Influential Periods in Longitudinal Clinical Cardiovascular Health Scores.

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 to 55 years were included. These factors were categorized and summed into a clinical CVH score ranging from 0 (worst) to 8 (best). Adjusted, segmented, linear mixed models were used to estimate the change in CVH over time. Among the 18,343 participants, 9,461 (52%) were female and 12,346 (67%) were White. The baseline mean (standard deviation) clinical CVH score was 6.9 (1.2) at an average age of 17.6 (8.1) years. Two inflection points were estimated: at 16.9 years (95% confidence interval: 16.4, 17.4) and at 37.2 years (95% confidence interval: 32.4, 41.9). Late adolescence and early middle age appear to be influential periods during which the loss of CVH accelerates.

Dichotomy between Regulation of Coral Bacterial Communities and Calcification Physiology under Ocean Acidification Conditions.

Ocean acidification (OA) threatens the growth and function of coral reef ecosystems. A key component to coral health is the microbiome, but little is known about the impact of OA on coral microbiomes. A submarine CO2 vent at Maug Island in the Northern Mariana Islands provides a natural pH gradient to investigate coral responses to long-term OA conditions. Three coral species (Pocillopora eydouxi, Porites lobata, and Porites rus) were sampled from three sites where the mean seawater pH is 8.04, 7.98, and 7.94. We characterized coral bacterial communities (using 16S rRNA gene sequencing) and determined pH of the extracellular calcifying fluid (ECF) (using skeletal boron isotopes) across the seawater pH gradient. Bacterial communities of both Porites species stabilized (decreases in community dispersion) with decreased seawater pH, coupled with large increases in the abundance of Endozoicomonas, an endosymbiont. P. lobata experienced a significant decrease in ECF pH near the vent, whereas P. rus experienced a trending decrease in ECF pH near the vent. In contrast, Pocillopora exhibited bacterial community destabilization (increases in community dispersion), with significant decreases in Endozoicomonas abundance, while its ECF pH remained unchanged across the pH gradient. Our study shows that OA has multiple consequences on Endozoicomonas abundance and suggests that Endozoicomonas abundance may be an indicator of coral response to OA. We reveal an interesting dichotomy between two facets of coral physiology (regulation of bacterial communities and regulation of calcification), highlighting the importance of multidisciplinary approaches to understanding coral health and function in a changing ocean.IMPORTANCE Ocean acidification (OA) is a consequence of anthropogenic CO2 emissions that is negatively impacting marine ecosystems such as coral reefs. OA affects many aspects of coral physiology, including growth (i.e., calcification) and disrupting associated bacterial communities. Coral-associated bacteria are important for host health, but it remains unclear how coral-associated bacterial communities will respond to future OA conditions. We document changes in coral-associated bacterial communities and changes to calcification physiology with long-term exposure to decreases in seawater pH that are environmentally relevant under midrange IPCC emission scenarios (0.1 pH units). We also find species-specific responses that may reflect different responses to long-term OA. In Pocillopora, calcification physiology was highly regulated despite changing seawater conditions. In Porites spp., changes in bacterial communities do not reflect a breakdown of coral-bacterial symbiosis. Insights into calcification and host-microbe interactions are critical to predicting the health and function of different coral taxa to future OA conditions.

Polymerase chain reaction for human parechovirus on blood samples improves detection of clinical infections in infants.

Human parechovirus (HPeV) is an emerging pathogen for infants. Improved diagnostics are needed due to the non-specific clinical presentation. Real-time reverse transcription polymerase chain reaction (RT-PCR) on blood samples may be an adjunct to diagnosis. A retrospective cohort of HPeV-affected infants was used to assess sensitivity and specificity of a HPeV RT-PCR on blood and cerebrospinal fluid (CSF). As a secondary analysis, the Ct value of the PCR results was compared to clinical correlates of severity. Between 2017 and 2018 blood samples were obtained from 97 infants of whom 44 had HPeV clinical and laboratory proven infection. Eighty-three concurrent CSF samples were available. Sensitivity was 93.3% [95% CI 82-99] for blood HPeV RT-PCR and 85% [95% CI 73.9-96.1] for CSF HPeV RT-PCR. Blood HPeV RT-PCR Ct values < 25 cycles were associated with age < 28 days and < 3 days of symptoms. No statistical associations were identified between potential clinical markers of severity and Ct value. HPeV RT-PCR on blood is a valuable adjunct to diagnostic testing for acute HPeV-related illness in infants. Results can be expected to be robust until at least day 5 of symptoms, with optimal sampling occurring close to onset of symptoms.

