Temporal drivers of tryptophan-like fluorescent dissolved organic matter along a river continuum.

Tryptophan-like fluorescence (TLF) is used to indicate anthropogenic inputs of dissolved organic matter (DOM), typically from wastewater, in rivers. We hypothesised that other sources of DOM, such as groundwater and planktonic microbial biomass can also be important drivers of riverine TLF dynamics. We sampled 19 contrasting sites of the River Thames, UK, and its tributaries. Multivariate mixed linear models were developed for each site using 15 months of weekly water quality observations and with predictor variables selected according to the statistical significance of their linear relationship with TLF following a stepwise procedure. The variables considered for inclusion in the models were potassium (wastewater indicator), nitrate (groundwater indicator), chlorophyll-a (phytoplankton biomass), and Total bacterial Cells Counts (TCC) by flow cytometry. The wastewater indicator was included in the model of TLF at 89 % of sites. Groundwater was included in 53 % of models, particularly those with higher baseflow indices (0.50-0.86). At these sites, groundwater acted as a negative control on TLF, diluting other potential sources. Additionally, TCC was included positively in the models of six (32 %) sites. The models on the Thames itself using TCC were more rural sites with lower sewage inputs. Phytoplankton biomass (Chlorophyll-a) was only used in two (11 %) site models, despite the seasonal phytoplankton blooms. It is also notable that, the wastewater indicator did not always have the strongest evidence for inclusion in the models. For example, there was stronger evidence for the inclusion of groundwater and TCC than wastewater in 32 % and 5 % of catchments, respectively. Our study underscores the complex interplay of wastewater, groundwater, and planktonic microbes, driving riverine TLF dynamics, with their influence determined by site characteristics.

Safety outcomes in patients with rheumatoid arthritis treated with abatacept: results from a multinational surveillance study across seven European registries.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept. METHODS: Data were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Antirheumatic and Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of the study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as the number of events per 1000 p-y of follow-up with 95% confidence intervals. RESULTS: Over 5000 patients with RA treated with abatacept were included. Most patients (78-85%) were female, and the mean age range was 52-58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y. CONCLUSIONS: Despite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.

Venous thromboembolism incidence and risk factors associated with immune checkpoint inhibitors among patients with advanced non-small cell lung cancer.

BACKGROUND: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with lung cancer. Systemic therapies, such as chemotherapy (chemo), are associated with increased risk of VTE. Immune checkpoint inhibitors (ICIs) are a new standard of care for the treatment of lung cancer, but their association with VTE is not fully understood. We evaluated the incidence of VTE and risk factors for patients with advanced non-small cell lung cancer (aNSCLC) treated with first-line ICI-based, chemo-based, or ICI+chemo regimens. METHODS: This retrospective cohort study used HealthCore Integrated Research Environment - Oncology data, an integrated database of administrative claims, coupled with clinical data from a cancer-care quality program. Patients with first-line treatment of stage IV non-small cell lung cancer from July 2014 to August 2020 were grouped based on three treatment types: ICI-based, chemo-based, or ICI+chemo. Patients with VTE before initiation of systemic treatment were excluded. Newly diagnosed VTE events were identified via inpatient and outpatient diagnosis codes. Cox proportional hazards models were used to investigate the factors associated with VTE risk. RESULTS: Among 2299 eligible patients (ICI-based, n=605; chemo-based, n=1092; ICI+chemo, n=602) with a median follow-up of 9.1 months, the VTE incidence rates (95% CI) per 100 person-years were 17.8 (95% CI 16.0 to 19.5) overall, 13.5 (95% CI 10.6 to 16.5) for ICI-based, 18.0 (95% CI 15.5 to 20.5) for chemo-based, and 22.4 (95% CI 20.2 to 24.5) for ICI+chemo. The 6-month cumulative incidence of VTE was 8.1% for ICI-based, 10.9% for chemo-based, and 12.8% for ICI+chemo. Pulmonary embolism was most common, accounting for 63% of the VTE events. After controlling for baseline patient characteristics, the risk of VTE was 26% lower for ICI-based regimens than for chemo-based regimens (HR 0.74, p=0.03). There was no meaningful difference in the risk between ICI+chemo and chemo-based regimens (HR 1.12, p=0.36). Previous radiation and severe obesity (body mass index ≥40) were associated with VTE. CONCLUSIONS: VTE incidence rate per 100 person-years was common across regimens in patients with aNSCLC, but numerically lower for patients receiving ICI-based regimens compared with those receiving chemo-based and ICI+chemo regimens. VTE is a common complication of lung cancer, and there is a continued need for awareness of VTE as a comorbidity in this population.

