Search

Objective: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort., Methods: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality., Results: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 - 1.5)., Conclusion: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Intravenous infusion therapy is a common and challenging invasive treatment procedure in hospital wards. Administration mistakes can have serious, even life-threatening, consequences. The Monidor solution was developed to help nurses administer gravity-based infusions and monitor them remotely, to avoid complications and reduce workload. Its real-world effects and economic consequences were unknown., Methods: An exploratory survey was carried out to estimate the potential impact of the Monidor solution on events and nurse time use. At the end of their shift, nurses estimated effects in terms of routine room visits avoided, prevention of complications, and impact on nurse time requirements. Linear regression was applied to estimate predictors of time freed. A health economic model was developed to evaluate economic consequences and to calculate the net return on investment for a hypothetical hospital ward. A 1-month time horizon was used, and discounting was not applied., Results: A total of 216 responses were obtained from 6 Finnish hospitals, from a total of 15 wards, and 56.3% of nurses found that the Monidor solution freed nurse time, while < 3.5% experienced additional time requirements. Per nurse shift, the Monidor solution avoided on average 2.064 routine room visits, helped detect end of infusion 1.340 times, and led to 5.045 min of time freed. One routine visit avoided was associated with 2.453 min of time freed in the linear regression. In the conservative setting, the freed monthly capacity in the hypothetical ward amounted to €1270.90 per month (year 2021), yielding a return on investment of 2.63. Uncertainty of linear regression coefficient values was identified as a driver of uncertainty in sensitivity analysis, with return on investment ranging from 1.55 to 3.71., Conclusions: The study demonstrated that management and remote monitoring with the Monidor solution frees nurse time and reduces routine activities associated with gravity-based intravenous infusions. These findings could be confirmed in a comparative empirical study., (© 2022. The Author(s).)

Objective: Abdominal aortic graft and endograft infection (AGI) is primarily treated by resection of the infected graft and restoration of distal perfusion through extra-anatomic bypass (EAB) or in situ reconstruction/repair (ISR). The aim of this study was to compare these surgical strategies in a nationwide multicentre retrospective cohort study., Methods: The Swedish Vascular Registry (Swedvasc) was used to identify surgically treated abdominal AGIs in Sweden between January 1995 and May 2017. The primary aim was to compare short and long term survival, as well as complications for EAB and ISR., Results: Some 126 radically surgically treated AGI patients were identified - 102 graft infections and 24 endograft infections - treated by EAB: 71 and ISR: 55 (23 neo-aorto-iliac systems, NAISs). No differences in early 30 day (EAB 81.7% vs. ISR 76.4%, p = .46), or long term five year survival (48.2% vs. 49.9%, p = .87) were identified. There was no survival difference comparing NAIS to other ISR strategies. The frequency of recurrent graft infection during follow up was similar: EAB 20.3% vs. ISR 17.0% (p = .56). Survival and re-infection rates of the new conduit did not differ between NAIS and other ISR strategies. Age ≥ 75 years (odds ratio [OR] 4.0, confidence interval [CI] 1.1 - 14.8), coronary artery disease (OR 4.2, CI 1.2 - 15.1) and post-operative circulatory complications (OR 5.2, CI 1.2 - 22.5) were associated with early death. Prolonged antimicrobial therapy (> 3 months) was associated with reduced long term mortality (HR 0.3, CI 0.1 - 0.9)., Conclusion: In this nationwide multicentre study comparing outcomes of radically treated AGI, no differences in survival or re-infection rate could be identified comparing EAB and ISR., Competing Interests: Conflict of interest and Funding None., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The impoundment of the Three Gorges Dam on the Yangtze River begins in 2003 and a full pool level is first attained in 2010. This process leads to reciprocal adjustments in flow discharge, sediment transport and morphology downstream of the dam. Based on 26-year recorded hydrologic data 1990-2015 and surveyed bathymetries 1998, 2010 and 2015, this study elucidates, before and after the commissioning of the dam, the alterations along the 500-km reach of the river. Two-dimensional numerical simulations are performed to predict future morphological changes by 2025. The analyses demonstrate that the impoundment modulates the seasonal flow discharges and traps an appreciable amount of sediment, resulting in enhanced erosion potential and coarsening of sediment. On a multi-year basis, the maximum discharge varies by a factor of 1.3 and the corresponding suspended load concentration and transport rate differ by a factor of 3.0 and 3.8, respectively. Combinations of surveyed and simulated bathymetries reveal its morphological responses to the changes. A general pattern of erosion is observed along the reach. In its upper 120 km, the process slows down towards 2025. In the middle 200 km, the erosion shifts, following the gradual impounding, to slight deposition, which then shifts back to erosion around September 2018. In the final 180 km, erosion continues without any sign of de-escalation, which is presumedly ascribed to tidal actions. The reach has not yet achieved a hydro-morphological equilibrium; the riverbed down-cutting is supposed to continue for a while. The combination of the field and numerical investigations provides, with the elapse of time, insight into the morpho-dynamics in the 500 km river reach.

Importance: It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk., Objective: To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk., Design, Setting, and Participants: A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa., Interventions: Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins., Main Outcomes and Measures: The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization., Results: When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil-treated patients (14.7%)., Conclusions and Relevance: Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02104817.

Background: This study is the first to evaluate the short-term efficacy and long-term safety of AZD0585, a mixture of omega-3 free fatty acids, in Japanese patients with dyslipidemia., Methods and results: In this randomized double-blind placebo-controlled Phase III study, 383 patients were randomized to 2 g AZD0585, 4 g AZD0585, or placebo once daily for 52 weeks. Eligible patients had low-density lipoprotein cholesterol (LDL-C) levels controlled regardless of statin use, and triglyceride levels between 150 and 499 mg/dL. The least-squares (LS) mean percentage changes in triglyceride concentrations from baseline to the 12-week endpoint (mean of measurements at Weeks 10 and 12) in the 2 and 4 g AZD0585 and placebo groups were -15.57%, -21.75%, and 11.15% respectively (P<0.0001 for both AZD0585 doses vs. placebo). No clinically significant changes from baseline to the 12-week endpoint in total cholesterol, LDL-C, and LDL-C/apolipoprotein (Apo) B were found with AZD0585. High-density lipoprotein cholesterol (HDL-C) was slightly increased and very low-density lipoprotein cholesterol, non-HDL-C, ApoC-II, and ApoC-III were decreased with AZD0585 compared with placebo at the 12-week endpoint. Lipid profiles up to Week 52 were consistent with those up to the 12-week endpoint. No clinically important safety concerns were raised., Conclusions: AZD0585 significantly decreased serum triglyceride levels compared with placebo at the 12-week endpoint and was generally safe and well tolerated in Japanese patients with dyslipidemia.

