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Neonatal care needs more robust guidance on pharmacotherapy, (formulation, dosage regimen, safety and efficacy information). This requires structured advocacy. We therefore discuss advocacy related to improving information about medicines including current practices, clinical trials, the current setting, and trial preparedness. This steps can improve neonatal drug development by generating evidence, particularly if a programmatic approach (identify dosing, eligibility criteria, and outcomes) to evidence generation is followed. Trial design should be guided by the intended use of the medicine and the benefits/risks that the study participant is exposed to. Regulatory trials (explanatory, controlled environment, internal validity, endpoints reflect clinically important outcomes, strong causal evidence) are sometimes necessary. However, some research questions are best addressed with informative trials. In either case, trial design can be supported by real world data and evidence, extrapolation from other subpopulations, or physiologically-based pharmacokinetic modeling. Data management, safety reporting, and management of drugs should be specified and proportionate. Trial design and conduct also necessitate awareness of Good Clinical Practice specific to neonates. Relevant aspects include protocol and trial design, research skills and interactions with Ethics Committees or Institutional Research Boards, capacities and competences needed within the research team, and aspects related to consent and recruitment., Competing Interests: Declaration of competing interest The research activities of A. Smits are supported by a Senior Clinical Investigatorship of the Research Foundation Flanders (FWO) (18E2H24N)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To study the 30-month safety and effectiveness of Cladribine tablets (CladT) in relapsing multiple sclerosis (RMS) months in a real-world setting., Methods: Retrospective single-centre observational study in Qatar (January 2018-Feb 2023). Clinical and MRI data, lymphocyte counts and adverse events (AE) were recorded for patients with RMS who received at least one course of CladT., Results: Forty-six patients were included (mean follow-up 22 months); 34 (74 %) were female, 22 (48 %) were disease-modifying therapy (DMT) naïve, 16 (35 %) had switched from platform DMT and 8 (17 %) from high efficacy (HE) DMD. Mean age was 26.7±7.2 y, mean disease duration was 7.2±6.0 y. Common reasons for treatment with CladT were MS activity (91 %), pregnancy planning (17 %), AE (20 %), compliance (9 %). 44/46 ( 96 %) received the year 2 course of CladT. Annualised relapse rate (ARR) fell from 1.02 (baseline) to 0.1, 0, 0.1, 0.1 and 0.1 for years 1-5 post-treatment, respectively; 87.5-100 % were free of relapses at these times, vs. 21 % at baseline. There were no relapses in year 2; 78 %, 100 %, 84 %, 80 % and 100 %, respectively, were free of GD+ MRI lesions at years 1-5, vs. 31 % at baseline. Most clinical AE were mild (1 moderate, no severe AE); 12 contracted Covid-19 (no hospitalisations). Grade 3 lymphopenia occurred in 5 patients., Conclusions: CladT appeared to be effective and safe in our retrospective study, irrespective of prior treatments, consistent with other real world data that support the early use of CladT in the management of RRMS., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Multiple treatment options are recommended for Systemic Lupus Erythematosus (SLE) by clinical guidelines. This study aimed to explore SLE treatment patterns as there is limited real-world data of SLE medication utilisation, especially in childhood-onset SLE (cSLE)., Methods: We conducted a longitudinal cohort study using five routinely collected healthcare databases from four European countries (United Kingdom, France, Germany, and Spain). We described the characteristics of adult and paediatric patients at time of SLE diagnosis. We calculated the percentage of patients commencing SLE treatments in the first month and year after diagnosis, reported number of prescriptions, starting dose, cumulative dose, and duration of each treatment, and characterised the line of therapy., Results: We characterised 11,255 patients with a first diagnosis of SLE and included 5718 in our medication utilisation analyses. The majority of adult SLE patients were female (range 80-88 %), with median age of 49 to 54 years at diagnosis. In the paediatric cohort (n = 378), 66-83 % of SLE patients were female, with median age of 12 to 16 years at diagnosis. Hydroxychloroquine and glucocorticoids were common first-line treatments in both adults and children, with second-line treatments including mycophenolate mofetil and methotrexate. Few cases of monoclonal antibody use were seen in either cohort. Initial glucocorticoid dosing in paediatric patients was often higher than in adults., Conclusion: Treatment choices for adult SLE patients across four European countries were in line with recent therapeutic consensus guidelines. High glucocorticoid prescriptions in paediatric patients suggests the need for steroid-sparing treatment alternatives and paediatric specific guidelines., Competing Interests: Declarations of competing interest DPA's department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department. James Brash and Hanne van Ballegooijen are employees of IQVIA. All other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background & Aims: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD)., Methods: From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks., Results: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed., Conclusion: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In the current paper, we will focus on requirements to ensure big data can advance the outcomes of our patients suffering from kidney disease. The associated ethical question is whether and how we as a nephrology community can and should encourage the collection of big data of our patients. We identify some ethical reflections on the use of big data, and their importance and relevance. Furthermore, we balance advantages and pitfalls and discuss requirements to make legitimate and ethical use of big data possible. The collection, organization and curation of data come upfront in the pipeline prior to any analyses. Great care must therefore be taken to ensure quality of the data at this stage, to avoid the garbage in garbage out problem and suboptimal patient care as a consequence of such analyses. Access to the data should be organized so that correct and efficient use of data is possible. This means that data must be stored safely, so that only those entitled to do so can access them. At the same time, those who are entitled to access the data should be able to do so in an efficient way, so as not to hinder relevant research. Analysis of observational data is itself prone to many errors and biases. Each of these biases can finally result in provision of low-quality medical care. Secure platforms should therefore also ensure correct methodology is used to interpret the available data. This requires close collaboration of a skilled workforce of experts in medical research and data scientists. Only then will our patients be able to benefit fully from the potential of AI and big data., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Multi-gene panel sequencing streamlines treatment selection for advanced non-small cell lung cancer (NSCLC). Implementation continues to be uneven across jurisdictions, partly due to uncertain clinical and economic impacts. In British Columbia (BC), Canada, the public healthcare system reimbursed a multi-gene panel in September 2016. This study determined the population-level cost-effectiveness of publicly reimbursed multi-gene panel sequencing compared to single-gene testing for advanced NSCLC., Methods: Our population-based retrospective study design used patient-level linked administrative health databases. We considered adult BC residents with a panel-eligible lung cancer diagnosis between September 2016 and December 2018. Using a machine learning approach, we conducted 1:1 genetic algorithm matching of recipients receiving multi-gene panel sequencing to controls receiving single-gene testing, maximising balance on observed demographic and clinical characteristics. Following matching, we estimated mean three-year survival time and costs (public healthcare payer perspective; 2021 CAD) and calculated the incremental net monetary benefit (INMB) for life-years gained (LYG) at conventional willingness-to-pay thresholds using inverse probability of censoring weighted linear regression and nonparametric bootstrapping., Findings: We matched 858 panel-eligible advanced NSCLC patients to controls, achieving balance for the 16 included covariates. Average test turnaround times were 18.6 days for multi-gene panel sequencing and 7.0 days for single-gene testing. After matching, mean incremental costs were $3529 (95% CI: -$4268, $10,942) and mean incremental LYG were 0.08 (95% CI: -0.04, 0.18). Among the 1000 bootstrap samples, 14.5% had lower costs and increased survival and 78.6% had higher costs and increased survival. The INMB was $523 (95% CI: -$6256, $7023) at $50,000/LYG, with a 57.5% probability of being cost-effective, and $4575 (95% CI: -$5468, $14,064) at $100,000/LYG, with an 84.0% probability of being cost-effective., Interpretation: Using population-based real-world data, we found a moderate to high probability that panel-based testing to inform targeted treatment for NSCLC would be cost-effective at higher thresholds., Funding: This research was supported by Genome British Columbia/Genome Canada (G05CHS) and the Terry Fox Research Institute., Competing Interests: The authors declare no competing non-financial interests but the following competing financial interests: D.A.R. has received travel funding from Illumina; his institution has received research funding for a project from Roche Canada. C.H. has received honoraria from Abbvie, Amgen, AstraZeneca, Bayer, BMS, Janssen, Jazz, Merck, Novartis, Pfizer, Roche and Sanofi; her institution has received research funding from AstraZeneca Canada and Roche Canada. D.W. & S.P. co-direct IMPRINT Research Consulting and have consulted for Roche Canada and AstraZeneca Canada. D.W. has also received travel funding from Illumina. S.Y. is a member of the advisory boards of and has received honoria from Amgen, AstraZeneca, Bayer, Incyte, Pfizer, Roche Canada and Servier. H.J.L. has received Honoria from Roche, Amgen, Pfizer, Eisai, Taiho, Astellas, Ipsen, BMS, and Merck for consultancy work. T.P.H. is the Ontario Health Cancer-Care Ontario (OH-CCO) Radiation Oncology Clinical Quality Lead for the Radiation Treatment Program., (© 2024 The Author(s).)

