Incremental Reduction Research Articles

Benefit Sharing on Transboundary Rivers: Case Study and Theoretical Exploration

Benefit sharing on transboundary rivers is an approach to address equitable and reasonable development and utilization of transboundary water resources (TWR). Through analyzing a few typical benefit sharing cases, this paper provides a systematic discussion of the theory of TWR benefits sharing. TWR features a kind of common pool resources (CPRs). Its benefit sharing subjects are the riparian countries. The shared benefits usually include flood prevention, power generation, navigation, irrigation, contributions to society and culture, etc. The benefit sharing modes mainly include shared benefits and responsibilities, reciprocal rights and obligations, equal benefit distribution, cost proportion-based benefit sharing, and demand-based benefit sharing. The first step in the realization process of benefit sharing is the sharing of data and information. Second is the benefit identification and evaluation. Third is the establishment of a mechanism to guarantee the benefit sharing. The conditions for realizing benefit sharing depends on, first, if the riparian countries are willing to cooperate with each other; second, whether the cooperation can bring incremental benefit or cost reduction in comparison with unilateral operation; and third, if the benefit distribution is equitable and reasonable and can stand the test of time.

Influence of Cold Rolling Reduction on Microstructure and Mechanical Properties in 204C2 Austenitic Stainless Steel

The present study investigated the effect of cold rolling reduction on microstructure and mechanical properties of a 204C2 Cr–Mn austenitic stainless steel which contained 16%Cr, 2%Ni, 9%Mn and 0.083 %C). The 204C2 austenitic stainless steels were cold rolled at multifarious thickness reductions of 10%, 20%, 30%,40% and 50%, which were compared with the solution-treated one. Microstructure of them was investigated by means of optical microscopy, X-ray diffraction technique and scanning electron microscopy. For mechanical properties investigations, hardness and tensile tests were carried out. Results shows that the cold rolling reduction induced the martensitic transformation (γ→α ́) in the structure of the austenitic stainless steel. With the increase of the rolling reduction, the amount of strain-induced martensite increased gradually. Hardness, ultimate tensile strength and yield strength increased with the incremental rolling reduction in 204C2 stainless steels, while the elongation decreased. At the thickness reduction of 50%, the specimen obtained best strength and hardness. Hardness of 204C2 stain steel reached 679HV. Ultimate tensile strength reached 1721 MPa. Yield strength reached 1496 MPa.

La politica estera dell'Italia dopo la Guerra fredda. Vincoli e opportunità

Caratterizzata dall'ambizione a farsi impero e potenza europea nel periodo liberale e durante il fascismo, l'Italia repubblicana ha dovuto riadattarsi al ruolo di "media potenza" incardinata nell'alveo del mondo occidentale e dell'integrazione europea. La fine della Guerra fredda ha però messo in discussione quel modello, sempre meno in grado di rispondere alle trasformazioni della globalizzazione. Ma nulla lo ha rimpiazzato. Diventata meno influente e al tempo stesso meno capace di reagire proattivamente alle sfide poste dai cambiamenti del sistema internazionale, l'Italia degli ultimi tre decenni ha subito - grazie alla scarsa autorevolezza ed efficacia del proprio sistema istituzionale e al persistere di un'illusione federalista - una costante erosione dei propri spazi d'azione nella politica estera.

Progressive structural capacity loss assessment-A framework for modern reinforced concrete buildings.

By the virtue of burgeoning terrorism, the exponential growth of advanced weaponry, and allied aids for explosions, it is quite evident that infrastructural facilities in the world have increasingly become more susceptible to sabotaging activities. The ever enhancing employment of reinforced concrete (RC) in the construction industry around the globe, the progressive collapse mechanisms, and respective mitigation strategies in the context of terrorism have garnered quite an attraction by the structural engineering community. The proficiency to envisage the complete collapse under the chain reaction of structural failures, partial collapse of key structural members, or the strength degradation of fundamental structural elements under the blast or impact loading can deliver significant information to cope with partial or complete structural failure. It is quite convenient to say that during the service life, a structure may experience extreme loading conditions. The current study has proposed a new methodology to cover the effect of uncertainty involved in loading on key structural elements of new and complex structures by emphasizing a very realistic structural capacity loss mechanism that allows the incremental reduction in the structural capacities of pivotal structural elements against any sort of impact loading instead of their complete annihilation. To demonstrate the application of the proposed methodology, a 13-story complex structure was selected that was comprised of a diverse structural configuration. The outcomes and results ensured the structural integrity against the applied loadings, as well as the effectiveness of the proposed methodology.

