Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn's disease: analyses from the 7-year PRECiSE 3 study.

BACKGROUND: Clinical factors were previously identified as predictors of short-term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7-year trial provides an opportunity to study predictors of short- and long-term clinical remission among CD patients treated with certolizumab pegol (CZP). AIM: To identify factors that influence long-term remission of CD with CZP treatment. METHODS: Patients who had completed placebo-controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open-label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey-Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used. RESULTS: Predictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models. CONCLUSIONS: These analyses identified several influential parameters for short-and long-term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed. (ClinicalTrials.gov identifier NCT00552058).

The influence of sludge interchange times on the oxic-settling-anoxic process.

The oxic-settling-anoxic (OSA) system operated as a sequencing batch reactor was studied. Sludge was interchanged between the aerobic and anaerobic reactors, and the number of daily interchange times was changed from 1 to 4 during the experiments. When the sludge was interchanged 1 time/d, the reduction of excess sludge mass was only 52.8%. When the sludge was interchanged 4 times/d, the reduction of excess sludge mass was 77.4%; reductions in the total chemical oxygen demand, total solids, and total volatile solids of both the anaerobic sludge and the aerobic settled sludge were the greatest; and more soluble iron was released from the anaerobic sludge. The water quality of the final effluent in the two systems was close. The investigation showed that interchange times are important in improving sludge reduction efficiency, and the parameter should be regarded as an important operating factor in the OSA process.

Aerobic production of activated sludge polyhydroxyalkanoates from nutrient deficient wastewaters.

It was found that aerobic strategies combined with multiple nutrient limitations produced greater quantities of polyhydroxyalkanoates (PHAs) than strategies relying on oxygen limitation (either microaerophilic or anaerobic/aerobic). This was true both for a synthetic wastewater composed of acetic and propionic acid, and also for a nutrient deficient industrial wastewater. PHA/substrate yields were shown to be comparable to axenic systems for many operating strategies analyzed, and it was found that PHA composition could be affected by process operational conditions. The molecular weight and melting point of the PHA produced were found to be in a desirable range with respect to material properties, which have not been well studied in the previous literature for mixed cultures (Salehizadeh and Van Loodsrecht, 2004). The effects of process staging, multiple treatment cycles, and inocula source were also addressed.

Evaluation of the performance of the Tyson Foods wastewater treatment plant for nitrogen removal.

In this paper, the performance of the Tyson Foods wastewater treatment plant with an average flow rate of 6500 m3/d was evaluated before and after upgrading of the treatment system for nitrogen removal. This study was also covered with an additional recommendation of BIOWIN BNR program simulation after the modification period to achieve an additional nutrient removal. The results clearly show that the upgrading was very successful for improved nitrogen removal, with a 57% decrease on the total nitrogen discharge. There also were slight reductions in the discharged loads of biological oxygen demand, total suspended solids, ammonium and total phosphorus with denitrification, even though the effluent flow was higher during operation of the nitrogen removal configuration.

Performance of IFAS wastewater treatment processes for biological phosphorus removal.

Integrated fixed film activated sludge (IFAS) is a promising process for the enhancement of nitrification and denitrification in conventional activated sludge systems that need to be upgraded for biological nutrient removal (BNR), particularly when they have space limitations or need modifications that will require large monetary expenses. Several studies have reported successful implementations of IFAS at temperate zone wastewater treatment facilities, typically by placement of fixed film media into aerobic zones. However, nearly all of the implementations have not included enhanced biological phosphorus removal (EBPR) in the upgraded systems. This is possibly because the treatment plants have been operated at low mixed liquor mean cell residence times (MCRTs), and EBPR would wash out of the systems at the low temperatures encountered, making it difficult to maintain EBPR. The primary objective of this study was to investigate the incorporation of EBPR into IFAS systems, and study the interactions between the fixed biomass and the mixed liquor suspended solids with respect to substrate competition and nutrient removal efficiencies. Three pilot-scale UCT/VIP configuration systems were used, one as a control and the other two with Bioweb media integrated into some of the anoxic and aerobic reactors. The systems were operated at different MCRTs, and influent COD/TP ratios, and with split influent flows. The experimental results confirmed that EBPR could be incorporated successfully into IFAS systems, but the redistribution of biomass resulting from the integration of fixed film media, and the competition of organic substrate between EBPR and denitrification would affect performances. Also, the integration of fixed film media into the anoxic reactors affected performances differently from media in aerobic reactors.

