Wastewater management decision-making: A literature review and synthesis.

Wastewater management decision-making is complicated because of: (1) a complex regulatory structure, (2) the wide variety of conflicting expectations by stakeholders external and internal to the responsible utility, and (2) constrains including regulatory requirements, available technologies and practices, and customer willingness to pay. This review synthesizes the results from over 200 papers published since 2000 and presents a decision-making structure and process which is (1) science and fact-based, (2) reflects sustainability, (3) clear and transparent, (4) inclusive, (5) produces an objective-oriented decision, (6) scalable, (7) repeatable, and (8) efficient. Tools supporting the decision-making process are reviewed, including Multi-Criteria Decision Analysis (MCDA), Data Envelopment Analysis (DEA), Analytic Hierarchy Process (AHP), process modeling, economic assessments, Life Cycle Assessment (LCA), and Social Life Cycle Assessment (SLCA). Ultimately it was determined that engagement of decision-makers and relevant stakeholders to assess their values and preferences, coupled with supporting data and analyses, is necessary to reach a decision that, critically, has the support needed for it to be implemented. The results demonstrate that an understanding of the components of the decision process, coupled with an orderly process, enables good wastewater management decision-making. PRACTITIONER POINTS: A decision-making structure and process leading to the selection of implementable solutions is presented. The process possesses the following attributes: (1) science and fact-based, (2) reflect sustainability, (3) clear and transparent, (4) inclusive, (5) produce an objective-oriented decision, (6) scalable, (7) repeatable, and (8) efficient An extensive summary and analysis of tools supporting the decision process are provided, including Multi-Criteria Decision Analysis (MCDA), Data Envelopment Analysis (DEA), Analytic Hierarchy Process (AHP), process modeling, economic assessments, Life Cycle Assessment (LCA), and Social Life Cycle Assessment (SLCA). The critical role of internal and external stakeholders and differentiating their involvement relative to decision-makers is emphasized.

National trends in prescription drug expenditures and projections for 2024.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2024 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2024 were reviewed-including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2023, overall pharmaceutical expenditures in the US grew 13.6% compared to 2022, for a total of $722.5 billion. Utilization (a 6.5% increase), new drugs (a 4.2% increase) and price (a 2.9% increase) drove this increase. Semaglutide was the top drug in 2023, followed by adalimumab and apixaban. Drug expenditures were $37.1 billion (a 1.1% decrease) and $135.7 billion (a 15.0% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small impact from price and new products. In nonfederal hospitals, a drop in utilization led the decrease in expenditures, with price and new drugs modestly contributing to growth in spending. Several new drugs that will influence spending are expected to be approved in 2024. Specialty, endocrine, and cancer drugs will continue to drive expenditures. CONCLUSION: For 2024, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 0% to 2.0% increase, respectively, compared to 2023. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending.

Smoothing the Phosphorus Resource Stress under the Socioeconomic Development in China.

Phosphorus (P) is the key in maintaining food security and ecosystem functions. Population growth and economic development have increased the demand for phosphate rocks. China has gradually developed from zero phosphate mining to the world's leading P miner, fertilizer, and agricultural producer since 1949. China released policies, such as designating phosphate rock as a strategic resource, promoting eco-agricultural policies, and encouraging the use of solid wastes produced in mining and the phosphorus chemical industry as construction materials. However, methodological and data gaps remain in the mapping of the long-term effects of policies on P resource efficiency. Here, P resource efficiency can be represented by the potential of the P cycle to concentrate or dilute P as assessed by substance flow analysis (SFA) complemented by statistical entropy analysis (SEA). P-flow quantification over the past 70 years in China revealed that both resource utilization and waste generation peaked around 2015, with 20 and 11 Mt of mined and wasted P, respectively. Additionally, rapidly increasing aquaculture wastewater has exacerbated pollution. The resource efficiency of the Chinese P cycle showed a U-shaped change with an overall improvement of 22.7%, except for a temporary trough in 1975. The driving force behind the efficiency decline was the roaring phosphate fertilizer industry, as confirmed by the sharp increase in P flows for both resource utilization and waste generation from the mid-1960s to 1975. The positive driving forces behind the 30.7% efficiency increase from 1975 to 2018 were the implementation of the resource conservation policy, downstream pollution control, and, especially, the circular agro-food system strategy. However, not all current management practices improve the P resource efficiency. Mixing P industry waste with construction materials and the development of aquaculture to complement offshore fisheries erode P resource efficiency by 2.12% and 9.19%, respectively. With the promotion of a zero-waste society in China, effective P-cycle management is expected.