Context: The Bigfoot Unity Diabetes Management System integrates Abbott FreeStyle Libre 2 continuous glucose monitoring (CGM) data into a smart pen cap and mobile app enabling clinician-directed insulin dose recommendations and real-time alerts., Objective: The objective was to analyze real world 6-month glycemic control in a prospective study for individuals using the System for multiple daily insulin injections (MDI)., Methods: We conducted a 6-month analysis from the BURST study (NCT05088265) of individuals with type 1 or type 2 diabetes (T2D). Participants reported baseline demographics, adverse event and other surveys electronically. Either at-home kit or electronic medical record glycated hemoglobin A1c (HbA1c) data were collected., Results: Of 102 participants in the per-protocol cohort, median age was 59 years, 87% had T2D, 42% used CGM previously, 62% were White non-Hispanic and 59% female. Mean HbA1c decreased from 9.1 ± 1.7% at baseline to 8.0 ± 1.2% at 6 months (mean difference -1.1%, 95% confidence interval -1.4 to -0.8, P < 0.001). At 6 months, time in range 70-180 mg/dL, time <70 mg/dL and <54 mg/dL were 56 ± 23%, 1.0 ± 1.4% and 0.04 ± 0.14%, respectively. Six severe hypoglycemia events occurred in 4 participants (none system related) and no diabetic ketoacidosis events occurred in the per-protocol cohort., Conclusion: In this study primarily of older adults with T2D using MDI, durable glycemic improvement occurred using the System at 6 months, with the frequency of hypoglycemia being substantially below established targets of <4% and <1% for time below 70 and 54 mg/dL, respectively., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To provide an introduction to the uses of generative Artificial Intelligence (AI) and foundation models, including large language models (LLMs), in the field of health technology assessment (HTA)., Methods: We reviewed applications of generative AI in three areas: systematic literature reviews, real world evidence (RWE) and health economic modeling., Results: (1) Literature reviews: generative AI has the potential to assist in automating aspects of systematic literature reviews by proposing search terms, screening abstracts, extracting data and generating code for meta-analyses; (2) Real World Evidence (RWE): generative AI can facilitate automating processes and analyze large collections of real-world data (RWD) including unstructured clinical notes and imaging; (3) Health economic modeling: generative AI can aid in the development of health economic models, from conceptualization to validation. Limitations in the use of foundation models and LLMs include challenges surrounding their scientific rigor and reliability, the potential for bias, implications for equity, as well as nontrivial concerns regarding adherence to regulatory and ethical standards, particularly in terms of data privacy and security. Additionally, we survey the current policy landscape and provide suggestions for HTA agencies on responsibly integrating generative AI into their workflows, emphasizing the importance of human oversight and the fast-evolving nature of these tools., Conclusions: While generative AI technology holds promise with respect to HTA applications, it is still undergoing rapid developments and improvements. Continued careful evaluation of their applications to HTA is required. Both developers and users of research incorporating these tools, should familiarize themselves with their current capabilities and limitations., (Copyright © 2024. Published by Elsevier Inc.)

Over the last decade, innovative treatments have enlarged the therapeutic arsenal against NSCLC. Although there is clinical evidence supporting treatment options, controversy surrounds the impact of their combinations and sequence. The goal of this study was to fill this gap using real world data (Symphony Health). 9676 Patients with a diagnosis of non-metastatic (NM) and metastatic (M) NSCLC between July 2016 and December 2016 were included and followed till December 2021. The following data were collected: diagnostic date, age, gender, comorbidities, metastases, treatments (SUrgery, RAdiotherapy, CHemotherapy, IMmunotherapy, and TArgeted therapies), sequence (L1-L4), and death. Treatment patterns (Sankey graphs), and outcomes (Kaplan-Meyer and Cox regressions) were derived. Amongst NM patients, the most frequently observed treatments were RA, IM, IM and CH in first, second, third and fourth lines respectively. In M patients, the most frequent treatments were CH, IM, IM, and IM in first, second, third and fourth lines respectively. The overall 5-years survival in the cohort was 23.7 % (36 % in NM, 16 % in M). The corresponding median survival time were 1.98 years (3.2 NM, 1.27 M). In NM, best median survival times were recorded for those with only one line SU. For patients who had 2 lines, CH→IM; 3 lines, CH→IM→CH. In M, best median survival times were recorded for those with only one line RA. For patients who had 2 lines CH→IM; 3 lines CH→IM→CH. These new insights could guide further studies and improve the management of patients with NSCLC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Introduction: Immunosuppressive treatment is effective in most Myasthenia gravis patients, but 10-15% of patients areconsidered refractory due to inadequate response or intolerance to therapy. Eculizumab, a humanized monoclonalantibody directed against C5 complement protein, was approved in Italy to treat Ab-AchR generalized refractoryMG (rMG) in October 2022., Aim: We aim to describe a real-world Italian experience in a population of refractory myasthenia gravis patients with oneyear follow up., Methods: A retrospective data analysis was conducted on patients with refractory generalized MG treated with eculizumabbetween November 2022 and May 2024. Clinical assessment through specific scales (MG ADL - QMG - MGFA -PIS), rescue, and background therapy was recorded after one, three, six, and twelve months., Results: 21 rMG patients were treated with eculizumab with a medium follow up of 10.4 months and 14 patients had at leastone year follow up. A clinically meaningful reduction in total MG-ADL and QMG scores was achieved in the firstmonth. It was maintained throughout the first, third, sixth, and twelfth month along with concomitant reduction ofimmunosuppressive treatments. A drastic reduction of myasthenic exacerbations and crisis was observed duringfollow up and intravenous immunoglobulin treatment was discontinued in all patients except one. The total dailydose of prednisone was significantly reduced., Discussion: This single-center real-world study confirmes safety and effectiveness of eculizumab. Eculizumab improved rapidlyall clinical outcome measures, leading to discontinuation of intravenous immunoglobulin treatment and remarkable immunosuppressant-sparing benefits., (© 2024. Fondazione Società Italiana di Neurologia.)

Aim: To examine the likelihood of mortality or rehospitalization following acute coronary syndrome with glyburide versus gliclazide use in adults with type 2 diabetes undergoing cardiac catheterization., Research Design and Methods: This retrospective cohort study used clinical data linked with administrative health data from Alberta, Canada between April 2008 and March 2021. Three methods were used to define exposure to glyburide and gliclazide in the year before catheterization. Multivariable logistic regression was used to compare the likelihood of a composite outcome of 1-year mortality or rehospitalization with use of glyburide versus use of gliclazide., Results: A total of 11 140 individuals with type 2 diabetes had a cardiac catheterization for acute coronary syndrome. Their mean age was 66 years and 31% were female. In the year before catheterization, 5% used glyburide and 19% used gliclazide. Any glyburide or gliclazide exposure in the year before catheterization was associated with a similar likelihood of all-cause mortality or rehospitalization (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 0.93-1.41; p = 0.20). However, current glyburide exposure (aOR 1.37, 95% CI 1.06-1.79; p = 0.018) and long exposure to glyburide (aOR 1.37, 95% CI 1.03-1.83; p = 0.030) were associated with a higher likelihood of the composite outcome compared to current and long exposure to gliclazide, respectively., Conclusions: Current and long exposure to glyburide was associated with a greater likelihood of mortality or rehospitalization following cardiac catheterization for acute coronary syndrome, when compared to similar gliclazide exposure definitions. This study adds further evidence of the need to avoid using glyburide if a sulphonylurea is required for type 2 diabetes management., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: This paper summarizes the results from a forum of healthcare experts, academia representatives, and public agency officials from emerging and established market countries on Value-Based Healthcare (VBHC) and Health Technology Assessment (HTA). Presentations from experts provided insights into current developments and challenges, followed by interactive roundtable discussions. Emerging markets have unique healthcare systems, patient populations, resource constraints and needs., Areas Covered: Each roundtable explored specific topics including the role of HTA and Real-world evidence (RWE) in healthcare decision-making, challenges in biosimilar value assessment and incorporating non-price criteria reflecting context-related specifications of emerging markets such as the multifaceted nature of value in healthcare decision-making, emphasizing stakeholder perspectives and system complexities., Expert Opinion: RWE emerged as important in understanding biosimilar value recognition and decision-making processes, with insights into its applications and challenges. Recommendations were provided for utilizing Multi-Criteria Decision Analysis (MCDA) in pharmaceutical procurement, particularly for off-patent medicines, underscoring the importance of comprehensive evaluation frameworks and adherence to value-based principles. Overall findings suggest avenues for collaboration between industry, academia, and public agencies to address implementation barriers and promote equitable, efficient, and high-quality healthcare systems in emerging markets through public-private partnerships, joint capacity building and training initiatives, and knowledge transfers.