His Resynchronization Versus Biventricular Pacing in Patients With Heart Failure and Left Bundle Branch Block

BackgroundHis bundle pacing is a new method for delivering cardiac resynchronization therapy (CRT). ObjectivesThe authors performed a head-to-head, high-precision, acute crossover comparison between His bundle pacing and conventional biventricular CRT, measuring effects on ventricular activation and acute hemodynamic function. MethodsPatients with heart failure and left bundle branch block referred for conventional biventricular CRT were recruited. Using noninvasive epicardial electrocardiographic imaging, the authors identified patients in whom His bundle pacing shortened left ventricular activation time. In these patients, the authors compared the hemodynamic effects of His bundle pacing against biventricular pacing using a high-multiple repeated alternation protocol to minimize the effect of noise, as well as comparing effects on ventricular activation. ResultsIn 18 of 23 patients, left ventricular activation time was significantly shortened by His bundle pacing. Seventeen patients had a complete electromechanical dataset. In them, His bundle pacing was more effective at delivering ventricular resynchronization than biventricular pacing: greater reduction in QRS duration (−18.6 ms; 95% confidence interval [CI]: −31.6 to −5.7 ms; p = 0.007), left ventricular activation time (−26 ms; 95% CI: −41 to −21 ms; p = 0.002), and left ventricular dyssynchrony index (−11.2 ms; 95% CI: −16.8 to −5.6 ms; p < 0.001). His bundle pacing also produced a greater acute hemodynamic response (4.6 mm Hg; 95% CI: 0.2 to 9.1 mm Hg; p = 0.04). The incremental activation time reduction with His bundle pacing over biventricular pacing correlated with the incremental hemodynamic improvement with His bundle pacing over biventricular pacing (R = 0.70; p = 0.04). ConclusionsHis resynchronization delivers better ventricular resynchronization, and greater improvement in hemodynamic parameters, than biventricular pacing.

Patient adherence, compliance, and perspectives on evolocumab for the management of resistant hypercholesterolemia.

Evolocumab is a PCSK9 inhibitor which is administered subcutaneously, and when added to statin therapy it has been shown to cause a significant incremental LDL-C reduction, leading to a reduction of cardiovascular risk. Evolocumab has a favorable side effect profile, and its self-administration at home appears to be safe and effective with the appropriate training and instructions from a health care provider. Current studies are showing encouraging results regarding adherence to evolocumab in real-life settings, and adherence rates to evolocumab appear to be better than those to statins. However, further larger studies are needed for a more definitive assessment of the short- and long-term patient adherence rates to evolocumab. In addition, reductions in the price of evolocumab may also be necessary to improve cost-effectiveness of the drug.

Subcutaneous adipose tissue accumulation protects systemic glucose tolerance and muscle metabolism

ABSTRACTThe protective effects of lower body subcutaneous adiposity are linked to the depot functioning as a ”metabolic sink” receiving and sequestering excess lipid. This postulate, however, is based on indirect evidence. Mechanisms that mediate this protection are unknown. Here we directly examined this with progressive subcutaneous adipose tissue removal. Ad libitum chow fed mice underwent sham surgery, unilateral or bilateral removal of inguinal adipose tissue or bilateral removal of both inguinal and dorsal adipose tissue. Subsequently mice were separated into 5 week chow or 5 or 13 week HFD groups (N = 10 per group). Primary outcome measures included adipocyte distribution, muscle and liver triglycerides, glucose tolerance, circulating adipocytokines and muscle insulin sensitivity. Subcutaneous adipose tissue removal caused lipid accumulation in femoral muscle proximal to excision, however, lipid accumulation was not proportionally inverse to adipose tissue quantity excised. Accumulative adipose removal was associated with an incremental reduction in systemic glucose tolerance in 13 week HFD mice. Although insulin-stimulated pAkt/Akt did not progressively decrease among surgery groups following 13 weeks of HFD, there was a suppressed pAkt/Akt response in the non-insulin stimulated (saline-injected) 13 week HFD mice. Hence, increases in lower body subcutaneous adipose removal resulted in incremental decreases in the effectiveness of basal insulin sensitivity of femoral muscle. The current data supports that the subcutaneous depot protects systemic glucose homeostasis while also protecting proximal muscle from metabolic dysregulation and lipid accumulation. Removal of the “metabolic sink” likely leads to glucose intolerance because of decreased storage space for glucose and/or lipids.

