Impact of RFID information-sharing coordination over a supply chain with reverse logistics

Companies have adopted environmental practices such as reverse logistics over the past few decades. However, studies show that aligning partners inside the green supply chain can be a substantial problem. This lack of coordination can increase overall supply chain cost. Information technology such as Radio Frequency Identification (RFID) has the potential to enable decentralized supply chain coordinate their information. Even though there are research that address RFID on traditional supply chain, few researches address how to coordinate RFID information sharing in a green supply chain. We study, through simulation experiments, two types of RFID information-sharing coordination under different configurations related with their inventory policies: basic and advanced. Statistical analyses show that better results can be presented in advanced RFID configuration given new coordination and inventory policy decisions presented. In addition, these findings shows what are the RFID information-sharing coordination that can provide better system improvement depending on the supply chain scenarios and factors

Temporal Trends of Wild-Type Transthyretin Amyloid Cardiomyopathy in the Transthyretin Amyloidosis Outcomes Survey.

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Impact of Delayed Diagnosis and Misdiagnosis for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM): A Targeted Literature Review

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal and under-recognized disease. This targeted literature review assessed the extent and consequences of diagnostic delay and misdiagnosis in ATTR-CM. Methods: The Embase database was searched together with proceedings of eight cardiology conferences to identify publications or abstracts on ATTR-CM. Outcomes of interest were time from symptom onset to diagnosis, rates of delayed diagnosis and misdiagnosis, and costs, healthcare resource use or clinical outcomes whilst undiagnosed/misdiagnosed. Results: Twenty-three articles were included. Weighted means of reported mean and median diagnostic delays were 6.1 and 3.4 years for wild-type (ATTRwt-CM) and 5.7 and 2.6 years for hereditary (ATTRv-CM). Misdiagnosis occurred in 34-57% of patients when reported. Evaluation and misdiagnosis by multiple healthcare providers before receiving an ATTR-CM diagnosis was common, and there was evidence that patients undergo unnecessary or inappropriate evaluations or treatments while misdiagnosed. Diagnostic "red flags" were reported to be underused. Data on the consequences of delay for patients and health systems were sparse, but given the progressive nature of ATTR-CM, delay is likely to have adverse consequences. Conclusion: ATTR-CM patients commonly experience diagnostic delay and misdiagnosis. Efforts are required to provide timely diagnosis so that patients can benefit from earlier access to new disease-modifying therapies

Liver Directed Drugs for Transthyretin-Mediated Amyloidosis

AIM: Transthyretin-mediated amyloidosis (ATTR) is a rare, under-recognized, progressively debilitating, fatal disease caused by the aggregation and extracellular deposition of amyloid transthyretin (TTR) fibrils in multiple organs and tissues throughout the body. TTR is predominantly synthesized by the liver, and normally circulates as a homotetramer, while misfolded monomers aggregate to form amyloid fibrils. One strategy to treat ATTR amyloidosis is to reduce the amount of TTR produced by the liver using drugs that directly target the TTR mRNA or gene. METHODS: This narrative review focuses on how TTR gene silencing tools act to reduce TTR production, describing strategies for improved targeted delivery of these agents to hepatocytes where TTR is preferentially expressed. RESULTS: Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), termed RNA silencers, cause selective degradation of TTR mRNA, while a TTR gene editing tool reduces TTR expression by introducing nonsense mutations into the TTR gene. Two strategies to facilitate tissue-specific delivery of these nucleic acid-based drugs employ endogenous receptors expressed by hepatocytes. Lipid nanoparticles (LNPs) that recruit apolipoprotein E support low density lipoprotein receptor-mediated uptake of unconjugated siRNA and is now used for CRISPR gene editing tools. Additionally, conjugating N-acetylgalactosamine (GalNAc) moieties to ASOs or siRNAs facilitates receptor-mediated uptake by the asialoglycoprotein receptor. CONCLUSION: ATTR is a progressive disease with various clinical manifestations due to TTR aggregation, deposition, and amyloid formation. Receptor-targeted ligands (e.g., GalNAc) and nanoparticle encapsulation (e.g., LNPs) are technologies to deliver ASOs, siRNAs, and gene editing tools to hepatocytes, the primary location of TTR synthesis