Biochemistry of enhanced biological phosphorus removal and anaerobic COD stabilization.

Improved design strategies at BNR plants should include cost reductions so that the consumers and water authorities will be more willing to build EBPR plants instead of conventional activated sludge plants. Through efficient design, actual savings in construction and operation costs can be realized. For this reason, anaerobic stabilization of COD needs to be seriously considered during design for direct energy savings at the plants. The existence of anaerobic stabilization has been demonstrated through experimental work. Evaluation of operational data from existing plants has also indicated the definite presence of anaerobic stabilization at plants that include anaerobic zones for EBPR as part of their operation. By exploring the biochemical reactions taking place in EBPR process, particularly the involvement of the storage mechanisms for PHA, poly-P and glycogen storage, the potential mechanisms of the anaerobic stabilization of COD in EBPR systems was explored. The resultant balances pointed out the importance of glycogen metabolism in terms of conserving carbon and providing a sink for the reducing equivalents produced under aerobic conditions. This mechanism is different from those observed in anoxic-aerobic and conventional aerobic activated sludge systems, and appears to be at least partially responsible for the observed anaerobic stabilization of COD.

Effects of phosphorus limitation and temperature on PHA production in activated sludge.

The study was designed to investigate the effects of temperature and phosphorus limitation on polyhydroxyalkanoate (PHA) production and storage by activated sludge biomass. The two-stage operation approach, i.e. a growth phase followed by a nutrient limitation phase, was applied to induce PHA accumulation. The pre-selected temperatures of 10, 20 and 30 degrees C were investigated under phosphorus limitation conditions using three four-litre fully aerobic SBR systems operated at an SRT of 10 days with cycle time and HRT of 6 and 10 hours. PHA production was greater in the 10 degrees C system than in the 20 degrees C and 30 degrees C systems but there was little difference between the two higher temperatures. The maximum PHA fractions of the sludge were 52, 45 and 47%TSS for the three temperatures from low to high, and the maximum PHA concentrations in the mixed liquors were 1,491, 1,294 and 1,260 mg/l, respectively. However, it was observed that very low values of PHA yield per unit COD consumed were obtained, i.e., 0.05, 0.03 and 0.04 mgPHA/mgCODu, for the 10, 20 and 30 degrees C reactors, respectively. This was because all three systems required several days to reach maximum PHA accumulation in their mixed liquor biomasses. It is probable the bacteria still had some stored poly-P in their cells upon initiation of the phosphorus limited influent, and PHA accumulation was delayed until the stored phosphorus was depleted. Also, PHA productivity was reduced by the large amounts of biomass lost from the systems because of sludge bulking.

Effects of pH and substrate on the competition between glycogen and phosphorus accumulating organisms.

This article evaluates effects of pH and substrate on the competition between glycogen (GAOs) and phosphorus accumulating organisms (PAOs). A sequencing batch reactor system was operated for enhanced biological phosphorus removal (EBPR) with acetate as the sole carbon source and acetate added domestic wastewater at different influent acetate/phosphate ratios. Some batch tests were performed using acetate added domestic wastewater at different influent acetate, phosphate ratios, with different initial pH values of acetate and domestic wastewater mixture. The resulting experimental data supported the presence of GAOs for all tested HAC P ratios, especially under P limiting conditions for acetate as sole carbon source. Strong evidence is observed that acetate added domestic wastewater system had higher PAOs fraction than acetate system as sole source carbon, with using model components, namely substrate uptake, glycogen utilization and P release.

