Qualifying Criteria Research Articles

Prognostic Importance of WBC Count in Acute Myocardial Infraction

Background: The objective of this study was to determine whether the WBC count is associated with in-hospital mortality & morbidity for patients with ischemic heart disease after controlling for potential confounders.
 Methods: This study was prospective study. 100 patients presenting within 24hrs with Acute MI and qualifying inclusion criteria were enrolled and written consent was taken regarding participation in the study.
 Results: Out of 100 patients had LV dysfunction, among these 30 patients 21were having elevated WBC count and 9 had normal WBC count. Among 100 patients 14 had cardiogenic shock, among these patients 9 had elevated WBC count and 5 had normal WBC count. Among 100 patients 8 patients died, among these patients 7 patients had elevated WBC count and 1 patient had normal WBC count.
 Conclusion: Elevated WBC count within 24 hours was associated with high rate of complications after acute myocardial infarction.
 Keywords: ST, Non ST, WBC.

Simultaneous Estimation of Bilastine and Montelukast in Bulk by Rp-hplc and Assessment of Its Applicability in Marketed Tablet Dosage Form

Aim: This study proposes to develop and validate the RP-HPLC method for Bilastine and Montelukast and to substantiate the RP-HPLC analysis bestowing to ICH validation guideline Q2R1.
 Place and Duration of Study: Y. B. Chavan College of Pharmacy, Aurangabad, MS, India, between January 2020 and October 2021.
 Methodology: The mixture of drugs was subjected to optimization by trial runs with different chromatographic parameters, viz. flow rate, λ in nm, etc. The system suitability was performed by repeated injections of Bilastine (200µg/mL) and Montelukast (200µg/mL) to confirm the optimization. Furthermore, the demonstrated method was validated as per ICH Q2R1 recommendations for parameters like accuracy, precision, robustness, the limit of detection and quantitation, etc.
 Results: The outcomes of the method in terms of percent relative standard deviation (%RSD) of retention time (RT) and mean peak area were seen as 0.09, 0.35, and 0.35, 0.56 for Bilastine and Montelukast, respectively. The method was successful in achieving the qualifying criteria entrusted to ICH guidelines. The correlation coefficient, slope, and y-intercept were illustrated to be 0.9971, 17595, 217883, 0.998, 35458, and 17147, correspondingly for Bilastine and Montelukast, respectively. The range was seen in the order of 160-260µg/mL and 80-130µg/mL for Bilastine and Montelukast. The precision of the method was established with %RSD of repeatability and intermediate precision was < 2 at three standard levels across the range. The %accuracy of the method was observed in the range of 96.95-101.41 %w/w and 97.37-101.89 %w/w in the order for Bilastine and Montelukast. The robustness of the method displayed the results within the prescribed boundaries. The recovered amount of Bilastine and Montelukast by spike method was observed to be 96.37-98.88 %w/w and 96.11-100.06%w/w.
 Conclusion: The author has accomplished the predefined goals by successful development and validation of the RP-HPLC method for the quantification of Bilastine and Montelukast as per ICH Q2R1 guidelines.

Statistical characterization of available reinforcement bars to establish qualifying acceptance criteria

The paper is based on an experimental study to elaborate the characterization process of mechanical properties of available reinforcement bars in the market. The quality of reinforcement bars depends on the various factors and recognizing them is very important to ensure the safety of the structures. Tensile strength, yield strength and percentage of elongation are used to characterize the rebars. It is observed that there is considerable dispersion of the properties among the available reinforcement bars of various diameters and sources in the Indian Market. Adequate characterization of the mechanical properties through statistical methods such as confidence interval, ANOVA and cumulative probability analysis provides a useful technique to determine the qualifying criteria of these rebars in addition to the existing provisions of codes. Reinforcement bars of diameters 8 mm, 10 mm, 12 mm, 16 mm, 20 mm, and 25 mm were tested from nine different sources or brands available in India. It is found that qualifying criteria should be established through a set of characterization methods and not only based on average values in reference to the existing codes. The findings are useful for site engineers to ensure the quality of the reinforcement bars and enhance understanding of the safety margin.