How did transthyretin amyloid cardiomyopathy progress in patients who took placebo in the study ATTR-ACT? A plain language summary

What is this plain language summary about? This plain language summary describes some results of a study called ATTR-ACT. This was the first large study to include people with wild-type and hereditary transthyretin amyloid cardiomyopathy (ATTR-CM for short). ATTR-CM is a type of heart disease that happens when abnormal clumps of protein build up in the heart. This build-up prevents the heart from working properly, causing a condition called heart failure. Wild-type ATTR-CM happens for unknown reasons in some people as they get older. Hereditary ATTR-CM can happen because of changes in people's genes (known as gene variants or mutations). Important information about ATTR-ACT In this study, 441 people with ATTR-CM took either a medicine called tafamidis or a placebo (a capsule that looked like tafamidis but didn't contain any active medicine) by mouth for 30 months, once a day. The researchers' main aim was to find out how tafamidis treatment affected the risk of people dying or being admitted to the hospital for heart problems. They found that tafamidis lowered these risks by about one-third compared with placebo. What else did researchers find out in ATTR-ACT? As described in this summary, after ATTR-ACT was completed, researchers looked back at the results from people who took placebo to learn how ATTR-CM progressed without treatment. The researchers found that about 4 in 10 people with wild-type ATTR-CM who took placebo died and 6 in 10 were admitted to the hospital because of heart problems over 30 months. People who took placebo also could not walk as far at the end of the study as they did at the start because their heart function worsened over time. Why are these results important? By showing how ATTR-CM affects people's health when they do not take treatment, these results highlight the benefits of early diagnosis and treatment of ATTR-CM. ClinicalTrials.gov NCT number: NCT0199488

Natural history and progression of transthyretin amyloid cardiomyopathy: insights from ATTR‐ACT

Aims Transthyretin amyloid cardiomyopathy (ATTR‐CM) is a progressive, fatal disorder that remains underdiagnosed. The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) was the first large clinical trial to include both wild‐type (ATTRwt) and hereditary (ATTRv) patients. A description of the natural history of ATTR‐CM, utilizing data from placebo‐treated patients in ATTR‐ACT, will provide a greater understanding of presentation and progression of ATTR‐CM and may aid in disease awareness, earlier diagnosis and treatment monitoring. Methods and results Changes in clinical endpoints (mortality, cardiovascular [CV]‐related hospitalizations, 6‐min walk test [6MWT] distance and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ‐OS] score) from baseline to Month 30 in the 177 patients (134 ATTRwt, 43 ATTRv) who received placebo in ATTR‐ACT were assessed. ATTRwt patients tended to have less severe disease at baseline. Over the duration of ATTR‐ACT, there were 76 (42.9%) all‐cause deaths, and 107 (60.5%) patients had a CV‐related hospitalization. There was a lower proportion of all‐cause deaths in ATTRwt (49, 36.6%) than ATTRv (27, 62.8%). There was a similar, steady decline in mean (SD) 6MWT distance from baseline to Month 30 in ATTRwt (93.9 [93.7] m) and ATTRv (89.1 [107.2] m) patients. The decline in mean (SD) KCCQ‐OS score was less severe in ATTRwt (13.8 [20.7]) than ATTRv (21.0 [26.4]) patients. Conclusions Patients with ATTR‐CM experience a severe, progressive disease. In ATTR‐ACT, placebo‐treated patients with ATTRv, compared with ATTRwt, had more severe disease at baseline, and their disease progressed more rapidly as shown by mortality, hospitalizations and quality of life over time

Expert consensus on the monitoring of transthyretin amyloid cardiomyopathy

© 2021 European Society of CardiologyTransthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening condition with a heterogeneous clinical presentation. The recent availability of treatment for ATTR-CM has stimulated increased awareness of the disease and patient identification. Stratification of patients with ATTR-CM is critical for optimal management and treatment; however, monitoring disease progression is challenging and currently lacks best-practice guidance. In this report, experts with experience in treating amyloidosis and ATTR-CM developed consensus recommendations for monitoring the course of patients with ATTR-CM and proposed meaningful thresholds and frequency for specific parameters. A set of 11 measurable features across three separate domains were evaluated: (i) clinical and functional endpoints, (ii) biomarkers and laboratory markers, and (iii) imaging and electrocardiographic parameters. Experts recommended that one marker from each of the three domains provides the minimum requirements for assessing disease progression. Assessment of cardiac disease status should be part of a multiparametric evaluation in which progression, stability or improvement of other involved systems in transthyretin amyloidosis should also be considered. Additional data from placebo arms of clinical trials and future studies assessing ATTR-CM will help to elucidate, refine and define these and other measurements.info:eu-repo/semantics/publishedVersio

