Efficacy of a device to narrow the coronary sinus in refractory angina.

BACKGROUND: Many patients with coronary artery disease who are not candidates for revascularization have refractory angina despite standard medical therapy. The balloon-expandable, stainless steel, hourglass-shaped, coronary-sinus reducing device creates a focal narrowing and increases pressure in the coronary sinus, thus redistributing blood into ischemic myocardium. METHODS: We randomly assigned 104 patients with Canadian Cardiovascular Society (CCS) class III or IV angina (on a scale from I to IV, with higher classes indicating greater limitations on physical activity owing to angina) and myocardial ischemia, who were not candidates for revascularization, to implantation of the device (treatment group) or to a sham procedure (control group). The primary end point was the proportion of patients with an improvement of at least two CCS angina classes at 6 months. RESULTS: A total of 35% of the patients in the treatment group (18 of 52 patients), as compared with 15% of those in the control group (8 of 52), had an improvement of at least two CCS angina classes at 6 months (P=0.02). The device was also associated with improvement of at least one CCS angina class in 71% of the patients in the treatment group (37 of 52 patients), as compared with 42% of those in the control group (22 of 52) (P=0.003). Quality of life as assessed with the use of the Seattle Angina Questionnaire was significantly improved in the treatment group, as compared with the control group (improvement on a 100-point scale, 17.6 vs. 7.6 points; P=0.03). There were no significant between-group differences in improvement in exercise time or in the mean change in the wall-motion index as assessed by means of dobutamine echocardiography. At 6 months, 1 patient in the treatment group had had a myocardial infarction; in the control group, 1 patient had died and 3 had had a myocardial infarction. CONCLUSIONS: In this small clinical trial, implantation of the coronary-sinus reducing device was associated with significant improvement in symptoms and quality of life in patients with refractory angina who were not candidates for revascularization. (Funded by Neovasc; COSIRA ClinicalTrials.gov number, NCT01205893.).

Norovirus Dynamics in Wastewater Discharges and in the Recipient Drinking Water Source: Long-Term Monitoring and Hydrodynamic Modeling.

Norovirus (NoV) that enters drinking water sources with wastewater discharges is a common cause of waterborne outbreaks. The impact of wastewater treatment plants (WWTPs) on the river Göta älv (Sweden) was studied using monitoring and hydrodynamic modeling. The concentrations of NoV genogroups (GG) I and II in samples collected at WWTPs and drinking water intakes (source water) during one year were quantified using duplex real-time reverse-transcription polymerase chain reaction. The mean (standard deviation) NoV GGI and GGII genome concentrations were 6.2 (1.4) and 6.8 (1.8) in incoming wastewater and 5.3 (1.4) and 5.9 (1.4) log10 genome equivalents (g.e.) L-1 in treated wastewater, respectively. The reduction at the WWTPs varied between 0.4 and 1.1 log10 units. In source water, the concentration ranged from below the detection limit to 3.8 log10 g.e. L-1. NoV GGII was detected in both wastewater and source water more frequently during the cold than the warm period of the year. The spread of NoV in the river was simulated using a three-dimensional hydrodynamic model. The modeling results indicated that the NoV GGI and GGII genome concentrations in source water may occasionally be up to 2.8 and 1.9 log10 units higher, respectively, than the concentrations measured during the monitoring project.

Incorporating expert judgments in utility evaluation of bacteroidales qPCR assays for microbial source tracking in a drinking water source.

Several assays for the detection of host-specific genetic markers of the order Bacteroidales have been developed and used for microbial source tracking (MST) in environmental waters. It is recognized that the source-sensitivity and source-specificity are unknown and variable when introducing these assays in new geographic regions, which reduces their reliability and use. A Bayesian approach was developed to incorporate expert judgments with regional assay sensitivity and specificity assessments in a utility evaluation of a human and a ruminant-specific qPCR assay for MST in a drinking water source. Water samples from Lake Rådasjön were analyzed for E. coli, intestinal enterococci and somatic coliphages through cultivation and for human (BacH) and ruminant-specific (BacR) markers through qPCR assays. Expert judgments were collected regarding the probability of human and ruminant fecal contamination based on fecal indicator organism data and subjective information. Using Bayes formula, the conditional probability of a true human or ruminant fecal contamination given the presence of BacH or BacR was determined stochastically from expert judgments and regional qPCR assay performance, using Beta distributions to represent uncertainties. A web-based computational tool was developed for the procedure, which provides a measure of confidence to findings of host-specific markers and demonstrates the information value from these assays.