Role of community health nurse in the prevention of elderly dehydration: A mini-review

As dehydration is related to negative health outcomes in the elderly, including an increased risk of disability and death, prevention may help improve health, functional status, and quality of life. Dehydration diagnosis can be challenging in the elderly as the traditional physical indications of dehydration may be absent or ambiguous. Numerous etiologies place the elderly at an increased risk. The role of the community health nurse (CHN) derives from the responsibilities attached to her, and the Betty Neuman's Systems Model of health care with three levels of protection is usually applied to the CHN. In this mini-review, we try to integrate the Betty Neuman's Systems Model with the results of identified articles. This study includes a literature search of reputable international databases such as SpringerLink, PubMed, Embase, and Wanfang, particularly for the period 2005 to the present. Ten articles that met the qualifying criteria were included in this study. The findings of this study draw a picture of the role of CHN in preventing dehydration across the three levels of prevention as mentioned by Betty Neuman.

Association of ABO Blood Grouping and Periodontal Disease: A Literature Review

AbstractAlthough the correlation between the ABO blood group and certain systematic diseases is a well-documented fact. Few studies have explored the relationship of ABO with oral disorders including periodontal diseases (PD). This literature review aimed to assess the possible association between ABO blood grouping and PD. For this purpose, we searched online databases like PubMed and google scholar with the following terms in different combinations PD, ABO blood groups, gingivitis, the prevalence of periodontitis, aggressive periodontitis, risk factors of periodontitis, Association of PD and ABO, ABO Rh factor. English version papers describing the Oral health status are covered through research that includes clinical investigations, case studies, and retrospective studies on the subject. Historic reviews, articles with unpublished data, and letters to the editors were omitted from the survey following publications. The author thoroughly checked the titles and abstracts of the papers. The complete text was thoroughly assessed, and the relevant articles were analyzed in accordance with qualifying criteria. For further original and review research, references were further reviewed. Since our targeted subject was answered by a restricted number of original research. We identified fourteen articles describing the association of ABO blood types with PD. findings of our study concluded the genetic basis of the association of ABO blood types for the development of PD. six of the research provided here showed that the blood type O can serve as a prognostic factor for the development of PD. ABO blood types and Rhesus factors can be a risk predictors in the development of PD.

Leadership Styles in Childcare Directors.

Leadership is of paramount importance to any organization, as leaders can set the tone for the organization’s employees. The path to leadership in childcare can be markedly different from other professions, as there is no qualifying criteria; however, previous research has identified that for leaders to be effective they must possess skills, characteristics, and traits of effective leadership. The present study used The Multifactor Leadership Questionnaire (MLQ) (in Bass and Avolio, Multifactor leadership questionnaire (TM), Mind Garden, Inc., Menlo Park, 1995) with childcare directors to determine their self-identified leadership styles including transformational, transactional, and passive/avoidant to determine if their leadership style was consistent with recommendations from the field. Results suggest that childcare directors who remain in the role of managers (displaying either transactional or passive/avoidant leadership styles) do not provide the leadership needed to provide a high quality of education for young children, which is consistent with previous research. This research echoes concern from the field for credentialing of childcare directors.

Impact of Race-Adjusted Glomerular Filtration Rate Estimation on Eligibility for Simultaneous Liver-Kidney Transplantation.

