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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. [ABSTRACT FROM AUTHOR]

• Characteristics and treatment patterns of 11,255 systemic lupus erythematosus patients analysed across four countries. • Glucocorticoids and hydroxychloroquine were the most common first-line treatments. • Mycophenolate mofetil was the most common second-line treatment for both adults and pediatric patients. • Higher glucocorticoid doses were often prescribed to pediatric patients compared to adults. 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). 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

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). 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background In the Belgian DISCOVER study, conducted in 2011–2012 before the advent of the IL‐17 and IL‐23 Inhibitors, significant undertreatment of patients with plaque psoriasis was reported. Objectives The present study aimed to re‐evaluate the real‐world clinical management and quality of care of moderate‐to‐severe plaque psoriasis patients treated with systemic treatment for at least 24 weeks in clinical practice in Belgium. Methods This cross‐sectional and retrospective chart review (REDISCOVER) was conducted in 2021–2022 in private practices and hospitals in Belgium. Patient data were collected during one single visit and included assessments of psoriasis severity (Psoriasis Area Severity Index [PASI], Body Surface Area [BSA], Pruritus VAS scale) and Health‐Related Quality of Life (Dermatology Life Quality Index [DLQI]) and other selected criteria of the Belgian treat‐to‐target (T2T) outcome set. Results Of the 306 patients included in the study, 81.4% received treatment with biologicals and 18.6% with traditional systemics, that is, methotrexate or apremilast. IL‐23 Inhibitors (33.7%) and methotrexate (10.8%) were the most prescribed biologicals and traditional systemic, respectively. Between the time of treatment initiation and enrolment, the average PASI and BSA scores decreased, indicating treatment benefits. PASI scores were lower in patients treated with biologicals versus patients treated with traditional systemics. Full achievement of the two Belgian T2T guidelines dimensions was observed in 51% of the patients. Nonetheless, patients were generally satisfied with their treatment (96.1%) and physicians evaluated the treatment as adequate for most patients (87.3%). Conclusions Compared to 10 years ago, a demonstrable improvement in care of moderate‐to‐severe psoriasis patients was observed in Belgium. This was reflected by substantial achievement of the current treatment goals and high treatment satisfaction by both patients and physicians. While one out of five patients is not achieving targeted goals, and is not treated with a biological, it seems there is still room for improvement.

ABSTRACT 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.

Abstract 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.

Abstract 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.

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 practicemakes 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 secondand 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. [ABSTRACT FROM AUTHOR]

