Development of national stressor-specific genus sensitivity values.

Effective water quality management is based on associations between at least two pieces of information: a stressor and a response. However, assessments are hindered by the lack of pre-developed stressor-response associations. To remedy this, I developed genus stressor-specific sensitivity values (SVs) for up to 704 genera to estimate a sensitive genera ratio (SGR) metric for as many as 34 common stream stressors. The SVs were estimated from a large, paired macroinvertebrate and environmental data set for the contiguous United States. Environmental variables measuring potential stressors were selected that were generally uncorrelated and usually had several thousand station observations. I calculated relative abundance weighted averages (WA) for each genus and environmental variable meeting data requirements in a calibration data set. Each environmental variable was split into 10 intervals along each stressor gradient. Genera were assigned an SV from 1 to 10 based on the interval consistent with the WA for each environmental parameter. Using the calibration derived SVs, SGRs were calculated for the calibration and a validation subsets. SGRs are the number of genera with SV ≤ 5 divided by the total number of genera in a sample. In general, as stress increased, the SGR (range: 0-1) decreased for many environmental variables, but for five environmental variables, the decrease was not consistent. The 95 % confidence intervals of the mean of the SGRs were greater for least disturbed stations compared to all other stations for 23 of the remaining 29 environmental variables. Regional performance of SGRs was evaluated by subdividing the calibration data set into West, Central, and East subsets and recalculating SVs. SGR mean absolute errors were smallest in the East and Central regions. These stressor-specific SVs expand the available tools for assessing stream biological impairments from commonly encountered environmental stressors.

Dense granule biogenesis, secretion, and function in Toxoplasma gondii.

Toxoplasma gondii is an obligate intracellular parasite and the causative agent of Toxoplasmosis. A key to understanding and treating the disease lies with determining how the parasite can survive and replicate within cells of its host. Proteins released from specialized secretory vesicles, named the dense granules (DGs), have diverse functions that are critical for adapting the intracellular environment, and are thus key to survival and pathogenicity. In this review, we describe the current understanding and outstanding questions regarding dense granule biogenesis, trafficking, and regulation of secretion. In addition, we provide an overview of dense granule protein ("GRA") function upon secretion, with a focus on proteins that have recently been identified.

Improving the diagnosis of heart failure in patients with atrial fibrillation.

OBJECTIVE: To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval. METHODS: Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides. RESULTS: 160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels. CONCLUSIONS: Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.

Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. Objective: To compare low-dose digoxin with bisoprolol (a ß-blocker). Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Interventions: Digoxin (n = 80; dose range, 62.5-250 µg/d; mean dose, 161 µg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group. Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points. Trial Registration: ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.

Consideration of spatial and temporal scales in stream restorations and biotic monitoring to assess restoration outcomes: A literature review, Part 1.

Stream and river restoration practices have become common in many parts of the world. We ask the question whether such restorations improve freshwater biotic assemblages or functions over time, and if not, can general reasons be identified for such outcomes. We conducted a literature survey and review of studies in which different types of stream restorations were conducted and outcomes reported. These restoration types included culvert restoration; acid mine restoration or industrial pollutant restoration; urban stream restoration; dam removal, changes in dam operation, or fish passage structures; instream habitat modification; riparian restoration or woody material addition; channel restoration and multiple restorations. The streams ranged from headwater streams to large rivers, and the regions included North America, Europe, Australia and New Zealand, and a small number of sites in Asia and Africa. In this part of the review, we describe the methods used for the review and present reviews for the first three types of stream restorations. For culvert restorations, the small sample size and variable study design and biotic responses limited generalizing about temporal and spatial scale effects for that restoration type. The complex and often lengthy time to restore streams from acid mine drainage and industrial pollutants often resulted in positive biotic responses, but restored sites had reduced responses compared to reference sites. Most urban stream restorations had minimal or mixed improvements in biotic responses, with one mismatch in spatial scale evidenced by hydraulic structures used in a restoration unable to withstand peak discharge.

Consideration of spatial and temporal scales in stream restorations and biotic monitoring to assess restoration outcomes: A literature review, Part 2.