Estimated glomerular filtration rate (eGFR) is adjusted for Black race in commonly used formulas. This has potential implications for access to simultaneous liver-kidney transplantation (SLKT) as qualifying criteria rely on eGFR. We performed a retrospective study of United Network for Organ Sharing national transplant registry data between February 28, 2002, and March 31, 2019, to evaluate the proportion of Black patients who would be reclassified as meeting SLKT criteria (as defined per current policies) if race adjustment were removed from 2 prominent eGFR equations (Modification of Diet in Renal Disease-4 [MDRD-4] and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). Of the 7937 Black patients listed for transplant during the study period, we found that 3.6% would have been reclassified as qualifying for chronic kidney disease (CKD)-related SLKT with removal of race adjustment for MDRD-4, and 3.0% would have been reclassified with CKD-EPI; this represented 23.7% and 18.7% increases in SLKT candidacy, respectively. Reclassification impacted women more than men (eg, 4.5% versus 3.0% by MDRD-4; P<0.05). In an exploratory analysis, patients meeting SLKT criteria by race-unadjusted eGFR equations were significantly more likely to receive liver transplantation alone (LTA) compared with SLKT. Approximately 2.0% of reclassified patients required kidney transplantation within 1 year of LTA versus 0.3% of nonreclassified patients. In conclusion, race adjustment in eGFR equations may impact SLKT candidacy for 3.0% to 4.0% of Black patients listed for LTA overall. Approximately 2.0% of patients reclassified as meeting SLKT criteria require short-term post-LTA kidney transplantation. These data argue for developing novel algorithms for glomerular filtration rate estimation free of race to promote equity.

Explorations in Corporate Hypocrisy and Proposing a Direction for a Sustainable Future

Despite dire warnings that the potential for environmental catastrophe is growing, most corporate sustainability efforts today, driven by the business case are limited to only those situations where financial outcomes are not in jeopardy. We argue that many of these efforts are in fact a co-opting of the sustainability agenda while creating the illusion of change. In effect, these efforts are hypocritical. We propose a categorization of these hypocrisies, which are manifested in various ways. Firms adopt sustainability to different degrees and we propose a continuum for Business-as-usual to Purposeful firms specifying qualifying criteria for each type. To make sustainability sustainable, we argue that the purpose of the firm must focus on the wellbeing of humanity and the planet. We propose the development of a Double Contribution Line to replace the ubiquitous Triple Bottom Line.

PROGNOSTIC IMPORTANCE OF WBC COUNT IN ACUTE MYOCARDIAL INFRACTION

Background: Coronary artery disease is a major cause of death and is a global health problem becoming an epidemic in both developed as well as in developing countries.&#x0D; Methods: 100 patients presenting to hospital within 24hrs with Acute MI and qualifying inclusion criteria were enrolled and written consent was taken regarding participation in the study.&#x0D; Results: In a total of 100 patients participated in our study 69 patients were male and 31 patients were females. Out of 100 patients 26 had LV dysfunction, among these 23 patients 17 were having elevated WBC count and 9 had normal WBC count. Among 100 patients 11 had cardiogenic shock, among these 11 patients 8 had elevated WBC count and 3 had normal WBC count. &#x0D; Conclusion: Elevated WBC count within 24 hours was associated with high rate of complications after acute myocardial infarction.&#x0D; Keywords: STEMI, NSTEMI, WBC

Soluble factors differ in platelets derived from separate niches: a pilot study comparing the secretome of peripheral blood and bone marrow platelets

Background aimsPlatelet-rich plasma (PRP) and bone marrow aspirate are commonly used in orthobiologics for their anti-inflammatory, anabolic/regenerative and immunomodulatory characteristics via platelet degranulation and cell secretions. Although platelets are derived from megakaryocytes in the bone marrow, no attention has been paid to the potential benefits of bone marrow platelets and whether their contents differ from aging platelets in peripheral blood. MethodsIn the present study, leukocyte-poor peripheral blood-derived platelets in plasma (LPP) and leukocyte-poor bone marrow platelets in plasma (BMP) were prepared from six donors, activated with calcium chloride, incubated and sampled at day 0, day 3 and day 6. LPP and BMP are platelet preparations intended to evaluate the respective platelet secretomes but are not classified as conventional PRPs, as they are not concentrated to the extent necessary to meet the qualifying criteria. At each time point, 15 growth and immunomodulatory factors were quantitated in LPP and BMP: platelet-derived growth factor AA, basic fibroblast growth factor/fibroblast growth factor 2, granulocyte-macrophage colony-stimulating factor, hepatocyte growth factor, macrophage colony-stimulating factor, stem cell factor, vascular endothelial growth factor, tumor necrosis factor alpha, IL-1β, interferon gamma, IL-4, IL-10, IL-1 receptor antagonist protein, IL-12p40 and arginase-1. ResultsThe results illustrate that platelets derived from bone marrow have a unique secretome profile compared with those derived from peripheral blood, with significant differences in anti-inflammatory cytokines, which are associated with monocyte polarization. ConclusionsUltimately, bone marrow-derived platelets may be useful as a stand-alone orthobiologic or as an effective adjuvant to autologous cell therapies where anti-inflammatory and anabolic processes are desired, especially with respect to monocyte function.