Objective: This retrospective longitudinal study analyzed the demographic profile, insulin usage pattern, and outcomes of insulin-naive adults with type 2 diabetes mellitus (T2DM) who initiated insulin glargine. Methods: The study included 1006 insulin naive T2DM individuals aged ≥ 18 years, treated with any insulin type between January 2016 and December 2018, using electronic medical records. Results: Majority of participants were men (55.8%) with a mean age of 59.8 ± 11.9 years and average T2DM duration of 12.0 ± 6.6 years. Insulin glargine was the most commonly used insulin (66.9%), followed by insulin aspart (16.4%), insulin degludec (15.1%), human insulin (11.1%), and insulin isophane (9.2%). At baseline, the mean glycated hemoglobin (HbA1c) was 8.9 ± 1.9%, mean fasting plasma glucose (FPG) was 190 ± 59 mg/dL, and mean post-prandial plasma glucose (PPG) was 264 ± 78 mg/dL. In the insulin glargine group, baseline HbA1c was 9.0 ± 1.7%, FPG was 196 ± 62 mg/dL, and PPG was 283 ± 81 mg/dL. Throughout the study, there was an improvement in HbA1c, FPG, and PPG levels in the insulin glargine group. Body weight remained relatively stable, and the number of hypoglycemic events was minimal and non-life-threatening. Conclusion: The REALITY study in India demonstrated that initiating basal insulin treatment in insulin-naive individuals with T2DM led to improved glycemic parameters over a 12-month period. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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?" 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To assess real-world clinical outcomes with standard therapies for advanced non-small-cell lung cancer (aNSCLC) with METexon14 skipping mutation (METex14). Methods: In an oncologists-led retrospective review of medical records, data were abstracted and analyzed for patients initiating first-line (1L) systemic therapy after 1 January 2017. Results: In total 287 aNSCLC patients with METex14, the real-world best overall response rate was 73.4% for capmatinib (n = 146), 68.8% for immunotherapy (IO) monotherapy (n = 48), 52.0% for chemotherapy (CT, n = 30), and 54.8% for IO + CT (n = 63). As compared with capmatinib, patients receiving IO (hazard ratio [HR]: 1.57; 95% CI: 0.77–3.20; p = 0.220), CT (HR: 2.41; 95% CI: 1.19–4.85; p = 0.014) and IO + CT (HR: 2.33; 95% CI: 1.35–4.04; p = 0.003) had higher rates of progression. Further, patients receiving CT (HR: 4.43; 95% CI: 1.54–12.75; p = 0.006) and IO + CT (HR: 3.53, 95% CI: 1.41-8.85; p = 0.007) had higher rates of mortality than patients receiving capmatinib. Conclusion: The study showed better clinical outcomes with capmatinib than other standard therapies in 1L setting for aNSCLC harboring METex14. Plain Language Summary Real-world study that investigated the outcomes of different therapies used to treat non-small-cell lung cancer patients with mesenchymal-epithelial transition exon 14 skipping mutation What is this article about? A real-world study that investigated clinical outcomes in patients with diagnosis of advanced non-small-cell lung cancer (aNSCLC) with mesenchymal-epithelial transition exon 14 (METex14) skipping–a rare form of genetic mutation–who received treatment with one of the commonly used therapies for this disease: immunotherapy, chemotherapy, immunotherapy + chemotherapy combination and capmatinib, which is a highly selective inhibitor of MET tyrosine kinase protein involved in the growth of cancer cells. What were the results? The study showed that, in general, patients treated with capmatinib as the frontline therapy more frequently achieved a clinical response in the form of complete tumor resolution or tumor shrinkage, had a lower risk of disease worsening and lived longer than patients who were treated with immunotherapy, chemotherapy or immunotherapy + chemotherapy combination. What do the results of the study mean? This study suggests that capmatinib is effective in treating patients with aNSCLC with METex14 skipping who have not been treated with another anticancer therapy previously. It provides evidence to support the use of capmatinib in the frontline setting and may inform clinical decision-making in routine practice. Tweetable Abstract This real-world study of clinical outcomes showed capmatinib to be effective in first-line treatment of patients with advanced/metastatic NSCLC with MET exon 14 skipping mutation. Capmatinib, a tyrosine kinase inhibitor, was the first targeted therapy approved by the US FDA for METex14 patients with advanced non-small-cell lung cancer (aNSCLC). Capmatinib has shown significant efficacy in clinical studies; however, data on capmatinib activity in comparison with other standard therapies when treating patients with aNSCLC harboring METex14, particularly from the real-world settings, are limited. This study conducted a medical record review to assess real-world clinical outcomes of patients with METex14 in aNSCLC treated with capmatinib, or immunotherapy (IO) and/or chemotherapy (CT) at various sites in the USA. Study reviewed 287 patient charts, of whom 146 patients received capmatinib, 48 received IO monotherapy, 30 received CT and 63 received IO + CT as their first-line (1L) for aNSCLC. The study population was approximately 71% male; 49.1% were Non-Hispanic White, with a median duration of follow-up of 11 months from aNSCLC diagnosis and 10 months from the 1L therapy initiation, and most patients (63.1%) had stage IV NSCLC at 1L therapy initiation. Capmatinib in aNSCLC with MET exon 14 had higher real-world overall response rate (73.4% [95% CI: 65.2–80.5%]) and longer time to treatment discontinuation (median- 19.1 months [95% CI: 12.4–not estimable (NE)]), real-world progression-free survival (Median–NE) and overall survival (Median–NE) compared with other standard of care therapies. Multivariable cox regression models indicated that after controlling for demographic and clinical characteristics, 1L CT and IO + CT versus capmatinib had significantly higher rates of treatment discontinuation, progression and mortality. This study provides evidence to support the use of capmatinib in 1L treatment of patients with aNSCLC/mNSCLC with MET exon 14 skipping mutation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pragmatic Clinical Trials (PCTs) are valuable tools for evaluating interventions in real-world settings, providing insights for clinical practice. Unlike traditional randomized controlled trial (RCTs), PCTs generate real-world evidence for better decision-making. With 615 reported globally between 1967 and 2017, a 58% increase from 2013 to 2017, India has only one registered PCT, indicating a gap in its adoption. This review examines national clinical trial registries, PubMed database for PCTs till 2024, comparing data across different nations. The study reveals a significant shortage of PCTs in India and a lack of awareness of frameworks like Pragmatic Explanatory Continuum Indicator Summary 2. India faces challenges in implementing PCTs due to low awareness, inadequate infrastructure, and logistical hurdles. However, with regulatory reforms, international collaboration, and infrastructure improvements, India can become a key player in advancing PCTs. Increased awareness and researcher training will contribute to better healthcare outcomes both domestically and globally.