Stream and river restoration practices have become common in many parts of the world. To answer the question whether such restoration measures improve freshwater biotic assemblages or functions over time, and if not, can general reasons be identified for such outcomes, we conducted a literature survey and review of studies in which different types of stream restorations were conducted and outcomes assessed. In the first paper, we reviewed studies of culvert restorations, acid mine drainage or industrial pollution restoration; and urban stream restoration projects. Here, we review studies of restoration via dam removal, changes in dam operation or fish passage structures; instream habitat modification; riparian restoration or woody material addition; channel restoration and multiple restoration measures and develop some general conclusions from these reviews. Biomonitoring in different studies detected improvements for some restoration measures; other studies found minimal or no statistically significant increases in biotic assemblage richness, abundances or functions. In some cases, untreated stressors may have influenced the outcomes of the restoration, but in many cases, there were mismatches in the temporal or spatial scale of the restoration measure undertaken and associated monitoring. For example, either biomonitoring to measure restoration effects was conducted over a too short a time period after restoration for effects to be observed, or the sources and stressors needing remediation occurred at a larger catchment scale than the restoration. Also, many restoration measures lack observations from unimpaired reference sites for use in predicting how much of a beneficial effect might be expected.

Uptake of Sulfate from Ambient Water by Freshwater Animals.

To better understand how the sulfate (SO4 2-) anion may contribute to the adverse effects associated with elevated ionic strength or salinity in freshwaters, we measured the uptake and efflux of SO4 2- in four freshwater species: the fathead minnow (Pimephales promelas, Teleostei: Cyprinidae), paper pondshell (Utterbackia imbecillis, Bivalvia: Unionidae), red swamp crayfish (Procambarus clarkii, Crustacea: Cambaridae), and two-lined mayfly (Hexagenia bilineata, Insecta: Ephemeridae). Using δ( 34 S/ 32 S) stable isotope ratios and the concentrations of S and SO4 2-, we measured the SO4 2- influx rate (J in ), net flux (J net ), and efflux rate (Jout) during a 24 h exposure period. For all four species, the means of J in for SO4 2- were positive, and J in was significantly greater than 0 at both target SO4 2- concentrations in the fish and mollusk and at the lower SO4 2- concentration in the crayfish. The means of J out and J net were much more variable than those for J in , but several species by target SO4 2- concentration combinations for J out and J net , were negative, which suggests the net excretion of SO4 2- by the animals. The results of our experiments suggest a greater regulation of SO4 2- in freshwater animals than has been previously reported.

Quality of life benefits from arrhythmia ablation: A longitudinal study using the C-CAP questionnaire and EQ5D.

AIMS: To investigate long-term efficacy of cardiac ablation for symptomatic arrhythmia by gathering generic and arrhythmia-related quality of life data using patient-reported outcome measures before and after ablation. METHODS: Consecutive patients undergoing cardiac ablation procedures at three sites in the United Kingdom were enrolled (n = 561). Data were collected at baseline, at 8-16 weeks, and 12 months after the ablation with responses from 390 patients received at all three time points. Nonparametric tests were used to identify any changes in patient outcomes due to nonnormal data. RESULTS: There were significant improvements in symptom severity, impact on life scores, EQ-5D-5L indices, and visual analogue score (VAS) scores at pre- versus 3 months and at preablation versus 1 year. Impact on life score showed additional improvement at 1 year versus 3 months, while improvements in symptom severity, EQ-5D-5L indices, and VAS scores continued to be maintained between 3 months and 1 year. CONCLUSION: Cardiac ablation provides patients with arrhythmias relief from symptoms, and results in an improvement in quality of life. Improvements observed at 3 months are maintained at 1 year follow-up.

Questions remain regarding the long-term efficacy of cardiac ablation. We enrolled 561 consecutive patients undergoing ablation procedures at three UK sites. Data were collected at baseline, and at 3 and 12 months. Improvement in symptoms was reported following treatment, with patients continuing to maintain or show continued improvement at 1 year.

Passive noise datasets at regolith sites.

The data presented in this article contain datasets of passive noise measurements at regolith sites in Adelaide, South Australia. The data were acquired using three component (3C) LE-3Dlite Lennartz seismometers with an eigenfrequency of 1 Hz. The data were acquired at eight sites across Adelaide׳s regolith in a hexagonal array layout. Four tests, each with a duration of 30 min, were conducted at different times. The ambient noise data can be used for both horizontal to vertical spectral ratio (HVSR) analysis and array analyses, which are essential to obtain the site fundamental frequency and the ellipticity of the fundamental mode Rayleigh waves at the measured site. The array analyses are useful to obtain the dispersion curves, which are needed to estimate the shear wave velocity profile.

Using extirpation to evaluate ionic tolerance of freshwater fish.