The impact of emotions on stereotyping in workplace selection: The role of certainty appraisals

AbstractAn appraisal tendency approach was adopted to explore the influence of emotional certainty on stereotyping and judgment in a workplace context. Across two studies, participants completed an emotional memory task designed to induce emotions representing two different levels of emotional certainty (certain versus uncertain). They then reviewed interview footage, a résumé, and qualifying criteria before rating a hypothetical job candidate’s personality and employability. Study 1 revealed that emotions high in certainty (compared to uncertainty) led to more favorable personality and employability ratings for attractive compared to unattractive candidates. Study 2 produced the same pattern of results for younger (compared to older) candidates. We conclude that certainty appraisals associated with temporary, incidental emotions are a useful predictor of the likelihood that stereotypes will be applied during decision making.

The Subject Of A Land Lease Agreement In Conjunction With A Water Facility Located On It

The publication is devoted to the study of legal and doctrinal trends in solving the issue of the subject of a land lease agreement in complex with a water object located on it.&#x0D; The author makes a reservation that the difficulty of clearly defining the subject of the studied treaty is due not only to the absence in the civil doctrine of a unanimous approach to understanding the essence of the subject of the treaty, but also to the natural inseparability of the water body with the land located on it.&#x0D; In the article, the author found that the legislative modelling of the contract, which mediates modern relations of use of the water body, was preceded by scientific studies of the features of ownership and use of this natural resource in conjunction with the land on which it is located.&#x0D; The author established the practical and doctrinal significance of using one contractual design for the lease of a water body and a land plot located under it. Such a legislative approach positively solves the problematic issues of the moment of acquisition of the right to lease a water object and the moment of transfer of the use object to the tenant, since the legislator connects these points with the time of state registration of the right to lease a land plot.&#x0D; The doctrinal effect of the application of this treaty model is manifested in the possibility of defining this contract in the system of civil law contracts, and affects the scope of application of civil, land and water legislation to the lease relations of a water body.&#x0D; In the publication, the author established that both natural resources - a land plot and a water object, together constitute the subject of a land lease agreement in conjunction with a water object located on it, formally correspond to the qualifying criteria of the thing as the subject of a hire (lease) agreement.&#x0D; The author concludes that the name of the contract model, simultaneously with the time of occurrence of the right to lease a land plot and a water object located on it, and the mandatory inclusion of a water body passport in such an agreement, make it possible to conclude that in the lease agreement of a land plot in complex with the water object located on it, it is not necessary to indicate technical data (volume and area) of the water body, since they are presented in its passport.

The Behavior of Welded Moment Connections in Box-Columns and Investigating Applied Demands for Different Cyclic Loading Protocols

The strength and deformation capacity of structural elements are influenced by their cumulative damages received through load cycles. Loading protocols would provide the estimation of the structural components’ capacities and a proper simulation of the seismic reality, which are used to assess the performance of connections. Given the widespread application of I-beam to box-column moment connections, the seismic performance of moment connections in the box-columns should be thoroughly investigated. However, most regulation details for the qualification of moment connections are presented for the H-shaped columns. Accordingly, in this study, 12 prequalified types of RBS and WUF-W moment connections in the box-columns are selected and analyzed under different cyclic loading scenarios. Therefore, the seismic behavior of such moment connections is studied for the drift qualifying criteria and collapse threshold when they are subjected to the SAC and ATC-24 loading protocols. Besides, energy dissipation, demand, loading protocols’ impact, and their influences are examined.