Background: The role of saliva composition and dietary sugar in development of infundibular caries in equine cheek teeth is not fully understood. This study analysed electrolyte and urea concentrations in saliva in relation to different forage and measured pH changes after sucrose application in vivo in sound and carious cheek teeth., Results: Forage type had no effect on the equine saliva electrolyte concentrations, which varied considerably both intra- and inter-individually. Chewing resulted in increased values for all electrolytes except bicarbonate. Compared with stimulated human saliva, horse saliva after mastication, contained higher amounts of potassium, calcium and bicarbonate, and less phosphate. The in vivo pH measurements showed a lower resting pH and a more pronounced pH drop after sucrose application in carious teeth compared to sound teeth., Conclusions: No large differences were found between the composition of equine saliva and human saliva. A more pronounced acidogenicity was found for the carious than sound teeth. Thus, the caries process in equine cheek teeth seems to follow the same pattern as in human teeth, caused by acid production by oral microorganisms after sugar consumption.

Introduction: Cost assessment modelling (CAM) of treatments in highly active relapsing multiple sclerosis was conducted., Methods: The CAM was developed using the R programming language. The PICOSTEPS health technology assessment framework was applied in the CAM. Modelled patients were 280 adults with highly active relapsing multiple sclerosis eligible for disease-modifying treatment. Intervention was cladribine tablets, a new and reimbursed oral treatment for highly active relapsing multiple sclerosis in Finland. Comparators included fingolimod, the most used oral reimbursed treatment for the highly active disease, and natalizumab, the most used intravenous treatment, and a treatment mix (80% use fingolimod, 20% use natalizumab) in Finland. Outcomes presented expected annual and cumulative drug-associated costs in the overall population and per patient. Setting was modelled public specialist care in Finland. Time was set to 4 years, without discounting. Effects covered expected drug-associated costs (screening, acquisition, administration, monitoring, adverse events, travelling, productivity). Perspective was a limited societal perspective. Sensitivity analyses regarding all PICOSTEPS components were conducted., Results: Cladribine tablets were projected to be cost saving in comparison to fingolimod, natalizumab and treatment mix. The respective modelled savings were €4,598,742, €16,249,701 and €6,928,934 in the overall population, and €16,424, €58,035 and €24,746 per patient, respectively, during the 4 years. The most important cost driver was drug costs, representing 96.3%, 96.0% and 83.4% of modelled costs associated with cladribine tablets, fingolimod and natalizumab, respectively. Cladribine tablets sustained their affordability in the sensitivity analyses. From the perspective of health care payer, cladribine tablets' savings were projected to be €4,514,509, €15,145,366 and €6,640,680 in the overall population, and €16,123, €54,091 and €23,717 per patient in comparison to fingolimod, natalizumab and treatment mix, respectively., Conclusion: Based on the CAM, cladribine tablets were projected to robustly save modelled drug-associated costs in comparison to fingolimod, natalizumab and their mix in Finland.

It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels., (© 2018 Wiley Periodicals, Inc.)

OM3-CA (omega-3-carboxylic acids) is a complex mixture of omega-3 carboxylic acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which is approved in the United States for the treatment of hypertriglyceridemia. As part of its clinical development in Japan, we performed a phase 1 study to investigate the safety, tolerability, and pharmacokinetics after single and multiple doses of OM3-CA in healthy male Japanese subjects. Eighteen Japanese subjects were allocated to receive 2 or 4 g/day OM3-CA, or placebo (n = 6 per group). In addition, 6 white subjects received 4 g/day OM3-CA. The primary objective was to determine the safety and tolerability of OM3-CA. Plasma concentrations of EPA and DHA were adjusted for baseline values for pharmacokinetic analysis. Overall, OM3-CA was well tolerated in healthy Japanese subjects. Two Japanese subjects in each group and 5 white subjects experienced adverse events (AEs). Alanine aminotransferase increase was the most common AE in Japanese subjects, also seen with placebo, and diarrhea was the most common AE in white subjects. The maximum plasma concentrations of EPA and DHA were observed 5-6 hours postdose. The pharmacokinetic profiles of EPA and DHA after administration of OM3-CA were comparable between Japanese and white subjects., (© 2017, The American College of Clinical Pharmacology.)

This study assesses the efficacy and exposure-response relationship of omega-3-carboxylic acids (OM-3 CA) in models of crystal-based inflammation. Human THP-1 macrophages and primary peripheral blood mononuclear cells exposed to multiple inflammatory crystal types were used to determine the anti-inflammatory potential of omega-3 (OM-3) fatty acids in vitro. Anti-inflammatory effects of OM-3 CA in vivo were tested in rat monosodium urate (MSU) crystal air pouch and rat knee intra-articular MSU injection models. Acute treatment with the OM-3 fatty acid docosahexaenoic acid suppressed MSU-, cholesterol crystal-, and calcium pyrophosphate crystal-mediated interleukin-1β (IL-1β) production in vitro. In vivo, OM-3 CA dose-dependently reduced crystal-mediated cell migration, exudate volume, and levels of IL-1β and prostaglandin E 2 . Following intra-articular injection of MSU, treatment with OM-3-CA (1 mL/kg) and indomethacin (1 mg/kg) resulted in similar mean reductions in pain (23% and 41%, respectively) and swelling (58% and 50%, respectively), compared with controls. Additionally, in complex formulations of OM-3 fatty acids, high levels of palmitic acid could reduce the in vivo effect on crystal-mediated IL-1β elevation. OM-3 CA has a broadly efficacious anti-inflammatory effect with a strong exposure-response relationship that could be beneficial in prevention and treatment of crystal arthritis, with potential applications in other IL-1β-mediated diseases.