PDB32 - Cost-Effectiveness Analysis of Linagliptin Versus Sulfonylurea As Add-On Treatment to Metformin for the Treatment of Diabetes Mellitus Type 2 Patients in Indonesia

This study aimed to assess the cost-effectiveness of linagliptin versus sulfonylurea as an add-on treatment to metformin for the treatment of diabetes mellitus type 2 patients in Indonesian healthcare setting. An economic evaluation using real-world data was used to assess the costs and health outcomes of therapy using linagliptin versus sulfonylurea as an add-on treatment to metformin for the treatment of diabetes mellitus type 2 patients. Costs were assessed from healthcare provider perspective thus including only the direct medical cost. Health outcomes were measured in term of clinical outcome of type 2 diabetes mellitus, namely HbA1C reduction. The time horizon was one year. Cost-effectiveness was calculated from the ratio of cost and HbA1C reduction of the two therapy strategies. The result was presented as incremental cost-effectiveness ratio (ICER) per 1% HbA1C reduction. Adding linagliptin to metformin increased total cost per year compared to adding sulfonylurea (IDR 20,065,287 ± 20,193,381 vs IDR 19,324,506 ± 32,945,431). However, the increasing cost in linagliptin group was offset by the reduction of HbA1C in linagliptin group compared to sulfonylurea group with the incremental reduction of % HbA1C was 0.15 (p>0.05). The ICER of linagliptin versus sulfonylurea as an add-on treatment to metformin was, therefore, IDR 4,698,808 per 1% HbA1C. The value of ICER was about 10% of Indonesia GDP per capita. Adding linagliptin versus sulfonylurea as an add-on treatment to metformin for the treatment of diabetes mellitus type 2 patients in Indonesian appeared resulting slight additional cost and a similar outcome. This study provides economic evidence to add an information for selecting therapy option in the treatment of type 2 diabetes mellitus.

Does a Reduction in Readmissions Result in Net Savings for Most Hospitals? An Examination of Medicare's Hospital Readmissions Reduction Program.

This study aimed (1) to estimate the impact of an incremental reduction in excess readmissions on a hospital's Medicare reimbursement revenue, for hospitals subject to penalties under the Medicare's Hospital Readmissions Reduction Program and (2) to evaluate the economic case for an investment in a readmission reduction program. For 2,465 hospitals with excess readmissions in the Fiscal Year 2016 Hospital Compare data set, we (1) used the Hospital Readmissions Reduction Program statute to estimate hospital-specific Medicare reimbursement gains per an avoided readmission and (2) carried out a pro forma analysis of investment in a broad-scale readmission reduction program under conservative assumptions regarding program effectiveness and using program costs from earlier studies. For an average hospital, avoiding one excess readmission would result in reimbursement gains of $10,000 to $58,000 for Medicare discharges. The economic case for investments in a readmission reduction effort was strong overall, with the possible exception of hospitals with low excess readmissions.

Effect of sacubitril/valsartan on cardiac filling pressures in patients with left ventricular systolic dysfunction

BackgroundSacubitril/valsartan is the newest neurohormonal agent approved for therapy in patients with heart failure with reduced ejection fraction (HFrEF). Little is known about its acute and incremental hemodynamic effects. We aimed to evaluate the change in hemodynamic profiles measured using an implanted monitoring device in HFrEF patients initiated on sacubitril/valsartan therapy. MethodsWe prospectively enrolled 13 subjects with HFrEF and pre-implanted CardioMEMS™ device on maximally tolerated guideline-directed medical therapy and no contraindications to sacubitril/valsartan therapy. Transmitted pulmonary artery diastolic pressures (PAdP) from CardioMEMS™ were averaged and compared for one week before and after initiation of sacubitril/valsartan, as well as after change in medication strength and finally at three months. ResultsSacubitril/valsartan dose increase was tolerated in 7/13 subjects with drug discontinuation in one subject after a week due to renal dysfunction. There was a significant reduction in mean PAdP after sacubitril/valsartan initiation compared to standard therapy (20.8 vs 18.3 mm Hg, p = 0.020). No further PAdP reduction was noted after sacubitril/valsartan dose increase (19.7 vs 20 mm Hg, p = 0.673) and at 3-month follow-up compared to baseline (20.8 vs 19.2 mm Hg, p = 0.352). ConclusionsSacubitril/valsartan causes an acute reduction mean pulmonary artery pressures after initiation. However, no incremental reduction in PAdP was noted after dose increase and short-term follow-up. The current study demonstrates the utility of CardioMems™ device to study the drug's impact on hemodynamic profile in both short- and long-term follow-up.