Qualifying for a Type of Pension and Poverty Measurement

The period of exiting from once full-time years of daily employment to a period of less time constraint can be a period of excitement or misery in poverty. It is pathetic that at one period, an individual is on a payroll of an employer but at another period the individual is not on any pension roll. The objective of the paper is to examine the qualification criteria for a pension and the effect of a pension type on poverty. Primary data was gathered from residences with at least one person aged 60 years old or older across 24 sampled localities in the country. A logistic regression estimation method was employed for the data analyses. The findings of the study indicate that different pension systems have different qualifying criteria that the individual must satisfy to be able to get the monthly pension. The conceptual framework indicates that although some individuals contributed to the SSNIT pension scheme, they could not qualify for the monthly pension due to the inability to satisfied the minimum number of months. The findings also show that the SSNIT pension recipients household were less likely of being poor compared to the CAP30 pensioners. It is recommended that SSNIT should embark on vigorous awareness creation exercise to educate the general public about the tenets of social security pension.

Abnormal Central Venous Oxygen Saturation as a Predictor of Mortality in Patients with Sepsis and Polytrauma in the Surgical Intensive Care Unit

Background: In postoperative heart surgery patients and patients with sepsis, pathological (low and supranormal) central venous oxygen satura- tion (ScvO2) was shown to be associated with lower mortality. The objective is we want to examine the effect of sepsis and polytrauma infection on our surgical ICU and the incidence of morbidity and death in the population. Subjects and Methods: In such patients who met the qualifying criteria and had a history of scepticism and multi-trauma, a retrospective observational review was conducted. We investigated and evaluated the association between SCV02 and mortality and other variables, such as lactate and baseline excess and period of the ICU stay and inotropic assistance within the first 6 hours, using a multivariate model review. Their entry was measured and 6 hours later. Result: The incidence of deaths in the hyperoxia group was 2.4 times higher in comparison to the general population, and the death rate in the hypoxia category was 1.25 times higher. The risk of death for the hyperoxic population was 2.4 times higher. There was no statistically relevant discrepancy of ICU, inotropic treatment, coagulopathy, dialysis, apache-11 score, baseline excess and lactate between the three levels of Scv02. Conclusion: The base excess and Scv02 were not significant when the lactates were calculated to a mortality point, but the j curve revealed that both the hypoxia group and the hyperoxia mortality had improved in contrast with the normal oxy group. Since the small sample size was sufficient to predict a trend, secondary targets were not

PNS178 DUAL-Branding: A Practical Option to Bolster Patient Access to NOVEL Medicines?

Optimising patient access to new medicines is a key priority for healthcare systems, who continually seek value-based approaches for reimbursement of innovative therapies. One such approach is dual-branding for a drug with the same active ingredient. Regulators permit dual-branding if the product meets a specific set of qualifying criteria. Although historically there have been challenges associated with this process, there are potential benefits for payers and healthcare systems. This research aims to assess the value and impact of dual branding on patient access in European markets. Eight dual-brand case studies were analysed through secondary research. Insights were validated in thirty-minute interviews with three European payer advisors. Analysis of the key drivers for achieving successful regulatory approval of a dual-brand indicates it is a nuanced process determined by pre-defined qualifiers, which have varying levels of importance depending on the agent and therapy area. If regulatory approval is successful, the launch of a second brand has wide-ranging implications on market access. For example, the launch of cabozantinib’s second brand resulted in multiple benefits for patients, notably improved access in Italy and Spain, and faster time to market in France. However, trade-offs also exist with reimbursement of a dual brand, particularly the cost impact for payers, with manufacturers avoiding the price reduction typically associated with the indication expansion of a single-brand - although interestingly this was not always the case. Dual-branding of drugs can provide value to payers and healthcare systems by improving patient access to novel treatments. However, the three traditional interdependent drivers of reimbursement: broad access, time to market and therapy cost, are seldom - if ever - achieved together. Payers will therefore need to carefully evaluate and balance the trade-offs when assessing dual-brands as a feasible and practical option to bolster patient access and achieve patient-centricity.

