Overset meshing in combination with novel blended weak-strong fluid-structure interactions for simulations of a translating valve in series with a second valve.

Mechanical circulatory support (MCS) devices can bridge the gap to transplant whilst awaiting a viable donor heart. The Realheart Total Artificial Heart is a novel positive-displacement MCS that generates pulsatile flow via bileaflet mechanical valves. This study developed a combined computational fluid dynamics and fluid-structure interaction (FSI) methodology for simulating positive displacement bileaflet valves. Overset meshing discretised the fluid domain, and a blended weak-strong coupling FSI algorithm was combined with variable time-stepping. Four operating conditions of relevant stroke lengths and rates were assessed. The results demonstrated this modelling strategy is stable and efficient for modelling positive-displacement artificial hearts.

Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model.

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5-6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate. The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2, and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5-6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

Production of mobile invertebrate communities on shallow reefs from temperate to tropical seas.

Primary productivity of marine ecosystems is largely driven by broad gradients in environmental and ecological properties. By contrast, secondary productivity tends to be more variable, influenced by bottom-up (resource-driven) and top-down (predatory) processes, other environmental drivers, and mediation by the physical structure of habitats. Here, we use a continental-scale dataset on small mobile invertebrates (epifauna), common on surfaces in all marine ecosystems, to test influences of potential drivers of temperature-standardized secondary production across a large biogeographic range. We found epifaunal production to be remarkably consistent along a temperate to tropical Australian latitudinal gradient of 28.6°, spanning kelp forests to coral reefs (approx. 3500 km). Using a model selection procedure, epifaunal production was primarily related to biogenic habitat group, which explained up to 45% of total variability. Production was otherwise invariant to predictors capturing primary productivity, the local biomass of fishes (proxy for predation pressure), and environmental, geographical, and human impacts. Highly predictable levels of epifaunal productivity associated with distinct habitat groups across continental scales should allow accurate modelling of the contributions of these ubiquitous invertebrates to coastal food webs, thus improving understanding of likely changes to food web structure with ocean warming and other anthropogenic impacts on marine ecosystems.

The efficacy of toltrazuril treatment for reducing the infection intensity of Theileria orientalis Ikeda type in dairy calves.

The aim of this study was to test the hypothesis that toltrazuril administered at 4 weeks post-turnout reduces the infection intensity of Theileria orientalis Ikeda type in dairy calves and so prevents serious clinical disease in these animals at 2-3 months of age. Two groups of 40 dairy calves on two separate dairy farms in the Waikato were followed for 16 weeks post-turnout onto pasture. On each farm, 20 calves were randomly selected and orally treated with toltrazuril (15 mg/kg) at 4 weeks post-turnout, whilst the remaining 20 calves were left untreated. All 40 calves were blood sampled and weighed at 2, 4, 6, 8, 12, and 16 weeks post-turnout i.e. 6 samplings per calf. A random subset of 10 calves from each treatment group on each farm were faecal sampled at each visit. The blood samples were used to estimate the T. orientalis Ikeda type infection intensity and haematocrit for each calf and the faecal samples were used to estimate the number of coccidia oocysts per gram of faeces. Three linear mixed effects models, to evaluate the effect of toltrazuril treatment on infection intensity, haematocrit (HCT) and weight respectively were fitted to the data. No calves on either farm developed clinical theileriosis or coccidiosis and the three mixed effects linear models, controlling for the effect of farm and days from turnout, showed that there was no effect of treatment on infection intensity (p = 0.81), on HCT (p = 0.99) and on weight gain (p = 0.79). In conclusion, this study showed no evidence supporting the use of toltrazuril to control T. orientalis Ikeda type infection levels and prevent disease.

Ventricular Flow Field Visualization During Mechanical Circulatory Support in the Assisted Isolated Beating Heart.