Summary: 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.

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.

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.

Abstract 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 (

Background: HER2 (Human Epidermal Growth Receptor 2) positive breast cancer is an aggressive subtype. Treatment for patients with HER2-positive breast cancer has advanced significantly over time with the introduction of targeted therapies like trastuzumab, pertuzumab, lapatinib, trastuzumab emtansine, trastuzumab, deruxtecan, and tucatinib. In a lower-middle-income nation, accessibility is still problematic for any newer therapy. This study aimed to describe the safety and practical effectiveness of the first T-DM1 biosimilar in India for treating patients with HER2-positive mBC. Methodology: This is a retrospective, observational, single-center study of patients with HER2-positive metastatic breast cancer treated with T-DM1 biosimilar. The study involved 16 mBC patients. The primary goal was to assess T-DM1's effectiveness regarding PFS and ORR, with safety and OS as the secondary goals. Results: The ORR was observed to be 81.3%. One (6.29%) of the patients achieved CR, while 3 patients (18.8%) are on stable disease, and 12 patients (75 %) achieved PR. The major adverse events reported among study patients were thrombocytopenia (31.25%) and anemia (31.25%), followed by neutropenia, hyperglycemia, and fatigue in 12.5 % of cases. Grade 3 thrombocytopenia was seen in 2 patients, and grade 3-4 fatigue was observed in 1 patient. Median PFS was nearly six months, and OS data is available for only 25% of patients; the rest continue the therapy. Conclusion: This retrospective observational study offers significant information about the safety and efficacy of T-DM1 biosimilar in treating HER2 positive mBC.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cancer-associated thrombosis is a common problem in cancer patients and one of the leading causes of death in this population. Randomised clinical trials have shown that both low-molecular-weight heparins and direct oral anticoagulants are the treatments of choice for cancer-associated thrombosis. Despite this, small sample sizes, poor representation of some patient subgroups and lack of information about real-world clinical situations are some of the limitations of randomised trials. To overcome these problems, registries have been established to collect real-world data from patients with cancer-associated thrombosis, offering new evidence and information to supplement the findings of randomised clinical trials. However, few registries have focused exclusively on cancer patients, and some have excluded various subgroups of patients. Additionally, data collection and processing are another major challenge in analysing registry results, where the emergence of artificial intelligence will play a fundamental role.

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.

IntroductionRandomized 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.MethodsThe 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.ResultsOverall, 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.DiscussionOur 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.