Optimizing Air Scouring Energy for Sustainable Membrane Bioreactor Operation by Characterizing the Combination of Factors Leading to Threshold Limiting Conditions.

Key operating variables to predict the necessary scour air flowrate in full-scale Membrane Bioreactor (MBR) systems are identified, aiming to optimize energy consumption while avoiding the limiting condition (i.e., rapid increasing total resistance). The resulting metric, referred to here as the K value, was derived by balancing hydrodynamic conditions between the particle deposit rate imposed by permeate flux normalized by fouling condition and its removal by shear stress induced from air scouring. The metric includes air scouring flow, permeate flow, Mixed Liquor Suspended Solids (MLSS) concentration, Mixed Liquor (ML) viscosity, membrane packing density, and total resistance. Long-term (year-long) data from two full-scale MBR plants were analyzed. The value of K corresponding to limiting operational operation and referred to as the limiting K value, KLim, is estimated by detecting the occurrence of threshold limiting flux from the data stream and calculating the resulting value for K. Then, using KLim, the minimum required specific air demand per permeate (SADp,Crit) is calculated, indicating a potential reduction of over half the air scouring energy in typical operational conditions. The results from this data driven analysis suggest the feasibility of employing KLim to predict the adequate scour air flowrate in terms of dynamically varying operational conditions. This approach will lead to the development of energy-efficient algorithms, significantly reducing scour air energy consumption in the full-scale MBR system.

Adherence and persistence of HIV pre-exposure prophylaxis use in the United States.

PURPOSE: To describe medication adherence and persistence of HIV PrEP overall and compare between sex and age groups of commercially insured individuals in the United States. METHODS: We conducted a national retrospective cohort study of the Merative MarketScan Claims Database from 2011 to 2019 to describe adherence and persistence of PrEP overall and compared between sex and age groups. High adherence was defined as ≥80% of proportion of days covered and persistence was measured in days from initiation to the first day of a 60-day treatment gap. RESULTS: A total of 29 689 new PrEP users identified. Overall adherence was high (81.9%; 95% confidence interval [CI]: 81.5%-82.3%). Females were more adherent than males (adjusted odds ratio [aOR] 1.87; 95% CI: 1.50-2.34), while those ≥45-years were less adherent than individuals <45-years (aOR 0.87: 95% CI: 0.81-0.93). More than half of individuals discontinued therapy within the first year (median 238.0 days; interquartile range 99.0-507.0 days). Females were less persistent than males (hazard ratio [HR] 1.49; 95% CI: 1.34-1.65), and people ≥45-years old were more persistent (i.e., lower risk of discontinuation) than those <45-years (HR 0.43; 95% CI: 0.33-0.55). CONCLUSIONS: These findings show adherence to daily PrEP is high among commercially insured individuals but the majority still discontinue in the first year. Future research should investigate what factors influence PrEP discontinuation among this population and ways to reduce barriers to therapy maintenance to ensure the population-level benefits of PrEP treatment.

Monitoring biofilm thickness using the membrane aerated biofilm reactor (MABR) fingerprint soft sensor to optimize nitrogen removal.

The ongoing commercialization and installation of full-scale membrane aerated biofilm reactors (MABRs) stimulate the increasing need to monitor biofilm development. Biofilm thickness in MABRs can be assessed indirectly by plotting the exhaust oxygen purity versus bulk ammonia concentration, defined here as the MABR fingerprint soft sensor. Dynamic simulations with diurnal flow variations of an MABR unit model were implemented over a broad range of biofilm thicknesses and influent conditions consisting of variable C/N ratios and applied ammonia fluxes to assess the utility of the MABR fingerprint. Results show that the continuously decreasing trend of the MABR fingerprint plot slopes can be employed as a useful signal for biofilm thickness control in nitrogen removal processes. This technique is useful in a wide range of influent conditions and is helpful for MABR operators and designers to arrange biofilm thickness control events efficiently and determine where in an overall treatment process the technique can be applied to control biofilm thickness and optimize process performance. PRACTITIONER POINTS: The linear relationship between exhaust oxygen purity and bulk ammonia concentration is defined as the MABR fingerprint plot. MABR fingerprint plots are generated for a given biofilm thickness with diurnal flow or short-term loading variations implemented. Continuously decreasing trends of the MABR fingerprint plot slopes are useful signals for biofilm control in nitrogen removal. The MABR fingerprint is useful over a wide range of influent conditions regarding C/N ratios and applied ammonia fluxes. MABR practitioners can use the fingerprint plots to determine when biofilm control measures should be taken.