Effect of Stress Ball Use or Hand-holding on Anxiety During Skin Cancer Excision

Patients undergoing skin surgery under local anesthesia can experience anxiety. Adjuvant intraoperative anxiety reduction methods may help. To assess whether hand-holding or holding a stress ball reduces patient anxiety during excisional surgery of head or neck skin cancer with the patient under local anesthesia and to measure pain and patient satisfaction. In this nonblinded, single-center randomized clinical trial, performed from January 24 through April 26, 2017, at a dermatology outpatient service in an urban, academic medical center, a consecutive sample of 135 adults who required excisional removal of nonmelanoma skin cancer of the head or neck was randomized and studied. Participants were randomized 1:1:1 to 3 groups: hand-holding, stress ball, or control (treatment as usual). Participants in the hand-holding group had a female researcher hold one of their hands during administration of anesthesia and extirpation, and those in the stress ball group held a round compressible ball and squeezed it as desired during the same period. The primary outcome was anxiety, measured by a visual analog scale (VAS), 6-item State Trait Anxiety Inventory (STAI), and physiologic measures (blood pressure and heart rate). Secondary outcomes were pain during the procedure and overall participant satisfaction. In addition, participants were asked how many hours they spent researching the procedure before surgery. A total of 135 participants, 45 per study arm, were enrolled (mean [SD] age, 65.5 [13.9] years; 84 [62.2%] male; 134 [99.3%] white). There were no withdrawals or dropouts. Anxiety decreased over time in all groups, but no significant differences were found in the 3 anxiety measures across the 3 groups (VAS anxiety score before: control group, 3.11; hand-holding group, 3.04; stress ball group, 3.09 [P > .99]; VAS anxiety score during: control group, 1.89; hand-holding group, 2.31; stress ball group, 2.47 [P = .55]; STAI score: control group, 8.91; hand-holding group, 8.93; stress ball group, 8.76 [P = .96]). The 3 groups also did not significantly differ in postprocedure pain scores (control group, 0.78; hand-holding group, 0.64; stress ball group, 0.67; P = .85). Almost all participants (134 [99.2%]) were very satisfied. Participants who had done research had higher preoperative VAS anxiety scores (researched, 3.84; did not research, 2.62; P = .04). Hand-holding and squeezing a stress ball do not appear to provide incremental anxiety reduction in patients during excisional skin cancer surgery. It is possible that some subgroups may respond better or that patients may respond better when able to select and tailor their preferred anxiety reduction method. ClinicalTrials.gov identifier: NCT02816996.

Tensor-based Big Biometric Data Reduction in Cloud

When dealing with big biometric data, data reduction becomes a challenge. This article proposes a novel big biometric data reduction solution in the cloud environment, including a big biometric data reduction approach based on tensor decomposition, an incremental big biometric tensor reduction approach, and a secure big biometric data reduction approach, which can significantly reduce big biometric data.

A unified incremental reduction with the variations of the object for decision tables

Attribute reduction is one of the issues in the rough set theory, and many reduction algorithms have been proposed to process the static decision systems. However, in real-life applications, the object may vary dynamically with time. In order to deal with common variations of the object (i.e., adding the object, deleting the object and modifying the object’s value) in the decision systems, the paper presents a unified incremental reduction algorithm for three types of the dynamic object from the viewpoint of the discernibility matrix. Firstly, the concepts of the equivalence class linked table (ECLT) and the simplified decision table are proposed. On the basis of ECLT, the incremental mechanisms are analyzed and the corresponding functions for updating the discernibility matrix are designed for three variations of the object. And then, the dynamic criterions how to add new attributes into the original reduct or delete redundant attributes from the original reduct are studied. Subsequently, a unified incremental reduction algorithm with varying the object is presented. A serial of experiments are validated to explain the feasibility and effectiveness of the proposed algorithms on different data sets from UCI.