The environmental, economic and societal consequences of inadequate nitrogen pollution controls.

Because adequate nutrient controls were not established in the USA and other countries when there were past opportunities to do so, nutrient pollution of estuaries and coastal waters has resulted in the impairment of ecosystems and major reductions or collapse of fisheries at numerous sites around the world, resulting in major economic and societal impacts. The root problem is that political policies and processes have permitted municipalities, developers, industries and farmers to expand and operate without paying the full cost of their activities. Their expanded activities have occurred at the expense and displacement of those who rely on the productivity and recreational value of our estuarine and coastal waters. Some governments have developed remedial nutrient control programs, but most of them have been poorly conceived, under funded and inadequately enforced, resulting in small increments of progress that tend to be lost because of inadequate land use and immigration controls. It is proposed that establishment of comprehensive nutrient controls is needed throughout the world to preserve and protect estuarine and coastal waters, and to protect or re-establish fisheries, for both economic and societal stability. Nitrogen is the key nutrient for the establishment of control strategies. It is recommended that nutrient recovery from wastewaters and controlled reuse of both water and nutrients be widely implemented as a part of nutrient control strategies.

The effects of diquat dibromide on biological wastewater treatment plants.

The objective of the study was to investigate the fate and effects of diquat dibromide which is the active ingredient in formulations used to control the growth of roots into sewers when applied as Razorooter and mixed with raw sewage, settled sewage, and activated sludge, and when introduced into activated sludge wastewater treatment systems. Both fully aerobic and biological nutrient removal (BNR) activated sludge systems were used for experimental purpose, and both continuous flow and batch reactors were used. The sorption of diquat by both raw sewage particles and activated sludge suspended solids was determined. Diquat dibromide concentrations ranged from 0.93 to 12.6 mg/L in the influent flow. Both the fully aerobic and two full biological nutrient removal systems were fed municipal sewage spiked with diquat dibromide, and operated at a mixed liquor temperature of 10 degrees C and an MCRT of 10 days. One of the BNR systems was a control system. The results showed that only about 20% of the diquat in raw sewage flow was removed by adsorptions to the sewage solids, but 80% or more of the diquat was removed in activated sludge systems. When the influent diquat dibromide concentration was approximately 1mg/L, over 99% of the diquat dibromide was removed by the activated sludge process. Some of the removal was believed to be by biodegradation. The diquat dibromide used in this study had no observable detrimental effects on any of the biological processes of the continuous flow fully aerobic and BNR activated systems.

The competition between PAOs (phosphorus accumulating organisms) and GAOs (glycogen accumulating organisms) in EBPR (enhanced biological phosphorus removal) systems at different temperatures and the effects on system performance.

It is well known and firmly established that the rate of chemical and biochemical reactions slow down as temperature decreases. Nevertheless, several studies have reported that the efficiency of enhanced biological phosphorus removal (EBPR) improves as temperature decreases. However, several recent studies have reported that EBPR reaction rates decrease with temperature decrease in accordance with the Arrhenius relationship. This study was designed to more thoroughly investigate this controversy using two UCT plants fed with a synthetic wastewater consisting primarily of acetate as the COD form, and a small amount of supplemental yeast extract. Experiments were performed over temperatures ranging from 5 to 20 degrees C. The results showed that, even though the kinetic rates decrease as temperature decreases, EBPR systems perform better at colder temperatures. The reason for better system performance is apparently related to reduced competition for substrate in the non-oxic zones, which results in an increased population of PAOs and, thus, greater EBPR efficiency. The proliferation of PAOs apparently occurs because they are psychrophilic whereas their competitors are not. The experiments showed that the EBPR sludges accumulated high concentrations of both PHA and glycogen at 20 degrees C, but accumulated more PHA and much less glycogen at 5 degrees C. Although the results could be interpreted as the result of changes in the PAO-GAO competition, Mann-Whitney non-parametric comparisons of transmission electron microscopy examinations revealed no indication of the presence of GAOs population under any temperature conditions. Regardless, mass balances of the glycogen data showed that the involvement of glycogen is less at cold temperature, even though EBPR was greater. Unlike current EBPR models (e.g. Mino model), the results suggest that glycogen metabolism is not a precursor for EBPR biochemistry. The results also indicate that temperature not only may cause selective pressure on the dominant organisms, but also may force them to use a different metabolic pathway as temperature decreases.