A considerable amount of continuing professional development (CPD) for health professionals is online and voluntary. There is evidence that some CPD activities impact clinical practice outcomes from self-reported and objective, administrative data. Some studies have shown that there is a potential mediating effect of knowledge/competency and/or self-efficacy between participation in CPD activities and the outcomes of that participation, specifically clinical practice. However, because clinical practice in those studies has been self-report, little is known about how this relationship impacts real world clinical practice. The purpose of the current study is to examine the relationship between knowledge/competency, self-efficacy, and real-world clinical practice so that we can begin to understand whether our focus on knowledge/competency and self-efficacy to change real-world clinical practice is empirically supported. We employed secondary data analysis from pre-participation questionnaire and medical and pharmacy claims data originally collected in three evaluations of online CPD interventions to examine if the relationship between knowledge/competency and self-efficacy contributed to physicians' real-world clinical practice. Results show an association between knowledge/competency scores and ratings of self-efficacy and suggest unique contributions of knowledge/competency and self-efficacy to clinical practice. Study results support the value of knowledge/competency scores and self-efficacy ratings as predictors of clinical practice. The effect size was larger for self-efficacy suggesting it may be a more practical indicator of clinical practice for CPD evaluators because its process of question development is simpler than the process for knowledge and case-based decision-making questions. However, it is important to conduct thorough need assessments which may include knowledge/competency assessments to identify topics to cover in CPD activities that are more likely to increase self-efficacy and ultimately, clinical practice., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 Medscape, LLC. Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Cannabis-based medicinal products (CBMPs) are increasingly demonstrating effectiveness in treating a wide range of conditions, with a relatively high safety profile in clinical usage compared to other prescription pain medications and few contraindications. Consultation and other prescription-related costs are, at present, higher for CBMPs than for some other treatment options, leading to some concern around wider prescribing., Research Design and Methods: An early cost-effectiveness model was developed to estimate the impact of prescribing CBMPs alone and/or in addition to analgesics, physiotherapy, and cognitive behavioral therapy for chronic pain in the UK for 1 year., Results: Due to their comparative effectiveness, CBMPs were found to be cost saving. Various scenarios were model tested; in all scenarios where CBMPs decrease pain-level states, less resource use is required. Increased efficacy of 5% was conservatively assumed based on current Real-World Evidence. In this scenario, CBMPs were significantly more cost-effective, and as costs relating to the prescribing of these continue to fall, relative savings are predicted to increase., Conclusion: These findings highlight the substantial cost saving that CBMPs may represent for the treatment of chronic pain patients, and the benefits for healthcare providers as a treatment for this often hard-to-treat population.

Purpose: On August 20, 2020, the United States (U.S.) Food and Drug Administration (FDA) issued a Drug Safety Communication (DSC) along with labeling updates to inform the public about a small increased risk of non-melanoma skin cancer (NMSC) associated with hydrochlorothiazide (HCTZ) use. This study aims to assess whether the DSC impacted HCTZ use in the U.S., Methods: We conducted a trend analysis in the Sentinel Distributed Database using national healthcare administrative data from January 2017 to November 2022. We identified two cohorts each month: An overall cohort of all enrollees and a skin cancer cohort of those with a history of NMSC. For each cohort, we plotted the monthly proportion of patients receiving HCTZ-containing products among those receiving any thiazide diuretics. We performed interrupted time series analyses to quantify the impact of the DSC on these monthly proportions. Secondary analyses were conducted on the proportion of HCTZ users among patients receiving any antihypertensives., Results: In the overall cohort, the DSC was only associated with a statistically significant but clinically negligible trend change of monthly HCTZ proportion within this cohort (0.018%; 95% CI, 0.012%-0.025%). Similar results were observed in the skin cancer cohort. The secondary analysis found no significant level change or trend change in the monthly proportion of HCTZ use among antihypertensive users., Conclusions: We did not observe significant changes in HCTZ use following the DSC about its NMSC risk, among the overall population and those with a history of NMSC. Our findings were in accordance with the DSC recommendation., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Purpose: Galcanezumab is a calcitonin gene-related peptide monoclonal antibody indicated for migraine prevention in adults. Due to the long half-life of galcanezumab and the prevalence of migraine in women of childbearing age, galcanezumab exposure may occur during pregnancy. However, real-world use and safety of galcanezumab during pregnancy has not been fully described. To help fill this gap, galcanezumab has two ongoing pregnancy safety studies, one of which is an insurance claims database study., Methods: This database study is actively identifying and following pregnancies exposed to galcanezumab using commercial claims from the Healthcare Integrated Research Database (HIRD). Patient accrual is planned from September 2018 to June 2026, with a final study report planned for December 2027. This study requires 430 galcanezumab-exposed pregnancies with linked infants to reach power for comparative analysis of major congenital malformations., Results: Recent monitoring of patient accrual, including data from 28 September 2018 to 31 January 2023, identified 207 galcanezumab-exposed pregnancies in women with migraine in the HIRD, of which 110 were live births and 73 of which were linked to an infant. This represents an annual accrual rate of approximately 17 pregnancies linked to infants, which is substantially lower than the 55 required annually to reach target size within current regulatory-committed study timelines., Conclusions: The accrual of a sufficient number of galcanezumab-exposed pregnancies represents a substantial, but not uncommon, barrier to conducting comparative analyses in pregnancy studies. Potential solutions that would allow for timely dissemination of important safety information to patients and providers may be available., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Aims/introduction: The FreeStyle Libre (FSL) intermittently scanned continuous glucose monitoring (isCGM) system continually measures interstitial glucose levels and provides the data to users in numerical and graphical formats that guide users in their daily diabetes self-management. Although numerous studies have demonstrated the glycemic benefits of FSL in pediatric and adult populations, few studies have characterized FSL use specifically by Japanese adults with type 1 or 2 diabetes. We utilized established CGM metrics to assess glycemic control in a large cohort of Japanese adults with type 1 and 2 diabetes., Materials and Methods: A total of 3,463 anonymized FSL users provided categorization into one of four therapy groups of interest: type 1 diabetes (n = 1,768), type 2 diabetes-multiple daily injections (MDI) (n = 612), type 2 diabetes-basal (BOI) (n = 343), and type 2 diabetes-non-insulin (NIT) (n = 740). Established CGM metrics were used to assess glycemic control., Results: All study groups showed relatively good glycemic control. Type 1 diabetes users showed the highest glucose variability (SD, 61 mg/dL; and %CV, 40%), above the established target level (%CV ≤ 36%). type 2 diabetes-MDI and type 2 diabetes-BOI users had similar levels of glucose variability (both within target). Type 2 diabetes-NIT users had the highest mean % time in range (TIR) (84.3%) and largest percentage of users that met the target of %TIR > 70% (87.4%). In contrast, type 1 diabetes users had the lowest mean %TIR (62.6%) and the lowest percentage meeting the established %TIR target (30.5%)., Conclusions: By utilizing CGM devices in daily diabetes care, both healthcare professionals and patients can monitor glycemic excursions and gain insights into their historical glucose control patterns., (© 2024 Abbott Laboratories and The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Chronic myeloid leukemia (CML), characterized by the presence of the BCR::ABL1 fusion gene, has undergone a transformative shift with the introduction of tyrosine kinase inhibitors (TKIs). The current availability of six different TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib) in clinical practice makes it important to know their efficacy and toxicity profile for treatment optimization. This review examines the latest insights regarding the use of bosutinib in CML treatment. Clinical trials have demonstrated the effectiveness of bosutinib, positioning it as a first-line treatment that can induce sustained molecular responses. Importantly, it can also be effective in patients who have experienced treatment failure or intolerance with prior TKIs, revealing the potential of bosutinib also in second- and later-line settings. Even in the advanced phase of CML, bosutinib has demonstrated its capacity to achieve molecular responses, expanding its usefulness. Real-world evidence studies echo these findings, emphasizing bosutinib's effectiveness in achieving deep molecular responses, maintaining remissions, and serving as an alternative for patients intolerant or resistant to other TKIs as a second-line therapy. Notably, one of the greatest strengths of bosutinib is its favorable safety profile, in particular the low incidence of vascular complications with its use, which is undoubtedly a comparative advantage over other TKIs. In summary, the latest research highlights the versatility of bosutinib in CML treatment and underscores its pivotal role in optimizing patient management in challenging cases. Continuing research and investigation will further establish bosutinib's place in the evolving landscape of CML therapy, offering an alternative for CML patients across different treatment stages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 García-Gutiérrez, Gómez-Casares, Xicoy, Casado-Montero, Orti, Giraldo and Hernández-Boluda.)