Trends, determinants and differences in antibiotic use in 68 residential aged care homes in Australia, 2014-2017: a longitudinal analysis of electronic health record data.

BACKGROUND: Internationally, point prevalence surveys are the main source of antibiotic use data in residential aged care (RAC). Our objective was to describe temporal trends in antibiotic use and antibiotics flagged for restricted use, resident characteristics associated with use, and variation in use by RAC home, using electronic health record data. METHODS: We conducted a retrospective cohort study of 9793 unique residents aged ≥65 years in 68 RAC homes between September 2014 and September 2017, using electronic health records. We modelled the primary outcome of days of antibiotic therapy /1000 resident days (DOT/1000 days), and secondary outcomes of number of courses/1000 days and the annual prevalence of antibiotic use. Antibiotic use was examined for all antibiotics and antibiotics on the World Health Organization's (WHO) Watch List (i.e. antibiotics flagged for restricted use). RESULTS: In 2017, there were 85 DOT/1000 days (99% CI: 79, 92), 8.0 courses/1000 days (99% CI: 7.6, 8.5), and 63.4% (99% CI: 61.9, 65.0) of residents received at least one course of antibiotics. There were 7.7 DOT/1000 days (99% CI: 6.69, 8.77) of antibiotics on the WHO Watch List administered in 2017. Antibiotic use increased annually by 4.09 DOT/1000 days (99% CI: 1.18, 6.99) before adjusting for resident factors, and 3.12 DOT/1000 days (99% CI: - 0.05, 6.29) after adjustment. Annual prevalence of antibiotic use decreased from 68.4% (99% CI: 66.9, 69.9) in 2015 to 63.4% (99% CI: 61.9, 65.0) in 2017, suggesting fewer residents were on antibiotics, but using them for longer. Resident factors associated with higher use were increasing age; chronic respiratory disease; a history of urinary tract infections, and skin and soft tissue infections; but dementia was associated with lower use. RAC home level antibiotic use ranged between 44.0 to 169.2 DOT/1000 days in 2016. Adjusting for resident factors marginally reduced this range (42.6 to 155.5 DOT/1000 days). CONCLUSIONS: Antibiotic course length and RAC homes with high use should be a focus of antimicrobial stewardship interventions. Practices in RAC homes with low use could inform interventions and warrant further investigation. This study provides a model for using electronic health records as a data source for antibiotic use surveillance in RAC.

Priority setting for adult malnutrition and nutritional screening in healthcare: a James Lind Alliance.

BACKGROUND: Malnutrition is one the greatest global health challenges of our generation, leading to the increased utilisation of healthcare resources, as well as morbidity and mortality. Research has primarily been driven by industry, academia and clinical working groups and has had little involvement from patients and carers. The project described in the present study aimed to establish a priority setting partnership allowing patients, carers and healthcare professionals an opportunity to influence the research agenda. METHODS: A national survey was conducted to gather malnutrition uncertainties and identify key issues (i.e. areas within scope where an evidence-base is lacking) from those with experience of malnutrition. Uncertainties were analysed according to themes. Similar questions were grouped and summary questions were developed. A second survey was conducted and respondents were asked to choose their 10 most important summary questions. A workshop was conducted to finalise the top 10 research priorities from the most frequently indicated uncertainties on the interim survey. RESULTS: Overall, 1128 uncertainty questions were submitted from 268 people. The interim survey had 71 responses and a list of the top 26 questions was generated for the workshop. There were 26 questions discussed, ranked and agreed by healthcare professionals, carers and patients at the workshop. The top 10 research priorities were then chosen. These included questions on oral nutritional supplements, vulnerable groups, screening, community care, use of body mass index and technology. CONCLUSIONS: The top 10 research priorities in malnutrition and nutritional screening have been identified from a robust process involving patients, carers and healthcare professionals.