Quadrivalent influenza vaccines in low and middle income countries: Cost-effectiveness, affordability and availability

In high-income countries, there is an increased tendency to replace inactivated seasonal trivalent influenza (TIV) vaccines with quadrivalent (QIV) vaccines as these are considered to give a greater public health benefit. In addition, several recent studies from the USA and Europe indicate that replacement with QIV might also be cost-effective; however, the situation in low- and middle-income countries (LMIC) is less clear as few studies have investigated this aspect.The paper by de Boer et al. (2018) describes a dynamic modelling study commissioned by WHO that suggests that in LMICs, under certain conditions, QIV might also be more cost-effective than TIV. In this commentary, we discuss some important aspects that policymakers in LMICs might wish to take into account when considering replacing TIV by QIV.Indeed, from the data presented in the paper by de Boer et al. it can be inferred that replacing QIV for TIV would mean a 25–29% budget increase for seasonal influenza vaccination in South Africa and Vietnam, resulting in an incremental influenza-related health impact reduction of only 7–8% when a 10% symptomatic attack rate is assumed. We argue that national health budget considerations in LMIC might lead decision-makers to choose other investments with higher health impact for a budget equivalent to roughly a quarter of the yearly TIV immunization costs.In addition to an increased annual cost that would be associated with a decision to replace TIV with QIV, there would be an increased pressure on manufacturers to produce QIV in time for the influenza season requiring manufacturers to produce some components of the seasonal vaccine at risk prior to the WHO recommendations for influenza vaccines.Unless the current uncertainties, impracticalities and increased costs associated with QIVs are resolved, TIVs are likely to remain the more attractive option for many LMICs. Each country should establish its context-specific process for decision-making based on national data on disease burden and costs in order to determine whether the health gains out-weigh the additional cost of moving to QIV. For example, immunizing more people in the population, especially those in higher risk groups, with TIV might not only provide better value for money but also deliver better health outcomes in LMICs.Countries with local influenza vaccine manufacturing capacity should include in their seasonal influenza vaccine procurement process an analysis of the pros- and cons- of TIV versus QIV, to ensure both feasibility and sustainability of local manufacturing.

Continued Tumor Reduction of Metastatic Pheochromocytoma/Paraganglioma Harboring Succinate Dehydrogenase Subunit B Mutations with Cyclical Chemotherapy.

Patients harboring germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene present with pheochromocytomas and paragangliomas (PPGL) that are more likely malignant and clinically aggressive. The combination chemotherapy cyclophosphamide, vincristine, and dacarbazine (CVD) was retrospectively evaluated in patients with SDHB-associated metastatic PPGL.Query Twelve metastatic PPGL patients harboring SDHB mutations/polymorphisms with undetectable SDHB immunostaining were treated with CVD. CVD therapy consisted of 750mg/m2 cyclophosphamide with 1.4mg/m2 vincristine on day1 and 600mg/m2 dacarbazine on days1 and 2, every 21-28days. Treatment outcome was determined by RECIST criteria as well as determination of response duration and progression-free and overall survivals. A median of 20.5 cycles (range 4-41) was administered. All patients had tumor reduction (12-100% by RECIST). Complete response was seen in two patients, while partial response was observed in 8. The median number of cycles to response was 5.5. Median duration of response was 478days, with progression-free and overall survivals of 930 and 1190days, respectively. Serial [18F]-fluorodeoxyglucose positron emission tomography and computed tomography imaging demonstrated continued incremental reduction in maximal standardized uptake values (SUVmax) values in 26/30 lesions. During treatment administration, the median SUV decreased from >25 to <6, indicating the efficacy of chemotherapy over a prolonged period of time. Prolonged therapy results in continued incremental tumor reduction, and is consistent with persistent drug sensitivity. CVD chemotherapy is recommended to be considered part of the initial management in patients with metastatic SDHB-related PPGL.

Cost effectiveness of focal impulse and rotor modulation guided ablation added to pulmonary vein isolation for atrial fibrillation.