Field data of fish occurrences and specific conductivity were used to estimate the tolerance of freshwater fish to elevated ion concentrations and to compare the differences between species- and genus-level analyses for individual effects. We derived extirpation concentrations at the 95th percentile (XC95) of a weighted cumulative frequency distribution for fish species inhabiting streams of the central and southern Appalachians by customizing methods used previously with macroinvertebrate genera. Weighting factors were calculated based on the number of sites in basins where each species occurred, reducing overweighting observations of species restricted to fewer basins. Comparing the species- and genus-level fish XC95 values, XC95s for fish genera were near the XC95s for the most salt-tolerant species in the genus. Therefore, a genus-level effect threshold is not reliably predictive of species-level extirpation, unless the genus is monospecific in the assessed assemblage. Of the 101 fish species XC95 values, 5% were <509 and 10% were <565 µS/cm. The lowest XC95 for a species was 322 µS/cm, which is >300 µS/cm, the exposure estimated to extirpate 5% of macroinvertebrate genera in the central Appalachians. Above 509 µS/cm, 41 of the 101 species are expected to decline in occurrence. Environ Toxicol Chem 2018;37:871-883. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial.

BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. DESIGN AND INTERVENTION: The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. PARTICIPANTS: Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. OUTCOME MEASURES: The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. ETHICS AND DISSEMINATION: East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results.

Toxicological perspective on the osmoregulation and ionoregulation physiology of major ions by freshwater animals: Teleost fish, crustacea, aquatic insects, and Mollusca.

Anthropogenic sources increase freshwater salinity and produce differences in constituent ions compared with natural waters. Moreover, ions differ in physiological roles and concentrations in intracellular and extracellular fluids. Four freshwater taxa groups are compared, to investigate similarities and differences in ion transport processes and what ion transport mechanisms suggest about the toxicity of these or other ions in freshwater. Although differences exist, many ion transporters are functionally similar and may belong to evolutionarily conserved protein families. For example, the Na+ /H+ -exchanger in teleost fish differs from the H+ /2Na+ (or Ca2+ )-exchanger in crustaceans. In osmoregulation, Na+ and Cl- predominate. Stenohaline freshwater animals hyperregulate until they are no longer able to maintain hypertonic extracellular Na+ and Cl- concentrations with increasing salinity and become isotonic. Toxic effects of K+ are related to ionoregulation and volume regulation. The ionic balance between intracellular and extracellular fluids is maintained by Na+ /K+ -adenosine triphosphatase (ATPase), but details are lacking on apical K+ transporters. Elevated H+ affects the maintenance of internal Na+ by Na+ /H+ exchange; elevated HCO3- inhibits Cl- uptake. The uptake of Mg2+ occurs by the gills or intestine, but details are lacking on Mg2+ transporters. In unionid gills, SO42- is actively transported, but most epithelia are generally impermeant to SO42- . Transporters of Ca2+ maintain homeostasis of dissolved Ca2+ . More integration of physiology with toxicology is needed to fully understand freshwater ion effects. Environ Toxicol Chem 2017;36:576-600. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Haemodynamic effects of cardiac resynchronization therapy using single-vein, three-pole, multipoint left ventricular pacing in patients with ischaemic cardiomyopathy and a left ventricular free wall scar: the MAESTRO study.

AIMS: The clinical response to cardiac resynchronization therapy (CRT) is variable. Multipoint left ventricular (LV) pacing could achieve more effective haemodynamic response than single-point LV pacing. Deployment of an LV lead over myocardial scar is associated with a poor haemodynamic response to and clinical outcome of CRT. We sought to determine whether the acute haemodynamic response to CRT using three-pole LV multipoint pacing (CRT3P-MPP) is superior to that to conventional CRT using single-site LV pacing (CRTSP) in patients with ischaemic cardiomyopathy and an LV free wall scar. METHODS AND RESULTS: Sixteen patients with ischaemic cardiomyopathy [aged 72.6 ± 7.7 years (mean ± SD), 81.3% male, QRS: 146.0 ± 14.2 ms, LBBB in 14 (87.5%)] in whom the LV lead was intentionally deployed straddling an LV free wall scar (assessed using cardiac magnetic resonance), underwent assessment of LV + dP/dtmax during CRT3P-MPP and CRTSP. Interindividually, the ΔLV + dP/dtmax in relation to AAI pacing with CRT3P-MPP (6.2 ± 13.3%) was higher than with basal and mid CRTSP (both P < 0.001), but similar to apical CRTSP. Intraindividually, significant differences in the ΔLV + dP/dtmax to optimal and worst pacing configurations were observed in 10 (62.5%) patients. Of the 8 patients who responded to at least one configuration, CRT3P-MPP was optimal in 5 (62.5%) and apical CRTSP was optimal in 3 (37.5%) (P = 0.0047). CONCLUSIONS: In terms of acute haemodynamic response, CRT3P-MPP was comparable an apical CRTSP and superior to basal and distal CRTSP. In the absence of within-device haemodynamic optimization, CRT3P-MPP may offer a haemodynamic advantage over a fixed CRTSP configuration.