Over the past two decades, diabetes pharmacopoeia has flourished, with new drugs that, on top of their glucose-lowering efficacy, have been shown to protect the heart and the kidney. Despite these new opportunities, metformin retains a pivotal role among glucose-lowering agents. As one of the few available insulin sensitizers, metformin is an effective, safe, and overall well-tolerated drug backed by over 60 years of clinical experience, including evidence for potential benefits beyond glucose reduction across different ages, sexes, genetic backgrounds, geographical areas, and stages of disease. Although there is some discussion of whether metformin offers the most effective front-line option in newly diagnosed type 2 diabetes (T2D), it remains a natural companion to all other glucose-lowering agents. Furthermore, metformin comes at a very low cost and, as such, it has extremely high cost-effectiveness, particularly given the serious economic burden associated with diabetes complications. This financial advantage is particularly relevant in resource-constrained healthcare systems, where the affordability of metformin may be instrumental in implementing an effective treatment in an evergrowing number of individuals. We present here compelling real-world evidence in support of the clinical efficacy and cost-effectiveness of metformin across different patient populations, highlighting areas where more population-based studies are needed to further incorporate and consolidate its use in the pharmacological management of T2D., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions., Methods: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients' symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed., Results: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment., Conclusion: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments., (© 2024 S. Karger AG, Basel.)

Objective: Our study examined the impact of sex, ADHD subtype, and comorbid illnesses (depression/anxiety) on the timing of diagnosis and treatment for ADHD., Method: To analyze ADHD patients, four health databases were used to assess subtype, comorbid mood, and antidepressant or anxiolytic drug exposure. Analyses were stratified by sex and age. Standardized mean differences measured intergroup differences., Results: Females with ADHD were identified at older ages and had higher rates of depression and anxiety diagnoses and treatments before and after their initial ADHD diagnosis. Predominantly inattentive ADHD patients were diagnosed later and more likely to receive mood disorder diagnosis and treatment than hyperactive impulsive ADHD patients., Conclusions: Results suggest a more complex ADHD presentation in females, potentially causing late diagnosis and delayed treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JA, MMC, DMK, and US are employees of Janssen Research & Development, LLC, and shareholders of Johnson & Johnson (J&J) stock.

Disruptive behavior disorders (DBDs) are common mental health problems among early childhood American youth that, if poorly managed, pose costly psychological and societal burdens. There is limited real world evidence on how parent management training (PMT) - the evidence-based treatment model of choice - implemented in common practice settings within the United States influences the behavioral progress of early childhood DBDs, and the risk factors associated with poor outcomes. This study used data from a measurement feedback system implemented within a U.S.-based private practice to study how behavioral outcomes change as a function of PMT treatment engagement and associated risk factors for 4-7 year-old children diagnosed with DBDs. Over 50% of patients reached optimal outcomes after 10 appointments. Attending 24-29 appointments provided maximum treatment effect - namely, 75% of patients reaching optimal outcomes by end of treatment. Outcomes attenuate after reaching the maximum effect. Patients also had higher odds of reaching optimal outcomes if they had consistent attendance throughout the treatment course. Notable risk factors associated with lower odds of reaching optimal outcomes included Medicaid insurance-type, greater clinical complexity, and having siblings concurrently in treatment. Increased implementation of systems that monitor and provide feedback on treatment outcomes in U.S.-based practice settings and similar investigations using its data can further enhance 'real world' management of early childhood DBDs among American youth., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Endoscopic Healing Index (EHI) analyzes biomarkers in a patient's peripheral blood to assess mucosal healing. We aimed to characterize the effectiveness of the EHI as a predictor of disease activity in a real world clinical setting., Methods: This retrospective study looked at patients treated and followed up at the University of Chicago Medicine IBD center who had EHI tests done as part of routine clinical care. The results of the EHI were compared with radiological imaging or endoscopy performed within 3 months of the EHI in order to determine accuracy at diagnosing active inflammation., Results: Fifty-five patients with CD and with an available EHI were included in this study. Four (50%) patients with an EHI of < 20 (n = 8) had evidence of objective inflammation. A cutoff of ≤ 20 had a sensitivity of 89% and specificity of 23.5% for predicting no evidence of any objective inflammation with an AUROC of 0.69. This score had a negative predictive value (NPV) of 50% and positive predictive value (PPV) of 72.3%. A cutoff EHI of 30 tended to classify patients as either having objective evidence of inflammation or not more often than FCAL (Correctly classifying inflammation: 89% vs 64%, respectively; p = 0.32)., Conclusion: In this real world analysis, the EHI showed poor predictive value for the absence of active inflammation as assessed by imaging or endoscopy, has limited utility in confirming deep remission and should be used with another objective modality., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Amyotrophic lateral sclerosis (ALS) is an incurable, progressive neurodegenerative disease with a significant health burden and poorly understood etiology. This analysis assessed the narrative responses from 3,061 participants in the Centers for Disease Control and Prevention's National ALS Registry who answered the question, "What do you think caused your ALS?", Methods: Data analysis used qualitative methods and artificial intelligence (AI) using natural language processing (NLP), specifically, Bidirectional Encoder Representations from Transformers (BERT) to explore responses regarding participants' perceptions of the cause of their disease., Results: Both qualitative and AI analysis methods revealed several, often aligned themes, which pointed to perceived causes including genetic, environmental, and military exposures. However, the qualitative analysis revealed detailed themes and subthemes, providing a more comprehensive understanding of participants' perceptions. Although there were areas of alignment between AI and qualitative analysis, AI's broader categories did not capture the nuances discovered using the more traditional, qualitative approach. The qualitative analysis also revealed that the potential causes of ALS were described within narratives that sometimes indicate self-blame and other maladaptive coping mechanisms., Conclusions: This analysis highlights the diverse range of factors that individuals with ALS consider as perceived causes for their disease. Understanding these perceptions can help clinicians to better support people living with ALS (PLWALS). The analysis highlights the benefits of using traditional qualitative methods to supplement or improve upon AI-based approaches. This rapidly evolving area of data science has the potential to remove barriers to accessing the rich narratives of people with lived experience.

Background: There are limited real-world data in Switzerland examining the impact of erenumab, a fully human IgG2 monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, on migraine-related quality of life., Objective: This 18-month interim analysis of 172 patients with episodic or chronic migraine from the SQUARE study provides first prospective insights on the impact of mandatory erenumab treatment interruption, following Swiss-reimbursement requirements, in a real-world clinical setting in Switzerland., Findings: Recruited patients receiving 70 or 140 mg erenumab underwent treatment interruption on average 11.2 months after therapy onset with a mean duration of 4 months. There were sustained improvements in mean monthly migraine days (MMD) and migraine disability (mMIDAS) during initial treatment with erenumab. Treatment interruption was associated with a temporary worsening of condition. Symptoms ameliorated upon therapy reuptake reaching improvements similar to pre-break within 3 months., Conclusions: Treatment interruption was associated with a temporary worsening of condition, which improved again after therapy restart., (© 2024. The Author(s).)

Background: Antibiotic use during pregnancy is widespread with notable variations across regions., Methods: This systematic review and meta-analysis (Prospero protocol CRD42023418979) examines the prevalence and variability of antibiotic use in pregnancy globally and regionally, considering different methodologies and maternal characteristics. We searched Embase, PubMed, and Web of Science for observational studies published in English from the year 2000 and onwards. Random-effect meta-analyses were used to pool the prevalence of antibiotic consumption during pregnancy, presented as percentages with 95% confidence intervals (CI). Joanna Briggs Institute Critical appraisal checklist for prevalence studies was used for bias assessment., Findings: Overall, 116 studies (14 from Africa, 24 from the Americas, six from Eastern Mediterranean, 57 from Europe, four from South-East Asia and 11 from Western Pacific) were included (33,821,194 pregnancies). The majority of studies (84.5%) were appraised with a low risk of bias. The prevalence of antibiotic consumption during pregnancy ranged between 0.04 to 90%, with a pooled estimate of 23.6% (95% CI: 20.1-27.5, I 2 =100%). Low-income countries had the highest pooled prevalence (45.3%, 95% CI: 15.4-79.1, I 2 =99.6%). Regionally, the Western Pacific had the highest pooled prevalence (34.4%, 95% CI: 13.4-64.1, I 2 =100%). The prevalence of antibiotic consumption during pregnancy increased over time in the Americas and Western Pacific. The studies exhibited considerable heterogeneity (I 2 >95%), and the trim-and-fill method estimated a potential 10% underestimation of the overall pooled prevalence, suggesting publication bias., Interpretation: This meta-analysis suggests that about 1/4 of women worldwide use antibiotics during pregnancy. This study suggests a high prevalence of antibiotic consumption during pregnancy with disparities according to region and level of country income, ethnicity and whether antibiotics were prescribed or self-medicated. There was a variability in reported findings across age categories, potential bias from small sample sizes, and language bias from including only studies published in English., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical development for orphan drugs presents significant difficulties and challenges. There is no unique or standard design, conduct, and outcome assessment methodology and it is sometimes impractical to fit design models of rare disease trials in any practiced and well-known framework. In the European Union (EU) these challenges encompass a broad array of subjects, including trial design, study outcomes, patient recruitment, trial conduct ethics, trial cost, and chances of success. This literature-based review study aims to provide a thorough overview of the critical aspects of rare disease trials in the EU by analyzing the current landscape of rare disease trials, highlighting key challenges, delving into regulatory and research initiatives and innovation in trial designs, and proposing multi-faceted solutions to implement effective rare disease clinical trials in the region., Discussion: Traditional clinical trial designs, validation, and evaluation methodologies used for nonorphan drugs often prove unsuitable for orphan drugs, given the small patient populations, sometimes fewer than 1000 cases. There is an increasing need for accessible therapies and both regulators as well as industry are trying to develop affordable and effective drugs to address this need. Despite several steps that have been taken, the timely development of drugs remains a challenge. One of the reasons behind the long development timeline is the recruitment, retention, and conduct of rare disease trials. To optimize the development timelines of orphan drugs in the EU, it is important to ensure that the safety and efficacy of the product is not compromised. Industry and regulatory agencies must implement innovative trial designs, devise flexible policies, and incorporate real-world data for assessing clinical outcomes., Conclusion: Collaboration among academic institutions, pharmaceutical companies (both small and major), patient groups, and health authorities is crucial in overcoming obstacles related to clinical trials and providing assistance and creative ideas. The ultimate objective of granting rare disease patients timely and affordable access to medications with a positive balance between benefits and risks is to be met., (© 2024. The Author(s).)