Analysis of G-induced Loss of Consciousness (G-LOC) and Almost Loss of Consciousness (A-LOC) incidences in high-performance human centrifuge at Institute of Aerospace Medicine Indian Air Force

Introduction: Institute of Aerospace Medicine (IAM) Indian Air Force (IAF) conducts operational training in Aerospace Medicine for IAF fighter aircrew since 2009. This includes high-G training with qualifying criteria of demonstrating ability of the aircrew to sustain 9G for 5 s in closed-loop run (pilot-in-control) wearing anti-G suit while performing anti-G straining maneuver (AGSM). Incidences of inadvertent almost loss of consciousness (A-LOC)/G-induced loss of consciousness (G-LOC) are an unavoidable unintended consequence of such training. The aim of the paper is to study the incidence of G-LOC and A-LOC and its nature in the high-performance human centrifuge (HPHC) and compare it with our previous experiences. Material and Methods: A G-LOC/A-LOC proforma was designed at the Department of Acceleration Physiology and Spatial Orientation at IAM IAF to understand the nature and cause of the G-LOC/A-LOC. This was to be filled up by the aircrew on a voluntary basis. The data were analyzed using Microsoft Excel with a significance level set at 95% confidence interval and alpha ≤0.05. Results: Fifty-two aircrew (19.92%) experienced inadvertent G-LOC/A-LOC in 83 such episodes (54 G-LOC and 29 A-LOC) during the period January 2018–December 2018. Forty-seven aircrew experiencing G-LOC/ALOC agreed to be part of the study and filled up the proforma after the episodes. The incidence of G-LOC in the institute has reduced significantly over the past two decades, perhaps due to change in the HPHC used for training of aircrew. The incidence of G-LOC found in this study is comparable to the global incidence. Rise in heart rate was higher during A-LOC than G-LOC and was found to be statistically significant (t statistic = 2.33; P = 0.01). Relative incapacitation period was lesser than absolute incapacitation period during G-LOC and was found to be statistically significant (t statistic = 3.29, P = 0.001). G-level at which Type II G-LOC occurred was significantly higher than the Type I G-LOC. Conclusion: The incidence of A-LOC/G-LOC has reduced over the past two decades of high G training in IAF and is comparable to global incidence.

Insurance Payer Status Predicts Postoperative Speech Outcomes in Adult Cochlear Implant Recipients.

Cochlear implant qualifying criteria for adult patients with public insurance policies are stricter than the labeled manufacturer criteria. It remains unclear whether insurance payer status affects expedient access to implants for adult patients who could derive benefit from the devices. This study examined whether insurance payer status affected access to cochlear implant services and longitudinal speech-perception outcomes in adult cochlear implant recipients. Retrospective cross-sectional study. Sixty-eight data points were queried from the Health Insurance Portability and Accountability Act-Secure, Encrypted, Research Management and Evaluation Solution database which consists of 12,388 de-identified data points from adult and pediatric cochlear implant recipients. Linear mixed-effects models were used to determine whether insurance payer status affected expedient access to cochlear implants and whether payer status predicted longitudinal postoperative speech-perception scores in quiet and noise. Results from linear mixed-effects regression models indicated that insurance payer status was a significant predictor of behavioral speech-perception scores in quiet and in background noise, with patients with public insurance experiencing poorer outcomes. In addition, extended wait time to receive a cochlear implant was predicted to significantly decrease speech-perception outcomes for patients with public insurance. This study documented patients covered by public health insurance wait longer to receive cochlear implants and experience poorer postoperative speech-perception outcomes. These results have important clinical implications regarding the cochlear implant candidacy criteria and intervention protocols.