Although ablation with focal impulse and rotor modulation (FIRM), as an adjunct to pulmonary vein isolation (PVI), has been shown to decrease atrial fibrillation (AF) recurrence, cost-effectiveness has not been assessed. We aimed to evaluate the cost effectiveness of FIRM-guided ablation when added to PVI in a mixed AF population. We used a Markov model to estimate the costs, quality-adjusted survival, and cost effectiveness of adding FIRM ablation to PVI. AF recurrence rates were based on 3-year data from the CONFIRM trial. Model inputs for event probabilities and utilities were obtained from literature review. Costs were based on Medicare reimbursement, wholesale acquisition costs, and literature review. Three-year total costs FIRM+PVI versus PVI alone were $27,686versus $26,924. QALYs were 2.338versus 2.316, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of $34,452 per QALY gained. Most of the cost (65-81%) was related to the index ablation procedure. Lower AF recurrence generated cost offsets of $4,266, primarily due to a reduced need for medications and repeat ablation. Probabilistic sensitivity analysis demonstrated ICER below $100,000/QALY in 74% of simulations. Based on data from the CONFIRM study, the addition of FIRM to PVI does have the potential to be cost-effective due to higher quality-adjusted life years and lower follow-up costs. Value is sensitive to the incremental reduction in AF recurrence, and FIRM may have the greatest economic value in patients with greater AF symptom severity. Results from ongoing randomized trials will provide further clarity.

Cost utility, budget impact, and scenario analysis of racecadotril in addition to oral rehydration for acute diarrhea in children in Malaysia.

ObjectiveTo perform cost utility (CU) and budget impact (BI) analyses augmented by scenario analyses of critical model structure components to evaluate racecadotril as adjuvant to oral rehydration solution (ORS) for children under 5 years with acute diarrhea in Malaysia.MethodsA CU model was adapted to evaluate racecadotril plus ORS vs ORS alone for acute diarrhea in children younger than 5 years from a Malaysian public payer’s perspective. A bespoke BI analysis was undertaken in addition to detailed scenario analyses with respect to critical model structure components.ResultsAccording to the CU model, the intervention is less costly and more effective than comparator for the base case with a dominant incremental cost-effectiveness ratio of −RM 1,272,833/quality-adjusted life year (USD −312,726/quality-adjusted life year) in favor of the intervention. According to the BI analysis (assuming an increase of 5% market share per year for racecadotril+ORS for 5 years), the total cumulative incremental percentage reduction in health care expenditure for diarrhea in children is 0.136578%, resulting in a total potential cumulative cost savings of −RM 73,193,603 (USD −17,983,595) over a 5-year period. Results hold true across a range of plausible scenarios focused on critical model components.ConclusionAdjuvant racecadotril vs ORS alone is potentially cost-effective from a Malaysian public payer perspective subject to the assumptions and limitations of the model. BI analysis shows that this translates into potential cost savings for the Malaysian public health care system. Results hold true at evidence-based base case values and over a range of alternate scenarios.

Parkinson's Patients with Dyskinesia Switched from Immediate Release Amantadine to Open-label ADS-5102.

BackgroundADS‐5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS‐5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility.MethodsIn an ongoing, open‐label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS‐5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years. Study outcomes included safety and assessment of motor complications, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part IV. This manuscript focuses on those patients switched to ADS‐5102 from amantadine IR. Results in two groups of patients who previously completed a randomized controlled trial (EASE LID or EASE LID 3) are also presented according to use of ADS‐5102 or placebo in that study before enrollment in the open‐label study.ResultsChange in MDS‐UPDRS Part IV at week 8 was –0.3 in the previous ADS‐5102 subgroup (n = 61), –3.4 in the previous placebo subgroup (n = 79), and –3.4 in the previous amantadine IR subgroup (n = 32). Effects were maintained to week 64. In the previous amantadine IR subgroup (mean treatment duration, 2.5 years), mean amantadine IR dose was 221 mg. Safety data were consistent with previous randomized controlled trials of ADS‐5102.ConclusionThese open‐label data suggest ADS‐5102 provides incremental reduction from baseline in MDS‐UDPRS Part IV score in patients switched directly from amantadine IR, without exacerbating adverse events.

Prevalence and Management of Drug-Related Problems in Chronic Kidney Disease Patients by Severity Level: A Subanalysis of a Cluster Randomized Controlled Trial in Community Pharmacies.