The efficacy of pembrolizumab in the treatment-naïve non-small-cell lung cancer (NSCLC) patients was proved in the KEYNOTE-024 randomized trial. The aim of this systematic literature review was to identify and summarize the real world evidence (RWE) of overall survival (OS) in previously untreated patients with NSCLC receiving pembrolizumab monotherapy. A systematic search was conducted in PubMed (MEDLINE®) and EMBASE databases. Analyses were focused on survival data (median OS and survival rates at specific time points). To explore the population comparable with the KEYNOTE-024 study, we focused on studies enrolling at least 50% of patients at stage IV of cancer and ECOG performance status 0-2. A total of 41 RWE studies covering over 7600 advanced NSCLC patients naïve to systemic treatment were identified. Overall, survival outcomes reported in those studies vary considerably (median OS range: 3.0-34.6 months). Most RWE studies reported median OS shorter to that reported in KEYNOTE-024 (26.3 months), but about half of reported OS medians were in range of 95% confidence interval for OS as reported in KEYNOTE-024 trial (18.3-40.4 months). Patients with similar characteristics of stage and performance status to those of KEYNOTE-024 trial benefited the same with pembrolizumab monotherapy as their survival outcomes (18.9-22.8 months) were consistent with those reported in the clinical trial. RWE data showed substantially worse outcomes in patients with ECOG-PS 2+ compared to ECOG-PS 0-1 patients., (© 2024. The Author(s).)

Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. The effects of migalastat were examined in a cohort of 125 Fabry patients with migalastat-amenable GLA variants in the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient-focused registry evaluating outcomes for current Fabry disease treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry-associated clinical events (FACEs) in a cohort of patients who had received ≥3 years of migalastat treatment in a real-world setting. As of August 2022, 125 patients (60% male) had a mean migalastat exposure of 3.9 years. At enrolment, median age was 58 years (males, 57; females, 60) with a mean eGFR of 83.7 mL/min/1.73 m 2 (n = 122; males, 83.7; females, 83.8) and a median left ventricular mass index of 115.1 g/m 2 (n = 61; males, 131.2; females, 98.0). Mean (95% confidence interval) eGFR annualised rate of change in the overall cohort (n = 116) was -0.9 (-10.8, 9.9) mL/min/1.73 m 2 /year with a similar rate of change observed across patients with varying levels of kidney function at enrolment. Despite population age and baseline morbidity, 80% of patients did not experience a FACE during the mean 3.9 years of migalastat exposure. The incidence of renal, cardiac, and cerebrovascular events was 2.0, 83.2, and 4.1 events per 1000 patient-years, respectively. These data support a role of migalastat in preserving renal function and multisystem effectiveness during ≥3 years of migalastat treatment in this real-world Fabry population., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Objective: To assess the evolution of the COVID-19 pandemic in Brazil and its macro-regions, considering disease incidence and mortality rates, as well as identifying territories with still rising disease indices and evaluating vaccine coverage and population adherence to COVID-19 immunization., Methods: An ecological study conducted in Brazil with COVID-19 cases and deaths reported between February 2020 and April 2024, obtained through the Coronavirus Panel. Historical series were constructed from incidence and mortality rates to assess the pandemic's evolution, and temporal trends were estimated using the Seasonal Trend Decomposition using Loess (STL) method. The Spatial Variation in Temporal Trends (SVTT) technique was employed to identify clusters with significant variations in temporal trends. Vaccination was analyzed considering the percentage of vaccinated and unvaccinated population in each municipality of the country., Results: Brazil recorded a total of 38,795,966 cases and 712,038 deaths from COVID-19 during the study period. Incidence and mortality rates showed three waves of the disease, with a fourth wave of smaller amplitude. Four clusters with significant case growth and two with increased deaths were identified. Vaccine coverage varied among municipalities, with some regions showing low vaccination rates and others with high immunization adherence., Conclusion: The study provided a comprehensive overview of coronavirus behavior in Brazil, and its results highlight the ongoing importance of vaccination and the need to direct efforts and resources to areas of higher risk., (© 2024. The Author(s).)

Introduction: Randomized clinical trials (RCTs) represent the mainstay for the approval of new treatments. However, stringent inclusion criteria often cause them to depart from the daily clinical practice. Real-world (RW) evidence have a complementing role, filling the gap between the efficacy of a treatment and its effectiveness. Immune checkpoint inhibitors (ICIs) have changed the treatment scenario for non-small cell lung cancer (NSCLC); immune-related adverse events (irAEs) could become life-threatening events, when not timely managed. We performed a systematic review and meta-analysis on the RW impact of irAEs through the years., Methods: The systematic review focused on irAEs occurred in locally advanced or metastatic NSCLC patients, treated with ICIs in a RW setting. We queried two electronic databases (Embase and Medline) from 1996 to August 2022. We then conducted a meta-analysis dividing the results in two cohorts (2015-2018 and 2019-2021). We described the prevalence of patients with irAEs of any or severe grade (G). Estimates were expressed as proportions up to the second decimal point (effect size, ES). IrAEs of interest were those involving the skin, the liver, the endocrine system or the gastro-intestinal system., Results: Overall, 21 RW studies on 5,439 patients were included in the quantitative and qualitative synthesis. The prevalence of G≥3 irAEs was slightly lower in the 2015-2018 subgroup, while the prevalence of irAEs of any grade was similar for both periods. Overall, we observed a higher ES for gastrointestinal, hepatic and lung irAEs, while a lower ES was reported for skin or endocrine irAEs. Endocrine irAEs were reported in 10 out of 21 studies, with a slight increase in the most recent studies, while cutaneous toxicities were mostly reported in two studies lead within the first time-period. Pulmonary, gastrointestinal, and hepatic toxicities, showed a more heterogeneous distribution of ES over time., Discussion: Our findings showed that the frequency of irAEs remained stable across the two calendar periods examined in our meta-analysis. This finding suggests that RW data might not be able to identify a potential learning curve in detection and management of irAEs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pasello, Pavan, De Nuzzo, Frega, Ferro, Dal Maso, Bonanno, Guarneri and Girardi.)

Cardiovascular disease (CVD) is a leading cause of death globally. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), compared in the ONTARGET trial, each prevent CVD. However, trial results may not be generalisable and their effectiveness in underrepresented groups is unclear. Using trial emulation methods within routine-care data to validate findings, we explored generalisability of ONTARGET results. For people prescribed an ACEi/ARB in the UK Clinical Practice Research Datalink GOLD from 1/1/2001-31/7/2019, we applied trial criteria and propensity-score methods to create an ONTARGET trial-eligible cohort. Comparing ARB to ACEi, we estimated hazard ratios for the primary composite trial outcome (cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure), and secondary outcomes. As the pre-specified criteria were met confirming trial emulation, we then explored treatment heterogeneity among three trial-underrepresented subgroups: females, those aged ≥75 years and those with chronic kidney disease (CKD). In the trial-eligible population (n=137,155), results for the primary outcome demonstrated similar effects of ARB and ACEi, (HR 0.97 [95% CI: 0.93, 1.01]), meeting the pre-specified validation criteria. When extending this outcome to trial-underrepresented groups, similar treatment effects were observed by sex, age and CKD. This suggests that ONTARGET trial findings are generalisable to trial-underrepresented subgroups., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