Short-term microbial release during rain events from on-site sewers and cattle in a surface water source.

The protection of drinking water from pathogens such as Cryptosporidium and Giardia requires an understanding of the short-term microbial release from faecal contamination sources in the catchment. Flow-weighted samples were collected during two rainfall events in a stream draining an area with on-site sewers and during two rainfall events in surface runoff from a bovine cattle pasture. Samples were analysed for human (BacH) and ruminant (BacR) Bacteroidales genetic markers through quantitative polymerase chain reaction (qPCR) and for sorbitol-fermenting bifidobacteria through culturing as a complement to traditional faecal indicator bacteria, somatic coliphages and the parasitic protozoa Cryptosporidium spp. and Giardia spp. analysed by standard methods. Significant positive correlations were observed between BacH, Escherichia coli, intestinal enterococci, sulphite-reducing Clostridia, turbidity, conductivity and UV254 in the stream contaminated by on-site sewers. For the cattle pasture, no correlation was found between any of the genetic markers and the other parameters. Although parasitic protozoa were not detected, the analysis for genetic markers provided baseline data on the short-term faecal contamination due to these potential sources of parasites. Background levels of BacH and BacR makers in soil emphasise the need to including soil reference samples in qPCR-based analyses for Bacteroidales genetic markers.

Decay of Bacteroidales genetic markers in relation to traditional fecal indicators for water quality modeling of drinking water sources.

The implementation of microbial fecal source tracking (MST) methods in drinking water management is limited by the lack of knowledge on the transport and decay of host-specific genetic markers in water sources. To address these limitations, the decay and transport of human (BacH) and ruminant (BacR) fecal Bacteroidales 16S rRNA genetic markers in a drinking water source (Lake Rådasjön in Sweden) were simulated using a microbiological model coupled to a three-dimensional hydrodynamic model. The microbiological model was calibrated using data from outdoor microcosm trials performed in March, August, and November 2010 to determine the decay of BacH and BacR markers in relation to traditional fecal indicators. The microcosm trials indicated that the persistence of BacH and BacR in the microcosms was not significantly different from the persistence of traditional fecal indicators. The modeling of BacH and BacR transport within the lake illustrated that the highest levels of genetic markers at the raw water intakes were associated with human fecal sources (on-site sewers and emergency sewer overflow). This novel modeling approach improves the interpretation of MST data, especially when fecal pollution from the same host group is released into the water source from different sites in the catchment.

Estimation of pathogen concentrations in a drinking water source using hydrodynamic modelling and microbial source tracking.

The faecal contamination of drinking water sources can lead to waterborne disease outbreaks. To estimate a potential risk for waterborne infections caused by faecal contamination of drinking water sources, knowledge of the pathogen concentrations in raw water is required. We suggest a novel approach to estimate pathogen concentrations in a drinking water source by using microbial source tracking data and fate and transport modelling. First, the pathogen (norovirus, Cryptosporidium, Escherichia coli O157/H7) concentrations in faecal contamination sources around the drinking water source Lake Rådasjön in Sweden were estimated for endemic and epidemic conditions using measured concentrations of faecal indicators (E. coli and Bacteroidales genetic markers). Afterwards, the fate and transport of pathogens within the lake were simulated using a three-dimensional coupled hydrodynamic and microbiological model. This approach provided information on the contribution from different contamination sources to the pathogen concentrations at the water intake of a drinking water treatment plant. This approach addresses the limitations of monitoring and provides data for quantitative microbial risk assessment (QMRA) and risk management in the context of faecal contamination of surface drinking water sources.

Cross-connections in drinking water distribution networks: Quantitative microbial risk assessment in combination with fault tree analysis and hydraulic modelling.