Exposure of the static magnetic fields on the microbial growth rate and the sludge properties in the complete-mix activated sludge process (a Lab-scale study).

BACKGROUND: In this study, the effect of static magnetic fields (SMFs) on improving the performance of activated sludge process to enhance the higher rate of microbial growth biomass and improve sludge settling characteristics in real operation conditions of wastewater treatment plants has been investigated. The effect of SMFs (15 mT), hydraulic retention time, SRT, aeration time on mixed liquor suspended solids (MLSS) concentrations, mixed liquor volatile suspended solids (MLVSS) concentrations, α-factor, and pH in the complete-mix activated sludge (CMAS) process during 30 days of the operation, were evaluated. RESULTS: There were not any differences between the concentration of MLSS in the case (2148.8 ± 235.6 mg/L) and control (2260.1 ± 296.0 mg/L) samples, however, the mean concentration of MLVSS in the case (1463.4 ± 419.2 mg/L) was more than the control samples (1244.1 ± 295.5 mg/L). Changes of the concentration of MLVSS over time, follow the first and second-order reaction with and without exposure of SMFs respectively. Moreover, the slope of the line and, the mean of α-factor in the case samples were 6.255 and, - 0.001 higher than the control samples, respectively. Changes in pH in both groups of the reactors were not observed. The size of the sluge flocs (1.28 µm) and, the spectra of amid I' (1440 cm-1) and II' (1650 cm-1) areas related to hydrogenase bond in the case samples were higher than the control samples. CONCLUSIONS: SMFs have a potential to being considered as an alternative method to stimulate the microbial growth rate in the aeration reactors and produce bioflocs with the higher density in the second clarifiers.

Trends of nonoccupational postexposure prophylaxis in the United States.

OBJECTIVE: To describe national annual rates of nonoccupational postexposure prophylaxis (nPEP) in the United States. DESIGN: Retrospective cohort study of commercially insured individuals in the Merative MarketScan Database from January 1, 2010 to December 31, 2019. METHODS: Patients at least 13 years old prescribed nPEP per recommended Centers for Disease Control and Prevention guidelines were identified using pharmacy claims. Rates of use were described overall and stratified by sex, age group, and region. These rates were qualitatively compared to the diagnosis rates of human immunodeficiency virus (HIV) observed in the data. Joinpoint analysis identified inflection points of nPEP use. RESULTS: Eleven thousand, three hundred and ninety-seven nPEP users were identified, with a mean age of 33.7 years. Most were males (64.6%) and lived in the south (33.2%) and northeast (32.4%). The rate of nPEP use increased 515%, from 1.42 nPEP users per 100 000 enrollees in 2010 to 8.71 nPEP users per 10 000 enrollees in 2019. The comparative nPEP use rates among subgroups largely mirrored their HIV diagnosis rates, that is, subgroups with a higher HIV rate had higher nPEP use. In the Joinpoint analysis significant growth was observed from 2012 to 2015 [estimated annual percentage change (EAPC): 45.8%; 95% confidence interval (CI): 29.4 - 64.3] followed by a more moderate increase from 2015 to 2019 (EAPC 16.0%; 95% CI: 12.6-19.6). CONCLUSIONS: nPEP use increased from 2010 to 2019, but not equally across all risk groups. Further policy interventions should be developed to reduce barriers and ensure adequate access to this important HIV prevention tool.

The hybrid MABR process achieves intensified nitrogen removal while N2O emissions remain low.

The hybrid membrane aerated biofilm reactor (MABR) process represents a full-scale solution for sustainable municipal wastewater treatment. However, most of the existing hybrid MABR processes retain large aerobic bioreactor volumes for nitrification, which is undesirable for energy and carbon savings. In this study, we used the plant-wide modeling approach with dynamic simulations to examine a novel hybrid MABR configuration with aeration controls that change the anoxic and aerobic fractions of the bioreactor volume. Result showed that the novel hybrid MABR showed "swinging" nitrification and denitrification capacities in response to diurnal loadings, achieving intensified nitrogen removal performance under both warm and cold temperature scenarios. N2O emissions from the hybrid MABR were only 1/5 of the emissions from the conventional activated sludge. The model predicted higher CH4 emissions from the hybrid MABR than the activated sludge process due to the methanogen growth in the oxygen-depleted MABR biofilm layer. Future measurements for CH4 emission are needed to obtain a holistic picture of the carbon footprint of the hybrid MABR process.