Collapse of superconductivity in cuprates via ultrafast quenching of phase coherence.

The possibility of driving phase transitions in low-density condensates through the loss of phase coherence alone has far-reaching implications for the study of quantum phases of matter. This has inspired the development of tools to control and explore the collective properties of condensate phases via phase fluctuations. Electrically gated oxide interfaces1,2, ultracold Fermi atoms3,4 and cuprate superconductors5,6, which are characterized by an intrinsically small phase stiffness, are paradigmatic examples where these tools are having a dramatic impact. Here we use light pulses shorter than the internal thermalization time to drive and probe the phase fragility of the Bi2Sr2CaCu2O8+δ cuprate superconductor, completely melting the superconducting condensate without affecting the pairing strength. The resulting ultrafast dynamics of phase fluctuations and charge excitations are captured and disentangled by time-resolved photoemission spectroscopy. This work demonstrates the dominant role of phase coherence in the superconductor-to-normal state phase transition and offers a benchmark for non-equilibrium spectroscopic investigations of the cuprate phase diagram.

What Do Providers Want from a Pain Screening Measure Used in Daily Practice?

Objectives: We aimed to understand providers' experiences and preferences regarding several brief pain screening measures. Methods: We collected two waves of data for this analysis. Wave one: We conducted nine focus groups with multidisciplinary Department of Veterans Affairs (VA) providers. Wave two: To understand an emergent theme in wave one, we conducted 15 telephone interviews with prescribing providers where we used a semistructured guide comparing screening measures currently used in VA practices. Using content analysis of the wave two interviews, we evaluated providers' perceptions of important aspects of brief pain screening measures and reported emergent themes. Results: Five emergent themes underlie providers' perceptions of the utility of brief pain screening measures: 1) item abstractness: how bounded and concrete a patient's interpretation of an individual item is; 2) item distinctness: belief in the patient's ability to differentiate between the meaning of various items in a pain measure; 3) item anchoring: presence of a description under each response option making the meaning explicit; 4) item look-back period: the period of time over which patients are asked to remember and comment on their pain; 5) parsimony: identifying the shortest and simplest approach possible to acquire desired information. Conclusions: Overly complex or adaptive screening tools may include information that is ultimately not used by providers. Conversely, overly simplistic pain screening tools may omit information that helps providers understand the impact of pain on patients' lives. As pain is nuanced, complex, and subjective, all screening measures exhibit some limitations. No single pain measure serves all chronic pain patients, and specific contexts or settings may warrant additional specific items.

Proportion of Orofacial Clefts Attributable to Recognized Risk Factors.

OBJECTIVE: Estimate the population attributable fraction (PAF) for a set of recognized risk factors for orofacial clefts. DESIGN: We used data from the National Birth Defects Prevention Study. For recognized risk factors for which data were available, we estimated crude population attributable fractions (cPAFs) to account for potential confounding, average-adjusted population attributable fractions (aaPAFs). We assessed 11 modifiable and 3 nonmodifiable parental/maternal risk factors. The aaPAF for individual risk factors and the total aaPAF for the set of risk factors were calculated using a method described by Eide and Geffler. SETTING: Population-based case-control study in 10 US states. PARTICIPANTS: Two thousand seven hundred seventy-nine cases with isolated cleft lip with or without cleft palate (CL±P), 1310 cases with isolated cleft palate (CP), and 11 692 controls with estimated dates of delivery between October 1, 1997, and December 31, 2011. MAIN OUTCOME MEASURES: Crude population attributable fraction and aaPAF. RESULTS: The proportion of CL±P and CP cases attributable to the full set of examined risk factors was 50% and 43%, respectively. The modifiable factor with the largest aaPAF was smoking during the month before pregnancy or the first month of pregnancy (4.0% for CL±P and 3.4% for CP). Among nonmodifiable factors, the factor with the largest aaPAF for CL±P was male sex (27%) and for CP it was female sex (16%). CONCLUSIONS: Our results may inform research and prevention efforts. A large proportion of orofacial cleft risk is attributable to nonmodifiable factors; it is important to better understand the mechanisms involved for these factors.