With geroscience research evolving at a fast pace, the need arises for human randomized controlled trials to assess the efficacy of geroprotective interventions to prevent age-related adverse outcomes, disease, and mortality in normative aging cohorts. However, to confirm efficacy requires a long-term and costly approach as time to the event of morbidity and mortality can be decades. While this could be circumvented using sensitive biomarkers of aging, current molecular, physiological, and digital endpoints require further validation. In this review, we discuss how collecting real-world evidence (RWE) by obtaining health data that is amenable for collection from large heterogeneous populations in a real-world setting can help speed up validation of geroprotective interventions. Further, we propose inclusion of quality of life (QoL) data as a biomarker of aging and candidate endpoint for geroscience clinical trials to aid in distinguishing healthy from unhealthy aging. We highlight how QoL assays can aid in accelerating data collection in studies gathering RWE on the geroprotective effects of repurposed drugs to support utilization within healthy longevity medicine. Finally, we summarize key metrics to consider when implementing QoL assays in studies, and present the short-form 36 (SF-36) as the most well-suited candidate endpoint., Competing Interests: Declaration of Competing Interest none., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Axial spondyloarthropathy(AS) is a chronic inflammatory disease primarily affecting the axial skeleton, often characterized by sacroiliitis. While pulmonary embolism (PE), a potentially lethal condition, has been linked to several autoimmune diseases, limited data exist regarding PE risk among patients with AS. Methods: This retrospective cohort study utilized the Clalit Healthcare Services (CHS) database, including 5825 patients with AS and 28,356 matched controls. Follow-up began at the date of first AS diagnosis for patients and at the matched patient's diagnosis date for controls and continued until PE diagnosis, death, or study end date. Results: Prevalence of PE before AS diagnosis in patients compared to controls was 0.4% vs. 0.2% ( p < 0.01). The incidence rate of PE was 11.6 per 10,000 person-years for patients with AS and 6.8 per 10,000 person-years for controls. The adjusted hazard ratio (HR) for PE in patients with AS was 1.70 ( p < 0.001). Subgroup analysis demonstrated excess risk for PE in patients with AS regardless of gender and age, with variations among AS treatment categories. Discussion: Our findings highlight a significant association between AS and PE, indicating an increased risk in patients with AS independent of age and sex and suggests a subclinical level of inflammation. Preliminary results suggest a protective role of immunosuppressing drugs. Further research into the impact of treatment strategies should be conducted and could inform clinical management and reduce the life-threatening risk of PE in Patients with AS.

Background: Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community)., Methods: This Swedish nationwide population-based cohort study (2006-2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up., Results: Overall, 91.6% of CDI cases were hospital acquired, and 16.8% presented with recurrence(s); 74.8%of cases were ≥ 65 years and 54.2% were women. Compared to individuals without CDI, in-hospital stay rates were 18.01 times higher after CDI (95% CI 17.40-18.63, first-year: 27.4 versus 1.6 days), 9.45 times higher in-hospital admission (95% CI 9.16-9.76, first-year: 2.6 versus 1.3 hospitalisations), 3.94 times higher outpatient visit (95% CI 3.84-4.05, first-year: 4.0 versus 1.9 visits) and 3.39 times higher dispensed prescriptions rates (95% CI 3.31-3.48, first-year: 25.5 versus 13.7 prescriptions). For all outcomes, relative risks were higher among the younger (< 65 years) than the older (≥ 65 years), and in those with fewer comorbidities, but similar between sexes. Compared to those without recurrence, individuals with recurrence particularly showed a higher rate of hospital admissions (IRR = 1.18, 95% 1.12-1.24). Compared to community-acquired CDI, those with hospital-acquired CDI presented with a higher rate of hospital admissions (IRR = 7.29, 95% CI 6.68-7.96) and a longer length of stay (IRR = 7.64, 95% CI 7.07-8.26)., Conclusion: CDI was associated with increased health consumption in all affected patient groups. The majority of the CDI burden could be contributed to hospital-acquired CDI (~ 9/10), older patients (~ 3/4) and those with multiple comorbidities (~ 6/10 Charlson score ≥ 3), with 1/5 of the total CDI burden contributed to individuals with recurrence. Yet, relatively speaking the burden was higher among the younger and those with fewer comorbidities, compared to their peers without CDI., (© 2024. The Author(s).)

Objective: People with epilepsy (PWE) may be at an increased risk of severe COVID-19. It is important to characterize this risk to inform PWE and for future health and care planning. We assessed whether PWE were at higher risk of being hospitalized with, or dying from, COVID-19., Methods: We performed a retrospective cohort study using linked, population-scale, anonymized electronic health records from the SAIL (Secure Anonymised Information Linkage) databank. This includes hospital admission and demographic data for the complete Welsh population (3.1 million) and primary care records for 86% of the population. We identified 27 279 PWE living in Wales during the study period (March 1, 2020 to June 30, 2021). Controls were identified using exact 5:1 matching (sex, age, and socioeconomic status). We defined COVID-19 deaths as having International Classification of Diseases, 10th Revision (ICD-10) codes for COVID-19 on death certificates or occurring within 28 days of a positive SARS-CoV-2 polymerase chain reaction (PCR) test. COVID-19 hospitalizations were defined as having a COVID-19 ICD-10 code for the reason for admission or occurring within 28 days of a positive SARS-CoV-2 PCR test. We recorded COVID-19 vaccinations and comorbidities known to increase the risk of COVID-19 hospitalization and death. We used Cox proportional hazard models to calculate hazard ratios., Results: There were 158 (.58%) COVID-19 deaths and 933 (3.4%) COVID-19 hospitalizations in PWE, and 370 (.27%) deaths and 1871 (1.4%) hospitalizations in controls. Hazard ratios for COVID-19 death and hospitalization in PWE compared to controls were 2.15 (95% confidence interval [CI] = 1.78-2.59) and 2.15 (95% CI = 1.94-2.37), respectively. Adjusted hazard ratios (adjusted for comorbidities) for death and hospitalization were 1.32 (95% CI = 1.08-1.62) and 1.60 (95% CI = 1.44-1.78)., Significance: PWE are at increased risk of being hospitalized with, and dying from, COVID-19 when compared to age-, sex-, and deprivation-matched controls, even when adjusting for comorbidities. This may have implications for prioritizing future COVID-19 treatments and vaccinations for PWE., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: This study was undertaken to characterize changes in health care utilization and mortality for people with epilepsy (PWE) during the COVID-19 pandemic., Methods: We performed a retrospective study using linked, individual-level, population-scale anonymized health data from the Secure Anonymised Information Linkage databank. We identified PWE living in Wales during the study "pandemic period" (January 1, 2020-June 30, 2021) and during a "prepandemic" period (January 1, 2016-December 31, 2019). We compared prepandemic health care utilization, status epilepticus, and mortality rates with corresponding pandemic rates for PWE and people without epilepsy (PWOE). We performed subgroup analyses on children (<18 years old), older people (>65 years old), those with intellectual disability, and those living in the most deprived areas. We used Poisson models to calculate adjusted rate ratios (RRs)., Results: We identified 27 279 PWE who had significantly higher rates of hospital (50.3 visits/1000 patient months), emergency department (55.7), and outpatient attendance (172.4) when compared to PWOE (corresponding figures: 25.7, 25.2, and 87.0) in the prepandemic period. Hospital and epilepsy-related hospital admissions, and emergency department and outpatient attendances all reduced significantly for PWE (and all subgroups) during the pandemic period. RRs [95% confidence intervals (CIs)] for pandemic versus prepandemic periods were .70 [.69-.72], .77 [.73-.81], .78 [.77-.79], and .80 [.79-.81]. The corresponding rates also reduced for PWOE. New epilepsy diagnosis rates decreased during the pandemic compared with the prepandemic period (2.3/100 000/month cf. 3.1/100 000/month, RR = .73, 95% CI = .68-.78). Both all-cause deaths and deaths with epilepsy recorded on the death certificate increased for PWE during the pandemic (RR = 1.07, 95% CI = .997-1.145 and RR = 2.44, 95% CI = 2.12-2.81). When removing COVID deaths, RRs were .88 (95% CI = .81-.95) and 1.29 (95% CI = 1.08-1.53). Status epilepticus rates did not change significantly during the pandemic (RR = .95, 95% CI = .78-1.15)., Significance: All-cause non-COVID deaths did not increase but non-COVID deaths associated with epilepsy did increase for PWE during the COVID-19 pandemic. The longer term effects of the decrease in new epilepsy diagnoses and health care utilization and increase in deaths associated with epilepsy need further research., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: Patients with cancer are vulnerable to Clostridioides difficile infection (CDI) due to their disease, treatment and regular hospital contact, yet if CDI-recurrence is more common remains unclear, and differences among cancer types remain unexplored., Methods: This Swedish nationwide population-based cohort included all 43,150 individuals with recorded CDI (2006-2019) to assess CDI-recurrence in individuals with and without cancer, with binary multivariable logistic regression, stratified by anatomical location, and survival status., Results: Compared to those without cancer (N = 29,543), ongoing cancer (diagnosis < 12 months; N = 3,882) was associated with reduced recurrence (OR = 0.81, 95% CI 0.73-0.89), while there was no association with cancer history (diagnosis ≥ 12 months; N = 9,725). There was an increased 8-week all-cause mortality (Ongoing cancer: OR = 1.58, 95% CI 1.43-1.74; Cancer history: OR = 1.45, 95% CI 1.36-1.55) compared to those without cancer. Among CDI-survivors, those with ongoing cancer presented with a decreased odds of recurrence (OR = 0.84, 95% CI 0.76-0.94), compared to those without cancer history, with no association for those with cancer history (OR = 1.04, 95% CI 0.97-1.1). Large variations were seen across cancer types, with the highest observed proportion of recurrence in oral and mesothelial cancer, and the lowest for esophageal cancer, although no statistically significant OR were found., Conclusion: The population-based study indicates that individuals with cancer may have fewerrecurrences than expected, yet variations by cancer type were large, and mortality was high., (© 2024. The Author(s).)