A review of microplastic fibres: generation, transport, and vectors for metal(loid)s in terrestrial environments.

The laundering of synthetic fabrics has been identified as an important and diffuse source of microplastic (<5 mm) fibre contamination to wastewater systems. Home laundering can release up to 13 million fibres per kg of fabric, which end up in wastewater treatment plants. During treatment, 72-99% of microplastics are retained in the residual sewage sludge, which can contain upwards of 56 000 microplastics per kg. Sewage sludge is commonly disposed of by application to agricultural land as a soil amendment. In some European countries, application rates are up to 91%, representing an important pathway for microplastics to enter the terrestrial environment, which urgently requires quantification. Sewage sludge also often contains elevated concentrations of metals and metalloids, and some studies have quantified metal(loid) sorption onto various microplastics. The sorption of metals and metalloids is strongly influenced by the chemical properties of the sorbate, the solution chemistry, and the physicochemical properties of the microplastics themselves. Plastic-water partition coefficients for the sorption of cadmium, mercury and lead onto microplastics are up to 8, 32, and 217 mL g-1 respectively. Sorptive capacities of microplastics may increase over time, due to environmental degradation processes increasing the specific surface area and surface density of oxygen-containing functional groups. A range of metal(loid)s, including cadmium, chromium, and zinc, have been shown to readily desorb from microplastics under acidic conditions. Sorbed metal(loid)s may therefore become more bioavailable to soil organisms when the microplastics are ingested, due to the acidic gut conditions facilitating desorption. Polyester (polyethylene terephthalate) should be of particular focus for future research, as few quantitative sorption studies currently exist, it is potentially overlooked from density separation studies due to its high density, and it is by far the most widely used fibre in apparel textiles production.

Drivers of variation in occurrence, abundance, and behaviour of sharks on coral reefs.

Quantifying the drivers of population size in reef sharks is critical for the development of appropriate conservation strategies. In north-west Australia, shark populations inhabit coral reefs that border growing centres of human population, industry, and tourism. However, we lack baseline data on reef sharks at large spatial scales (hundreds of km) that might enable managers to assess the status of shark populations in the face of future development in this region. Here, we examined the occurrence, abundance and behaviour of apex (Galeocerdo cuvier, Carcharhinus plumbeus) and reef (C. amblyrhynchos, C. melanopterus, Triaenodon obesus) sharks using > 1200 deployments of baited remote underwater stereo-video systems (stereo-BRUVs) across > 500 km of coastline. We found evidence for species-specific influences of habitat and fishing activities on the occurrence (probability of observation), abundance (MaxN) and behaviour of sharks (time of arrival to the stereo-BRUVs and likelihood of feeding). Although the presence of management zoning (No-take areas) made little difference to most species, C. amblyrhynchos were more common further from boat ramps (a proxy of recreational fishing pressure). Time of arrival for all species was also influenced by distance to boat ramp, although patterns varied among species. Our results demonstrate the capacity for behavioural metrics to complement existing measures of occurrence and abundance in assessing the potential impact of human activities on shark populations.

Aluminum-induced generation of lipopolysaccharide (LPS) from the human gastrointestinal (GI)-tract microbiome-resident Bacteroides fragilis.