Aims: Omega-3-carboxylic acids (OM3-CA) contain omega-3 free fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as carboxylic acids. Food intake is known to affect the bioavailability of ethyl ester fatty acid formulations. We conducted a phase I study to investigate the effects of the timing of OM3-CA administration relative to food intake on the pharmacokinetics of EPA and DHA., Methods: In this randomized, open-label, three-period crossover study, Japanese healthy male subjects were administered 4×1 g OM3-CA capsules with continued fasting, before a meal, or after a meal. All subjects fasted for ≥10 h prior to drug/meal administration. The primary objective was to examine the effect of meal timing on the pharmacokinetics of EPA and DHA after OM3-CA administration. The secondary objectives were to examine the safety and tolerability of OM3-CA., Results: A total of 42 Japanese subjects was enrolled in the study. The baseline-adjusted maximum concentration and area under the concentration-time curve from 0 to 72 h for EPA, DHA, and EPA +DHA were lower in the fasting and before meal conditions than in the after meal condition. The maximum total EPA, total DHA, and total EPA+DHA concentrations were reached later when administered in fasting conditions than in fed conditions, indicating slower absorption in fasting conditions. Diarrhea was reported by five, six, and no subjects in the fasting, before meal, and after meal conditions, respectively., Conclusions: The timing of OM3-CA administration relative to food intake influences the systemic bioavailability of EPA and DHA in healthy Japanese male subjects., Trial Registration: NCT02372344.

This study aimed to increase the knowledge on salivary antibodies in the horse since these constitute an important part of the immune defence of the oral cavity. For that purpose assays to detect horse immunoglobulin A (IgA) including secretory IgA (SIgA) were set up and the molecular weights of different components of the horse IgA system were estimated. Moreover, samples from 51 clinically healthy horses were tested for total SIgA and IgG amounts in saliva and relative IgG3/5 (IgG(T)) and IgG4/7 (IgGb) content were tested in serum and saliva. Results showed a mean concentration of 74μg SIgA/ml horse saliva and that there was a large inter-individual variation in salivary SIgA concentration. For total IgG the mean concentration was approx. 5 times lower than that of SIgA, i.e. 20μg IgG/ml saliva and the inter-individual variation was lower than that observed for SIgA. The saliva-serum ratio for IgG isotypes IgG3/5 and IgG4/7 was also assessed in the sampled horses and this analysis showed that the saliva-serum ratio of IgG4/7 was in general approximately 4 times higher than that of IgG3/5. The large inter-individual variation in salivary SIgA levels observed for the normal healthy horses in the present study emphasises the need for a large number of observations when studying this parameter especially in a clinical setting. Moreover, our results also indicated that some of the salivary IgG does not originate from serum but may be produced locally. Thus, these results provide novel insight, and a base for further research, into salivary antibody responses of horses., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: Data from two clinical studies (hyperCholesterolaemia in cHildren and Adolescents taking Rosuvastatin OpeN label [CHARON; NCT01078675] and Study 4522IL/0086) were used to describe rosuvastatin pharmacokinetics in patients with heterozygous familial hypercholesterolemia aged ≥6 to <18 years., Methods: Rosuvastatin concentration-time data were analyzed via non-linear mixed-effects modeling (NONMEM), with clearance (CL/F) as the pre-defined key pharmacokinetic parameter of interest. In addition, descriptive comparisons between pediatric patients and adults (healthy and dyslipidemic) were performed. The dataset included 214 pediatric patients, with 2,029 rosuvastatin concentrations., Results: A linear two-compartment model with first-order absorption and elimination processes adequately described the combined dataset. Weight and gender were significant covariates for CL/F, with moderate between-patient variability remaining (coefficient of variation (CV) 40 %): CL/F in female children was approximately 30 % lower than in male children, and there was a twofold mean difference in CL/F across the observed weight range. Age was not a significant covariate after accounting for weight and gender differences. However, weight and gender only reduced between-patient variability from 45 (without covariates) to 40 % and are considered unlikely to be clinically relevant., Conclusions: Rosuvastatin pharmacokinetics appeared generally predictable with respect to dose, and time (study duration) and the exposure (dose-normalized area under the plasma concentration-time curve at steady state (AUCss)) in children and adolescents appeared to be similar or lower than adult patients with dyslipidemia.

Objective: To compare the effects of bisoprolol and metoprolol CR/ZOK (metoprolol succinate controlled release) on systolic blood pressure (bpsys) over a 24-h period in an in silico model., Methods: On the basis of the observed data from ambulatory blood pressure measurements (ABPM), a model with an appropriate distribution and correlation structure was derived for simulation of 24-h bpsys patterns during treatment with commonly studied doses, assumed to be equipotent, of bisoprolol and metoprolol CR/ZOK. Input into the simulations was aligned with the available data on the diurnal efficacy and pharmacology profiles of these substances. The validity of the model was tested in a bootstrap model., Results: The simulation model reproduced the observed data with high congruence (p = 1.0). The mean 24-h bpsys values did not significantly differ between the two simulated groups (estimated overall change in bpsys [∆bpsys] for metoprolol versus bisoprolol = 2.7 mmHg [95% confidence interval -0.3 to 5.7 mmHg]; p = 0.08). There were clear diurnal differences, with bisoprolol being more effective earlier and metoprolol CR/ZOK being more effective later in the 24-h day. A validity test with 100 repeated samples gave an overall mean group difference of 1.4 ± 3.59 mmHg (p = 0.63 relative to simulation)., Conclusion: In a robust model for the simulation of 24-h ABPM, comparisons between bisoprolol and metoprolol CR/ZOK indicate a comparable overall blood pressure-lowering effect but different diurnal patterns, consistent with the pharmacokinetics of the two drugs. This difference may be of clinical relevance, given the recognized diurnal pattern of cardiovascular events.

