharmacists was trained in the use of the CoaguChek S International Normalized Ratio (INR) monitor and then conducted pharmacy-based testing for approximately 3 months. Two types of testing were performed in the pharmacy: (i) comparison testing was defined as pharmacy-based tests taken within 4 h of conventional laboratory testing or (ii) additional testing, which was a pharmacy-based test with no direct comparison laboratory test taken. Pharmacists, GPs and patients completed anonymous satisfaction surveys after the completion of the pharmacy-based testing. RESULTS: Pharmacists from 16 rural pharmacies were trained to use the CoaguChek S monitor. During the trial period, 518 INR tests were performed in the pharmacies on 137 different patients. A total of 120 tests were evaluated against results from laboratory testing. The pharmacy-based INR values were significantly correlated with the laboratory INR values (mean of 2.32+/-0.77 and 2.32+/-0.59 respectively; r=0.88, P<0.0001). A total of 398 additional pharmacy-based tests were conducted in the pharmacy and 8.5% of the additional tests resulted in a subsequent dosage change. The monitoring was well received by pharmacists, GPs and patients. CONCLUSIONS: The results of the trial were very positive. The CoaguChek S monitor in pharmacy-based testing performed accurately compared with conventional laboratory testing. Further research needs to be conducted on the impact of community pharmacy-conducted INR monitoring on patient care and outcomes.

Improving the outcomes of anticoagulation: an evaluation of home follow-up of warfarin initiation.

OBJECTIVES: A number of studies have reported that the risk of bleeding associated with warfarin is highest early in the course of therapy. This study examined the effect of a programme focused on the transition of newly anticoagulated patients from hospital to the community. DESIGN: Open-label randomized controlled trial. SETTING: Home-based follow-up of patients discharged from acute care hospital in southern Tasmania, Australia. SUBJECTS: A total of 128 patients initiated on warfarin in hospital and subsequently discharged to general practitioner (GP) care were enrolled in the study. Sixty were randomized to home monitoring (HM) and 68 received usual care (UC). INTERVENTIONS: HM patients received a home-visit by the project pharmacist and point-of-care international normalized ratio (INR) testing on alternate days on 4 occasions, with the initial visit two days after discharge. The UC group was solely managed by the GP and only received a visit 8 days after discharge to determine anticoagulant control. RESULTS: At discharge, 42% of the HM group and 45% of the UC group had a therapeutic INR. At day 8, 67% of the HM patients had a therapeutic INR, compared with 42% of UC patients (P < 0.002). In addition, 26% of UC patients had a high INR, compared with only 4% of HM patients. Bleeding events were assessed 3 months after discharge and occurred in 15% of HM patients, compared with 36% of the UC group (P < 0.01). CONCLUSIONS: This programme improved the initiation of warfarin therapy and resulted in a significant decrease in haemorrhagic complications in the first 3 months of therapy.

Accuracy, reproducibility and clinical utility of the CoaguChek S portable international normalized ratio monitor in an outpatient anticoagulation clinic.

The accuracy and reproducibility of the CoaguChek S, and its clinical agreement with conventional laboratory international normalized ratio (INR) determination, were evaluated in an outpatient anticoagulation clinic setting. Forty-three patients provided 248 paired INR measurements for analysis. The paired results were highly correlated (r = 0.90). The mean coefficient of variation for the CoaguChek S for a random sample of 21 patients with three repeated tests each, was 4%. Clinical applicability was also measured by discrepant INR values, as defined in the literature by expanded and narrow agreement, and by INR values resulting in a different clinical decision by a blinded haematology registrar. Expanded agreement and narrow agreement between the two INR values occurred 90 and 88% of the time, respectively. The stricter criteria set down by the clinician resulted in 73% of paired results producing the same dosage decision. The CoaguChek S displayed good correlation with laboratory determination of INR and compared relatively well with expanded and narrow clinical agreement criteria.