Real-world Practice Research Articles

Efficacy and safety of trifluridine/tipiracil and bevacizumab (FTD/TPI+BEV) in patients with metastatic colorectal cancer (mCRC) in real-world practice.

204 Background: In Sunlight trial, the combination of FTD/TPI + BEV showed a significant improvement in Overall Survival (OS) and Progression-Free Survival (PFS), along with better Objective Response Rate (ORR) and Disease Control Rate (DCR), compared to FTD/TPI alone, in patients with mCRC progressing after two chemotherapy regimens. The BeTAS trial aimed to evaluate the effectiveness and safety of the FTD/TPI + BEV combination in real-world practice. Methods: This was a retrospective, observational, multicenter study of mCRC patients treated with FTD/TPI+BEV in routine clinical practice across 11 Spanish university hospitals. It included patients with mCRC who were refractory or intolerant to standard therapies. Results: A total of 208 patients treated with FTD/TPI+BEV between July 2019 and December 2023 were included. The median age was 69 years (range 33 to 88 years), with 59.8% being male. 15.3% had an ECOG performance status of 2, 55.9% had RAS mutations, 30.3% had three or more metastatic sites, and 81.2% had liver metastases. Additionally, 19.8% had a time from diagnosis of first metastasis of less than 18 months, and 55.3% were categorized in Tabernero's Unfavorable Prognostic Subgroup. Most patients (81.3%) received FTD/TPI+BEV as third-line therapy, with 90.5% having previously received anti-VEGF therapy. The median number of treatment cycles was 4 (range 1 to 31 cycles). The ORR was 4.6%, and the DCR was 50%. The median PFS was 4.9 months (95% CI, 4.0-5.7 months), and the median OS was 11.1 months (95% CI, 9.5-12.8 months). The most common grade 3-4 toxicities included neutropenia (41.8%), asthenia (7.2%), and hepatic toxicity (5.5%). No treatment-related deaths were reported. Conclusions: Our series confirms the efficacy and safety of FTD/TPI + BEV in routine clinical practice, even in a population with poor prognosis and an extensive history of previous treatments.

Pharmacological interventions for patients with chronic primary musculoskeletal pain: disparity between synthesized evidence and real-world clinical practice.

Chronic primary musculoskeletal pain (CPMP) poses a major problem of public health, with high prevalence rates and economic burden. There is a wealth of clinical trials examining pharmacological interventions for patients with CPMP. Nevertheless, evidence from such trials does not necessarily mirror clinical realities. We aimed to compare data sets from a clinical sample with an randomized controlled trial (RCT)-based sample. Both data sets included participants living with CPMP who received pharmacological interventions. The clinical sample was retrieved from electronic health records. The RCT-based sample stemmed from a network meta-analysis project. The following outcomes were used: demographic information, diagnosis-specific data, and pharmacological interventions (categorized according to the World Health Organization [WHO] analgesic ladder). The clinical sample consisted of 103 patients (mean age: 50.25 years; SD: 14.0) and the RCT-based samples contributed 8665 participants (mean age: 51.97 years; SD: 6.74). In both samples, the proportion of women was higher than that of men (ie, 74.8% vs 58.9%). Psychiatric disorders were the most common comorbidities in the clinic sample but also the most frequent reason for patient exclusion in RCTs. The 2 samples differed significantly in medication classified as WHO III (clinical sample: 12.9%; RCT sample: 23.5%; P = 0.023) and WHO IV (clinical sample: 23.4%; RCT sample: 8.6%; P < 0.001), yet not WHO I and II. Our findings suggest a disparity between research-based study populations and clinical populations with CPMP. We advocate for future investigations on how to implement robust scientific evidence into real-world clinical practice, with a particular focus on addressing psychiatric comorbidities.

Immune checkpoint inhibitors in digestive tumors with mismatch repair deficiency or microsatellite instability (dMMR/MSI-H): Effectiveness, safety, and prognostic factors in real-world practice.

202 Background: ICIs have shown durable responses in dMMR/MSI-H digestive tumors in phase II-III clinical trials. The aim of this study is to evaluate the efficacy, safety and prognostic factors in the context of real-world practice. Methods: We conducted a retrospective multicenter observational study of patients with dMMR/MSI-H digestive tumors treated with ICIs in routine clinical practice across seven university hospitals in northwest Spain. We analyzed clinicopathological characteristics, treatment response data, efficacy, and adverse events. Results: A total of 122 patients treated with ICIs between November 2015 and February 2024 were included. The median age was 70.4 years (range 29-89), and 52.4% were male. The most frequent origin was colorectal (54.9%; 67.2% located in the right colon and 37.3% BRAF V600mt), followed by gastroesophageal adenocarcinoma (34.4%). 16.4% had &gt;3 metastatic sites (including 30.3% liver metastases and 44.3% peritoneal metastases). Baseline performance status (ECOG PS) was 0/1/2 in 21.7%/58.7%/19.8%, respectively. 39.3% had received one prior line of treatment. 92.6% received pembrolizumab monotherapy. The objective response rate (ORR) was 77.7% (including 31.3% complete response, 46.4% partial response, 13.4% stable disease, and 8.9% progressive disease), and the disease control rate (DCR) was 90.1%. Median overall survival (OS) was 53.2 months (95% CI: 42.6 – 63.7 months), and progression-free survival (PFS) was 46 months (95% CI: 30.6 – 61.4 months). The most common grade 3-4 treatment-related adverse events included nephritis (4.0%), hepatitis (3.3%), asthenia (2.5%), and pneumonitis (1.6%). 81.1% of patients discontinued treatment (including 24.6% due to progression, 21.3% after completing 2 years of treatment, and 14.8% due to toxicity). Potential prognostic factors identified in univariate analysis included ECOG PS, primary tumor resection, number of metastatic sites, and best treatment response. In multivariate analysis, a significant association was confirmed between ECOG PS, the presence of liver metastases, and best response to treatment with ICIs and overall survival. Conclusions: Our series confirms the efficacy and safety of ICIs in dMMR/MSI-H digestive tumors in routine clinical practice. The identified prognostic factors may be useful for identifying patients who could benefit the most from ICI treatment.