A thermal adaptation of bacteria to cold temperatures in an enhanced biological phosphorus removal system.

Temperature is one of the key parameters that affects the reaction kinetics and performance of enhanced biological phosphorus removal (EBPR) systems. Although studies agree regarding the effect of temperature on kinetic reaction rates, there are contradictory results in the literature regarding the effect of temperature on EBPR system performance. Early investigators (Sell, Ekama et al., Daigger et al.) reported better performance with lower temperatures, but others have reported partial or complete loss of EBPR functions at low temperatures (McClintock et al., Brdjanovic et a., Beatons et al.). One speculation is that deterioration in the EBPR system performance at cold temperatures can be attributed to rigid-like behavior of the cell membranes. Most cells (not all) on the other hand have the ability to alter their membrane fatty acid composition as temperature changes in order to keep their membrane at nearly the same fluidity despite the temperature changes. This unique ability is known as homeoviscous adaptation. In this study, homeoviscous adaptation by EBPR activated sludge was investigated for a series of temperatures ranging from 20 degrees C to 5 degrees C using a lab scale continuous flow EBPR system fed with acetate and supplemental yeast extract. The fatty acid analysis results suggested that the unsaturated to saturated fatty acid ratio increased from 1.40 to 3.61 as temperature dropped from 20 to 5 degrees C. The increased cis-9-hexadecanoic acid (C 16:1) at 5 degrees C strongly indicated the presence of homeoviscous adaptation in the EBPR bacterial community. Thus the cell membranes of the EBPR community were still in a fluid state, and solute transport and proton motive force were operable even at 5 degrees C. It was concluded that loss of EBPR performance at low temperatures is not related to the physical state of the cellular membranes, but is possibly related to the application of unsuitable operational conditions (low SRT, excessive electron acceptors, low anaerobic detention time, non-acclimated sludge, etc.).

Potential societal and economic impacts of wastewater nutrient removal and recycling.

Because adequate nutrient controls were not established when there were past opportunities to do so, nutrient pollution of estuaries and coastal waters has resulted in the impairment of ecosystems and major reductions or collapse of fisheries at numerous sites around the world, resulting in major economical and societal impacts. The root of the problem is that the political policies and processes have permitted municipalities, developers, industries and farmers to expand and operate without paying the full cost of their activities, and this has been done at the expense of those who rely on the productivity and recreational value of our estuarine and coastal waters. Some governments have developed remedial nutrient control programs, but most of them have been under funded and inadequately enforced, resulting in small increments of progress that tend to be lost because of inadequate land use and immigration controls. It is believed that nutrient recovery and controlled reuse can provide a major tool for the control of nutrient pollution and should be widely implemented. Plans are currently being developed to promote widespread use of nutrient recovery and reuse in the Chesapeake Bay region of the USA. An example of phosphorus reuse is presented.

Changing needs for appropriate excreta disposal and small wastewater treatment methodologies or The future technology of small wastewater treatment systems.