Investigations of ventricular flow patterns during mechanical circulatory support are limited to in vitro flow models or in silico simulations, which cannot fully replicate the complex anatomy and contraction of the heart. Therefore, the feasibility of using echocardiographic particle image velocimetry (Echo-PIV) was evaluated in an isolated working heart setup. Porcine hearts were connected to an isolated, working heart setup and a left ventricular assist device (LVAD) was implanted. During different levels of LVAD support (unsupported, partial support, full support), microbubbles were injected and echocardiographic images were acquired. Iterative PIV algorithms were applied to calculate flow fields. The isolated heart setup allowed different hemodynamic situations. In the unsupported heart, diastolic intra-ventricular blood flow was redirected at the heart's apex towards the left ventricular outflow tract (LVOT). With increasing pump speed, large vortex formation was suppressed, and blood flow from the mitral valve directly entered the pump cannula. The maximum velocities in the LVOT were significantly reduced with increasing support. For the first time, cardiac blood flow patterns during LVAD support were visualized and quantified in an ex vivo model using Echo-PIV. The results reveal potential regions of stagnation in the LVOT and, in future the methods might be also used in clinical routine to evaluate intraventricular flow fields during LVAD support.

Transcutaneous electrical nerve stimulation improves fatigue performance of the treated and contralateral knee extensors.

PURPOSE: Transcutaneous electrical nerve stimulation (TENS) can reduce acute and chronic pain. Unilateral fatigue can produce discomfort in the affected limb and force and activation deficits in contralateral non-exercised muscles. TENS-induced local pain analgesia effects on non-local fatigue performance are unknown. Hence, the aim of the study was to determine if TENS-induced pain suppression would augment force output during a fatiguing protocol in the treated and contralateral muscles. METHODS: Three experiments were integrated for this article. Following pre-tests, each experiment involved 20 min of TENS, sham, or a control condition on the dominant quadriceps. Then either the TENS-treated quadriceps (TENS_Treated) or the contralateral quadriceps (TENS_Contra) was tested. In a third experiment, the TENS and sham conditions involved two\; 100-s isometric maximal voluntary contractions (MVC) (30-s recovery) followed by testing of the contralateral quadriceps (TENS_Contra-Fatigue). Testing involved single knee extensors (KE) MVCs (pre- and post-test) and a post-test 30% MVC to task failure. RESULTS: The TENS-treated study induced greater (p = 0.03; 11.0%) time to KE (treated leg) failure versus control. The TENS_Contra-Fatigue induced significant (p = 0.04; 11.7%) and near-significant (p = 0.1; 7.1%) greater time to contralateral KE failure versus sham and control, respectively. There was a 14.5% (p = 0.02) higher fatigue index with the TENS (36.2 ± 10.1%) versus sham (31.6 ± 10.6%) conditions in the second fatigue intervention set (treated leg). There was no significant post-fatigue KE fatigue interaction with the TENS_Contra. CONCLUSIONS: Unilateral TENS application to the dominant KE prolonged time to failure in the treated and contralateral KE suggesting a global pain modulatory response.

Untargeted metabolic profiling of dogs with a suspected toxic mitochondrial myopathy using liquid chromatography-mass spectrometry.

'Go Slow myopathy' (GSM) is a suspected toxic myopathy in dogs that primarily occurs in the North Island of New Zealand, and affected dogs usually have a history of consuming meat, offal or bones from wild pigs (including previously frozen and/or cooked meat). Previous epidemiological and pathological studies on GSM have demonstrated that changes in mitochondrial structure and function are most likely caused by an environmental toxin that dogs are exposed to through the ingestion of wild pig. The disease has clinical, histological and biochemical similarities to poisoning in people and animals from the plant Ageratina altissima (white snakeroot). Aqueous and lipid extracts were prepared from liver samples of 24 clinically normal dogs and 15 dogs with GSM for untargeted liquid chromatography-mass spectrometry. Group-wise comparisons of mass spectral data revealed 38 features that were significantly different (FDR<0.05) between normal dogs and those with GSM in aqueous extracts, and 316 significantly different features in lipid extracts. No definitive cause of the myopathy was identified, but alkaloids derived from several plant species were among the possible identities of features that were more abundant in liver samples from affected dogs compared to normal dogs. Mass spectral data also revealed that dogs with GSM have reduced hepatic phospholipid and sphingolipid concentrations relative to normal dogs. In addition, affected dogs had changes in the abundance of kynurenic acid, various dicarboxylic acids and N-acetylated branch chain amino acids, suggestive of mitochondrial dysfunction.

Sex matters in massive parallel sequencing: Evidence for biases in genetic parameter estimation and investigation of sex determination systems.