The relationship of cervicothoracic mobility restrictions to fall risk and fear of falling in ankylosing spondylitis.

Objective: The objective of this study is to determine whether restricted cervical mobility in ankylosing spondylitis (AS) is associated with increased fall frequency or fear of falling. Methods: A total of 134 AS patients and 199 age- and gender-matched control subjects (CS) with soft-tissue cervicothoracic pain were prospectively evaluated for fall risk. Subjects were divided into non-fallers, single fallers, and multiple fallers. Dynamic cervical rotations and static cervicothoracic axial measurements were compared between the groups. In total, 88 AS patients were reviewed more than once; Kaplan-Meier plots were constructed for fall risk as a function of cervical rotation amplitudes. Falls Efficacy Scale-International (FES-I) questionnaire measured the fear of falling. Results: In total, 34% of AS patients and 29% of CS fell (p = 0.271) in the year prior to evaluation. In AS, static anatomical measurements were unrelated to fall occurrence. The trends of multiple AS fallers to greater flexed forward postures and reduced dynamic cervical rotations were not statistically significant. Cervicothoracic pain (p = 0.0459), BASDAI (p = 0.002), and BASFI (p = 0.003) scores were greater in multiple fallers. FES-I scores were greater in fallers (p = 0.004). Of the 88 AS patients reviewed (or seen) on more than one occasion, 46.5% fell over the 9-year observation period, including all multiple fallers and 71.4% of single fallers. Survival curves showed increased fall risk as cervical rotational amplitudes decreased. Conclusion: In AS, decreased cervical rotations increase fall risk and fear of falling. In multiple fallers, falls were associated with greater disease activity. Cervical muscle stiffness in AS may cause non-veridical proprioceptive inputs and contribute to increased fall frequency similar to individuals with soft-tissue cervicothoracic pain.

Diagnosing and characterizing the mechanisms of biological phosphorus removal at the Great Lakes Water Authority (GLWA) water resource recovery facility (WRRF).

Previous research has demonstrated that biological phosphorus removal (bio-P) occurs in the Great Lakes Water Authority (GLWA) water resource recovery facility (WRRF) high purity oxygen activated sludge (HPO-AS) process, suggesting that sludge fermentation in the secondary clarifier sludge blanket is key to bio-P occurrence. This study, combining batch reactor testing, the development of a process model for the HPO-AS process using Sumo21 (Dynamita), and the analysis of eight and a half years of plant operating data, showed that bio-P consistently occurs at the GLWA WRRF. This occurrence is attributed to the unique configuration of the HPO-AS process, which has a relatively large secondary clarifier compared to the bioreactor, and the characteristics of the influent wastewater, primarily particulate matter with limited concentrations of dissolved biodegradable organic matter. The volatile fatty acids (VFAs) needed for polyphosphate accumulating organisms (PAOs) growth are produced in the secondary clarifier sludge blanket, which provides more than four times the anaerobic biomass inventory compared to the anaerobic zones in the bioreactor, thus facilitating bio-P in the current system. Opportunities exist to further optimize the phosphorus removal performance of the HPO-AS process and reduce the amount of ferric chloride used. These findings may be of interest to researchers investigating biological phosphorus removal in similar systems. PRACTITIONER POINTS: Fermentation in the clarifier sludge blanket an essential component of bio-P process at this facility. Results suggest simple adjustments to the system could lead to further improvements in bio-P. It is possible to decrease the use of chemical phosphorus removal methods (i.e., ferric chloride) while simultaneously increasing bio-P. Determining the phosphorus mass balance from sludge streams provides insight into evaluating the effectiveness of the phosphorus recovery system.

Evaluating the use of methods to mitigate bias from non-transient medications in the case-crossover design: A systematic review.