Influence of Spin-Orbit Coupling in Iron-Based Superconductors.

We report on the influence of spin-orbit coupling (SOC) in Fe-based superconductors via application of circularly polarized spin and angle-resolved photoemission spectroscopy. We combine this technique in representative members of both the Fe-pnictides (LiFeAs) and Fe-chalcogenides (FeSe) with tight-binding calculations to establish an ubiquitous modification of the electronic structure in these materials imbued by SOC. At low energy, the influence of SOC is found to be concentrated on the hole pockets, where the largest superconducting gaps are typically found. This effect varies substantively with the k_{z} dispersion, and in FeSe we find SOC to be comparable to the energy scale of orbital order. These results contest descriptions of superconductivity in these materials in terms of pure spin-singlet eigenstates, raising questions regarding the possible pairing mechanisms and role of SOC therein.

Drug-drug interactions and their harmful effects in hospitalised patients: a systematic review and meta-analysis.

PURPOSE: Drug-drug interactions (DDIs) are often avoidable and, if undetected, can lead to patient harm. This review aimed to determine the prevalence of potential DDIs (pDDIs), clinically relevant DDIs (DDIs that could lead to measurable patient harm, taking into account the patient's individual clinical profile) and DDIs that resulted in actual patient harm during hospitalisation. METHOD: Four databases were scanned for English papers published from 2000 to 2016. Papers that reported prevalence of DDIs in the outpatient setting, at admission or discharge, involving only specific drugs, or in specific disease populations or age groups were excluded. RESULTS: Twenty-seven papers met the inclusion criteria and were graded for quality using the Critical Appraisal Skills Programme (CASP) cohort study checklist. Ten papers were rated as 'poor', 14 as 'fair' and only three papers as 'good'. Overall, the meta-analysis revealed that 33% of general patients and 67% of intensive care patients experienced a pDDI during their hospital stay. It was not possible to determine the prevalence of clinically relevant DDIs or DDIs that resulted in actual patient harm as data on these categories were limited. Of the very few studies that reported on harm, only a small proportion of DDIs were found to have resulted in actual patient harm. CONCLUSIONS: Standardisation of DDI definitions and research methods are required to allow meaningful prevalence rates to be obtained and compared. Studies that go further than measuring pDDIs are critically needed to determine the impact of DDIs on patient safety.

Interrogation of a longitudinal, national pharmacy claims dataset to explore factors that predict the need for add-on therapy in older and socioeconomically disadvantaged Australians with type 2 diabetes mellitus patients (T2DM).

PURPOSE: The management of type 2 diabetes mellitus (T2DM) is complex. The aim of this work is to explore factors that predict the need for add-on therapy in patients with T2DM in the community. METHODS: We accessed longitudinal, pharmacy payment claim records from the national Pharmaceutical Benefits Scheme (PBS) (Subsidises costs of medicines: government pays difference between patient co-payments, lower in concessional patients, and additional cost of drug.) for the period January 2006 to September 2014 (EREC/MI3127) from a 10% random sample of the Australian population validated to be representative of the population by the Australian Bureau of Statistics (ABS). Likely, T2DM patients were identified as those having been dispensed a single anti-hyperglycaemic drug (monotherapy). The time taken and possible factors that might lead to the addition of a second therapy were examined. An examination was made of trends in the co-prescription of either antihypertensive or anti-hyperlipidaemic agents in relation to the time (± 3 years) of initiating an anti-hyperglycaemic agent. RESULTS: Most (83%) presumed T2DM patients were initiated with metformin. The average time until the second agent was added was 4.8 years (95% CI 4.7-4.9). Satisfactory adherence, age, male gender, initiating therapy after 2012 and initiating with a sulphonylurea drug all were significant risks for add-on therapy. There was no overall trend in the initiation of antihypertensive and/or anti-hyperlipidaemic agents with respect to the time of anti-hyperglycaemic initiation. CONCLUSION: The usefulness of a longitudinal dataset of pharmacy-claim records is demonstrated. Over half of all older and socioeconmically disadvantaged T2DM patients captured in this longitudinal claims database will be prescribed a second anti-hyperglycaemic agent within 5 years of their first drug therapy. Several factors can predict the risk of prescription of add-on therapy, and these should be considered when prescribing medications to treat T2DM.