Gram-negative bacteria of the human gastrointestinal (GI) tract microbiome: (i) are capable of generating a broad-spectrum of highly neurotoxic, pro-inflammatory and potentially pathogenic molecules; and (ii) these include a highly immunogenic class of amphipathic surface glycolipids known as lipopolysaccharide (LPS). Bacteroides fragilis (B. fragilis), a commensal, Gram negative, non-motile, non-spore forming obligatory anaerobic bacillus, and one of the most abundant bacteria found in the human GI tract, produces a particularly pro-inflammatory and neurotoxic LPS (BF-LPS). BF-LPS: (i) is known to be secreted from the B. fragilis outer membrane into the external-medium; (ii) can damage biophysiological barriers via cleavage of zonula adherens cell-cell adhesion proteins, thereby disrupting both the GI-tract barrier and the blood-brain barrier (BBB); (iii) is able to transit GI-tract barriers into the systemic circulation and cross the BBB into the human CNS; and (iv) accumulates within CNS neurons in neurodegenerative disorders such as Alzheimer's disease (AD). This short communication provides evidence that the incubation of B. fragilis with aluminum sulfate [Al2(SO4)3] is a potent inducer of BF-LPS. The results suggest for the first time that the pro-inflammatory properties of aluminum may not only be propagated by aluminum itself, but by a stimulation in the production of microbiome-derived BF-LPS and other pro-inflammatory pathogenic microbial products normally secreted from human GI-tract-resident microorganisms.

Understanding factors that contribute to the disposal of unused opioid medication.

PURPOSE: Drivers of excess controlled substance disposal behaviors are not well understood. A survey of patients who had received opioid-based medications was conducted to inform the design of future innovative drug take-back programs. METHODS: This was a cross-sectional survey study conducted in 152 participants who received treatment with an opioid within the previous 2 years and had possession of unused medication following either switching to a different opioid or discontinuation of pain. RESULTS: Approximately one-third of patients had disposed of their unused opioid medication. Education about the importance of and appropriate methods for drug disposal was associated with a significantly increased likelihood of patients disposing of unused medication, and it was observed that patients prescribed an immediate-release/short-acting opioid were twice as likely to keep their medication compared to those prescribed an extended-release/long-acting opioid. The most commonly reported methods for disposal were via drug return kiosks and flushing the medication down the toilet. Some of the most impactful drivers of unused opioid disposal were routine practice of disposing of all unused drugs and instruction from a health care provider, and the most common driver of keeping unused medication was the desire to have it on-hand should there be a need to treat pain in the future. Over 80 % of patients indicated that they would be more likely to use a drug take-back service if they were offered compensation or if the kiosk was in a location that they visited frequently, and approximately half of the patients indicated that they would be willing to request an initial partial fill of an opioid prescription to reduce the volume of unused medication. CONCLUSION: There is a clear need to increase patient awareness about the importance and methods of proper medication disposal, and a great opportunity for health care providers to increase patient education efforts. These study findings also highlight key areas for improvement in drug take-back programs that may promote and incentivize more patients to utilize the services.

Fish associated with a subsea pipeline and adjacent seafloor of the North West Shelf of Western Australia.

Information on the potential ecological value of offshore oil and gas infrastructure is required as it reaches the end of its operational life and decisions must be made regarding the best practice option for decommissioning. This study uses baited remote underwater stereo-video systems to assess fish assemblages along an offshore subsea pipeline and in adjacent natural seabed habitats at ∼140 m depth on the North West Shelf of Western Australia. A total of 955 fish from 40 species and 25 families were recorded. Species richness was, on average 25% higher on the pipeline (6.48 ±â€¯0.37 SE) than off (4.81 ±â€¯0.28 SE) while relative abundance of fish was nearly double on the pipeline (20.38 ±â€¯2.81 SE) than in adjacent natural habitats (10.97 ±â€¯1.02 SE). The pipeline was characterised by large, commercially important species known to associate with complex epibenthic habitat and, as such, possessed a biomass of commercial fish ca 7.5 × higher and catch value ca. 8.6 × ($65.11 ±â€¯$11.14 SE) than in adjacent natural habitats ($7.57 ±â€¯$2.41 SE). This study has added to the knowledge of fish assemblage associations with subsea infrastructure and provides a greater understanding of the ecological and fisheries implications of decommissioning, helping to better inform decision-making on the fate of infrastructure.

Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events.