Cardiff cardiac ablation patient-reported outcome measure (C-CAP): validation of a new questionnaire set for patients undergoing catheter ablation for cardiac arrhythmias in the UK.

PURPOSE: To formally test and validate a patient-reported outcome measure (PROM) for patients with cardiac arrhythmias undergoing catheter ablation procedures in the UK [Cardiff Cardiac Ablation PROM (C-CAP)]. METHODS: A multicentre, prospective, observational cohort study with consecutive patient enrolment from three UK sites was conducted. Patients were sent C-CAP questionnaires before and after an ablation procedure. Pre-ablation C-CAP1 (17 items) comprised four domains: patient expectations; condition and symptoms; restricted activity and healthcare visits; medication and general health. Post-ablation C-CAP2 (19 items) comprised five domains including change in symptoms and procedural complications. Both questionnaires also included the generic EQ-5D-5L tool (EuroQol). Reliability, validity, and responsiveness measures were calculated. RESULTS: A total of 517 valid pre-ablation and 434 post-ablation responses were received; questionnaires showed good feasibility and item acceptability. Internal consistency was good (Cronbach's alpha >0.7) and test-retest reliability was acceptable for all scales. C-CAP scales showed high responsiveness (effect size >0.8). Patients improved significantly (p < 0.001) following ablation across all disease-specific and global scales. Minimal clinically important difference was calculated. Improvement beyond the smallest detectable change of 9 points (symptom severity scale), 3 points (frequency and duration of symptoms scale), and 8 points (impact on life scale) indicates an important change. Amendments to the C-CAP questionnaires were identified through the validation process and made to produce the final tools. CONCLUSIONS: The final C-CAP questionnaires are valid, reliable, and responsive tools for measuring symptom change, impact, and expectations in patients undergoing ablation for cardiac arrhythmias. C-CAP questionnaires provide a tool with disease-specific and generic domains to explore how cardiac ablation procedures in the UK impact upon patients' lives.

Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data.

OBJECTIVE: To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods. DATA SOURCES AND STUDY SELECTION: Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design ( PROSPERO: CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment). DATA EXTRACTION AND SYNTHESIS: Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias. MAIN OUTCOME MEASURES: Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling. RESULTS: 52 studies were systematically reviewed, comprising 621,845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4,006,210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P<0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P<0.001; n=29,525). CONCLUSIONS: Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data.

Living on a knife edge-the daily struggle of coping with symptomatic cardiac arrhythmias.

BACKGROUND: In 2010 a retrospective audit was undertaken to assess the viability of using PROMs in patients with symptomatic cardiac arrhythmias having undergone percutaneous arrhythmia ablation. A response rate of 74 % was achieved, with finding suggesting that arrhythmia patients reported a significant impact on their work, social and family life. AIMS: To conduct a qualitative cross sectional survey to understand patients' perspectives of how cardiac arrhythmias affect their daily lives, as part of a program to develop a Patient Reported Outcome Measure (PROM). METHOD: Twenty five patients aged 18 or over, diagnosed with a variety of symptomatic cardiac arrhythmias referred for a cardiac ablation procedure took part in cognitive interviews. These aimed to inform the development of a patient reported outcome measure and to determine factors important to this patient group. Common themes were identified using content analysis. RESULTS: Participants reported that symptoms of their arrhythmia caused them considerable problems and impacted adversely on their quality of life in many ways. This extended through daily routine, work and social activities and also to friends and family, with fear and anxiety being significant factors for most responders. Patients felt their illness was poorly understood, even by health professionals, and often reported that they felt isolated, lacking support and information. CONCLUSION: Symptomatic cardiac arrhythmias are a source of debilitating and life limiting symptoms, having a negative impact on quality of life. Symptoms and related complications are relevant across different arrhythmia substrates and patient groups. TRIAL REGISTRATION: The study is registered on the Clinical Trials website, Identifier NCT01672528.

Establishing content validity in a novel patient reported outcome measure for cardiac arrhythmia ablation patients.