Background: Oral lesions related to the use of the bit and bridle are reported to be common findings in horses worldwide and represent an important animal welfare issue. In order to provide an overview of bit-related lesions in Icelandic competition horses, a field examination of the rostral part of the oral cavity was performed in 424 competition horses coming to the two major national horse events in Iceland in 2012. Records from repeated examination of 77 horses prior to the finals were used to assess potential risk factors., Results: Mild lesions were recorded in 152 horses (36%) prior to the preliminary rounds. They were most often located in the commissures of the lips and the adjacent buccal mucosa (n=111). Severe lesions were found in 32 (8%) horses. For 77 horses examined prior to the finals, the frequency of findings in the area of the mandibular interdental space (bars of the mandible) had increased from 8% to 31% (P<0.0001). These findings were most often (16/24) regarded as severe. The presence of lesions on the bars was strongly associated to the use of curb bits with a port (OR=75, P=0.009)., Conclusions: Bit-related lesions were found to be a general problem in Icelandic competition horses. The type of bits used influenced both the location and the severity of the lesions. The use of curb bits with a port was found to be a decisive risk factor for lesions on the bars of the mandible, most of which were regarded as severe. The results also raised questions about the head and neck carriage demanded for the competition horses.

Phosphorus filter units containing mineral-based sorbents with a high phosphate (PO4) binding capacity have been shown to be appropriate for removing PO4 in the treatment of domestic wastewater in on-site facilities. However, a better understanding of their PO4 removal mechanisms, and reactions that could lead to the formation of PO4 compounds, is required to evaluate the potential utility of candidate sorbents. Models based on data obtained from laboratory-scale experiments with columns of selected materials can be valuable for acquiring such understanding. Thus, in this study the transport and removal of PO4 in experiments with a laboratory-scale column filled with a commercial silicate-based sorbent were modeled, using the hydro-geochemical transport code PHREEQC. The resulting models, that incorporated the dissolution of calcite, kinetic constrains for the dissolution of calcium oxide (CaO) and wollastonite (CaSiO3), and the precipitation of amorphous tricalcium phosphate, Ca3(PO4)2, successfully simulated the removal of PO4 observed in the experiments., (© 2013. Published by Elsevier B.V. All rights reserved.)

Sorption by active filter media can be a convenient option for phosphorus (P) removal and recovery from wastewater for on-site treatment systems. There is a need for a robust laboratory method for the investigation of filter materials to enable a reliable estimation of their longevity. The objectives of this study were to (1) investigate and (2) quantify the effect of hydraulic loading rate and influent source (secondary wastewater and synthetic phosphate solution) on P binding capacity determined in laboratory column tests and (3) to study how much time is needed for the P to react with the filter material (reaction time). To study the effects of these factors, a 2(2) factorial experiment with 11 filter columns was performed. The reaction time was studied in a batch experiment. Both factors significantly (α = 0.05) affected the P binding capacity negatively, but the interaction of the two factors was not significant. Increasing the loading rate from 100 to 1200 L m(-2) d(-1) decreased P binding capacity from 1.152 to 0.070 g kg(-1) for wastewater filters and from 1.382 to 0.300 g kg(-1) for phosphate solution filters. At a loading rate of 100 L m(-2) d(-1), the average P binding capacity of wastewater filters was 1.152 g kg(-1) as opposed to 1.382 g kg(-1) for phosphate solution filters. Therefore, influent source or hydraulic loading rate should be carefully controlled in the laboratory. When phosphate solution and wastewater were used, the reaction times for the filters to remove P were determined to be 5 and 15 minutes, respectively, suggesting that a short residence time is required. However, breakthrough in this study occurred unexpectedly quickly, implying that more time is needed for the P that has reacted to be physically retained in the filter.

Benzothiazole amides were identified as TRPV1 antagonists from high throughput screening using recombinant human TRPV1 receptor and structure-activity relationships were explored to pinpoint key pharmacophore interactions. By increasing aqueous solubility, through the attachment of polar groups to the benzothiazole core, and enhancing metabolic stability, by blocking metabolic sites, the drug-like properties and pharmokinetic profiles of benzothiazole compounds were sufficiently optimized such that their therapeutic potential could be verified in rat pharmacological models of pain., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Recent guidelines from the Swedish Environmental Protection Agency recommend stricter regulations for phosphorus (P) reduction in small-scale wastewater treatment, which raises the need for additional and novel treatment steps in small-scale facilities. Following a biological pretreatment, filter systems can be a convenient option. In this study, the P binding capacity of the filter material Filtra P was investigated in batch tests. The batch test method was evaluated with respect to the effects of liquid-to-solid ratio and particle size on P binding capacity. For initial concentrations (c(i)) between 3 and 100 mg L(-1), the P in the solution was completely and rapidly bound to the material, indicating that Filtra P was an efficient substrate for this process. The maximum amount of bound P was 4.3 +/- 0.64 g kg(-1) at c(i) = 300 mg L(-1). The P binding capacity and turbidity measured in the supernatant correlated positively. Turbidity was probably caused by calcium-P precipitates, suggesting precipitation was the major removal mechanism. Neither the liquid-to-solid ratio nor the particle size affected P binding capacity significantly (alpha = 0.05) at c(i) = 1000 mg L(-1), confirming that the conditions used in the batch tests were appropriate. In full-scale applications, the precipitate formed may be at risk of being washed out of the filter, leading to low total P reduction and recovery.

We present Raman spectra of numerous icosahedral boron-rich solids having the structure of α-rhombohedral, β-rhombohedral, α-tetragonal, β-tetragonal, YB 66 , orthorhombic or amorphous boron. The spectra were newly measured and, in some cases, compared with reported data and discussed. We emphasize the importance of a high signal-to-noise ratio in the Raman spectra for detecting weak effects evoked by the modification of compounds, accommodation of interstitial atoms and other structural defects. Vibrations of the icosahedra, occurring in all the spectra, are interpreted using the description of modes in α-rhombohedral boron by Beckel et al . The Raman spectrum of boron carbide is largely clarified. Relative intra- and inter-icosahedral bonding forces are estimated for the different structural groups and for vanadium-doped β-rhombohedral boron. The validity of Badger's rule is demonstrated for the force constants of inter-icosahedral B-B bonds, whereas the agreement is less satisfactory for the intra-icosahedral B-B bonds.