Using massively parallel sequencing data from two species with different life history traits, American lobster (Homarus americanus) and Arctic Char (Salvelinus alpinus), we highlight how an unbalanced sex ratio in the samples and a few sex-linked markers may lead to false interpretations of population structure and thus to potentially erroneous management recommendations. Here, multivariate analyses revealed two genetic clusters separating samples by sex instead of by expected spatial variation: inshore and offshore locations in lobster, or east and west locations in Arctic Char. To further investigate this, we created several subsamples artificially varying the sex ratio in the inshore/offshore and east/west groups and then demonstrated that significant genetic differentiation could be observed despite panmixia in lobster, and that FST values were overestimated in Arctic Char. This pattern was due to 12 and 94 sex-linked markers driving differentiation for lobster and Arctic Char, respectively. Removing sex-linked markers led to nonsignificant genetic structure in lobster and a more accurate estimation of FST in Arctic Char. The locations of these markers and putative identities of genes containing or nearby the markers were determined using available transcriptomic and genomic data, and this provided new information related to sex determination in both species. Given that only 9.6% of all marine/diadromous population genomic studies to date have reported sex information, we urge researchers to collect and consider individual sex information. Sex information is therefore relevant for avoiding unexpected biases due to sex-linked markers as well as for improving our knowledge of sex determination systems in nonmodel species.

Neutron Radiation Tolerance of Two Benchmark Thiophene-Based Conjugated Polymers: the Importance of Crystallinity for Organic Avionics.

Aviation and space applications can benefit significantly from lightweight organic electronics, now spanning from displays to logics, because of the vital importance of minimising payload (size and mass). It is thus crucial to assess the damage caused to such materials by cosmic rays and neutrons, which pose a variety of hazards through atomic displacements following neutron-nucleus collisions. Here we report the first study of the neutron radiation tolerance of two poly(thiophene)s-based organic semiconductors: poly(3-hexylthiophene-2,5-diyl), P3HT, and the liquid-crystalline poly(2,5-bis (3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene), PBTTT. We combine spectroscopic investigations with characterisation of intrinsic charge mobility to show that PBTTT exhibits significantly higher tolerance than P3HT. We explain this in terms of a superior chemical, structural and conformational stability of PBTTT, which can be ascribed to its higher crystallinity, in turn induced by a combination of molecular design features. Our approach can be used to develop design strategies for better neutron radiation-tolerant materials, thus paving the way for organic semiconductors to enter avionics and space applications.

The efficacy and plasma profiles of abamectin plus levamisole combination anthelmintics administered as oral and pour-on formulations to cattle.

In phase I, faecal egg count reduction tests (FECRT) were conducted on six commercial cattle farms to compare the performance of two pour-on and one oral combination anthelmintic. Groups of 12-15 calves were sampled for faecal nematode egg count (FEC) before treatment with either abamectin oral, levamisole oral, an abamectin+levamisole oral combination or one of two abamectin+levamisole combination pour-ons. Samples were collected again 14days after treatment to calculate the percentage reduction in FEC. The proportions of infective stage larvae (L3) in faecal cultures were used to apportion egg counts to, and calculate efficacy against, the main parasite genera. Abamectin oral was effective against Ostertagia except on one farm where resistance was indicated, but had reduced efficacy against Cooperia on four farms. Levamisole oral was effective against Cooperia on all farms, but had variable efficacy against Ostertagia. The abamectin+levamisole oral was effective against both species on all farms. The abamectin+levamisole pour-ons were effective on some farms but not on others. In particular, pour-on 2 failed to achieve 95% efficacy in 45% of evaluations, 4/6 against Cooperia and 1/5 against Ostertagia. On some farms the combination pour-ons were less effective than their constituent actives administered alone as orals. In phase II, 8 groups of 6 calves, grazing parasite-free pasture, were infected with putatively ML-resistant isolates of Cooperia oncophora and Ostertagia ostertagi. Once infections were patent groups were treated with oral or pour-on formulations of abamectin alone, levamisole alone, abamectin+levamisole (two pour-ons) or remained untreated. Blood samples were collected for analysis and after 8days all calves were euthanized and abomasa and intestines recovered for worm counts. All treatments were effective against O. ostertagi and all treatments containing levamisole were effective against C. oncophora. Animals treated with the oral combination had higher Cmax and AUC values for abamectin in plasma than animals treated orally with abamectin alone. In contrast, animals treated with the combination pour-ons tended to have lower plasma levels for abamectin than those treated with abamectin alone as a pour-on, with differences in the Cmax and AUC values approaching statistical significance (p-values ≤0.07). There were no differences detected in plasma concentrations of levamisole. The inconsistent and sometimes poor efficacy of the combination pour-ons on-farm is likely due to reduced levels of abamectin in the plasma and hence less active reaching the target worms in the gut.