Background Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the neutropenia-related efficacy and safety of lipegfilgrastim to those of pegfilgrastim and filgrastim. Methods Embase was searched for trials examining the efficacy/safety of lipegfilgrastim, pegfilgrastim, or filgrastim. Outcomes included febrile neutropenia, severe neutropenia, duration of severe neutropenia, time to recovery of absolute neutrophil count, and incidence of bone pain. Direct comparisons were made using random-effects models. No trials directly compared lipegfilgrastim and filgrastim. Indirect comparisons were made between lipegfilgrastim and filgrastim with pegfilgrastim as the common comparator. Results This meta-analysis included a total of 5769 patients from 24 studies. Over all cycles, lipegfilgrastim showed a lower, nonsignificant risk of febrile neutropenia compared with pegfilgrastim. Lipegfilgrastim has a lower risk of febrile neutropenia versus filgrastim but was also not statistically significant. The risk ratio for severe neutropenia in cycle 1 was 0.80, a 20% reduction in favor of lipegfilgrastim. For cycles 2-4, the risk ratio was 0.53 (0.35, 0.79) for lipegfilgrastim versus pegfilgrastim. The risk of severe neutropenia in cycles 2-4 was also significantly lower for lipegfilgrastim (risk ratio 0.45, 0.27, 0.75, respectively). No significant differences were found for febrile neutropenia and severe neutropenia in cycle 1. However, in cycles 2-4, lipegfilgrastim was associated with significant and clinically meaningful reductions in risk of severe neutropenia versus either pegfilgrastim or filgrastim. Conclusions Compared with pegfilgrastim or filgrastim, lipegfilgrastim has a statistically significantly lower absolute neutrophil count recovery time; however, differences in duration of severe neutropenia and bone pain were nonsignificant.

Real-world utilization of once-daily extended-release abuse deterrent formulation of hydrocodone: a comparison with the pre-approval randomized clinical trials.

BACKGROUND AND OBJECTIVE: Hydrocodone bitartrate extended release (Hysingla® ER, HYD) was previously studied in a 12-week randomized, double-blind, placebo-controlled trial and a 52-week open-label safety study. Both of these preapproval studies allowed dose titration to efficacy. The purpose of the present analysis was to compare dosing and utilization patterns in these previous clinical trials with real-world data (RWD) usage in a retrospective claim analysis performed 12-14 months post approval in the US. METHODS: In the claim analysis (Truven Health Analytics MarketScan® Research Database), patients prescribed HYD between January 1, 2015, and April 30, 2016, were followed for up to 6 months of continuous HYD use. Daily average consumption (DACON), initial dose, rescue opioid use and total milligram dose over time were also evaluated. RESULTS: HYD daily dose stabilized at ~60 mg dose once daily across all three studies. There was also a reduced need for rescue medication with HYD, resulting in a lower total opioid milligram dose over time. In the claim analysis, the mean monthly HYD dose increased from 49 to 55 mg in month 2 and then remained stable through month 6. The mean (standard deviation [SD]) time on drug was 79.5 days (61.42 days), and DACON was 1.04 pills/day, corresponding to the approved full prescribing information (FPI) and once-daily dosing. CONCLUSION: In 12-14 months post approval, real-world dosing and utilization of HYD mirrored registration and open-label study findings, with stable once-daily dosing of ~60 mg and no increase in rescue medicine utilization.

Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab.

BACKGROUND: Dermatomyositis and polymyositis (DM/PM) are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU). When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg), rituximab, or repository corticotropin injection (RCI). This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM. METHODS: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab) based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM) MRU and costs were compared using Poisson regression and generalized linear modeling, respectively. RESULTS: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049), shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004), PPPM hospital outpatient department (HOPD) visits (0.60 vs 1.39; P<0.001), and PPPM physician office visits (2.01 vs 2.33; P=0.035) than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001) than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001) and less PPPM HOPD visits (0.53 vs 1.26; P<0.001) than IVIg+rituximab. Total non-medication PPPM costs were 23%-75% lower for RCI compared to IVIg ($2,126 vs $3,964; P<0.001), rituximab ($2,008 vs $2,607; P=0.018), and IVIg+rituximab ($1,234 vs $4,858; P<0.001). CONCLUSION: Patients treated with RCI had less PPPM non-medication MRU and costs than those treated with IVIg and/or rituximab, particularly in the hospital setting where significant costs are incurred.

