Treatment Effect Waning Assumptions: A Review of National Institute of Health and Care Excellence Technology Appraisals.

Objectives: This study aims to review the National Institute of Health and Care Excellence (NICE) technology assessments to gain insights into the implementation of treatment effect (TE) waning, whereby the hazard or survival in an assessed technology converges to that of the comparator. This analysis aims to contribute to inform future guidance in this area.

Methods: Technology appraisals published October 20, 2021 to September 20, 2023 were reviewed and data extracted on TE waning circumstances, methods, and rationale to compile a database based on 3 research questions: When are TE waning assumptions used? What methods are used? Why have the company/Evidence Assessment Group/committee preferred these methods?

Results: Both the evidence assessment group/company and the committee included TE waning assumptions in 28 appraisals.

Targeted Delivery of Abaloparatide to Spinal Fusion Site Accelerates Fusion Process in Rats.

Spinal fusions are performed to treat congenital skeletal malformations, spondylosis, degenerative disk diseases, and other pathologies of the vertebrae that can be resolved by reducing motion between neighboring vertebrae. Unfortunately, up to 100,000 fusion procedures fail per year in the United States, suggesting that efforts to develop new approaches to improve spinal fusions are justified. We have explored whether the use of an osteotropic oligopeptide to target an attached bone anabolic agent to the fusion site might be exploited to both accelerate the mineralization process and improve the overall success rate of spinal fusions.

An Analysis of Uncertainties and Data Collection Agreements in the Cancer Drugs Fund.

Background: Managed Access Agreements (MAAs) are a commercial arrangement that provide patients earlier access to innovative health technologies while uncertainties in the evidence base are resolved through data collection. In the UK, data collection agreements (DCAs) outline the evidence that will be collected during the MAA period and are intended to resolve uncertainties in the clinical- and cost-effectiveness of a technology sufficient for the National Institute of Health and Care Excellence (NICE) committee to make a final decision on reimbursement.

Objective: The aim of this study was to identify the primary uncertainties leading to a recommendation for entry to the Cancer Drugs Fund (CDF) and evaluate how the corresponding DCAs attempt to address these.

An evaluation of managed access agreements in England based on stakeholder experience.

Objectives: The objective of this research was to evaluate managed access policy in England, drawing upon the expertise of a range of stakeholders involved in its implementation.

Methods: Seven focus groups were conducted with payer and health technology assessment representatives, clinicians, and representatives from industry and patient/carer organizations within England. Transcripts were analyzed using framework analysis to identify stakeholders' views on the successes and challenges of managed access policy.

Racehorse welfare across a training season.

Racehorse welfare is gaining increasing public attention, however scientific evidence in this area is lacking. In order to develop a better understanding of racehorse welfare, it must be measured and monitored. This is the first study to assess racehorse welfare using scientific objective methods across a training season.

Early access schemes for innovative health technologies: the views of international stakeholders.

Objectives: Early access schemes (EASs) are approaches used by payers to balance and facilitate earlier patient access to innovative health technologies while evidence generation is ongoing. Schemes require investment from payers and are associated with significant risk since not all technologies will be routinely reimbursed. The purpose of this study was to gain the perspectives of policy experts about the key challenges for EASs and potential solutions for their optimal design and implementation.

Risk factors for, and prediction of, exertional heat illness in Thoroughbred racehorses at British racecourses.

The development of exertional heat illness (EHI) is a health, welfare and performance concern for racehorses. However, there has been limited multivariable assessment of the possible risk factors for EHI in racehorses, despite such information being vital for regulators to effectively manage the condition. Consequently, this study aimed to identify the risk factors associated with the occurrence of EHI in Thoroughbred racehorses and assess the ability of the risk factor model to predict the occurrence of EHI in racehorses to assist in early identification.

The Testing Imperative: Why the US Ending the Human Immunodeficiency Virus (HIV) Epidemic Program Needs to Renew Efforts to Expand HIV Testing in Clinical and Community-Based Settings.

Data from several modeling studies demonstrate that large-scale increases in human immunodeficiency virus (HIV) testing across settings with a high burden of HIV may produce the largest incidence reductions to support the US Ending the HIV Epidemic (EHE) initiative's goal of reducing new HIV infections 90% by 2030. Despite US Centers for Disease Control and Prevention's recommendations for routine HIV screening within clinical settings and at least yearly screening for individuals most at risk of acquiring HIV, fewer than half of US adults report ever receiving an HIV test. Furthermore, total domestic funding for HIV prevention has remained unchanged between 2013 and 2019.

Assessing reproducibility of inherited variants detected with short-read whole genome sequencing.

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS.

Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers.

Author Correction: Best practices for benchmarking germline small-variant calls in human genomes.

In the version of this article initially published online, two pairs of headings were switched with each other in Table 4: "Recall (PCR free)" was switched with "Recall (with PCR)," and "Precision (PCR free)" was switched with "Precision (with PCR)." The error has been corrected in the print, PDF and HTML versions of this article.

Best practices for benchmarking germline small-variant calls in human genomes.