Expanding the role of clinical pharmacists on interdisciplinary primary care teams for chronic pain and opioid management.

BACKGROUND: Facilitating appropriate and safe prescribing of opioid medications for chronic pain management in primary care is a pressing public health concern. Interdisciplinary team-based models of primary care are exploring the expansion of clinical pharmacist roles to support disease management for chronic conditions, e.g. pain. Our study aims to 1) identify roles clinical pharmacists can assume in primary care team based chronic pain care processes and 2) understand the barriers to assuming these expanded roles. METHODS: Setting: Veterans Health Administration (VA) has implemented an interdisciplinary team-based model for primary care which includes clinical pharmacists. DESIGN: We employed an inductive two part qualitative approach including focus groups and semi-structured interviews with key informants. PARTICIPANTS: 60 members of VA primary care teams in two states participated in nine preliminary interdisciplinary focus groups where a semi-structured interview guide elucidated provider experiences with screening for and managing chronic pain. To follow up on emergent themes relating to clinical pharmacist roles, an additional 14 primary care providers and clinical pharmacists were interviewed individually. We evaluated focus group and interview transcripts using the method of constant comparison and produced mutually agreed upon themes. RESULTS: Clinical pharmacists were identified by primary care providers as playing a central role with the ongoing management of opioid therapy including review of the state prescription drug monitoring program, managing laboratory screening, providing medication education, promoting naloxone use, and opioid tapering. Specific barriers to clinical pharmacists role expansion around pain care include: limitations of scopes of practice, insufficient institutional support (low staffing, dedicated time, insufficient training, lack of interdisciplinary leadership support), and challenges and opportunities for disseminating clinical pharmacists' expanded roles. CONCLUSIONS: Expanding the role of the clinical pharmacist to collaborate with providers around primary care based chronic pain management is a promising strategy for improving pain management on an interdisciplinary primary care team. However, expanded roles have to be balanced with competing responsibilities relating to other conditions. Interdisciplinary leadership is needed to facilitate training, resources, adequate staffing, as well as to prepare both clinical pharmacists and the providers they support, about expanded clinical pharmacists' scopes of practice and capabilities.

A dosing algorithm for metformin based on the relationships between exposure and renal clearance of metformin in patients with varying degrees of kidney function.

PURPOSE: The aims of this study were to investigate the relationship between metformin exposure, renal clearance (CLR), and apparent non-renal clearance of metformin (CLNR/F) in patients with varying degrees of kidney function and to develop dosing recommendations. METHODS: Plasma and urine samples were collected from three studies consisting of patients with varying degrees of kidney function (creatinine clearance, CLCR; range, 14-112 mL/min). A population pharmacokinetic model was built (NONMEM) in which the oral availability (F) was fixed to 0.55 with an estimated inter-individual variability (IIV). Simulations were performed to estimate AUC0-τ, CLR, and CLNR/F. RESULTS: The data (66 patients, 327 observations) were best described by a two-compartment model, and CLCR was a covariate for CLR. Mean CLR was 17 L/h (CV 22%) and mean CLNR/F was 1.6 L/h (69%).The median recovery of metformin in urine was 49% (range 19-75%) over a dosage interval. When CLR increased due to improved renal function, AUC0-τ decreased proportionally, while CLNR/F did not change with kidney function. Target doses (mg/day) of metformin can be reached using CLCR/3 × 100 to obtain median AUC0-12 of 18-26 mg/L/h for metformin IR and AUC0-24 of 38-51 mg/L/h for metformin XR, with Cmax < 5 mg/L. CONCLUSIONS: The proposed dosing algorithm can be used to dose metformin in patients with various degrees of kidney function to maintain consistent drug exposure. However, there is still marked IIV and therapeutic drug monitoring of metformin plasma concentrations is recommended.

A kinetic Monte Carlo approach to study fluid transport in pore networks.