Impact of seizure frequency reduction on health-related quality of life among clinical trial subjects with refractory partial-onset seizures: A pooled analysis of phase III clinical trials of eslicarbazepine acetate.

BACKGROUND: Subjects who received eslicarbazepine acetate (ESL) as adjunctive therapy experienced significantly greater seizure frequency reduction (SFR) than placebo in three phase III, randomized, double-blind trials. This analysis compared changes in health-related quality of life (HRQOL) between treatment responders and non-responders across the pooled, per-protocol population (N=842) using the validated Quality of Life in Epilepsy Inventory-31 (QOLIE-31). METHODS: QOLIE-31 scores were calculated for Total Score (TS) and seven subscales; higher scores indicate better HRQOL. Mean changes from baseline were calculated. Analysis of covariance examined least square mean (LSM) differences in final scores between responders (≥50% and ≥75% SFR) and non-responders. Clinical significance was based on established minimal clinically important differences (MCIDs). RESULTS: Mean changes were greater among responders for TS (5.2 versus 1.4 for ≥50% SFR; 7.5 versus 1.9 for ≥75% SFR) and all subscales. Additionally, the percentage of subjects with changes meeting or exceeding MCIDs was higher among responders for TS (48.4% versus 33.9% for ≥50% SFR; 56.9% versus 35.8% for ≥75% SFR) and all subscales. Responders had significantly higher final scores for TS (LSM difference=4.0 for ≥50% SFR; LSM difference=5.7 for ≥75% SFR) and all subscales except emotional well-being at ≥50% SFR. LSM differences exceeded MCIDs at ≥75% SFR for TS and five of seven subscales, and two subscales at ≥50% SFR. In a subgroup analysis with placebo removed, LSM differences were larger overall. SIGNIFICANCE: In clinical trials of adjunctive ESL, higher levels of SFR were associated with greater improvements in HRQOL.

Optimising the bioreceptivity of porous glass tiles based on colonization by the alga Chlorella vulgaris.

Green façades on buildings can mitigate greenhouse gas emissions. An option to obtain green facades is through the natural colonisation of construction materials. This can be achieved by engineering bioreceptive materials. Bioreceptivity is the susceptibility of a material to be colonised by living organisms. The aim of this research was to develop tiles made by sintering granular waste glass that were optimised for bioreceptivity of organisms capable of photosynthesis. Tiles were produced by pressing recycled soda-lime glass with a controlled particle size distribution and sintering compacted samples at temperatures between 680 and 740°C. The primary bioreceptivity of the tiles was evaluated by quantifying colonisation by the algae Chlorella vulgaris (C. vulgaris), which was selected as a model photosynthetic micro-organism. Concentrations of C. vulgaris were measured using chlorophyll-a extraction. Relationships between bioreceptivity and the properties of the porous glass tile, including porosity, sorptivity, translucency and pH are reported. Capillary porosity and water sorptivity were the key factors influencing the bioreceptivity of porous glass. Maximum C. vulgaris growth and colonisation was obtained for tiles sintered at 700°C, with chlorophyll-a concentrations reaching up to 11.1±0.4µg/cm(2) of tile. Bioreceptivity was positively correlated with sorptivity and porosity and negatively correlated with light transmittance. The research demonstrates that the microstructure of porous glass, determined by the processing conditions, significantly influences bioreceptivity. Porous glass tiles with high bioreceptivity that are colonised by photosynthetic algae have the potential to form carbon-negative façades for buildings and green infrastructure.

Severity and burden of partial-onset seizures in a phase III trial of eslicarbazepine acetate.

OBJECTIVE: The objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures. METHODS: The Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (frequency and helpfulness of warning signs before seizures [BS]; severity and bothersomeness of ictal movement and altered consciousness during seizures [DS]; cognitive, emotional, and physical aspects of postictal recovery after seizures [AS]; and overall severity and bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms. RESULTS: Out of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200 mg/day was significantly lower than that for placebo (2.68 vs 3.20, p<0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200 mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800 mg/day than for placebo; only SB was significant (p=0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p=0.006), DS (p=0.031), and SB (p=0.001). CONCLUSIONS: Therapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores. CLASSIFICATION OF EVIDENCE: This study presents Class I evidence that adjunctive ESL (800 and 1200 mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.