Deficiencies in drinking water distribution networks, such as cross-connections, may lead to contamination of the drinking water and pose a serious health risk to consumers. Cross-connections and backflows are considered among the most severe public health risks in distribution networks. The aim of this paper was to provide a framework for estimating the risk of infection from cross-connection and backflow events. Campylobacter, norovirus, and Cryptosporidium were chosen as reference pathogens for this study. The theoretical framework was constructed based on the fault tree analysis methodology. National aggregated cross-connection incident data was used to calculate the probability of a contamination event occurring in Swedish networks. Three risk cases were evaluated: endemic, elevated, and extreme. Quantitative microbial risk assessment (QMRA) was used to assess daily risk of infection for average national estimates. The framework was also evaluated using local data from the Gothenburg network. The daily risk of infection from cross-connection and backflow events in Swedish networks was generally above an acceptable target level of 10-6 for all reference pathogens and modelled cases; the exception was for the Gothenburg system where the risk was lower than 10-7. An outbreak case study was used to validate the framework results. For the outbreak case study, contaminant transport in the network was simulated using hydraulic modelling (EPANET), and risk estimates were calculated using QMRA. The outbreak simulation predicted between 97 and 148 symptomatic infections, while the epidemiological survey conducted during the outbreak reported 179 cases of illness. The fault tree analysis framework was successfully validated using an outbreak case study, though it was shown on the example of Gothenburg that local data is still needed for well-performing systems. The framework can help inform microbial risk assessments for drinking water suppliers, especially ones with limited resources and expertise in this area.

Effects on blood pressure in patients with refractory angina pectoris after enhanced external counterpulsation.

OBJECTIVE: Enhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to reduce the frequency and severity of angina pectoris. Little is known how EECP affects the blood pressure. METHODS: 153 patients with refractory angina were treated with either EECP or retained on their pharmacological treatment (reference group). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP) and heart rate were measured pre- and post-treatment and at 12 months follow-up. RESULTS: EECP treatment altered the blood pressure in patients with refractory angina pectoris. A decrease in the blood pressure was more common in the EECP group compared with the reference group. In the reference group, an increase in the blood pressure was more common. A correlation between a decrease in blood pressure after EECP treatment and a higher baseline MAP, SBP and DBP was seen. No such correlation was seen in the reference group. The blood pressure response did not persist at 12 months follow-up. CONCLUSION: EECP treatment affects the blood pressure in patients with refractory angina pectoris. The decreased blood pressure may be a result of an improved exercise capacity, an improved endothelial function and vasoreactivity in general.

[Difficulties and shortcomings in decisions on treatment restrictions]. / Brister i beslut om att begränsa livsuppehållande behandling.

Using a questionnaire for doctors at the Central hospital in Kristianstad, Sweden, we have investigated how work on treatment restrictions is handled and documented, whether different circumstances affect the decisions taken, and what support and training the doctors consider is needed. Far from all patients/relatives are informed about decisions regarding life support treatment, and compliance with applicable laws and directives is low. The propensity to inform tend to be lower when the decision is that no life-sustaining measures will be taken. The decisions also tend not to be affected by several factors related to the patient, doctor, or the circumstances in which the decision was taken. The self-perceived level of knowledge, especially about documentation routines and current guidelines, is low and there are also shortcomings in terms of knowledge about palliative care, communication methodology and medical ethics.

Enhanced external counter pulsation in treatment of refractory angina pectoris: two year outcome and baseline factors associated with treatment failure.

BACKGROUND: Enhanced external counter pulsation (EECP) is a non-invasive treatment option for patients with refractory angina pectoris ineligible to further traditional treatment. The aim of this study was to evaluate the effect of EECP on patients at a Scandinavian medical centre and to investigate if outcome can be predicted by analysing baseline factors. METHODS: 86 consecutive patients (70 male, 16 female) were treated with EECP and followed for two years post treatment. Canadian cardiovascular society (CCS) class was analysed, and medication and adverse clinical events were researched prior to EECP, at the end of the treatment, and at six, 12 and 24 months thereafter. Patients responding to therapy by improving at least one CCS class were compared with those who failed to respond. Any differences in background factors were recorded and analysed. RESULTS: 79% of the patients responded to therapy by improving at least one CCS class. In general, the CCS class improved by one class after EECP treatment (3.05 before versus 2.14 after treatment). A total of 61.5% of the initial responders showed sustained improvement at the 12 month follow-up while 29% presented sustained improvement after 24 months. Treatment was most effective among patients suffering from CCS class III-IV angina pectoris, while patients suffering from CCS class II angina pectoris improved transiently but failed to show sustained improvement after the 12 month follow-up. Diabetes mellitus and calcium channel antagonists were more common among the non-responders (p < 0.05). CONCLUSION: This study confirms the safety and efficiency of EECP as a treatment option for patients suffering from refractory angina pectoris. The therapy is most beneficial in patients suffering from severe angina (CCS III-IV) while sustained response to therapy could not be verified among patients suffering from CCS class II angina pectoris.