The mechanism of fluid migration in porous networks continues to attract great interest. Darcy's law (phenomenological continuum theory), which is often used to describe macroscopically fluid flow through a porous material, is thought to fail in nano-channels. Transport through heterogeneous and anisotropic systems, characterized by a broad distribution of pores, occurs via a contribution of different transport mechanisms, all of which need to be accounted for. The situation is likely more complicated when immiscible fluid mixtures are present. To generalize the study of fluid transport through a porous network, we developed a stochastic kinetic Monte Carlo (KMC) model. In our lattice model, the pore network is represented as a set of connected finite volumes (voxels), and transport is simulated as a random walk of molecules, which "hop" from voxel to voxel. We simulated fluid transport along an effectively 1D pore and we compared the results to those expected by solving analytically the diffusion equation. The KMC model was then implemented to quantify the transport of methane through hydrated micropores, in which case atomistic molecular dynamic simulation results were reproduced. The model was then used to study flow through pore networks, where it was able to quantify the effect of the pore length and the effect of the network's connectivity. The results are consistent with experiments but also provide additional physical insights. Extension of the model will be useful to better understand fluid transport in shale rocks.

The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE).

BACKGROUND: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis. OBJECTIVE: Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). METHODS: Two hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for apremilast vs. etanercept comparisons. RESULTS: At Week 16, PASI-75 achievement was greater with apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept (P < 0.0001 vs. placebo). PASI-75 response was maintained in 47.3% (apremilast/apremilast), 49.4% (etanercept/apremilast) and 47.9% (placebo/apremilast) of patients at Week 52. Most common adverse events (≥5%) with apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with apremilast. CONCLUSION: Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of apremilast. Switching from etanercept to apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with apremilast through Week 52.

Contrasting patterns of population connectivity between regions in a commercially important mollusc Haliotis rubra: integrating population genetics, genomics and marine LiDAR data.

Estimating contemporary genetic structure and population connectivity in marine species is challenging, often compromised by genetic markers that lack adequate sensitivity, and unstructured sampling regimes. We show how these limitations can be overcome via the integration of modern genotyping methods and sampling designs guided by LiDAR and SONAR data sets. Here we explore patterns of gene flow and local genetic structure in a commercially harvested abalone species (Haliotis rubra) from southeastern Australia, where the viability of fishing stocks is believed to be dictated by recruitment from local sources. Using a panel of microsatellite and genomewide SNP markers, we compare allele frequencies across a replicated hierarchical sampling area guided by bathymetric LiDAR imagery. Results indicate high levels of gene flow and no significant genetic structure within or between benthic reef habitats across 1400 km of coastline. These findings differ to those reported for other regions of the fishery indicating that larval supply is likely to be spatially variable, with implications for management and long-term recovery from stock depletion. The study highlights the utility of suitably designed genetic markers and spatially informed sampling strategies for gaining insights into recruitment patterns in benthic marine species, assisting in conservation planning and sustainable management of fisheries.

Trends in metformin utilisation and dose appropriateness in Australia.

PURPOSE: The study aimed to (1) determine the trends in the utilisation of metformin in Australia, (2) determine the appropriateness of metformin dosing in an Australian teaching hospital and (3) gather the opinions of prescribers on the relationship between metformin dose and renal function. METHODS: National prescription data between 1990 and 2012 were accessed. A retrospective audit (2008-2012) of metformin doses and patient renal function (20 % random sample of all in-patients prescribed metformin) was conducted at St Vincent's Hospital (SVH), Sydney. Prescribers of metformin were interviewed (semi-structured; consultants at SVH) or surveyed (Australian endocrinologists) to gather their understanding of metformin dosing in relation to renal function. RESULTS: Metformin utilisation increased fivefold nationally between 1995 and 2012. Metformin tended to be under-dosed in SVH patients with normal renal function (83.5 %) and over-dosed in patients with impaired renal function (estimated glomerular filtration rate (eGFR) <30 mL/min, 50 %). Consultants indicated that metformin doses needed to be reduced in renal impairment. Most endocrinologists (61 %) were comfortable prescribing metformin down to eGFRs around 30 mL/min. CONCLUSION: The use of metformin increased greatly over the period of the study. Metformin is prescribed frequently for patients with eGFR values below the minimal level approved in the product label (60 mL/min). While prescribers expressed their understanding of the need to reduce metformin doses in patients with renal impairment, we found that metformin doses were higher than appropriate in patients with impaired renal function. Metformin may be used safely when renal function is poor provided dosage is appropriately reduced.