Ferric Citrate, an Iron-Based Phosphate Binder, Reduces Health Care Costs in Patients on Dialysis Based on Randomized Clinical Trial Data.

BACKGROUND: Patients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (i.v.) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases i.v. iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. The study objectives were to (1) quantify differences in ESA and i.v. iron usage among ESRD patients receiving FC compared with active control (AC) (sevelamer carbonate and/or calcium acetate) on the basis of data from a 52-week phase III clinical trial and (2) standardize trial data to the general United States (US) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA. STUDY DESIGN: The study was a randomized, controlled clinical trial. SETTING AND POPULATION: A total of 441 adult subjects with ESRD who received FC or AC for 52 weeks were included. MODEL, PERSPECTIVE, AND TIMELINE: Differences in ESA and i.v. iron usage between the treatment groups were modeled over time using generalized linear mixed models and zero-inflated Poisson models. Trends were modeled via logarithmic curves, and utilization patterns were applied to the general dialysis population to estimate expected resource savings. OUTCOMES: Study outcomes were costs saved/patient/year using FC versus AC (US dollars). RESULTS: Our model suggests an annual decrease of 129,106 U of ESAs and 1960 mg of i.v. iron per patient in the second year after a switch from AC to FC. Applying 2013 Medicare pricing, this would save $1585 in ESAs and $516 in i.v. iron: a total of $2101/patient/year; these savings would be expected to double for managed care plans. LIMITATIONS: The projections were made on 1 year of trial data. CONCLUSIONS: Phosphate binding with FC reduces i.v. iron and ESA usage. Given the high cost burden of ESRD, our model demonstrates significant potential cost savings. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01191255) http://clinicaltrials.gov/ct2/show/NCT01191255 .

Mortality rates do not differ among patients prescribed various vitamin D agents.

BACKGROUND: Limited well-controlled research exists examining the impact of different formulations of oral vitamin D on clinical outcomes in dialysis patients, specifically those on peritoneal dialysis. For this retrospective mortality analysis, we compared mortality rates of patients on 3 of the most commonly prescribed vitamin D agents. METHODS: We examined 2 years (7/1/2008 to 6/30/2010) of oral medication records of peritoneal dialysis patients from a large US dialysis organization. Patients were identified whose physicians prescribed a single form of vitamin D (calcitriol, paricalcitol, or doxercalciferol) for ≥ 90% of all patient-months. We excluded incident patients (< 90 days on dialysis) and patients whose physicians treated < 5 peritoneal dialysis patients at a dialysis facility, and we assessed mortality. RESULTS: The analysis inclusion criteria identified 1,707 patients. The subset in this analysis included 12.6% of all prevalent peritoneal dialysis patients and 11.8% of prevalent patient-months. Patients with physicians who predominately prescribed calcitriol had a lower mortality rate: 9.33 (confidence interval (CI) 7.06, 11.60) deaths per 100 patient-years than the doxercalciferol, 12.20 (CI 9.34, 15.06) or paricalcitol, 12.27 (CI 9.27, 15.28) groups. However, these differences were not statistically significant. A Cox proportional hazards model, adjusting for differences in age, vintage, gender, race, body mass index, and comorbidities also showed no significant differences. CONCLUSIONS: For this peritoneal dialysis population, instrumental variable analyses showed no significant difference in mortality in patients taking the most common oral vitamin D formulations (calcitriol, doxercalciferol, paricalcitol).