Occurrence and removal efficiency of parasitic protozoa in Swedish wastewater treatment plants.

Giardia intestinalis, Cryptosporidium spp., Entamoeba histolytica and Dientamoeba fragilis are parasitic protozoa and causative agents of gastroenteritis in humans. G. intestinalis and Cryptosporidium spp. in particular are the most common protozoa associated with waterborne outbreaks in high-income countries. Surveillance of protozoan prevalence in wastewater and evaluation of wastewater treatment removal efficiencies of protozoan pathogens is therefore imperative for assessment of human health risk. In this study, influent and effluent wastewater samples from three wastewater treatment plants in Sweden were collected over nearly one year and assessed for prevalence of parasitic protozoa. Quantitative real-time PCR using primers specific for the selected protozoa Cryptosporidium spp., G. intestinalis, E. histolytica, Entamoeba dispar and D. fragilis was used for protozoan DNA detection and assessment of wastewater treatment removal efficiencies. Occurrence of G. intestinalis, E. dispar and D. fragilis DNA was assessed in both influent (44, 30 and 39 out of 51 samples respectively) and effluent wastewater (14, 9 and 33 out of 51 samples respectively) in all three wastewater treatment plants. Mean removal efficiencies of G. intestinalis, E. dispar and D. fragilis DNA quantities, based on all three wastewater treatment plants studied varied between 67 and 87%, 37-75% and 20-34% respectively. Neither E. histolytica nor Cryptosporidium spp. were detected in any samples. Overall, higher quantities of protozoan DNA were observed from February to June 2012. The high prevalence of protozoa in influent wastewater indicates the need for continued monitoring of these pathogens in wastewater-associated aquatic environments to minimise the potential risk for human infection.

One year follow-up of patients with refractory angina pectoris treated with enhanced external counterpulsation.

BACKGROUND: Enhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to be effective in reducing both angina and myocardial ischemia in patients not responding to medical therapy and without revascularization alternatives. The aim of the present study was to assess the long-term outcome of EECP treatment at a Scandinavian centre, in relieving angina in patients with chronic refractory angina pectoris. METHODS: 55 patients were treated with EECP. Canadian cardiovascular society (CCS) class, antianginal medication and adverse clinical events were collected prior to EECP, at the end of the treatment, and at six and 12 months after EECP treatment. Clinical signs and symptoms were recorded. RESULTS: EECP treatment significantly improved the CCS class in 79 +/- 6% of the patients with chronic angina pectoris (p < 0.001). The reduction in CCS angina class was seen in patients with CCS class III and IV and persisted 12 months after EECP treatment. There was no significant relief in angina in patients with CCS class II prior to EECP treatment. 73 +/- 7% of the patients with a reduction in CCS class after EECP treatment improved one CCS class, and 22 +/- 7% of the patients improved two CCS classes. The improvement of two CCS classes could progress over a six months period and tended to be more prominent in patients with CCS class IV. In accordance with the reduction in CCS classes there was a significant decrease in the weekly nitroglycerin usage (p < 0.05). CONCLUSION: The results from the present study show that EECP is a safe treatment for highly symptomatic patients with refractory angina. The beneficial effects were sustained during a 12-months follow-up period.

Bacterial profile and burden of periodontal infection in subjects with a diagnosis of acute coronary syndrome.