Drug-related problems (DRPs) are prevalent among chronic kidney disease (CKD) patients. However, little is known about their severity and management by community pharmacists. To (a) describe the prevalence of DRPs by severity level in CKD patients and (b) assess the effect of a training-and-communication network program in nephrology (ProFiL) on these DRPs. This is a secondary analysis of a cluster randomized controlled trial evaluating the effect of the ProFiL-program. In 6 CKD clinics, patients at CKD stage 3 or 4 and their community pharmacists were recruited and assigned to the ProFiL group or a usual care (UC) group. Using validated criteria, 2 pharmacists identified DRPs and assessed their severity at baseline and after 12 months. The mean annual change in the number of DRPs per patient by severity level was assessed using a 2-level multivariable linear mixed-effects model. A total of 494 pharmacists and 442 patients participated. At baseline, the prevalence (mean number of DRPs per patient [SD]) of mild DRPs (e.g., requiring dosage adjustment) and moderate DRPs (e.g., drug adherence requiring a monitoring plan) were 0.55 (0.98) and 1.04 (1.51), respectively. After 12 months, an unadjusted incremental annual reduction of 0.34 moderate DRPs (95% CI = -0.66 to -0.01) was observed in the ProFiL group compared with the UC group. After adjustment, no between-group differences were observed. Among patients followed in CKD clinics, most DRPs have a moderate severity requiring specific monitoring by pharmacists. The benefit of continuing education programs, such as ProFiL, to reduce moderate DRPs remains to be determined. This study was supported by the Canadian Institutes of Health Research (grant number: MOP-230207). Part of the study was also funded by Pfizer Canada, Leo Pharma, and Amgen. The authors declare that they have no relevant financial interests. Study concept and design were contributed by Quintana-Bárcena, Lord, and Lalonde. Quintana-Bárcena, Lord, and Lizotte were responsible for the data analysis, and Quintana-Bárcena and Berbiche performed the statistical analysis. The manuscript was written by Quintana-Bárcena and Lalonde and revised by Quintana-Bárcena and Lalonde, along with the other authors.

Bayesian penalised likelihood reconstruction (Q.Clear) of 18F-fluciclovine PET for imaging of recurrent prostate cancer: semi-quantitative and clinical evaluation.

Objective:18F-Fluciclovine (FACBC) is an amino acid PET radiotracer approved for recurrent prostate cancer imaging. We investigate the use of Bayesian penalised likelihood (BPL) reconstruction for 18F-fluciclovine PET.Methods:15 18F-fluciclovine scans were reconstructed using ordered subset expectation maximisation (OSEM), OSEM + point spread function (PSF) modelling and BPL using β-values 100–600. Lesion maximum standardised uptake value (SUVmax), organ SUVmean and standard deviation were measured.Deidentified reconstructions (OSEM, PSF, BPL using β200–600) from 10 cases were visually analysed by two readers who indicated their most and least preferred reconstructions, and scored overall image quality, noise level, background marrow image quality and lesion conspicuity.Results:Comparing BPL to OSEM, there were significant increments in lesion SUVmax and signal-to-background up to β400, with highest gain in β100 reconstructions (mean ΔSUVmax 3.9, p < 0.0001). Organ noise levels increased on PSF, β100 and β200 reconstructions. Across BPL reconstructions, there was incremental reduction in organ noise with increasing β, statistically significant beyond β300–500 (organ-dependent). Comparing with OSEM and PSF, lesion signal-to-noise was significantly increased in BPL reconstructions where β ≥ 300 and ≥ 200 respectively.On visual analysis, β 300 had the first and second highest scores for image quality, β500 and β600 equal highest scores for marrow image quality and least noise, PSF and β 200 had first and second highest scores for lesion conspicuity. For overall preference, one reader preferred β 300 in 9/10 cases and the other preferred β 200 in all cases.Conclusion:BPL reconstruction of 18F-fluciclovine PET images improves signal-to-noise ratio, affirmed by overall reader preferences. On balance, β300 is suggested for 18F-fluciclovine whole body PET image reconstruction using BPL.Advances in knowledge:The optimum β is different to that previously published for 18F-fluorodeoxyglucose, and has practical implications for a relatively new tracer in an environment with modern reconstruction technologies.