Efficacy of Tafamidis in Patients With Hereditary and Wild-Type Transthyretin Amyloid Cardiomyopathy : Further Analyses From ATTR-ACT

Objectives: Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study aimed to determine whether there is a differential effect between variant transthyretin amyloidosis (ATTRv) and wild-type transthyretin (ATTRwt). Background: ATTR-CM is a progressive, fatal disorder resulting from mutations in the ATTRv or the deposition of denatured ATTRwt. Methods: In pre-specified analyses from ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), baseline characteristics, all-cause mortality, and change from baseline to month 30 in 6-min walk test distance and Kansas City Cardiomyopathy Questionnaire Overall Summary score were compared in patients with ATTRwt and ATTRv. Results: There were 335 patients with ATTRwt (201 tafamidis, 134 placebo) and 106 with ATTRv (63 tafamidis, 43 placebo) enrolled in ATTR-ACT. Patients with ATTRwt (vs. ATTRv) had less advanced disease at baseline and a lower rate of disease progression over the study. The reduction in all-cause mortality with tafamidis compared with placebo was not different between ATTRwt (hazard ratio: 0.706 [95% confidence interval (CI): 0.474 to 1.052]; p = 0.0875) and ATTRv (hazard ratio: 0.690 [95% CI: 0.408 to 1.167]; p = 0.1667). Tafamidis was associated with a similar reduction (vs. placebo) in the decline in 6-min walk test distance in ATTRwt (mean ± SE difference from placebo, 77.14 ± 10.78; p < 0.0001) and ATTRv (79.61 ± 29.83 m; p = 0.008); and Kansas City Cardiomyopathy Questionnaire Overall Summary score in ATTRwt (12.72 ± 2.10; p < 0.0001) and ATTRv (18.18 ± 7.75; p = 0.019). Conclusions: Pre-specified analyses from ATTR-ACT confirm the poor prognosis of untreated ATTRv-related cardiomyopathy compared with ATTRwt, but show the reduction in mortality and functional decline with tafamidis treatment is similar in both disease subtypes. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889

Evaluation of novel metrics of symptom relief in acute heart failure: the worst symptom score

Objective: To characterize a novel "worst"-symptom visual analogue scale (WS-VAS) versus the traditional dyspnea visual analogue scale (DVAS) in an acute heart failure (AHF) trial.Background: AFT trials assess symptom relief as a pivotal endpoint with the use of dyspnea scores. However, many AHF patients' worst presenting symptom (WS) may not be dyspnea. We hypothesized that a WS VAS may reflect clinical improvement better than DVAS in AHF.Methods and Results: AHF patients (n = 232) enrolled in the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF) Trial indicated their WS at enrollment and completed DVAS and WS VAS at enrollment and 24, 48, and 72 hours. Dyspnea was the WS in 61%, body swelling in 29%, and fatigue in 10% of patients. Clinical characteristics differed by WS. In all patients, DVAS scores were higher (less severe symptoms) than WS-VAS and the change in WS-VAS over 72 hours was greater than the change in DVAS (P < .001). Changes in DVAS were smaller in patients with body swelling and fatigue than in patients with dyspnea as their WS (P = .002), whereas changes in the WS-VAS were similar regardless of patients' WS. Neither score, nor its change, was associated with available decongestion markers (change in N-terminal pro B-type natriuretic peptide, weight or cumulative 72-hour urine volume).Conclusions: Many AHF patients have symptoms other than dyspnea as their most bothersome symptom. The WS-VAS better reflects symptom improvement across the spectrum of AHF phenotypes. Symptom relief and decongestion were not correlated in this AHF study