BACKGROUND: Periodontitis has been identified as a potential risk factor in cardiovascular diseases. It is possible that the stimulation of host responses to oral infections may result in vascular damage and the inducement of blood clotting. The aim of this study was to assess the role of periodontal infection and bacterial burden as an explanatory variable to the activation of the inflammatory process leading to acute coronary syndrome (ACS). METHODS: A total of 161 consecutive surviving cases admitted with a diagnosis of ACS and 161 control subjects, matched with cases according to their gender, socioeconomic level, and smoking status, were studied. Serum white blood cell (WBC) counts, high- and low-density lipoprotein (HDL/LDL) levels, high-sensitivity C-reactive protein (hsC-rp) levels, and clinical periodontal routine parameters were studied. The subgingival pathogens were assayed by the checkerboard DNA-DNA hybridization method. RESULTS: Total oral bacterial load was higher in the subjects with ACS (mean difference: 17.4x10(5); SD: 10.8; 95% confidence interval [CI]: 4.2 to 17.4; P<0.001), and significant for 26 of 40 species including Porphyromonas gingivalis, Tannerella forsythensis, and Treponema denticola. Serum WBC counts, hsC-rp levels, Streptococcus intermedius, and Streptococcus sanguis, were explanatory factors to acute coronary syndrome status (Nagelkerke r2=0.49). CONCLUSION: The oral bacterial load of S. intermedius, S. sanguis, Streptococcus anginosus, T. forsythensis, T. denticola, and P. gingivalis may be concomitant risk factors in the development of ACS.

Microbial risk assessment of drinking water based on hydrodynamic modelling of pathogen concentrations in source water.

Norovirus contamination of drinking water sources is an important cause of waterborne disease outbreaks. Knowledge on pathogen concentrations in source water is needed to assess the ability of a drinking water treatment plant (DWTP) to provide safe drinking water. However, pathogen enumeration in source water samples is often not sufficient to describe the source water quality. In this study, the norovirus concentrations were characterised at the contamination source, i.e. in sewage discharges. Then, the transport of norovirus within the water source (the river Göta älv in Sweden) under different loading conditions was simulated using a hydrodynamic model. Based on the estimated concentrations in source water, the required reduction of norovirus at the DWTP was calculated using quantitative microbial risk assessment (QMRA). The required reduction was compared with the estimated treatment performance at the DWTP. The average estimated concentration in source water varied between 4.8×10(2) and 7.5×10(3) genome equivalents L(-1); and the average required reduction by treatment was between 7.6 and 8.8 Log10. The treatment performance at the DWTP was estimated to be adequate to deal with all tested loading conditions, but was heavily dependent on chlorine disinfection, with the risk of poor reduction by conventional treatment and slow sand filtration. To our knowledge, this is the first article to employ discharge-based QMRA, combined with hydrodynamic modelling, in the context of drinking water.

Evaluation of a passive sampler for the speciation of metals in urban runoff water.

Metals in urban runoff water need to be monitored in order to estimate fluxes and assess their impact on the aquatic environment. Passive sampling is a useful and reliable emerging tool for measuring time averaged concentrations of metals in water bodies. This paper describes the deployment of a passive sampler to measure Cu, Ni and Zn in an urban runoff water treatment facility. The concentrations derived from the passive samplers are compared to concentrations obtained from an automated water sampler which provides pooled spot water samples and to model predictions from the visualMINTEQ computer speciation code. Results show that visualMINTEQ predictions partly describe the metal speciation in non-equilibrium systems. In addition we conclude that passive samplers are useful for monitoring and characterization of metal speciation under chemodynamic conditions.

The association of drinking water treatment and distribution network disturbances with Health Call Centre contacts for gastrointestinal illness symptoms.

There are relatively few studies on the association between disturbances in drinking water services and symptoms of gastrointestinal (GI) illness. Health Call Centres data concerning GI illness may be a useful source of information. This study investigates if there is an increased frequency of contacts with the Health Call Centre (HCC) concerning gastrointestinal symptoms at times when there is a risk of impaired water quality due to disturbances at water works or the distribution network. The study was conducted in Gothenburg, a Swedish city with 0.5 million inhabitants with a surface water source of drinking water and two water works. All HCC contacts due to GI symptoms (diarrhoea, vomiting or abdominal pain) were recorded for a three-year period, including also sex, age, and geocoded location of residence. The number of contacts with the HCC in the affected geographical areas were recorded during eight periods of disturbances in the water works (e.g. short stops of chlorine dosing), six periods of large disturbances in the distribution network (e.g. pumping station failure or pipe breaks with major consequences), and 818 pipe break and leak repairs over a three-year period. For each period of disturbance the observed number of calls was compared with the number of calls during a control period without disturbances in the same geographical area. In total about 55, 000 calls to the HCC due to GI symptoms were recorded over the three-year period, 35 per 1000 inhabitants and year, but much higher (>200) for children <3 yrs of age. There was no statistically significant increase in calls due to GI illness during or after disturbances at the water works or in the distribution network. Our results indicate that GI symptoms due to disturbances in water works or the distribution network are rare. The number of serious failures was, however limited, and further studies are needed to be able to assess the risk of GI illness in such cases. The technique of using geocoded HCC data together with geocoded records of disturbances in the drinking water network was feasible.