A time and motion study of junior doctor work patterns on the weekend: a potential contributor to the weekend effect?

BACKGROUND: Patients admitted to hospital on weekends have a greater risk of mortality compared to patients admitted on weekdays. Junior medical officers (JMO) make up the majority of medical staff on weekends. No previous study has quantified JMO work patterns on weekends. AIM: To describe and quantify JMO work patterns on weekends and compare them with patterns previously observed during the week. METHODS: Observational time and motion study of JMO working weekends using the Work Observation Method by Activity Timing (WOMBAT; Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia) software. Descriptive statistics were used to determine the proportion of total observed time spent in tasks. RESULTS: Weekend JMO predominately spent time in indirect care (32.0%), direct care (23.0%) and professional communication (22.1%). JMO spent 20.9% of time multitasking and were interrupted, on average, every 9 min. Weekend JMO spent significantly more time in direct care compared with weekdays (13.0%; P < 0.001) and nights (14.3%; P < 0.001). Weekend JMO spent significantly less time on breaks (8.5%), with less than 1 h in an 11-h shift, compared with JMO during weekdays (16.4%; P = 0.004) and nights (27.6%; P = <0.001). Weekend JMO were interrupted at a higher rate (6.6/h) than on weekdays (rate ratio (RR) 2.9, 95% confidence intervals (CI) 2.6, 3.3) or nights (RR 5.1, 95% CI 4.2, 6.1). Multitasking on weekends (20.9%) was comparable to weekdays (18.9%; P = 0.19) but significantly higher than nights (6.4%; P = <0.001). CONCLUSION: On weekends, JMO had few breaks, were interrupted frequently and engaged in high levels of multitasking. This pattern of JMO work could be a potential contributing factor to the weekend effect in terms of JMO abilities to respond safely and adequately to care demands.

Incidence and impact of postoperative atrial fibrillation after minimally invasive esophagectomy.

Atrial fibrillation (AF) following open esophagectomy has been associated with increased rates of pulmonary and anastomotic complications, and mortality. This study seeks to evaluate effects of AF after minimally invasive esophagectomy (MIE). A retrospective review of patients consecutively treated with MIE for esophageal carcinoma, dysplasia. and benign disease from November 2006 to November 2011 was performed. One hundred twenty-one patients underwent MIE. Median age was 65 years (range 26-88) with 85% being male. Thirty-eight (31.4%) patients developed AF postoperatively. Of these 38 patients, 7 (18.4%) had known AF preoperatively. Patients with postoperative AF were significantly older than those without postoperative AF (68.7 vs. 62.8 years, P = 0.008) and more likely to be male (94.7% vs. 80.7%, P = 0.04). Neoadjuvant chemoradiation showed a trend toward increased risk of AF (73.7% vs 56.6%, P = 0.07). Sixty-day mortality was 2 of 38 (5.3%) in patients with AF and 4 of 83 (6.0%) in the no AF cohort (P = 1.00). The group with AF had increased length of hospitalization (13.4 days vs. 10.6 days P = 0.02). No significant differences in rates of pneumonia (31.6% vs. 21.7% P = 0.24), stricture (13.2% vs. 26.5% P = 0.10), or leak requiring return to operating room (13.2% vs. 8.4% P = 0.51) were noted between groups. We did not find an increased rate of AF in our MIE cohort compared with prior reported rates in open esophagectomy populations. AF did result in an increased length of stay but was not a predictor of other short-term morbidities including anastomotic leak, pulmonary complications, stenosis, or 60-day mortality.

Ballistic Beloniformes attacking through Snell's Window.

Needlefishes (Beloniformes) were observed employing a range of stalking and attacking behaviours to attack schools of bait fishes ranging from the use of tactics common to predatory fishes to a novel behaviour: the use of leaping, aerial attacks. These aerial attacks are suggested to serve two purposes: to extend the attack range of the needlefishes and to reduce their prey's potential for evasion. Furthermore, a third purpose is hypothesized that the needlefishes are taking advantage of Snell's Window, an optical effect which may mask their approach to their prey.