Seascape genomics provides evidence for thermal adaptation and current-mediated population structure in American lobster (Homarus americanus).

Investigating how environmental features shape the genetic structure of populations is crucial for understanding how they are potentially adapted to their habitats, as well as for sound management. In this study, we assessed the relative importance of spatial distribution, ocean currents and sea surface temperature (SST) on patterns of putatively neutral and adaptive genetic variation among American lobster from 19 locations using population differentiation (PD) approaches combined with environmental association (EA) analyses. First, PD approaches (using bayescan, arlequin and outflank) found 28 outlier SNPs putatively under divergent selection and 9770 neutral SNPs in common. Redundancy analysis revealed that spatial distribution, ocean current-mediated larval connectivity and SST explained 31.7% of the neutral genetic differentiation, with ocean currents driving the majority of this relationship (21.0%). After removing the influence of spatial distribution, no SST were significant for putatively neutral genetic variation whereas minimum annual SST still had a significant impact and explained 8.1% of the putatively adaptive genetic variation. Second, EA analyses (using Pearson correlation tests, bayescenv and lfmm) jointly identified seven SNPs as candidates for thermal adaptation. Covariation at these SNPs was assessed with a spatial multivariate analysis that highlighted a significant temperature association, after accounting for the influence of spatial distribution. Among the 505 candidate SNPs detected by at least one of the three approaches, we discovered three polymorphisms located in genes previously shown to play a role in thermal adaptation. Our results have implications for the management of the American lobster and provide a foundation on which to predict how this species will cope with climate change.

Selection for anthelmintic resistant Teladorsagia circumcincta in pre-weaned lambs by treating their dams with long-acting moxidectin injection.

Administration of long-acting anthelmintics to pregnant ewes prior to lambing is a common practice in New Zealand. Today, most of these products contain macrocyclic lactone (ML) actives, which because of their lipophilic nature, are detectable in the milk of treated animals and in the plasma of their suckling offspring. This study was conducted to confirm the transfer of ML actives to lambs in the ewe's milk, and to assess whether this could result in selection for ML resistant nematodes in the lamb. Ninety, twin bearing Romney ewes were treated before lambing with a long-acting injectable formulation of moxidectin, a 100-day controlled release capsule (CRC) containing abamectin and albendazole, or remained untreated. After lambing, seven ewes from each treatment group were selected for uniformity of lambing date and, along with their twin lambs, relocated indoors. At intervals, all ewes and lambs were bled, and samples of ewe's milk were collected, for determination of drug concentrations. Commencing 4 weeks after birth all lambs were dosed weekly with 250 infective larvae (L3) of either an ML-susceptible or -resistant isolate of Teladorsagia circumcinta. At 12 weeks of age all lambs were slaughtered and their abomasa recovered for worm counts. Moxidectin was detected in the plasma of moxidectin-treated ewes until about 50 days after treatment and in their lambs until about day 60. Abamectin was detected in the plasma of CRC-treated ewes until the last sample on day 80 and in the plasma of their lambs until about day 60. Both actives were detectable in milk of treated ewes until day 80 after treatment. Establishment of resistant L3 was not different between the treatment groups but treatment of ewes with moxidectin reduced establishment of susceptible L3 by 70%, confirming the potential of drug transfer in milk to screen for ML-resistance in the suckling lamb.

Tobacco dependence, the most important cardiovascular risk factor: treatment in the Czech Republic.

Smoking is the most important cardiovascular (CV) risk factor. Stopping smoking halves the CV risk. Every clinician should provide a brief intervention with smokers. Intensive treatment should be available to those who need it. There are 37 Centers for Tobacco Dependence in the Czech Republic, which offer treatment including a psychobehavioral intervention and pharmacotherapy (varenicline, nicotine, bupropion). Czech physicians, pharmacists and nurses are regularly educated about smoking cessation. We describe the results of intensive treatment offered by our centers. Treatment includes screening (1 h), an intervention (2 h), and follow-up visits during the next 12 months. Among 3532 patients, 34.3 % had CO-validated abstinence at 12-months (including 489 patients who attended the screening visit + only the 12-month follow up visit). Among patients who underwent the intervention, the abstinence rate was 38.2 %. The majority of patients who underwent the intervention (N=2470) used some form of pharmacotherapy. After one year, the abstinence rate was 43.4 %, compared to 15.9 % (N=573) without pharmacotherapy. Only 28 % of patients came on the recommendation of a physician. Despite the decrease in CV risk following smoking cessation and the effectiveness of treatment, centers are underutilized.

