IQVIA (United Kingdom)

Clinical evidence is needed for performance of novel coronavirus disease (COVID-19) molecular tests in asymptomatic populations to support regulatory decisions. To support claim expansion of a direct molecular test, clinical use and performance of the Cobas® SARS-CoV-2 qualitative test for use on Cobas 5800/6800/8800 Systems ("candidate test") for detecting SARS-CoV-2 in individuals who are asymptomatic were investigated. This study leveraged real-world data from the 2020 National Football League (NFL) COVID-19 Surveillance Program during August 1, 2020-January 3, 2021. NFL players and staff from 32 clubs had nasal samples prospectively collected on a near-daily basis. Samples underwent reverse transcription polymerase chain reaction (RT-PCR) testing by a single provider across five laboratories. The study population included individuals whose samples were tested on the candidate test. A comparator algorithm was constructed based on comparator test results and clinical adjudication within the NFL program. Results from the candidate test were compared against the comparator algorithm to calculate positive and negative percent agreements (PPA and NPA). Two-sided 95% confidence intervals (CIs) for PPA and NPA were determined (Wilson score method). A total of 1776 samples were included in the final analysis. All 11 samples with positive comparator status were positive on the candidate test (PPA 100% [95%CI 74.1, 100]). Of 1765 samples with negative comparator status, 1762 were negative on the candidate test (NPA 99.8% [95%CI 99.5, 99.9]). Results were consistent when stratified by age and sex. Based on data collected during this occupational testing protocol, our study provides strong evidence supporting real-world performance of this test in an asymptomatic population. These findings, complemented by data from an existing clinical study, provided the totality-of-evidence that supported the US Food and Drug Administration clearance for the expanded claim of the candidate test for the qualitative detection of SARS-CoV-2 in the asymptomatic population.

Abstract Protein dynamics determine biological function, yet extracting structural ensembles from Hydrogen–Deuterium Exchange Mass Spectrometry (HDX-MS) remains a challenging inverse problem. Current ensemble-fitting approaches often achieve good agreement with uptake curves but lack rigorous validation and uncertainty quantification, limiting structural confidence. We propose ValDX, a validation framework for quantitative integration of HDX-MS data with structural ensembles. ValDX combines overlap-aware data splitting, replicate-based uncertainty estimation, and uptake-independent “Work Done” metrics that quantify how much an ensemble must be modified to match experiment. Across 22 ensembles spanning six proteins (58–474 residues), we show that conventional error metrics fail to distinguish structurally representative ensembles from incorrect ones, whereas Work Done metrics robustly discriminate global and local conformational quality. We further demonstrate that clustering yields compact, interpretable ensembles with minimal loss of accuracy, and that staged optimisation enables reliable fitting of both ensemble weights and forward-model parameters without requiring a reference structure. Together, this framework establishes HDX-MS ensemble integration as a quantitative structural hypothesis-testing problem, enabling inference of protein dynamics from HDX-MS data.

In multiple sclerosis, disease-modifying therapies aim to reduce relapse rate and slow disease progression. An important component of successful disease control is treatment persistence, which is the time a patient remains on a therapy. The primary objective of this study was to examine persistence with ofatumumab in a real-world setting. This was a retrospective cohort study using data from the Patient Support Program (clinicaltrials.gov number NCT06854341). Adults diagnosed with relapsing remitting multiple sclerosis who initiated ofatumumab were included. Persistence, defined as the number of days from ofatumumab initiation until discontinuation, was assessed from April 2021 to May 2024. Ofatumumab persistence was quantified by Kaplan-Meier estimates for discontinuation probabilities with corresponding 95% confidence intervals at 12, 24 and 36 months. Secondary objectives included a descriptive analysis of patients' baseline demographic and clinical characteristics, and their association with discontinuation. The PSP included a total of 6377 patients, of which 5436 patients met the inclusion criteria and had information to assess discontinuation. Persistence probability with ofatumumab was 96.94% at 12-months, 95.02% at 24-months, and 92.26% at 36-months post index. During this period, 167 patients (3.1%) discontinued ofatumumab. The most common reasons for discontinuation included side effects (0.9%), trying to conceive/pregnancy (0.5%), and patient request (0.5%). This study provides insights into real-world ofatumumab utilization among patients with multiple sclerosis and demonstrates that persistence with ofatumumab remained high over 3 years. These results complement data from controlled clinical trials and suggest that patients persist with ofatumumab.