Recent developments will strongly influence the design and utilization of small wastewater treatment systems in the future, e.g. population increases in non-sewered rural areas and developing countries; increasing impairment of surface water quality; the construction of occupied high-rise buildings in metropolitan areas; the development of planned but somewhat isolated communities, growing shortages of water that mandate reuse of wastewaters. It is well known that there is a very strong linkage between wastewater disposal methods in rural areas and developing countries and the general health of the population. These problems could be greatly reduced or prevented by the utilization of well known excreta disposal and small wastewater treatment system technologies, but the development of more innovative on-site systems is needed. It is expected that future environmental and public health pressures in developed countries will require increasingly stringent effluent limitations for small and on-site wastewater disposal systems, based primarily on nutrient discharges. Both on-site and small-scale technologies are available for the more stringent requirements, but innovative and more economical designs are needed for wide-spread acceptance. Water reuse should be a consideration for the designs of these systems. Implementation and utilization of well known technologies are needed, but the obstacles are often more social and political than economical.

Alternatives for upgrading the Wilderness Wastewater Treatment Plant for biological nutrient removal.

The Wilderness Wastewater Treatment Plant (WWTP) located in Orange County, Virginia is a four concentric ring oxidation ditch activated sludge system with a rated capacity of 1,935 m3/day. The three outer rings are used for wastewater treatment and the inner ring is used as an aerobic digester. The flow capacity has been increased from 1,935 to 3,760 m3/d, however, the desired design capacity has since been increased to 3,870 m3/d, and there are plans to eventually expand to approximately 4,840 m3/d with improved nitrogen removal. The design goal for the planned upgrade is to discharge an effluent that contains less than 10 mg/l total nitrogen (TN) at all times, with an annual average of 8 mg/l or less. In this study, the pre-upgrade performance of the Wilderness Wastewater Treatment Plant was evaluated and several modifications were recommended for the incorporation of biological nutrient removal (BNR).

Modification and expansion of a pure oxygen WWTP for biological nutrient removal (BNR).

A pure oxygen activated sludge system was converted to a VIP configuration BNR (biological nutrient removal) system wherein three of the five pure oxygen sections were retained, and performance was compared to that of a side-by-side air aeration MUCT (modified UCT) system. Because the pure oxygen BNR system could not obtain good nitrification, its treatment capacity had to be downgraded from 113,550 m3/d to a flow of only 60,000 m3/d. At the lesser flow, it was determined that adequate nitrification and improved denitrification could be accomplished in the pure oxygen system by continuously seeding it with 100% of the WAS from the MUCT system. Fortunately, while the capacity of the pure oxygen system had to be downgraded, it was determined that the capacity of the MUCT system was substantially greater than its design flow, and the combined system is capable of treating the entire design flow. However, this requires increasing the operating sludge age of the MUCT system. The pure oxygen BNR system performed better phosphorus removal than the MUCT system, both before and after seeding with the MUCT WAS. Apparently this was because the MUCT system was operated at a substantially higher sludge age than the pure oxygen system. However, both systems have consistently discharged effluent phosphorus concentrations of less than 2.0 mg/L TP, which is the Chesapeake Bay standard. Even with improved nitrification and denitrification in the pure oxygen BNR system, neither it nor the MUCT system have proven to be capable of meeting the Virginia Chesapeake Bay goal of 10 mg/L total nitrogen in the effluent.

Nutrient reduction policies and management strategies of the Chesapeake Bay water quality restoration program.

The Chesapeake Bay Program is a unique, regional, federal-state-local partnership established in 1983 by a formal Agreement between six signatories, the states of Maryland, Pennsylvania and Virginia, the District of Columbia, the US EPA, and the Chesapeake Bay Commission, to protect and restore the Bay's ecosystem. The system of governance adopted provides for dynamic interaction between the signatories, and provides for input from the interested citizens, the local governments, and the scientific and technical community. The Agreement is periodically reviewed, amended and added to by new agreements, with the most recent being the 2000 Agreement, referred to as "Chesapeake 2000: A Watershed Partnership". The new agreement, signed 28 June 2000, sets numeric goals to be accomplished during the next ten years, and includes land use policies and restrictions.

Oral health of ambulatory care patients.