PURPOSE: The case-crossover design is a self-controlled study design used to compare exposure immediately preceding an event occurrence with exposure in earlier control periods. The design is most suitable for transient exposures in order to avoid biases that can be problematic when using the case-crossover design for non-transient (i.e., chronic) exposures. Our goal was to conduct a systematic review of case-crossover studies and its variants (case-time-control and case-case-time-control) in order to compare design and analysis choices by medication type. METHODS: We conducted a systematic search to identify recent case-crossover, case-time-control, and case-case-time-control studies focused on medication exposures. Articles indexed in MEDLINE and EMBASE using these study designs that were published between January 2015 and December 2021 in the English language were identified. Reviews, methodological studies, commentaries, articles without medications as the exposure of interest, and articles with no available full text were excluded. Study characteristics including study design, outcome, risk window, control window, reporting of discordant pairs, and inclusion of sensitivity analyses were summarized overall and by medication type. We further evaluated the implementation of recommended methods to account for biases introduced by non-transient exposures among articles that used the case-crossover design on a non-transient exposure. RESULTS: Of the 2036 articles initially identified, 114 articles were included. The case-crossover was the most common study design (88%), followed by the case-time-control (17%), and case-case-time-control (3%). Fifty-three percent of the articles included only transient medications, 35% included only non-transient medications, and 12% included both. Across years, the proportion of case-crossover articles evaluating a non-transient medication ranged from 30% in 2018 to 69% in 2017. We found that 41% of the articles that evaluated a non-transient medication did not apply any of the recommended methods to account for biases and more than half of which were conducted by authors with no previous publication history of case-crossover studies. CONCLUSION: Using the case-crossover design to evaluate a non-transient medication remains common in pharmacoepidemiology. Researchers should apply appropriate design and analysis choices when opting to use a case-crossover design with non-transient medication exposures.

Biological and physical selectors for mobile biofilms, aerobic granules, and densified-biological flocs in continuously flowing wastewater treatment processes: A state-of-the-art review.

There have been significant advances in the use of biological and physical selectors for the intensification of continuously flowing biological wastewater treatment (WWT) processes. Biological selection allows for the development of large biological aggregates (e.g., mobile biofilm, aerobic granules, and densified biological flocs). Physical selection controls the solids residence times of large biological aggregates and ordinary biological flocs, and is usually accomplished using screens or hydrocyclones. Large biological aggregates can facilitate different biological transformations in a single reactor and enhance liquid and solids separation. Continuous-flow WWT processes incorporating biological and physical selectors offer benefits that can include reduced footprint, lower costs, and improved WWT process performance. Thus, it is expected that both interest in and application of these processes will increase significantly in the future. This review provides a comprehensive summary of biological and physical selectors and their design and operation.

Self-Reported Disadvantage in Medical School Admissions: A Call to Review, Revise, and Further Advance Holistic Review.

PURPOSE: This study examined how applicants interpret the self-reported disadvantaged (SRD) question in the American Medical College Application Service (AMCAS) application. METHOD: Data from 129,262 applicants who applied through AMCAS from 2017 through 2019 were used, including financial and family history, demographic characteristics, and work status and residence. Fifteen applicants from the 2020 and 2021 AMCAS cycles were interviewed about their experiences with the SRD question. RESULTS: Large effects were found for SRD applicants with fee assistance waivers ( h = 0.89), Pell grants ( h = 1.21), state or federal aid ( h = 1.10), and parents with less education ( h = 0.98) and non-SRD applicants with a large proportion of their education paid by family ( d = 1.03). Another large difference was found for reported family income distribution (73% of SRD applicants reporting family income < $50,000 vs 15% of non-SRD applicants). More SRD applicants were Black or Hispanic (26% vs 16% and 5% vs 5%), Deferred Action for Childhood Arrivals recipients (11% vs 2%), born outside the United States (32% vs 16%), and raised in a medically underserved area (60% vs 14%). There was a moderate effect for first-generation to college SRD applicants ( h = 0.61). SRD applicants had lower Medical College Admission Test scores ( d = 0.62) and overall and science grade point averages ( d = 0.50 and 0.49, respectively) but no meaningful differences in acceptance or matriculation rates. The interviews identified 5 themes: (1) unclear disadvantage definition; (2) different perceptions of disadvantage and overcoming challenges or obstacles ; (3) identification as disadvantaged or not; (4) SRD essay content; and (5) concerns about lack of transparency in how the SRD question is used in admissions. CONCLUSIONS: Revising the SRD question by including context, phrasing, and instructions for broader experience categories might be beneficial because of lack of transparency and understanding.

Adherence to HIV Pre-Exposure Prophylaxis Testing Guidelines in the United States.