To assess the relationship between haemoglobin A1c (HbA1c) levels and incidence of long-term complications in patients with type 2 diabetes (T2D). This long-term, retrospective study acquired patient data from the Swedish National Diabetes Registry and linked national registers between 1 January 1998 and 31 December 2019. The incidence rates (IR) of microvascular/macrovascular outcomes and cardiovascular death were reported for the overall study population. The hazard ratios (HR) for these outcomes were compared across HbA1c ranges assessed over time and between the early HbA1c control groups: early tight control (HbA1c ≤6.5%), no early tight control (HbA1c >6.5%), and early adverse control (HbA1c >7%), from 18 months after diagnosis. 57.2% of the overall population were male and a median age of 60 years. The IR per 100-patient-years of any microvascular complication remained relatively stable (2005: 8.75; 2014: 10.95; 2019: 8.71), while cardiovascular death increased from 2005 (IR: 0.12) to 2018 (IR: 0.46). Incidences of any macrovascular complication increased with HbA1c ranges (8.0% to <9.0%, HR:1.16 [95%CI: 1.12-1.20]; 7.0% to <8.0%, HR:1.08 [95%CI: 1.05-1.11]) compared to reference (6.0 to <7.0%). Between early HbA1c control groups, the rates of any microvascular/macrovascular complication, and cardiovascular death were reduced in the reference early tight control group compared to the no early tight control group (HR:0.84 [95%CI: 0.80-0.89]; HR:0.86 [95%CI: 0.79-0.93]; and HR:0.60 [95%CI: 0.46-0.79], respectively), with similar results achieved compared to the early adverse control group. Elevated HbA1c levels were closely associated with long-term complications, while early tight control of HbA1c corresponded to significantly improved clinical outcomes in patients with T2D.

The care of patients with rare diseases in Germany poses a challenge; endogenous Cushing's syndrome highlights this issue. An analysis of the care situation aims to identify areas for improvement. A systematic literature search on the care situation was compared with prescription data from Germany and France as well as physician statistics from various European countries. In Germany, there is a low density of endocrinologists, a lower treatment prevalence than in France and a longer time to diagnosis than in other countries with well-developed healthcare systems. In order to guarantee need-based care for rare diseases, investments in the training and further education of specialists, such as endocrinologists, and in new, cross-sectoral forms of care are necessary.

<title>Abstract</title> <bold>BACKGROUND</bold> Aflatoxin contamination is a significant yet under-addressed food safety challenge in low-resource settings, driven by a complex interplay of environmental, agricultural, and socio-economic factors. Limited access to agricultural inputs, inadequate post-harvest handling and storage, and weak regulatory enforcement alongside food scarcity and climate change heighten the risk of contamination and exposure. Human exposure is associated with serious health consequences, including hepatocellular carcinoma, immune suppression, and childhood stunting. Although aflatoxin is increasingly recognized as a global food safety concern, little is known about community-level knowledge, risk perceptions, and preventive practices. This study examined household heads’ awareness, perceptions, and behaviours related to aflatoxin exposure and mitigation in a rural coastal community in Kenya. <bold>METHODS</bold> We conducted a cross-sectional survey using a census approach within the Kaloleni-Rabai Health and Demographic Surveillance System (KRHDSS). Between July and December 2022, data were collected from 17,813 household heads through face-to-face, interviewer-administered, digitized questionnaires. <bold>RESULTS</bold> Farming was the predominant occupation (n = 5,757; 32.3%). Maize was sourced primarily from household harvests and local markets, with over three-quarters (n = 13,818; 77.6%) of respondents consuming maize flour three or more times weekly. Despite maize being a dietary staple, awareness of aflatoxin was limited: only 49.5% (n = 8,816) had heard of aflatoxin. Even fewer (&lt; 20%) respondents were able to identify foods at risk, signs of contamination, causes of fungal growth, or health consequences of exposure. Socio-economic status, rurality, education, and sex influenced aflatoxin-related knowledge, perceptions, and practices. <bold>CONCLUSION</bold> Low awareness of aflatoxin constrains rural households’ ability to prevent contamination and limit exposure. As aflatoxin risk arises at multiple points along the agricultural value chain, and vulnerability to exposure is heightened during periods of food scarcity, comprehensive approaches are required. Effective prevention will depend on integrated strategies that combine educational initiatives, infrastructural support, and policy interventions targeting agricultural practices, food security, and consumer behaviours.

Canadian real-world data (RWD) regarding palbociclib as a first-line therapy for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) is limited. The PALbociclib CANadian (PALCAN) study examined palbociclib utilization patterns as first-line treatment for HR+/HER2- MBC using Alberta health administrative data. The final PALCAN cohort included 472 female patients with a median age of 64 years and a median follow-up time of 22.8 months (IQR: 0.7-88.2). The median (95% CI) duration of treatment was 13.8 (12.7-15.1) months in the overall cohort (IQR: 5.6, 24.8 months), and the probability of treatment discontinuation within the first year was 45%. Aromatase inhibitors (AIs) and fulvestrant were the accompanying endocrine therapies (ETs) in 83% (N = 393) and 14% (N = 64) (15 with unknown accompanying therapy) of patients, respectively. The median duration of treatment for patients receiving an AI as an accompanying therapy was 15.1 (13.6-17.4) months and 7.9 months (5.8-12.6) for patients receiving fulvestrant, which may suggest endocrine resistance in the latter group. The PALCAN data provides insights into practice patterns and the effectiveness of palbociclib as a first-line therapy in female patients with HR+/HER2- breast cancer in the Canadian real-world setting.