Recent characterization of the mammalian transcriptome has confirmed its predicted complexity, with many loci encoding multiple splice variants and pseudogenes. The breast cancer susceptibility gene BRCA1 is a tumour suppressor gene that produces multiple functional transcripts. For example, BRCA1-IRIS is a splice variant of BRCA1, which encodes a protein that is functionally distinct from BRCA1. Here we describe the identification of ten novel Brca1 splice variants including Brca1-Iris, the mouse orthologue of human BRCA1-IRIS. We show that Brca1-Iris is differentially expressed during mammary epithelial differentiation and regulates survival of mammary epithelial cells. Another transcript, Brca1-Delta22, expressed in both mouse and human cells, was found to be defective in transcriptional activation capacity. Finally, we show that the human BRCA1 pseudogene produces a spliced pseudoBRCA1 transcript. The identification of these transcripts has implications for the understanding of the role of BRCA1 in biology and disease and for the interpretation of mouse knockout models.

A new method for investigating the detailed reaction and the energy absorption of trees during a rock impact was developed and applied to 15 subalpine Norway spruce (Picea abies L. Karst) trees. A wedge-shaped trolley, guided by prestressed steel wires, was mounted on a forested slope to simulate a falling rock. The trolley accelerates down the wires and hits a tree at a preselected stem height with variable energies. The tree displacements and accelerations during the impact were recorded to determine reactions and energy absorption for the stem, root-soil system, crown and the entire tree. Trees absorbed the kinetic energy of the trolley rapidly by mobilizing strain and inertia forces close to the impact location in the stem and the root-soil system. This energy was then gradually dissipated all over the tree through permanent deformations and damping. The stem assimilated more energy than the root-soil system. The tree's energy absorption capacity was limited by stem-bending stresses at impact height, by shear stresses at the stem base and by lack of resistance of the root-soil anchorage. It was positively and exponentially related to stem diameter at breast height and negatively related to impact height. The field experiment enabled a physical description of how a tree reacts to a rock impact and highlighted the most important and critical components of the tree for its energy absorption. Such descriptions should help make computer simulations of rock-forest interrelations more precise and thus improve management strategies to ensure that forests can provide protection against rockfall.

Oral soft tissue ulcers are common disorders of horses, but it is unclear if their prevalence is increased by riding horses with a bit and bridle. Oral examinations were performed on 113 horses and ponies, all which had received routine dental floating, that were divided into four groups depending on when they had last been ridden with a bit and bridle. The subjects comprised: group 1, a randomly selected population of ridden horses; group 2, a group of horses examined after being rested at pasture for 5 weeks; group 3, the previous group following 7 weeks of riding with a bit and bridle, and group 4, brood mares that had not been ridden for at least 11 months. Lip and intraoral soft tissue lesions were recorded at seven pre-determined locations, with lesions classified as large or small; acute or chronic. The examinations showed that horses that were currently being ridden with a bit and bridle had a significantly higher prevalence of large and acute buccal ulcers opposite the maxillary Triadan 06 teeth and of the commissures of the lips, as compared to horses that were not being currently ridden. It was concluded that using a bit and bridle can cause oral ulceration even in horses that have regular prophylactic dental floating. It is suggested that riding tack should be individually fitted for each horse and also that prophylactic dental treatments should be individually adapted for each horse.

The bending and growth characteristics of large fresh stems from four silver fir (Abies alba Mill.) and three Norway spruce (Picea abies (L.) Karst.) trees were studied. Twenty logs taken from different stem heights were subjected to four-point bending tests. From the bending test records, we calculated stress-strain curves, which accounted for detailed log taper, shear deformation and self weight. From these curves we determined, among other parameters, the modulus of elasticity (MOE), the modulus of rupture (MOR) and the work absorbed in bending (W). No significant differences were found between species for the wood properties examined. Values of MOE, MOR and W generally decreased with stem height, with MOR in the range of 43 to 59 MPa and MOE ranging from 10.6 to 15.6 GPa. These MOE values are twice or more those reported for stems of young Sitka spruce (Picea sitchensis (Bong.) Carr.) trees. Based on the radial growth properties measured in discs from the logs, we calculated predicted values of MOE and MOR for the stem cross section. The predictions of MOE were precise, whereas those of MOR were approximate because of a complex combination of different failure mechanisms. Methods to test and calculate MOE, MOR and W for the stems of living trees are discussed with the aim of improving analyses of tree biomechanics and assessments of forest stability protection.

Thirteen Norway spruce [Picea abies (L.) Karst.] trees of different size, age, and social status, and grown under varying conditions, were investigated to see how they react to complex natural static loading under summer and winter conditions, and how they have adapted their growth to such combinations of load and tree state. For this purpose a non-linear finite-element model and an extensive experimental data set were used, as well as a new formulation describing the degree to which the exploitation of the bending stress capacity is uniform. The three main findings were: material and geometric non-linearities play important roles when analysing tree deflections and critical loads; the strengths of the stem and the anchorage mutually adapt to the local wind acting on the tree crown in the forest canopy; and the radial stem growth follows a mechanically high-performance path because it adapts to prevailing as well as acute seasonal combinations of the tree state (e.g. frozen or unfrozen stem and anchorage) and load (e.g. wind and vertical and lateral snow pressure). Young trees appeared to adapt to such combinations in a more differentiated way than older trees. In conclusion, the mechanical performance of the Norway spruce studied was mostly very high, indicating that their overall growth had been clearly influenced by the external site- and tree-specific mechanical stress.

Eighty-four mature Norway spruce (Picea abies L. Karst), silver fir (Abies alba Mill) and Scots pine (Pinus sylvestris L.) trees were winched over to determine the maximum resistive turning moment (M(a)) of the root-soil system, the root-soil plate geometry, the azimuthal orientation of root growth, and the occurrence of root rot. The calculation of M(a), based on digital image tracking of stem deflection, accounted not only for the force application and its changing geometry, but also for the weight of the overhanging tree, representing up to 42% of M(a). Root rot reduced M(a) significantly and was detected in 25% of the Norway spruce and 5% of the silver fir trees. Excluding trees with root rot, differences in M(a) between species were small and insignificant. About 75% of the variance in M(a) could be explained by one of the four variables--tree mass, stem mass, stem diameter at breast height squared times tree height, and stem diameter at breast height squared. Among the seven allometric variables assessed above ground, stem diameter at breast height best described the root-soil plate dimensions, but the correlations were weak and the differences between species were insignificant. The shape of the root-soil plate was well described by a depth-dependent taper model with an elliptical cross section. Roots displayed a preferred azimuthal orientation of growth in the axis of prevailing winds, and the direction of frequent weak winds matched the orientation of growth better than that of rare strong winds. The lack of difference in anchorage parameters among species probably reflects the similar belowground growth conditions of the mature trees.