Public opinion of drug treatment policy: exploring the public's attitudes, knowledge, experience and willingness to pay for drug treatment strategies.

BACKGROUND: Research evidence is strong for opiate replacement treatment (ORT). However, public opinion (attitudes) can be at odds with evidence. This study explored the relationships between, attitudes, knowledge of drugs and a range of socio-demographic variables that potentially influence attitude. This is relevant in the current policy arena in which a major shift from harm reduction to, rehabilitation is underway. METHODS: A cross sectional postal questionnaire survey in Scotland was conducted where the drug, treatment strategy has changed from harm-reduction to recovery-based. A random sample (N=3000), of the general public, >18 years, and on the electoral register was used. The questionnaire was largely structured with tick box format but included two open questions for qualitative responses. Valuation was measured using the economic willingness-to-pay (WTP) method. RESULTS: The response rate was 38.1% (1067/2803). Less than 10% had personal experience of drug, misuse but 16.7% had experience of drug misuse via a friend/acquaintance. Regression modelling revealed more positive attitudes towards drug users in those with personal experience of drug misuse, (p<0.001), better knowledge of drugs (p=0.001) and higher income (those earning >£50,000 per, annum compared to <£15K; p=0.01). Over half of respondents were not willing to pay anything for drug treatment indicating they did not value these treatments at all. Respondents were willing-to-pay most for community rehabilitation and least for methadone maintenance treatment. Qualitative analysis of open responses indicated many strong negative attitudes, doubts over the efficacy of methadone and consideration of addiction as self-inflicted. There was ambivalence with respondents weighing up negative feelings towards treatment against societal benefit. CONCLUSIONS: There is a gap between public attitudes and evidence regarding drug treatment. Findings suggest a way forward might be to develop and evaluate treatment that integrates ORT with a community rehabilitative approach. Evaluation of public engagement/education to improve knowledge of drug treatment effectiveness is recommended.

Reduced efficacy of moxidectin and abamectin in young red deer (Cervus elaphus) after 20 years of moxidectin pour-on use on a New Zealand deer farm.

A study was undertaken on weaned 4-5 month old farmed red deer to test the efficacy of moxidectin and abamectin anthelmintics, given by three different routes of administration, compared with an untreated control. Faecal samples were collected on days 0, 7 and 14 for a faecal egg count reduction test (FECRT), blood samples were collected on days 0, 0.5, 1, 2, 3, 5, 7, 10 and 14 for pharmacokinetics, and the deer were killed on days 14 or 15 for total nematode count. The control group averaged 1264 adult Ostertagia-type nematode parasite species and treatment efficacy was 77.4% for moxidectin injection, 26% for oral moxidectin and 27.6% for pour-on moxidectin, while the treatment efficacy was 72.4% for abamectin injection, 70.1% for oral abamectin (Hi-Mineral) and 34.1% for pour-on abamectin. Both moxidectin and abamectin injections were significantly more efficacious than their equivalent pour-ons. There was a significant difference in efficacy between oral abamectin (Hi-Mineral) and oral moxidectin (P<0.01). The control group averaged 2956 adult lungworm (Dictyocaulus eckerti) and 50 Oesophagostomum venulosum in the large intestine and treatment efficacy against these nematodes was 100% for all treatments. There were negligible numbers of other gastro-intestinal nematodes. At slaughter, there was a significant correlation (P=0.02) between FEC and Ostertagia-type nematodes in the untreated controls. Relatively few eggs were found in faeces from treated animals at 7 and 14 days post-treatment despite significant worm burdens in all six treatment groups, suggesting egg-laying suppression in resistant nematodes, and all three different FECRT calculations tended to overestimate the efficacy of the treatments compared with actual nematode counts. Peak plasma concentrations (Cmax) for both actives were measured 12h after treatment for injection and oral and at 5 days for pour-on. Cmax (ng/ml) for moxidectin injection, oral and pour-on were 71.8, 8.3 and 0.4, respectively, and for abamectin injection, oral and pour-on were 62.1, 30.3 and 10.0, respectively. Area under the curve (AUC) estimates for moxidectin injection, oral and pour-on were 106.6, 12.9 and 6.1, respectively, and for abamectin injection, oral and pour-on were 162.7, 57.5 and 74.3, respectively. The results demonstrate that significant anthelmintic resistance to moxidectin and abamectin is present on this deer farm. However, the injection was the most effective route of administration in young deer for both anthelmintics, although <80% efficacious. We conclude that the FECRT is unreliable in deer when anthelmintic resistance is present.