Standardized benchmarking approaches are required to assess the accuracy of variants called from sequence data. Although variant-calling tools and the metrics used to assess their performance continue to improve, important challenges remain. Here, as part of the Global Alliance for Genomics and Health (GA4GH), we present a benchmarking framework for variant calling.

An adaptive grid to improve the efficiency and accuracy of modelling underwater noise from shipping.

Underwater noise pollution from shipping is a significant ecological concern. Acoustic propagation models are essential to predict noise levels and inform management activities to safeguard ecosystems. However, these models can be computationally expensive to execute.

Parvovirus B19 infection in an adult presenting with connective tissue disease-like symptoms: a report of the clinical and histological findings.

Parvovirus B19 infections in adults are usually associated with nonspecific and mild symptoms. However, cases presenting with a lupus-like syndrome have been described, leading to the hypothesis that parvovirus infection can induce connective tissue disease. Various histopathologic features of cutaneous manifestations of parvovirus have been reported, including features which overlap with those of connective tissue disease.

Major diversification of voltage-gated K+ channels occurred in ancestral parahoxozoans.

We examined the origins and functional evolution of the Shaker and KCNQ families of voltage-gated K(+) channels to better understand how neuronal excitability evolved. In bilaterians, the Shaker family consists of four functionally distinct gene families (Shaker, Shab, Shal, and Shaw) that share a subunit structure consisting of a voltage-gated K(+) channel motif coupled to a cytoplasmic domain that mediates subfamily-exclusive assembly (T1). We traced the origin of this unique Shaker subunit structure to a common ancestor of ctenophores and parahoxozoans (cnidarians, bilaterians, and placozoans).

Joint variant and de novo mutation identification on pedigrees from high-throughput sequencing data.

The analysis of whole-genome or exome sequencing data from trios and pedigrees has been successfully applied to the identification of disease-causing mutations. However, most methods used to identify and genotype genetic variants from next-generation sequencing data ignore the relationships between samples, resulting in significant Mendelian errors, false positives and negatives. Here we present a Bayesian network framework that jointly analyzes data from all members of a pedigree simultaneously using Mendelian segregation priors, yet providing the ability to detect de novo mutations in offspring, and is scalable to large pedigrees.

The public gets what the public wants: experiences of public reporting in long-term care in Europe.

Introduction: Public reporting of quality in long-term care is advocated on the basis of allowing providers to improve their performance by benchmarking and supporting users to choose the best providers. Both mechanisms are intended to drive improvements in quality. However, there is relatively scarce comparative research on the experiences and impact of public reporting on quality in long-term care in Europe.

Patients' opinions of health care providers for supporting choice and quality improvement.

Patients are increasingly using the internet to access information on health care and services, as well as writing reviews of their own experiences. With patient choice increasing in many health systems, payers, purchasers and providers are attempting to take control of this trend by designing and managing their own patient opinion websites. This essay identifies and explores three aspects of online reviews of health care: the role of patients as judges of health care quality; the motivation behind patients posting reviews; and patients' use of such information.

Reproducing social inequality and unequal treatment in the National Health Information Infrastructure: a discourse analysis of Institute of Medicine executive summaries.

This research analyzes how discourse constituting the currently proposed National Health Information Infrastructure (NHII) may reproduce existing social inequality in healthcare. Textually oriented critical discourse analysis and corpus linguistics methods compare 3 executive summaries from the Institute of Medicine reports: the Quality Chasm and Insuring Health series, and the stand-alone report Unequal Treatment. These methods proved effective in studying the social action of language used in those summaries and will be useful in studying a larger corpus of discourse constituting the NHII.

Social construction of the patient through problems of safety, uninsurance, and unequal treatment.

The purpose of this research was to study how the Institute of Medicine discourse promoting health information technology may reproduce existing social inequalities in healthcare. Social constructionist and critical discourse analysis combined with corpus linguistics methods have been used to study the subject positions constructed for receivers of healthcare across the executive summaries of 3 different Institute of Medicine reports. Data analysis revealed differences in the way receivers of healthcare are constructed through variations of social action through language use in the 3 texts selected for this method's testing.

Sibling violence silenced: rivalry, competition, wrestling, playing, roughhousing, benign.

In this article, sibling violence and the silence surrounding it is explicated through professional literature and research findings, exemplars from clinical practice, and statistics. Theoretical positions and discourse analysis have been used to help explain how regular broken bones, bruises, lacerations, and verbal humiliation can be minimized as normal sibling rivalry or roughhousing, which does not cause serious consequences. Nursing should be on the front lines of ending practices of violence.

Reproducing social inequality and unequal treatment in the national health information infrastructure: A discourse analysis of IOM executive summaries.

This paper reports on preliminary data analysis for a larger research project whose purpose is to study how the discourse constituting the currently proposed NHII may reproduce existing social inequality in healthcare. The purpose of this preliminary study is to test the methods planned for the larger study. Textually oriented critical discourse analysis and corpus linguistics methods have been used to compare three executive summaries, the first report of two recent series and one stand alone report from the Institute of Medicine: the Quality Chasm and the Insuring Health series, and the report Unequal Treatment.