OBJECTIVES: This project assessed the clinical oral health status of Veterans Administration (VA) patients and examined the relationship between oral health and both sociodemographic factors and dental care utilization. METHODS: Data were collected on 538 users of VA ambulatory medical care. Oral health was assessed by clinical examinations, and dental use and sociodemographic information are based on self-report. RESULTS: Younger, more educated VA patients with higher incomes had more teeth, fewer untreated and treated root caries, and were less likely to be edentulous or to have dentures. Dental utilization emerged as the most important aspect of veterans' oral health status, even after sociodemographic factors were controlled. Compared with the general population, veterans have poorer oral health with the exception of coronal caries. CONCLUSION: Compared with national studies, VA patients appear to have worse oral health. The importance of sociodemographic factors and dental utilization that has been found in other studies applies to veterans' oral health as well.

Self-reported and clinical oral health in users of VA health care.

BACKGROUND: This article describes the oral health of users of Veterans Administration (VA) health care using both clinical and self-report measures, and models relationships between these measures and self-perceived oral health. METHODS: We conducted a cross-sectional study of 538 male users of VA outpatient care in the Boston area. Questionnaires assessed self-reported oral health, oral-specific health-related quality of life, health behaviors, and sociodemographic information. Clinical data were collected on oral mucosa status, number of teeth and root tips, dental caries, and periodontal treatment need. We report clinical and self-reported oral health status by age group (era of military service). We regressed models of self-perceived oral health on clinical indices and self-reported measures of the impact of oral health on daily life, adjusting for sociodemographic characteristics and health behavior. RESULTS: Among those participants aged 65 to 91 years old, 2.8%, 18.7%, and 41.5% rated their oral health as excellent, very good, or good, respectively. Among 50- to 64-year-old men, the corresponding values were 1.4%, 18.5%, and 40.4%, while among those aged 22 to 49 years old, the values were 2.3%, 17%, and 34.1%. Tooth loss was common among users of VA care; 34% of those aged 65-90 years, 28% of those aged 50-64 years, and 8% of those aged 25-49 years had no teeth. Periodontal treatment needs were uniformly high among persons with teeth; mild mucosal change was common, and 10% had root tips. Regression models showed self-perceived oral health was better in persons with more teeth and recent dental treatment, and worse with tooth mobility, coronal decay, and more medical problems. Measures of the impact of oral conditions on daily life added significantly to the amount of explained variance in self-perceived oral health. CONCLUSIONS: Clinical conditions and the impact of oral health on daily life are important determinants of self-perceived oral health.

Heart murmurs: are older male dental patients aware of their existence?

BACKGROUND: The American Heart Association recommends that patients with certain abnormal and prosthetic heart valves receive antibiotic prophylaxis before undergoing invasive dental treatment, owing to the risk of bacterial endocarditis, or BE. However, it is not known how many patients are aware that they have such conditions and understand such recommendations. METHODS: The authors conducted a study to determine how many male users of three U.S. Department of Veterans' Affairs ambulatory medical care centers denied having a heart murmur, even though a murmur was noted in their medical record. The authors asked 637 potential subjects a series of questions to identify those who had a heart murmur that might place them at risk of developing BE. The authors then reviewed each subject's medical records for documentation of a heart murmur. RESULTS: Four hundred ninety-seven dentate men (mean age: 61.0 years) denied having a heart murmur. Seventy (14.1 percent) of these men had documentation of a heart murmur in their medical records, and 13 (2.6 percent) had murmurs that were likely to be pathological. The failure to accurately report having a heart murmur and having a potentially pathological heart murmur were positively related to age (P = .001). Failure to accurately report having a heart murmur also was related to lower educational levels. CONCLUSIONS: These results indicate that a substantially larger number of older men than younger men were unaware that they had a heart murmur. Since some of these murmurs necessitate administration of antibiotic prophylaxis before dental procedures, this failure to communicate their correct medical status may put them at risk of developing BE. CLINICAL IMPLICATIONS: Dental health care providers should be aware that patient self-report may not be a reliable indicator of cardiac status, particularly in older patients.