Most new drug approvals are based on data from large randomized clinical trials (RCTs). However, there are sometimes contradictory conclusions from seemingly similar trials and generalizability of conclusions from these trials is limited. These considerations explain, in part, the gap between conclusions from data of RCTs and those from registries termed real world data (RWD). Recently, real-world evidence (RWE) from RWD processed by artificial intelligence has received increasing attention. We describe the potential of using RWD in haematology concluding RWE from RWD may complement data from RCTs to support regulatory decisions., Competing Interests: Declaration of competing interest RPG is a consultant to BeiGene Ltd., Fusion Pharma LLC, La Jolla NanoMedical Inc., Mingsight Parmaceuticals Inc. and CStone Pharmaceuticals; advisor to Antegene Biotech LLC, Medical Director, FFF Enterprises Inc.; partner, AZAC Inc.; Board of Directors, Russian Foundation for Cancer Research Support; and Scientific Advisory Board: StemRad Ltd: F Passamonti received honoraria for lectures and advisory boards from Novartis, GSK, Bristol-Myers Squibb/Celgene, Sierra Oncology, AbbVie, Janssen, Roche, AOP Orphan, Karyopharma, Kyowa Kirin and MEI, Sumitomo., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Cancer incidence, comorbidity, and polypharmacy increase with age, but the interplay between these factors on receipt of systemic therapy (ST) in advanced cancer has rarely been studied., Materials and Methods: A retrospective cohort study was conducted including patients aged ≥18 years diagnosed from 2004 to 2015 with multiple myeloma (MM) (all stages), lung cancer (stage IV), and stage III-IV non-Hodgkin's lymphoma (NHL), breast, colorectal (CRC), prostate, or ovarian cancer in Manitoba, Canada. Clinical and administrative health data were used to determine demographic and cancer characteristics, treatment history, comorbidity (Charlson Comorbidity Index [CCI] and Resource Utilization Band [RUB]), and polypharmacy (≥6 medications). Multivariable logistic regression was used to evaluate variable associations with receipt of ST and interaction with age., Results: In total, 17,228 patients were diagnosed with advanced cancer. Ages were distributed as follows: 7% <50 years, 16% 50-59 years, 26% 60-69, 26% 70-79, 24% ≥80 years. ST was administered to 50% of patients. Increased age, polypharmacy, and comorbidity each independently decreased the likelihood of receiving ST. Significant interaction effects were found between age at diagnosis with stage of cancer and cancer type. Differences in probability of ST by cancer stage converged as age increased. In multivariable analysis, adjusting for covariates, patients with MM had the highest odds and lung cancer the lowest odds to receive ST. The impact of comorbidity and polypharmacy did not differ meaningfully with increasing age., Discussion: Increased age, polypharmacy, and comorbidity were each independently associated with decreased receipt of ST in people with advanced cancers. The impact of comorbidity and polypharmacy did not differ meaningfully with increasing age, while age meaningfully interacted with stage and cancer type., Competing Interests: Declaration of Competing Interest Rebekah Rittberg reports honorarium for educational content and research grant funding from AstraZeneca. Philip St. John reports speaking fees from McMaster University and Regional Geriatric Program of Eastern Ontario, and consulting fees from University Health Network. David E. Dawe reports advisory board attendance for Merck Canada, Jazz Pharmaceuticals, Novartis, Pfizer, and AstraZeneca, honoraria for education content from Boehringer-Ingelheim, Bristol Myers Squibb, and Roche, and grants from AstraZeneca Canada. Kathleen Decker, Pascal Lambert, Jen Bravo, Donna Turner, and Piotr Czaykowski report no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Our objective was to perform a feasibility study using real-world data from a learning health system (LHS) to describe current practice patterns of wound closure and explore differences in outcomes associated with the use of tissue adhesives and other methods of wound closure in the pediatric surgical population to inform a potentially large study., Methods: A multi-institutional cross-sectional study was performed of a random sample of patients <18 y-old who underwent laparoscopic appendectomy, open or laparoscopic inguinal hernia repair, umbilical hernia repair, or repair of traumatic laceration from January 1, 2019, to December 31, 2019. Sociodemographic and operative characteristics were obtained from 6 PEDSnet (a national pediatric LHS) children's hospitals and OneFlorida Clinical Research Consortium (a PCORnet collaboration across 14 academic health systems). Additional clinical data elements were collected via chart review., Results: Of the 692 patients included, 182 (26.3%) had appendectomies, 155 (22.4%) inguinal hernia repairs, 163 (23.6%) umbilical hernia repairs, and 192 (27.8%) traumatic lacerations. Of the 500 surgical incisions, sutures with tissue adhesives were the most frequently used (n = 211, 42.2%), followed by sutures with adhesive strips (n = 176, 35.2%), and sutures only (n = 72, 14.4%). Most traumatic lacerations were repaired with sutures only (n = 127, 64.5%). The overall wound-related complication rate was 3.0% and resumption of normal activities was recommended at a median of 14 d (interquartile ranges 14-14)., Conclusions: The LHS represents an efficient tool to identify cohorts of pediatric surgical patients to perform comparative effectiveness research using real-world data to support medical and surgical products/devices in children., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Observational designs can complement evidence from randomized controlled trials not only in situations when randomization is not feasible, but also by evaluating drug effects in real-world, considering a broader spectrum of users and clinical scenarios. However, use of such real-world scenarios captured in routinely collected clinical or administrative data also comes with specific challenges. Unlike in trials, medication use is not protocol based. Instead, exposure is determined by a multitude of factors involving patients, providers, healthcare access, and other policies. Accurate measurement of medication exposure relies on a similar broad set of factors which, if not understood and appropriately addressed, can lead to exposure misclassification and bias., Aim: To describe core considerations for measurement of medication exposure in routinely collected healthcare data., Methods: We describe the strengths and weaknesses of the two main types of routinely collected healthcare data (electronic health records and administrative claims) used in pharmacoepidemiologic research. We introduce key elements in those data sources and issues in the curation process that should be considered when developing exposure definitions. We present challenges in exposure measurement such as the appropriate determination of exposure time windows or the delineation of concomitant medication use versus switching of therapy, and related implications for bias., Results: We note that true exposure patterns are typically unknown when using routinely collected healthcare data and that an in-depth understanding of healthcare delivery, patient and provider decision-making, data documentation and governance, as well as pharmacology are needed to ensure unbiased approaches to measuring exposure., Conclusions: Various assumptions are made with the goal that the chosen exposure definition can approximate true exposure. However, the possibility of exposure misclassification remains, and sensitivity analyses that can test the impact of such assumptions on the robustness of estimated medication effects are necessary to support causal inferences., (© 2023 John Wiley & Sons Ltd.)

Background: Digital health studies using electronic patient reported outcomes (ePROs), wearables, and clinical data to provide a more comprehensive picture of patient health., Methods: Newly initiated patients on upadacitinib or adalimumab for RA will be recruited from community settings in the Excellence NEtwork in RheumatoloGY (ENRGY) practice-based research network. Over the period of three to six months, three streams of data will be collected (1) linkable physician-derived data; (2) self-reported daily and weekly ePROs through the ArthritisPower registry app; and (3) biometric sensor data passively collected via wearable. These data will be analyzed to evaluate correlations among the three types of data and patient improvement on the newly initiated medication., Conclusions: Results from this study will provide valuable information regarding the relationships between physician data, wearable data, and ePROs in patients newly initiating an RA treatment, and demonstrate the feasibility of digital data capture for Remote Patient Monitoring of patients with rheumatic disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Global Healthy Living Foundation receives grants, sponsorships and contracts from pharmaceutical manufacturers and private foundations. A full list of GHLF funders is publicly available here: https://www.ghlf.org/our-partners/ PZ is employed by 10.13039/100006483AbbVie. JRC receives grants from 10.13039/100000960ACR, 10.13039/100006483AbbVie, 10.13039/100002429Amgen, ArthritisPower, Aqtual, Bendcare, 10.13039/100002491BMS, CorEvitas, FASTER, 10.13039/100004330GSK, IlluminationHealth, Janssen, Labcorp, 10.13039/100004312Lilly, 10.13039/100016939Myriad, 10.13039/100008272Novartis, 10.13039/100004319Pfizer, 10.13039/100004339Sanofi, Scipher, Setpoint, 10.13039/100006978UCB, United Rheumatology. He has received honorariums from 10.13039/100000960ACR, 10.13039/100006483Abbvie, 10.13039/100002429Amgen, ArthritisPower, Aqtual, Bendcare, BMS, CorEvitas, FASTER, GSK, IlluminationHealth, Janssen, Labcorp, 10.13039/100004312Lilly Myriad, 10.13039/100004336Novartis, Revero, 10.13039/100004319Pfizer, 10.13039/100004339Sanofi, Scipher, Setpoint, TNacity, Blue Ocean, 10.13039/100006978UCB., (© 2024 The Authors.)