To provide data and methods for analyzing stem mechanics, we investigated bending, density and growth characteristics of 207 specimens of fresh wood from different heights and radial positions of the stem of one mature Norway spruce (Picea abies L. Karst.) tree. From the shape of each stress-strain curve, which was calculated from bending tests that accounted for shear deformation, we determined the modulus of elasticity (MOE), the modulus of rupture (MOR), the completeness of the material, an idealized stress-strain curve and the work involved in bending. In general, all mechanical properties increased with distance from the pith, with values in the ranges of 5.7-18 GPa for MOE, 23-90 MPa for MOR and 370-630 and 430-1100 kg m(-3) for dry and fresh wood densities, respectively. The first three properties generally decreased with stem height, whereas fresh wood density increased. Multiple regression equations were calculated, relating MOR, MOE and dry wood density to growth properties. We applied these equations to the growth of the entire stem and considered the annual rings as superimposed cylindrical shells, resulting in stem-section values of MOE, MOR and dry and fresh densities as a function of stem height and cambial age. The standing tree exhibits an inner stem structure that is well designed for bending, especially at a mature stage.

The impact of prothrombotic abnormalities on the risk of recurrent venous thromboembolism (VTE) and bleeding in patients receiving long-term anticoagulation remains unclear. This analysis evaluated the influence of potential prothrombotic risk factors (antithrombin, protein C, protein S, factor V Leiden mutation, prothrombin gene G20210A mutation, cardiolipin antibodies, number of risk factors) on the risk of recurrent VTE or bleeding during treatment with oral ximelagatran (24 mg twice daily) or placebo for 18 months [THRombin Inhibitor in Venous thromboEmbolism (THRIVE) III trial]. Of the 1223 patients in the intention-to-treat population, prothrombotic state was analysed in 559 patients receiving ximelagatran and 540 patients receiving placebo. It is possible that patients at a high risk of recurrent VTE were poorly represented in this analysis because of selection bias. Prothrombotic risk factors were reported in 41% of patients (8% had > or = 2 factors). No significant interactions were found between ximelagatran treatment and potential prothrombotic risk factors for the risk of recurrent VTE or bleeding by Cox proportionate hazard modelling. There was no clear evidence for a higher risk of recurrent VTE or bleeding across subgroups according to the potential prothrombotic factors analysed in this study.

In the randomized, double-blind THRIVE III trial, the oral direct thrombin inhibitor ximelagatran (24 mg twice daily) significantly reduced the incidence of recurrent venous thromboembolism (VTE) versus placebo over 18 months or until premature study drug discontinuation. A complementary follow-up analysis (intention-to-treat) was conducted post-study to evaluate the cumulative risks of locally-confirmed recurrent VTE and death (Kaplan-Meier procedure) over the full 18-month study period, regardless of whether patients discontinued study drug prematurely. Hazard ratios (HRs) between treatments were estimated using Cox proportional hazard modeling. Of 612 and 611 patients receiving ximelagatran and placebo, respectively, 149 and 181 discontinued treatment prematurely. Of these discontinuations, further information could not be collected for 14 and 13 patients in the ximelagatran and placebo groups, respectively; among the remaining patients, four VTE events and four deaths occurred in the ximelagatran group, and one VTE event and five deaths occurred in the placebo group. The resulting cumulative risks of VTE (3.2% vs. 12.7%; HR 0.21; 95% confidence interval [CI], 0.12, 0.36; P < 0.0001) and pulmonary embolism (0.8% vs. 5.2%; HR 0.13; 95% CI 0.04, 0.36; P < 0.0001) were significantly lower in the ximelagatran than in the placebo group over 18 months. Death from any cause over 18 months occurred in 10 and 12 patients, respectively (HR 0.83;95% CI 0.36, 1.93; P = 0.7). This complementary follow-up analysis confirms the benefit of oral ximelagatran 24 mg twice daily, administered without coagulation monitoring or dose adjustment, for the long-term secondary prevention of VTE.

The oral direct thrombin inhibitor ximelagatran (24 mg twice daily) has been shown to significantly reduce the incidence of recurrent venous thromboembolism (VTE) vs. placebo over 18 months, with no significant influence on bleeding (THRIVE III). The influence of potential prognostic factors on the risk of recurrent VTE or major and/or minor bleeding and their impact on ximelagatran treatment was evaluated in the THRIVE III study population. The effect of sex, age, body weight, renal function, malignancy, type of initial VTE event, and history of previous VTE events was investigated in the intention-to-treat population using Cox proportionate hazard modelling. Ximelagatran was administered to 612 patients and placebo to 611 patients. Within the placebo group, risk of recurrent VTE was higher among men than women (hazard ratio [HR]: 2.50,95% confidence interval [CI] 1.49,4.17), and in patients with one or more than one previous VTE event (HR: 1.73,95% CI 1.00, 2.99). There was a higher risk of bleeding among women than men in both the ximelagatran (HR: 1.49, 95% CI 1.06, 2.09) and placebo (HR: 1.48, 95% CI 1.01, 2.15) groups, and in placebo-treated patients with an initial pulmonary embolism (HR: 1.53, 95% CI 1.06,2.23) compared to those with initial deep vein thrombosis. There were no significant interactions between treatment effect and any of the potential prognostic factors. In conclusion, the superior efficacy of ximelagatran vs. placebo was maintained in all subgroups. Long-term use of oral ximelagatran, without coagulation monitoring or dose adjustment, should be feasible and well tolerated in a wide cross-section of patients for the secondary prevention of VTE.