ObjectivesGenerating and using real-world evidence (RWE) is a pragmatic solution for evaluating health technologies. RWE is recognized by regulators, health technology assessors, clinicians, and manufacturers as a valid source of information to support their decision-making. Well-designed registries can provide RWE and become more powerful when linked with electronic health records and administrative databases in coordinated registry networks (CRNs). Our objective was to create a framework of maturity of CRNs and registries, so guiding their development and the prioritization of funding.Design setting and participantsWe invited 52 stakeholders from diverse backgrounds including patient advocacy groups, academic, clinical, industry and regulatory experts to participate on a Delphi survey. Of those invited, 42 participated in the survey to provide feedback on the maturity framework for CRNs and registries. An expert panel reviewed the responses to refine the framework until the target consensus of 80% was reached. Two rounds of the Delphi were distributed via Qualtrics online platform from July to August 2020 and from October to November 2020.Main outcome measuresConsensus on the maturity framework for CRNs and registries consisted of seven domains (unique device identification, efficient data collection, data quality, product life cycle approach, governance and sustainability, quality improvement, and patient-reported outcomes), each presented with five levels of maturity.ResultsOf 52 invited experts, 41 (79.9%) responded to round 1; all 41 responded to round 2; and consensus was reached for most domains. The expert panel resolved the disagreements and final consensus estimates ranged from 80.5% to 92.7% for seven domains.ConclusionsWe have developed a robust framework to assess the maturity of any CRN (or registry) to provide reliable RWE. This framework will promote harmonization of approaches to RWE generation across different disciplines and health systems. The domains and their levels may evolve over time as new solutions become available.

Introduction: PRP is gaining increasing interest for pain relief and improvement of joint function in patients with knee osteoarthritis (KOA) but practices and results remain heterogeneous limiting its adoption as standard of care. Current international recommendations are to collect real-life evidence of efficacy with a systematic monitoring of PRP quality and patients' outcomes. We aimed to analyze the response of patients presenting KOA and treated with standardized PRP injection in routine care. We also investigated the potential contributing factors including patient's phenotype and PRP characteristics. Methods: Patients with symptomatic KOA and that failed first-line therapy received a single injection of a qualified PRP prepared using medical devices allowing to recover a high/very high volume of very pure PRP. Visual analogue scale (VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded at baseline and during 18 months follow-up. Results: 431 patients had available follow-up data at 3 months, 291 at 6 months, 137 at 12 months and 44 at 18 months. PRP induced a significant decrease of WOMAC score at all follow up endpoints (29.2 ± 19.2 at 3 months, p

Abstract 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.

Abstract Background When deciding whether to implement an intervention, decision-makers typically have questions on feasibility and acceptability and on factors affecting implementation. Descriptions of programme implementation and of policies and systems are rich sources of information for these questions. However, this information is often not based on empirical data collected using explicit methods. To use the information in unconventional source materials in syntheses or other decision support products, we need methods of assessing their strengths and limitations. This paper describes the development and content of the Assessing unConventional Evidence (ACE) tool, a new tool to assess the strengths and limitations of these sources. Methods We developed the ACE tool in four stages: first, we examined existing tools to identify potentially relevant assessment criteria. Second, we drew on these criteria and team discussions to create a first draft of the tool. Third, we obtained feedback on the draft from potential users and methodologists, and through piloting the tool in evidence syntheses. Finally, we used this feedback to iteratively refine the assessment criteria and to improve our guidance for undertaking the assessment. Results The tool is made up of 11 criteria including the purpose and context of the source; the completeness of the information presented; and the extent to which evidence is provided to support the findings made. Users are asked to indicate whether each of the criteria have been addressed. On the basis of their judgements for each criterion, users then make an overall assessment of the limitations of the source, ranging from no or very minor concerns to serious concerns. These assessments can then facilitate appropriate use of the evidence in decision support products. Conclusions Through focussing on unconventional source materials, the ACE tool fills an important gap in the range of tools for assessing the strengths and limitations of policy-relevant evidence and supporting evidence-informed decision-making.

Abstract 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

Abstract 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 FEV1% 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.