Testing guidelines for initiation of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) have been developed to ensure appropriate use of PrEP, such as among those with renal dysfunction or at high risk of seroconversion. While many studies have looked at the trends of use of PrEP in the United States, little is known about compliance with these guidelines, the quality of care of PrEP at a national level, or what provider-level factors are associated with high-quality care. We conducted a retrospective claims analysis of providers of commercially insured new users of PrEP between January 1, 2011, and December 31, 2019. Of the 4200 providers, quality of care was low, with only 6.4% having claims for ≥60% of guideline-recommended testing for their patients in the testing window for all visits. More than half of the providers did not have claims for HIV testing at initiation of PrEP and ≥40% did not for sexually transmitted infections at both initiation and follow-up visits. Even when extending the testing window, quality of care remained low. Logistic regression models found no association between provider type and high quality of care, but did find that providers with one PrEP patient were more likely to have higher quality of care than those with multiple patients for all tests [adjusted odds ratio 0.47 (95% confidence interval: 0.33-0.67)]. The study findings suggest further training and interventions, such as integrated test ordering through electronic health records, are needed to increase quality of care for PrEP and ensure appropriate monitoring of patients.

Granule formation mechanism, key influencing factors, and resource recycling in aerobic granular sludge (AGS) wastewater treatment: A review.

The high-efficiency and additionally economic benefits generated from aerobic granular sludge (AGS) wastewater treatment have led to its increasing popularity among academics and industrial players. The AGS process can recycle high value-added biomaterials including extracellular polymeric substances (EPS), sodium alginate-like external polymer (ALE), polyhydroxyfatty acid (PHA), and phosphorus (P), etc., which can serve various fields including agriculture, construction, and chemical while removing pollutants from wastewaters. The effects of various key operation parameters on formation and structural stability of AGS are comprehensively summarized. The degradable metabolism of typical pollutants and corresponding microbial diversity and succession in the AGS wastewater treatment system are also discussed, especially with a focus on emerging contaminants removal. In addition, recent attempts for potentially effective production of high value-added biomaterials from AGS are proposed, particularly concerning improving the yield, quality, and application of these biomaterials. This review aims to provide a reference for in-depth research on the AGS process, suggesting a new alternative for wastewater treatment recycling.

National trends in prescription drug expenditures and projections for 2023.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2023 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2023 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, diabetes medications, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2023 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2022, overall pharmaceutical expenditures in the US grew 9.4% compared to 2021, for a total of $633.5 billion. Utilization (a 5.9% increase), price (a 1.7% increase) and new drugs (a 1.8% increase) drove this increase. Adalimumab was the top-selling drug in 2022, followed by semaglutide and apixaban. Drug expenditures were $37.2 billion (a 5.9% decrease) and $116.9 billion (a 10.4% increase) in nonfederal hospitals and clinics, respectively. In clinics, new products and increased utilization growth drove growth, with a small impact from price changes. In nonfederal hospitals, a drop in utilization led to a decrease in expenditures, with price changes and new drugs contributing to growth in spending. Several new drugs that will influence spending have been or are expected to be approved in 2023. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. CONCLUSION: For 2023, we expect overall prescription drug spending to rise by 6.0% to 8.0%, whereas in clinics and hospitals we anticipate increases of 8.0% to 10.0% and 1.0% to 3.0%, respectively, compared to 2022. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

The best location for the application of static magnetic fields based on biokinetic coefficients in complete-mix activated sludge process.

The use of the kinetic coefficients for the mathematical expression of the biochemical processes and the relationship between the effective parameters is importance. Change of the biokinetic coefficients in the complete-mix activated sludge processes were calculated for 1 month operation of the activated sludge model (ASM) in a Lab-scale in three series. 15 mT intensity of static magnetic fields (SMFs) applied on the aeration reactor (ASM 1), clarifier reactor (ASM 2) and, sludge returning systems (ASM 3) for 1 h, daily. During the operation of the systems, five basic biokinetic coefficients such as maximum specific substrate utilization rate (k), heterotrophic half-saturation substrate concentration (Ks), decay coefficient (kd), yield coefficient (Y) and, maximum specific microbial growth rate (µmax) were determined. The rate of k (g COD/g Cells.d) in ASM 1 was 2.69% and, 22.79% higher than ASM 2 and, ASM 3. The value of Ks (mg COD/L) was 54.44 and, 71.13 (mg/L) lower than the ASM 2 and, ASM 3. The rate of kd ASM 1, ASM 2 and, ASM 3 was 0.070, 0.054 and, 0.516 (d-1). The value of Y (kg VSS/kg COD) in ASM 1 was 0.58% and, 0.48% lower than ASM 2 and, ASM 3. The rate of µmax (d-1) in ASM 1 was 0.197, this value for ASM 2 and ASM 3 were 0.324 and 0.309 (d-1). Related to the biokinetic coefficients analyses the best location for the application of 15 mT SMFs was the aeration reactor, where the present of oxygen, substrate and, SMFs have the greatest impact on the positive changes of these coefficients.