Objectives: Computerized clinical decision support software (CDSS) are digital health technologies that have been traditionally categorized as medical devices. However, the evaluation frameworks for traditional medical devices are not well adapted to assess the value and safety of CDSS. In this study, we identified a range of challenges associated with CDSS evaluation as a medical device and investigated whether and how CDSS are evaluated in Australia., Methods: Using a qualitative approach, we interviewed 11 professionals involved in the implementation and evaluation of digital health technologies at national and regional levels. Data were thematically analyzed using both data-driven (inductive) and theory-based (deductive) approaches., Results: Our results suggest that current CDSS evaluations have an overly narrow perspective on the risks and benefits of CDSS due to an inability to capture the impact of the technology on the sociotechnical environment. By adopting a static view of the CDSS, these evaluation frameworks are unable to discern how rapidly evolving technologies and a dynamic clinical environment can impact CDSS performance. After software upgrades, CDSS can transition from providing information to specifying diagnoses and treatments. Therefore, it is not clear how CDSS can be monitored continuously when changes in the software can directly affect patient safety., Conclusion: Our findings emphasize the importance of taking a living health technology assessment approach to the evaluation of digital health technologies that evolve rapidly. There is a role for observational (real-world) evidence to understand the impact of changes to the technology and the sociotechnical environment on CDSS performance.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making., (© 2024. The Author(s).)

Introduction: Pertussis is a highly contagious respiratory infection. It affects people of all ages, yet evidence of the impact of pertussis in adults with underlying conditions (UCs) is scarce. This study investigated the incidence and complication rate of pertussis in adult patients with and without UC., Methods: A retrospective analysis was conducted using routinely collected German claims data between 2015 and 2019. Patients with and without different pneumological, cardiovascular, endocrinological, musculoskeletal, and psychological UCs were matched for incidence estimation. Logistic regression models were used to estimate the risk of pertussis depending on the presence of UCs. Negative binomial models were used to assess complication rates in patients with pertussis and with and without UC., Results: In total, 4383 patients were diagnosed with pertussis during the study period. Patients with any UC had an increased risk for pertussis compared to matched patients without UC (odds ratio [OR] 1.72; 95% confidence interval [CI]1.60-1.84, p < 0.0001). Underlying asthma had the highest risk of pertussis (OR 2.70; 95% CI 2.50-2.91, p < 0.0001), followed by chronic obstructive pulmonary disease (OR 2.35; 95% CI 2.10-2.60, p < 0.0001) and depression (OR 2.08; 95% CI 1.95-2.22, p < 0.0001). Severe complications occurred in 10.8% of the pertussis cohort (13.4% with UC vs. 9.5% without UC). The UC-attributable effect on the risk of severe pertussis-related complications was significantly increased for any UC (incidence rate ratio [IRR] 1.29, 95% CI 1.19-1.39). The severe complication risk was also increased for patients aged 60+ (IRR 1.59, 95% CI 1.46-1.72)., Conclusion: This study shows that adults with certain UCs have an increased risk for pertussis and are more likely to have complications. These results provide further evidence that pertussis is a relevant and impactful infectious disease in adults with and without certain UC, indicating that these patients need to be considered when developing vaccination recommendations to avoid pertussis and its associated complications. A graphical abstract is available with this article., (© 2024. The Author(s).)

Objective: To determine the effect of the introduction of the calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in 2018 on the prescribing of older medications for the prevention of chronic migraine., Background: Prior to 2018, the preventive treatment of migraine borrowed from medications intended to treat other illnesses with the last medication, onabotulinumtoxinA, receiving Food and Drug Administration (FDA) approval for the prevention of chronic migraine in 2010. The FDA approval of three CGRP mAbs in 2018 provided the ideal natural experiment to assess how the introduction of these medications, and a fourth in 2020, affected the generally stable migraine preventive medications market., Methods: We performed a retrospective cohort analysis using the aggregated de-identified data of 6595 patients. The percentage of patients with chronic migraine who had been prescribed one of ten most prescribed oral preventive medications or onabotulinumtoxinA, or any of the four CGRP mAbs, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from our clinic during the pre-CGRP mAb years of 2015-2017 and post-approval years of 2019-2021., Results: We observed a statistically significant decrease in the prescription of the top 10 most prescribed medications after the introduction of the CGRP mAbs overall (1456/3144, 46.3%, to 1995/4629, 43.1%, p = 0.001), as well as with most individual medications, including large decreases in verapamil (230/3144, 7.3%, to 125/4629, 2.7%; p < 0.001), the tricyclic antidepressants (494/3144, 15.7%, to 532/4629, 11.5%; p < 0.001), topiramate (566/3144, 18.0%, to 653/4629, 14.1%; p < 0.001), and onabotulinumtoxinA (861/3144, 27.4%, to 1134/4629, 24.5%; p = 0.001)., Conclusion: The introduction of the CGRP mAbs during 2018 resulted in a decrease in utilization of most oral medications and onabotulinumtoxinA for the prevention of migraine. Future work should continue to observe how the prescription patterns of these medications evolve with time., (© 2023 American Headache Society.)

Background: Ozanimod is a first-in-class Sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited., Aim: To provide 1-year follow-up results of our UC patient cohort treated with ozanimod., Methods: This prospective, observational cohort study includes consecutive patients who initiated ozanimod at the University of Chicago IBD Center between 5/2021 and 12/2022. We collected demographic, clinical, and laboratory data. Clinical disease activity was prospectively assessed using the Simple Clinical Colitis Activity Index., Results: Forty-five patients with UC initiated ozanimod therapy and were included in the effectiveness analysis. The median age was 35 years (interquartile range (IQR) 28-52), median disease duration of 6 years (IQR 3-13), 26 (58%) were male, 23 (51%) had extensive colitis, 34 (76%) had previous advanced therapy exposure. Thirty-four patients had clinically active UC at the time of ozanimod initiation; week 10 clinical response and remission rates were 58% and 53%, respectively. By week 52, the rates were 25% for both clinical response and remission. In the 12 (39%) patients with a > 75% reduction in absolute lymphocyte count, numerically greater induction clinical response and remission rates were observed (80% vs 54%, p = 0.4 and 75% vs 53%, p = 0.4, respectively). There were no episodes of symptomatic bradycardia and no other new safety signals., Conclusion: Ozanimod effectively induced clinical response and remission patients with largely treatment refractory UC, however, had modest long-term effectiveness. The safety profile was favorable with no new signals., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Randomised control trials (RCTs) with strict eligibility criteria can lead to trial populations not commonly seen in clinical practice. We described the proportion of people with chronic obstructive pulmonary disease (COPD) in England eligible for RCTs investigating treatment with triple therapy., Methods: MEDLINE and Clinicaltrials.gov were searched for RCTs investigating triple therapy and eligibility criteria for each trial were extracted. Using routinely collected primary care data from Clinical Practice Research Datalink Aurum linked with Hospital Episode Statistics, we defined a population of COPD patients registered at a general practice in England, who were ≥ 40 years old, and had a history of smoking. Inclusion date was January 1, 2020. Patients who died earlier or left the general practice were excluded. Eligibility criteria for each RCT was applied to the population of COPD patients and the proportion of patients meeting each trial eligibility criteria were described., Results: 26 RCTs investigating triple therapy were identified from the literature. The most common eligibility criteria were post-bronchodilator FEV 1 % predicted 30-80%, ≥ 2 moderate/≥ 1 severe exacerbations 12-months prior, no moderate exacerbations one-month prior and no severe exacerbations three-months prior, and the use of maintenance therapy or ICS use prior to inclusion. After applying each RCT eligibility criteria to our population of 79,810 COPD patients, a median of 11.2% [interquartile range (IQR) 1.8-17.4] of patients met eligibility criteria. The most discriminatory criteria included the presence exacerbations of COPD and previous COPD related medication use with a median of 67.6% (IQR 8.5-73.4) and 63% (IQR 69.3-38.4) of COPD patients not meeting these criteria, respectively., Conclusion: Data from these RCTs may not be generalisable to the wider population of people with COPD seen in everyday clinical practice and real-world evidence studies are needed to supplement trials to understand effectiveness in all people with COPD., (© 2024. The Author(s).)