Reduced heart rate variability during sleep in long-duration spaceflight.

Limited data are available to describe the regulation of heart rate (HR) during sleep in spaceflight. Sleep provides a stable supine baseline during preflight Earth recordings for comparison of heart rate variability (HRV) over a wide range of frequencies using both linear, complexity, and fractal indicators. The current study investigated the effect of long-duration spaceflight on HR and HRV during sleep in seven astronauts aboard the International Space Station up to 6 mo. Measurements included electrocardiographic waveforms from Holter monitors and simultaneous movement records from accelerometers before, during, and after the flights. HR was unchanged inflight and elevated postflight [59.6 ± 8.9 beats per minute (bpm) compared with preflight 53.3 ± 7.3 bpm; P < 0.01]. Compared with preflight data, HRV indicators from both time domain and power spectral analysis methods were diminished inflight from ultralow to high frequencies and partially recovered to preflight levels after landing. During inflight and at postflight, complexity and fractal properties of HR were not different from preflight properties. Slow fluctuations (<0.04 Hz) in HR presented moderate correlations with movements during sleep, partially accounting for the reduction in HRV. In summary, substantial reduction in HRV was observed with linear, but not with complexity and fractal, methods of analysis. These results suggest that periodic elements that influence regulation of HR through reflex mechanisms are altered during sleep in spaceflight but that underlying system complexity and fractal dynamics were not altered.

Predicting survival following non-invasive ventilation for hypercapnic exacerbations of chronic obstructive pulmonary disease.

INTRODUCTION: Non-invasive ventilation (NIV) has revolutionised the management of hypercapnic exacerbations of chronic obstructive pulmonary disease (COPD). We wished to evaluate factors related to its overall success in the 'real-life' setting. METHODS: A retrospective analysis of patients receiving NIV for a hypercapnic exacerbation of COPD was performed. Demographics, laboratory data, blood gases and outcomes (hospital discharge or in-patient death) were extracted and subsequently analysed to identify factors relating to its overall success or failure. RESULTS: Over 6 years, 240 patients (mean age 70 years), received NIV with mean pH and pCO(2) prior to NIV 7.24 and 10.4kPa respectively; of these, 167 survived to hospital discharge with a median age (70 vs. 74; p = 0.02) lower than non-survivors. Absolute values of pH and pCO(2) (higher and lower respectively) prior to NIV and at 1 h were both associated with successful hospital discharge. An improvement (p = 0.02) in pH within an hour of receiving NIV - but not pCO(2) - was associated with surviving to hospital discharge. Of all laboratory data assessed, only baseline urea was significantly (p = 0.021) associated with a successful outcome. CONCLUSION: Younger patients with a lower urea, higher pH and lower pCO(2) at baseline and who demonstrate an improvement in pH within 1 h, are more likely to have a successful outcome when given NIV for a hypercapnic exacerbation of COPD on an unselected basis. Prospective studies evaluating many other parameters are now required to help identify patients in whom NIV is likely to be successful.

Economic impact of using inhaled corticosteroids without prior exacerbation among elderly patients with chronic obstructive pulmonary disorder.