Context: Ximelagatran, an oral direct thrombin inhibitor with a rapid onset of action and predictable antithrombotic effect, has the potential to be a simple therapeutic alternative to current standard treatment of acute venous thromboembolism., Objective: To compare the efficacy and safety of ximelagatran with standard enoxaparin/warfarin treatment for the prevention of recurrent venous thromboembolism., Design, Setting, and Patients: Randomized, double-blind, noninferiority trial (Thrombin Inhibitor in Venous Thromboembolism [THRIVE] Treatment Study) of 2489 patients with acute deep vein thrombosis, of whom approximately one third had concomitant pulmonary embolism. The study was conducted at 279 centers in 28 countries from September 2000 through December 2002., Interventions: Patients were randomized to receive 6 months of treatment with either oral ximelagatran, 36 mg twice daily, or subcutaneous enoxaparin, 1 mg/kg twice daily, for 5 to 20 days followed by warfarin adjusted to maintain an international normalized ratio of 2.0 to 3.0., Main Outcome Measures: Recurrent venous thromboembolism, bleeding, and mortality., Results: Venous thromboembolism recurred in 26 of the 1240 patients assigned to receive ximelagatran (estimated cumulative risk, 2.1%) and in 24 of the 1249 patients assigned to receive enoxaparin/warfarin (2.0%). The absolute difference between ximelagatran and enoxaparin/warfarin was 0.2% (95% confidence interval [CI], -1.0% to 1.3%). This met the prespecified criterion for noninferiority. Corresponding values for major bleeding were 1.3% and 2.2% (difference, -1.0%; 95% CI, -2.1% to 0.1%), and for mortality were 2.3% and 3.4% (difference, -1.1%; 95% CI, -2.4% to 0.2%). Alanine aminotransferase levels increased to more than 3 times the upper limit of normal in 119 patients (9.6%) and 25 patients (2.0%) receiving ximelagatran and enoxaparin/warfarin, respectively. Increased enzyme levels were mainly asymptomatic. Retrospective analysis of locally reported adverse events showed a higher rate of serious coronary events with ximelagatran (10/1240 patients) compared with enoxaparin/warfarin (1/1249 patients)., Conclusions: Oral ximelagatran administered in a fixed dose without coagulation monitoring, was as effective as enoxaparin/warfarin for treatment of deep vein thrombosis with or without pulmonary embolism and showed similar, low rates of bleeding. Increased levels of liver enzymes in 9.6% of ximelagatran-treated patients require regular monitoring; the mechanism requires further evaluation. Prospective assessment of coronary events in future studies is warranted.

Phenotypic and phylogenetic studies were performed on four unidentified Gram-positive staining, catalase-negative, alpha-hemolytic Streptococcus-like organisms recovered from the teeth of horses. SDS PAGE analysis of whole-cell proteins and comparative 16S rRNA gene sequencing demonstrated the four strains were highly related to each other but that they did not correspond to any recognised species of the genus Streptococcus. Phylogenetic analysis based on 16S rRNA gene sequences showed the unidentified organisms form a hitherto unknown sub-line within the Streptococcus genus, displaying a close affinity with Streptococcus mutans, Streptococcus ferus and related organisms. Sequence divergence values of > 5% with these and other reference streptococcal species however demonstrated the organisms from equine sources represent a novel species. Based on the phenotypic distinctiveness of the new bacterium and molecular chemical and molecular genetic evidence, it is proposed that the unknown species be classified as Streptococcus devriesei sp. nov. The type strain of Streptococcus devriesei is CCUG 47155T (= CIP 107809T).

Background: For many patients with venous thromboembolism, secondary prevention with vitamin K antagonists is not extended beyond six months, since the risk of recurrence may be outweighed by the risk of major bleeding., Methods: In a double-blind, multicenter trial, we randomly assigned 1233 patients with venous thromboembolism who had undergone six months of anticoagulant therapy to extended secondary prevention with the oral direct thrombin inhibitor ximelagatran (24 mg) or placebo, taken twice daily, for 18 months without monitoring of coagulation. At base line, bilateral ultrasonography of the legs and perfusion lung scanning were performed., Results: Data from 612 patients in the ximelagatran group and 611 in the placebo group were analyzed. The occurrence of the primary end point, symptomatic recurrent venous thromboembolism, was confirmed in 12 patients assigned to ximelagatran and 71 patients assigned to placebo (hazard ratio, 0.16; 95 percent confidence interval, 0.09 to 0.30; P<0.001). Death from any cause occurred in 6 patients in the ximelagatran group and 7 patients in the placebo group, and bleeding occurred in 134 patients and 111 patients, respectively (hazard ratio, 1.19; 95 percent confidence interval, 0.93 to 1.53; P=0.17). The incidence of major hemorrhage was low (six events in the ximelagatran group and five in the placebo group), and none of these hemorrhages were fatal. The cumulative risk of a transient elevation of the alanine aminotransferase level to more than three times the upper limit of normal was 6.4 percent in the ximelagatran group, as compared with 1.2 percent in the placebo group (P<0.001)., Conclusions: Oral ximelagatran was superior to placebo for the extended prevention of venous thromboembolism. There was no significant increase in the frequency of bleeding complications, but there was an increase in the number of patients with a transient elevation in the alanine aminotransferase level., (Copyright 2003 Massachusetts Medical Society)

We have evaluated survival and tumor-related symptoms in the presence of mesenteric lymph node and liver metastases in relation to surgical procedures in 314 patients (148 women, mean age at diagnosis 61 years; 249 with liver metastases) treated for midgut carcinoid tumors. Of the operated patients, 46% presented with severe abdominal pain and intestinal obstruction and were operated on before the diagnosis. Medical treatment (somatostatin analogs, interferon-a) was initiated in 67% and 86%, respectively. Surgical attempts included small intestine or ileocecal/right-sided colon resection with excision of mesenteric lymph node metastases. Most of the patients (n = 286) had mesenteric lymph node metastases; 33% of them had unresectable mesenteric lymph node metastases and underwent surgery without mesenteric dissection. Patients who underwent resection for the primary tumor had a longer survival than those with no resection (median survival 7.4 vs. 4.0 years; p <0.01). Patients who underwent successful excision of mesenteric metastases had a significantly longer survival than those with remaining lymph node metastases. Patients operated on for a primary tumor but with remaining lymph nodes but no liver metastases and who subsequently received interferon and somatostatin analog treatment had a median survival of 7.4 years. Resection of the primary tumor and the mesenteric lymph node metastases led to a significant reduction in tumor-related symptoms. Surgery to remove the primary intestinal tumor including mesenteric lymph node metastases is supported by the present results, even in the presence of liver metastases. Liver metastases and significant preoperative weight loss are identified as major negative prognostic factors for survival.