Prevalence of canine heartworm infection in Queensland, Australia: comparison of diagnostic methods and investigation of factors associated with reduction in antigen detection.

BACKGROUND: The prevalence of Dirofilaria immitis infection in dogs is increasing globally and spreading into new areas. Prevalence of dirofilariosis in the state of Queensland, Australia, was as high as 90% before the introduction of macrocyclic lactones. Limited research on prevalence of D. immitis infection in dogs in Queensland has been reported in the last 30 years. Antigen testing is the most common method for detection of dirofilariosis but its accuracy is reduced by antigen getting trapped (blocked antigen) in immune complexes (ICs). The objectives of this research were to determine the prevalence of D. immitis infection in dogs from two geographical areas (Brisbane and Townsville) in Queensland, to determine the extent to which blocked antigen affects the validity of antigen testing, and to explore whether this was associated with microfilaraemia, location, age or sex. METHODS: Blood samples from Brisbane (sub-tropical climate) and Townsville (tropical climate) shelter dogs were evaluated for the presence of D. immitis antigen before (conventional antigen testing, CAT) and after dissociation of ICs by heat treatment (antigen testing after heat treatment, ATHT), using a commercially available test. Microfilariae were detected using modified Knott's test (MKT). Test proportions were compared with McNemar's test and the association between antigen test-discordant results (positive for antigen after dissociation of ICs) and microfilaraemia, location, sex and age was modelled using logistic regression. RESULTS: Dirofilaria immitis prevalence in dogs from Townsville (22% by CAT, 32.1% by ATHT and 16.7% by MKT) was significantly higher than in dogs from Brisbane (1.1% by CAT and MKT and 1.7% by ATHT) [Formula: see text]. Dissociation of ICs allowed detection of significantly more D. immitis infected dogs than either conventional antigen testing or microfilariae detection, or the combined antigen and microfilariae detection [Formula: see text]. The odds of dogs being positive for antigen after dissociation of ICs were significantly higher for microfilaraemic, 3-4-year-old female dogs from Townsville. CONCLUSIONS: The high prevalence of infection with D. immitis in dogs from Townsville poses a health risk for local susceptible host species, including humans. Dissociation of ICs increases antigen detection and should be considered in dogs suspected of D. immitis infection but negative on routine testing.

Secondary thalamic atrophy related to brain infarction may contribute to post-stroke cognitive impairment.

BACKGROUND AND PURPOSE: The thalamus is a key brain hub that is globally connected to many cortical regions. Previous work highlights thalamic contributions to multiple cognitive functions, but few studies have measured thalamic volume changes or cognitive correlates. This study investigates associations between thalamic volumes and post-stroke cognitive function. METHODS: Participants with non-thalamic brain infarcts (3-42 months) underwent MRI and cognitive testing. Focal infarcts and thalami were traced manually. In cases with bilateral infarcts, the side of the primary infarct volume defined the hemisphere involved. Brain parcellation and volumetrics were extracted using a standardized and previously validated neuroimaging pipeline. Age and gender-matched healthy controls provided normal comparative thalamic volumes. Thalamic atrophy was considered when the volume exceeded 2 standard deviations greater than the controls. RESULTS: Thalamic volumes ipsilateral to the infarct in stroke patients (n=55) were smaller than left (4.4 ± 1.4 vs. 5.4 ± 0.5 cc, p < 0.001) and right (4.4 ± 1.4 vs. 5.5 ± 0.6 cc, p < 0.001) thalamic volumes in the controls. After controlling for head-size and global brain atrophy, infarct volume independently correlated with ipsilateral thalamic volume (ß= -0.069, p=0.024). Left thalamic atrophy correlated significantly with poorer cognitive performance (ß = 4.177, p = 0.008), after controlling for demographics and infarct volumes. CONCLUSIONS: Our results suggest that the remote effect of infarction on ipsilateral thalamic volume is associated with global post-stroke cognitive impairment.