Effect of implementing the 5As of obesity management framework on provider-patient interactions in primary care.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Obesity counselling in primary care is positively associated with self-reported behaviour change in patients with obesity. Obesity counselling is rare, and when it does occur, it is often of low quality because of poor training and/or competency of providers' obesity management, lack of time and economical disincentives, and negative attitude towards obesity and obesity management. 5As frameworks are routinely used for behaviour-change counselling and addiction management (e.g. smoking cessation), but few studies have examined its efficacy for weight management. WHAT THIS STUDY ADDS: This study presents pilot data from the implementation and evaluation of an obesity management tool (5As of Obesity Management developed by the Canadian Obesity Network) in a primary care setting. Results show that the tool facilitates weight management in primary care by promoting physician-patient communications, medical assessments for obesity and plans for follow-up care. Obesity remains poorly managed in primary care. The 5As of Obesity Management is a theory-driven, evidence-based minimal intervention designed to facilitate obesity counselling and management by primary care practitioners. This project tested the impact of implementing this tool in primary care clinics. Electronic self-administered surveys were completed by pre-screened obese subjects at the end of their appointments in four primary care clinics (over 25 healthcare providers [HCPs]). These measurements were performed before (baseline, n = 51) and 1 month after implementing the 5As of Obesity Management (post-intervention, n = 51). Intervention consisted of one online training session (90 min) and distribution of the 5As toolkit to HCPs of participating clinics. Subjects completing the survey before and after the intervention were comparable in terms of age, sex, body mass index, comorbidities, satisfaction and self-reported health status (P > 0.2). Implementing the 5As of Obesity Management resulted in a twofold increase in the initiation of obesity management (19 vs. 39%, P = 0.03), and caused a statistically significant increase in the perceived follow-up/coordination efforts (self-reported Patient Assessment of Chronic Illness Care components, 45 ± 22 vs. 67 ± 12 points, P = 0.002), as well as two components of the 5As framework: Assess (50 ± 29 vs. 66 ± 15 points, P = 0.03) and Assist (54 ± 26 vs. 72 ± 13 points, P = 0.01). Our results suggest that using the 5As of Obesity Management facilitates weight management in primary care by promoting physician-patient communications, medical assessments for obesity and plans for follow-up care.

Factors involved in sustained use of point-of-use water disinfection methods: a field study from Flores Island, Indonesia.

Many scientific studies have suggested that point-of-use water treatment can improve water quality and reduce the risk of infectious diseases. Despite the ease of use and relatively low cost of such methods, experience shows the potential benefits derived from provision of such systems depend on recipients' acceptance of the technology and its sustained use. To date, few contributions have addressed the problem of user experience in the post-implementation phase. This can diagnose challenges, which undermine system longevity and its sustained use. A qualitative evaluation of two household water treatment systems, solar disinfection (SODIS) and chlorine tablets (Aquatabs), in three villages was conducted by using a diagnostic tool focusing on technology performance and experience. Cross-sectional surveys and in-depth interviews were used to investigate perceptions of involved stakeholders (users, implementers and local government). Results prove that economic and functional factors were significant in using SODIS, whilst perceptions of economic, taste and odour components were important in Aquatabs use. Conclusions relate to closing the gap between factors that technology implementers and users perceive as key to the sustained deployment of point-of-use disinfection technologies.

Reduced use of erythropoiesis-stimulating agents and intravenous iron with ferric citrate: a managed care cost-offset model.

BACKGROUND: Ferric citrate (FC) is a phosphate binder in development for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). In clinical trials, FC improved patient serum phosphorus levels and increased serum ferritin and percent transferrin saturation. Because nephrologists respond to increases in these iron measures by reducing intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) doses, the decreased use of iron and ESA associated with FC may reduce costs. OBJECTIVES: To develop a cost-offset model from a managed care perspective estimating the cost savings associated with FC use. METHODS: We created a cost-offset model from the managed care payer perspective that compared the treatment costs of ESRD for patients given FC. The model considered the number of dialysis sessions per month; number of ESRD patients enrolled in the health plan; cost of ESAs, iron, and dialysis sessions; and the proportion of patients on phosphate binder therapy. The model assumed equivalent efficacy and cost neutrality between FC and other phosphate binders. Monte Carlo simulations were conducted by varying model inputs. RESULTS: When FC was compared to other phosphate binders, the monthly cost of ESA and IV iron per 500 patients with ESRD (85% treated with phosphate binders) was reduced by 8.15% and 33.2%, respectively. When incorporated into the total cost of dialysis for patients with ESRD (dialysis, ESA, and IV iron), the decrease in the monthly cost of dialysis care was US$80,214 per 500 ESRD patients. Monte Carlo simulations suggest that a plan serving 500 dialysis patients could save between US$626,000 and US$1,106,000 annually with the use of FC. CONCLUSION: The use of FC in ESRD patients with hyperphosphatemia may help reduce treatment costs.