Digital speckle photography (DSP) is used for velocity field measurements inside a fiber network. The width of the channels in which the flow is measured is typically less than 1 mm. Therefore a microscope is used to image the fiber network. When we sample 30 images/s and separate the moving parts of the images from the stationary parts, the velocity field can be deduced with DSP.

Background: Atrial filling pressures are increased in acute atrial fibrillation, which stimulates the release of atrial natriuretic factor pro-hormone, proANF., Methods: In a randomized trial comparing digoxin with placebo in 216 patients, we investigated whether the baseline plasma level of N-terminal proANF is a predictor for conversion to sinus rhythm and the relation among N-terminal proANF, conversion to sinus rhythm, and changes in heart rate., Results: N-terminal proANF was increased at baseline and decreased significantly in patients converting to sinus rhythm, whereas it was mainly unchanged in nonconverters. N-terminal proANF was not a predictor of conversion to sinus rhythm. A relation was found between relative changes in heart rate and N-terminal proANF in nonconverters., Conclusion: The level of N-terminal proANF does not predict conversion to sinus rhythm, which indicates that hemodynamics per se is not important. There is a correlation between relative changes in heart rate and N-terminal proANF in nonconverters.

The purpose of this study was to establish whether physical health and cognitive function in married long-term patients or in their spouses determines why some patients are cared for in home care while others reside in nursing homes. Out of 38 married couples with a sick spouse cared for in a nursing home, 23 couples were studied; out of 34 couples with a sick spouse cared for in home care, 22 patients and 25 spouses were studied. The results showed no significant differences in physical health score either between the two groups of patients, or between the two groups of spouses. Both home-care patients and nursing home patients had low cognitive function scores, but nursing home patients had significantly lower scores. A multivariate analysis showed that physical health and cognitive function explained only 20% of patients' residence. Between the two groups of spouses there was no difference in cognitive function score. The conclusion is that physical health status and cognitive function explain only to a small extent why married long-term care patients are cared for in nursing homes or in home care.

The purpose of this study was to assess hemodynamic and respiratory measures of submaximal and maximal exercise performance in patients with chronic atrial fibrillation, before and one month after cardioversion to sinus rhythm. Restoration of sinus rhythm (n = 16) produced significant reductions in resting and exercise heart rates, 14 percent to 20 percent (p < 0.01). Due to a proportionately larger increase in stroke volume, cardiac output increased by 9 percent during low-level exercise (p < 0.01) and by 7 percent during exercise above the anaerobic threshold (p < 0.05). Minute ventilation was reduced by 7 percent during low-level exercise (p < 0.01) and by 9 percent above the anaerobic threshold (p < 0.05). The ratio between minute ventilation and carbon dioxide elimination was significantly reduced (p < 0.01). Maximum oxygen uptake (+8 percent; p < 0.01) and maximal tolerated work load (+6 percent; p < 0.05) increased. Hemodynamic changes during exercise were similar in patients with (n = 7) or without (n = 9) disopyramide prophylaxis. Restoration of sinus rhythm induced improvement in hemodynamics and in efficiency of ventilation, thereby reducing the ventilatory demand during submaximal exercise.

In a placebo-controlled study the effects on ventricular rate regulation and exercise performance of xamoterol, 100 mg two times a day and 200 mg two times a day, and slow-release verapamil, 240 mg once a day, were assessed in 21 patients with chronic atrial fibrillation. The mean ventricular rate from noon to 6:00 PM was 101 +/- 20 beats/min with placebo, 95 +/- 17 beats/min with xamoterol 100 mg two times a day (not significant), 90 +/- 16 beats/min with xamoterol 200 mg two times a day (p less than 0.001 vs placebo) and 78 +/- 19 beats/min with verapamil (p less than 0.001 vs each other treatment). The mean ventricular rate from midnight to 6:00 AM was 69 +/- 16 beats/min with placebo, increased with xamoterol 100 mg two times a day and 200 mg two times a day to 75 +/- 15 beats/min and 74 +/- 16 beats/min, respectively (p less than 0.001 vs placebo), but decreased with verapamil to 62 +/- 15 beats/min (p less than 0.001 vs each other treatment). The number of ventricular pauses greater than 2.0 seconds was increased by verapamil (p less than 0.05). All active treatments reduced exercise ventricular rates (p less than 0.001), but the decrease was more pronounced with verapamil. The anaerobic threshold was reached significantly earlier with verapamil than with placebo (72 +/- 32 W vs 79 +/- 37 W; p less than 0.01). Xamoterol is preferable to verapamil for treatment of patients with chronic atrial fibrillation who exhibit both bradycardia at rest and excessive tachycardia during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of two calcium channel blockers, diltiazem (270 mg/day) and verapamil (240 mg/day), were studied in 18 patients with chronic atrial fibrillation. During 24 h Holter electrocardiographic monitoring, mean ventricular rate (beats/min) decreased from 88 +/- 14 with placebo to 76 +/- 13 (p less than 0.001) with diltiazem and 80 +/- 11 (p less than 0.01) with verapamil. Maximal symptom-limited exercise tolerance (W) increased from 127 +/- 39 during the placebo period to 136 +/- 42 (p less than 0.01) with diltiazem and 137 +/- 39 (p less than 0.01) with verapamil. Ventricular rate and rate-pressure product were lower at rest and during exercise with diltiazem and verapamil than with placebo (p less than 0.001), with the drugs being similarly effective. Ventricular rate at maximal exercise (beats/min) was 179 +/- 13 with placebo compared with 159 +/- 21 with diltiazem and 158 +/- 23 with verapamil. Maximal oxygen uptake (ml/kg per min) was 22.3 +/- 4.5 with placebo, 23.7 +/- 4.9 (p less than 0.05) with diltiazem and 22.9 +/- 4.5 with verapamil (p = NS). Respiratory gas exchange anaerobic threshold was reached at a work load (W) of 76 +/- 21 with placebo, 84 +/- 27 (p less than 0.05) with diltiazem and 85 +/- 23 (p less than 0.01) with verapamil. In conclusion, patients with chronic atrial fibrillation have modestly improved exercise tolerance with calcium channel blockade therapy. The dromotropic responses and the effects on physical performance are of similar magnitude for diltiazem and verapamil.