Replacement predictions for drinking water networks through historical data.

Lifetime distribution functions and current network age data can be combined to provide an assessment of the future replacement needs for drinking water distribution networks. Reliable lifetime predictions are limited by a lack of understanding of deterioration processes for different pipe materials under varied conditions. An alternative approach is the use of real historical data for replacement over an extended time series. In this paper, future replacement needs are predicted through historical data representing more than one hundred years of drinking water pipe replacement in Gothenburg, Sweden. The verified data fits well with commonly used lifetime distribution curves. Predictions for the future are discussed in the context of path dependence theory.

Cost-effectiveness analysis of risk-reduction measures to reach water safety targets.

Identifying the most suitable risk-reduction measures in drinking water systems requires a thorough analysis of possible alternatives. In addition to the effects on the risk level, also the economic aspects of the risk-reduction alternatives are commonly considered important. Drinking water supplies are complex systems and to avoid sub-optimisation of risk-reduction measures, the entire system from source to tap needs to be considered. There is a lack of methods for quantification of water supply risk reduction in an economic context for entire drinking water systems. The aim of this paper is to present a novel approach for risk assessment in combination with economic analysis to evaluate risk-reduction measures based on a source-to-tap approach. The approach combines a probabilistic and dynamic fault tree method with cost-effectiveness analysis (CEA). The developed approach comprises the following main parts: (1) quantification of risk reduction of alternatives using a probabilistic fault tree model of the entire system; (2) combination of the modelling results with CEA; and (3) evaluation of the alternatives with respect to the risk reduction, the probability of not reaching water safety targets and the cost-effectiveness. The fault tree method and CEA enable comparison of risk-reduction measures in the same quantitative unit and consider costs and uncertainties. The approach provides a structured and thorough analysis of risk-reduction measures that facilitates transparency and long-term planning of drinking water systems in order to avoid sub-optimisation of available resources for risk reduction.

Reduced peripheral vascular reactivity in refractory angina pectoris: Effect of enhanced external counterpulsation.

AIMS: To examine if the skin microvascular bed is altered and can be modified by enhanced external counterpulsation (EECP) in patients with chronic refractory angina. METHODS: Twenty patients diagnosed with refractory angina were divided into EECP (n = 10) or no EECP (n = 10) groups. The data were compared to matched healthy subjects (n = 20). The cutaneous forearm microvascular blood flow was measured by Laser-Doppler flowmetry. The vascular responsiveness to iontophoretic administration of acetylcholine (ACh), sodium nitroprusside (SNP) and local skin warming were studied. Measurements of Canadian Cardiovascular Society (CCS)-class, blood pressure and plasma samples were registered. RESULTS: EECP patients showed reduced CCS-class compared to no EECP (P < 0.05). Both EECP and no EECP (P < 0.05) groups had decreased systolic blood pressure (SBP) as compared to SBP at baseline (P < 0.05). There was no difference in resting blood flow between the two refractory groups at baseline as well as after EECP and seven weeks of follow-up. Responses to heating, the responses to ACh and SNP in the cutaneous microcirculation were lower in both groups of refractory angina patients as compared to healthy subjects (P < 0.05). EECP patients corresponded positively to the treatment shown by reduced plasma level of soluble interleukin-2 receptor and CCS-class. CONCLUSIONS: Refractory angina patients have reduced responsiveness in their cutaneous microcirculation to ACh, SNP and heat compared to healthy subjects. Although EECP reduced the CCS-class, this effect was not associated with improvements in responsiveness of the cutaneous microcirculation.