Cardiovascular Disease Burden Prior To Hereditary Transthyretin Amyloidosis Diagnosis

Introduction Hereditary transthyretin amyloidosis (ATTRv) is often associated with progressive infiltrative cardiac involvement, with cardiac symptoms occurring sometimes years prior to diagnosis. Hypothesis ATTRv patients demonstrate significant cardiovascular symptom manifestations and healthcare utilization prior to diagnosis. Methods Newly diagnosed ATTRv patients in IBM® MarketScan® Commercial and Medicare Supplemental data (US) were identified using a claims-based algorithm. Diagnosis required ≥1 claim with relevant amyloidosis diagnosis code (ICD-10-CM: E85.0-.4, E85.89, E85.9) during identification (ID) period (1/2016-12/2017), and the occurrence of ≥1 qualifying criteria during 2011-2017: ≥15 days diflunisal use, liver transplant, or claim with code E85.1 (neuropathic heredofamilial amyloidosis) or E85.2 (heredofamilial amyloidosis unspecified). Index date was defined as date of first claim with amyloidosis code in ID period, and the pre-index period as the 5 years prior to index date. Patients with an ICD-9/10 amyloidosis code during this period were excluded to focus on the newly diagnosed. Control subjects without ATTRv were identified and matched (age, gender, region) to ATTRv patients (ratio 3:1); meeting the same index and enrollment requirements. Frequency of selected cardiovascular (CV) conditions and healthcare use were measured in the pre-index period; demographics and Charlson comorbidity index (CCI) were measured 1 year pre-index. Results Among 141 patients with ATTRv and 423 matched controls, mean (SD) age was 62.5 (14.2) years and 53.9% were female. Mean CCI for ATTRv patients was 2.7 (3.0) vs 1.1 (1.9) for controls. In the pre-index period, CV conditions were more common among ATTRv patients relative to controls: chest pain (51.8 vs. 28.1%), dyspnea (49.6 vs 25.8%), bleeding (41.8 vs 21.3%), edema (27.0 vs 12.8%), heart failure (23.4 vs 5.9%), ventricular hypertrophy (19.9 vs 5.7%), hypotension (18.4 vs 6.1%), atrial fibrillation/flutter (18.0 vs 8.9%), stroke (12.8 vs 6.1%), and aortic stenosis (10.6 vs 4.5%); conditions were relatively higher in each pre-index year. Hospitalization (47.5 vs. 24.3%), emergency department visits (60.3 vs. 47.0%) and cardiac testing (81.6 vs. 65.7%) were also more frequent among ATTRv patients. Median time (months) to ATTRv diagnosis from initial symptom manifestation were largest for chest pain (43.0), dyspnea (41.1), aortic stenosis (39.2), and atrial fibrillation/flutter (34.3). Conclusions ATTRv patients have considerable CV disease burden in the 5 years preceding diagnosis. Increased awareness of characteristic CV manifestations may increase clinical suspicion, leading to early diagnosis and prompt intervention.

Streamlined approval of biosimilars: moving on from the confirmatory efficacy trial

Licensing of biosimilars is essential to promote patient access to 21st-century biological medicines. Regulatory approval of biosimilars is based on the totality of evidence from a head-to-head comparison with reference products (RPs). A clinical efficacy trial is usually required, but this is increasingly questioned. Based on a thorough review of biosimilar applications in the European Union (EU), we conclude that in-depth knowledge of the reference product, allied with high-performing analytical tools, largely predicts clinical comparability, subject to confirmation by a comparative pharmacokinetic (PK) trial. We provide a blueprint for a biosimilar pathway that reduces the need for clinical efficacy trials in exceptional cases, together with qualifying criteria and requirements for streamlined assessment to expedite wider access to affordable biological medicines.