AIM: Preliminary content validity testing of a UK Patient Reported Outcome Measure (PROM) for use in cardiac arrhythmia patients undergoing ablation treatment. METHODS: Twenty five patients diagnosed with symptomatic cardiac arrhythmias participated in qualitative interviews to obtain their perspective of a draft PROM. As part of the process to establish preliminary content validity, patients were asked to complete the questionnaires and to identify missing and redundant items within the PROM, while also reviewing the instructions and formatting. The questionnaires were updated iteratively to reflect patient feedback. RESULTS: Recurring themes were identified during qualitative interviews leading to improvements to the tool. Following modification of the PROM, based on patient feedback, subjects reported that the tool was fully inclusive and easy to comprehend. Patients found the instructions and layout of the tool acceptable and easy to use. CONCLUSION: Qualitative patient interviews are an important part of PROM tool development. In the case of this cardiac ablation PROM, it enabled end users to assess the tool for inclusivity and accessibility, and to ensure that it addressed concerns important to the patient. Cognitive interviews were able to obtain patients' perspectives to establish face validity and content validity of the PROM. This is part of a process which will ensure that this disease-specific PROM measures cardiac arrhythmia patient symptoms and impact on patients' lives accurately and sensitively. The next study will use the PROM prospectively in over 450 arrhythmia patients to prospectively validate the tool. CONDENSED ABSTRACT: Patients diagnosed with symptomatic cardiac arrhythmias provided feedback through cognitive interviews to facilitate improvements in a new disease specific PROM establishing preliminary face and content validity.

Proof of concept for the use of macroinvertebrates as indicators of polychlorinated biphenyls (PCB) contamination in Lake Hartwell.

The US Environmental Protection Agency (USEPA) develops methods and tools for evaluating risk management strategies for sediments contaminated with polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and other legacy pollutants. Monitored natural recovery is a risk management alternative that relies on existing physical, chemical, and biological processes to contain, destroy, and/or reduce the bioavailability or toxicity of in-place contaminants. These naturally occurring processes are monitored to ensure that management and recovery are progressing as expected. One approach frequently used to evaluate the recovery of contaminated sediments and associated biota is the assessment of contaminant tissue levels, or body burden concentrations, in top trophic level fish. In the present study, aquatic invertebrates were examined as an indicator of recent exposure to PCBs. The approach aimed to determine whether invertebrates collected using artificial substrates (i.e., Hester-Dendy samplers) could be used to discriminate among contaminated sites through the analyses of PCBs in whole homogenates of macroinvertebrates. Macroinvertebrates were sorted, preserved, and analyzed for total PCBs (t-PCBs), by summing 107 PCB congeners. Macroinvertebrate body burden concentrations showed similar trends to sediment t-PCB concentrations at the sites sampled. The results indicate that macroinvertebrates can be used to assess sediment contamination among sites that have different PCB contamination levels.

Patient reported outcome measures for cardiac ablation procedures: a multicentre pilot to develop a new questionnaire.

AIM: To assess the feasibility of administering Patient Reported Outcomes Measures (PROMs) in patients treated with ablation for cardiac arrhythmias, and to conduct the first stage of development and testing of a new PROM tool. METHODS AND RESULTS: A new tool was developed by a multidisciplinary team and tested alongside an adaptation of the patient perception of arrhythmia questionnaire (PPAQ) and EQ-5D-5L in a multicentre retrospective audit involving 791 consecutive cardiac arrhythmia patients treated with catheter ablation at three UK centres over 13 months. Data were recorded in the National Cardiac Rhythm Management Database, part of the National Institute for Cardiovascular Outcomes Research. The response rate was 71.9% (n = 569). Patients reported significant improvements across all outcomes and impacts, with reductions in symptoms of 51.7% (heart racing), 33.9% (fatigue) 31.8% (heart flutters), 43.5% (dizziness), 38.6% (breathlessness), 44.2% (chest pressure), 33.1% (trouble concentrating), 15.9% (headache), 28.3% (neck pressure), and 23.4% (fainting) (P < 0.001). The mean number of social days affected reduced by 7.49 days/month (P < 0.001); mean work/school days affected/month reduced by 6.26 (P < 0.001); mean GP/hospital visits reduced by 1.36 days/month (P < 0.001). The procedure met patient expectations in 72% of responders. CONCLUSIONS: The high response rate suggests that the use of PROMs in this patient group is feasible, with rates equalling those of the National PROMs Programme. The results showed that patients experienced significant improvements in their quality of life following ablation, while feedback allowed the tools to be improved. Further work is required to validate these tools; however, the findings suggest that PROMs could be useful in the audit of ablation techniques.