OBJECTIVE: To assess the economic impact of initiating inhaled corticosteroids (ICS) without evidence of prior exacerbation among elderly patients with chronic obstructive pulmonary disease (COPD) in the US. METHODS: This retrospective study used administrative claims to identify newly diagnosed COPD patients between 1/1/2005 and 6/30/2006 who were dispensed ICS. The dispense date of the first ICS was set as the index date. Patients with prior diagnoses for asthma, cystic fibrosis, or lung cancer were excluded. Cohorts were constructed based on whether ICS therapy was concordant with recommended guidelines of having prior COPD exacerbation. Each COPD patient with prior exacerbation was matched to four patients without exacerbation based on age, gender, Charlson Comorbidity Index, and whether COPD diagnosis code was not elsewhere specified (i.e., 496). Multivariate regressions were estimated to assess the association between use of ICS therapy without prior exacerbation and total healthcare costs, controlling for demographics and clinical characteristics. RESULTS: The study included 3650 patients: 730 with prior exacerbation and 2920 without prior exacerbation. Patients were 76 years of age and 54% were male. Those with prior exacerbation were more likely to have inpatient stays both prior to (74.4 vs. 44.1%, p<0.05) and following (37.0 vs. 33.1%, p<0.05) the index date. Controlling for patient characteristics, patients who were dispensed ICS without prior exacerbation had $1859 higher in total costs (p<0.05) compared to patients with prior exacerbation during the 12 months following ICS initiation. LIMITATIONS: The retrospective design of this study limits the interpretation of findings as association and not causality. This study is subject to selection bias due to unobservable confounders. CONCLUSIONS: Among COPD patients, initiation of ICS without prior exacerbation appears to be associated with increased healthcare costs. These findings suggest that ICS initiation without evidence of exacerbation as consistent with guidelines is associated with adverse economic consequences.

Factors associated with pain medication selection among patients diagnosed with diabetic peripheral neuropathic pain: a retrospective study.

OBJECTIVE: To assess the demographic and clinical characteristics associated with initiation of duloxetine therapy compared with other pharmacologic therapies for treatment of diabetic peripheral neuropathic pain (DPNP). METHODS: This study used administrative claims databases for commercially-insured individuals aged 18-64 years to examine factors associated with treatment among DPNP patients who initiated duloxetine versus tricyclic antidepressants (TCAs), venlafaxine, gabapentin, pregabalin, or opioids between 7/1/2005 and 12/31/2007. Treatment initiation was defined as no pill coverage of the same medication over the previous 90 days. Multiple logistic regression models were estimated to assess factors associated with initiating duloxetine versus each of the other DPNP therapies. RESULTS: The study included 11,060 DPNP patients with average age of 55 years old. Cardiovascular disease (63-70%), cerebrovascular/peripheral vascular disease (26-33%), low back pain (24-39%), and osteoarthritis (17-26%) were the most common diabetes- and pain-related comorbidities. Controlling for demographic and clinical characteristics, patients who received duloxetine or pregabalin in the prior 12-month period were more likely to initiate duloxetine. Patients from other DPNP treatment cohorts, except for those in the pregabalin cohort, were more likely to re-initiate the same prior therapy than begin treatment with duloxetine (all p<0.05). A history of anxiety disorder was significantly associated with initiation of all DPNP treatments other than duloxetine (all p<0.05), except for TCAs. Patients with low back pain were more likely to initiate duloxetine than TCAs or venlafaxine, but less likely to initiate duloxetine than pregabalin or opioids. Patients with infections related to diabetes were less likely to initiate duloxetine than venlafaxine, gabapentin, or opioids. LIMITATIONS: Because a retrospective administrative claims database was used, this study is subject to selection bias due to unobservable confounders, inability to measure prescriber preferences or characteristics or disease severity. CONCLUSIONS: Among commercially-insured DPNP patients, those with prior use of duloxetine or pregabalin were more likely to initiate duloxetine than other treatments. The presence of select comorbidities was also associated with specific medication initiation.

High-strength nanograined and translucent hydroxyapatite monoliths via continuous hydrothermal synthesis and optimized spark plasma sintering.

The synthesis of high-strength, completely dense nanograined hydroxyapatite (bioceramic) monoliths is a challenge as high temperatures or long sintering times are often required. In this study, nanorods of hydroxyapatite (HA) and calcium-deficient HA (made using a novel continuous hydrothermal flow synthesis method) were consolidated using spark plasma sintering (SPS) up to full theoretical density in ∼5 min at temperatures up to 1000°C. After significant optimization of the SPS heating and loading cycles, fully dense HA discs were obtained which were translucent, suggesting very high densities. Significantly high three-point flexural strength values for such materials (up to 158 MPa) were measured. Freeze-fracturing of disks followed by scanning electron microscopy investigation revealed selected samples possessed sub-200 nm sized grains and no visible pores, suggesting they were fully dense.