Overall survival (OS) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line (1L) FOLFIRINOX (FFX): Bridging the gap between the NAPOLI 3 trial and real-world practice.

690 Background: NALIRIFOX (liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin) demonstrated significantly improved OS compared to 1L gemcitabine + nab-paclitaxel in the phase 3 NAPOLI 3 trial (NCT04083235). The median OS (95% CI) in the NALIRIFOX intention-to-treat population (N= 383) was 11.1 (10.0, 12.1) months. However, the relative efficacy of NALIRIFOX versus FFX (irinotecan + 5-fluorouracil/leucovorin + oxaliplatin), another standard of care for 1L treatment of mPDAC, has not been studied. To further contextualize findings from NAPOLI 3 trial, the current study described OS among patients treated with 1L FFX in the real-world setting. Methods: Three cohorts of patients with mPDAC treated with 1L FFX were identified from the Flatiron Health database. The all-comer cohort included all adult patients with mPDAC treated with 1L FFX since January 2014. Among them, the trial-aligned cohort included patients with mPDAC treated with 1L FFX between January 1, 2020 and July 31, 2022 (to align with the time period of NAPOLI 3 trial) who met the eligibility criteria of NAPOLI 3. Finally, a subgroup of patients in the trial-aligned cohort who received modified FFX (mFFX) regimen composed the trial-aligned mFFX cohort. OS was assessed using Kaplan-Meier analysis. Results: The all-comer cohort consisted of 3,271 patients. The trial-aligned cohort included 219 patients, of whom 154 (70%) were treated with mFFX. The distribution of baseline characteristics was similar across three cohorts (Table). The median age of the trial-aligned cohort was 65 years old, with 46% of patients being female, 67% being White, and 47% having ECOG score of 1. The median OS (95% CI) in the all-comer cohort and trial-aligned cohort was 9.0 (8.5, 9.3) months and 9.1 (7.8, 10.9) months, respectively; the median OS (95% CI) was 8.6 (7.3, 10.5) months in the trial-aligned mFFX cohort. Conclusions: NALIRIFOX regimen in the NAPOLI 3 trial showed numerically improved OS compared to FFX, including mFFX, in the real-world setting. Analysis adjusting for baseline characteristics are warranted and will provide further insights for the comparative efficacy of the two regimens. Characteristics of real-world FOLFIRINOX cohorts. All-comer cohort(N=3,271) Trial-aligned cohort(N=219) Trial-aligned mFFX cohort (N=154) Baseline characteristics Age, years, mean (SD) 63.5 (9.0) 64.6 (8.2) 65.1 (8.5) Female, n (%) 1,377 (42.1) 100 (45.7) 68 (44.2) White, n (%) 2,118 (64.8) 146 (66.7) 100 (64.9) ECOG score = 1, n (%) 1,327 (48.9)* 103 (47.0) 77 (50.0) Endpoint Median OS, months (95% CI) 9.0 (8.5, 9.3) 9.1 (7.8, 10.9) 8.6 (7.3, 10.5) Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; OS, overall survival; SD, standard deviation. *Proportion calculated based on 2,711 patients with ECOG available at baseline.

Treatment sequences in patients with metastatic colorectal cancer in Japan: Real-world evidence of 1 st - to 5 th -line treatments.

76 Background: The development of later-line drugs for metastatic colorectal cancer (mCRC) has expanded treatment options for systemic chemotherapy in patients with mCRC. However, few studies have investigated patients who received later-line treatment in a real-world setting, and available information on treatment sequences and transition rates from early- to later-line treatments is limited. Methods: This was a retrospective study using hospital administrative data collected by MDV (Medical Data Vision, Tokyo, Japan) from April 2008 through February 2023 in Japan. Treatment regimens were derived from standard treatments recommended in the Japanese guidelines. The study population was determined using an algorithm from a similar study previously conducted in Japan. Our analysis focused on patients who started CRC surgery or 1 st -line treatment after January 2017 to reflect recent late-line real-world practice. Transition rates from 1 st - to 5 th -line treatment were calculated, and treatment sequences were summarized using a Sankey diagram. Logistic regression was performed to identify the factors associated with the transition from 2 nd - to 3 rd -line treatment. Results: A total of 722,005 patients with a CRC diagnosis record were identified in the MDV database. Of these, 26,456 patients were included in the study population. The median age was 69 years and 61.4% of patients were male. The rates of transition to subsequent lines from 1 st to 5 th line ranged from 65.7% to 70.4% (1 st to 2 nd 68.3%; 2 nd to 3 rd 70.4%; 3 rd to 4 th 69.9%; 4 th to 5 th 65.7%). Among 8528 patients who received 2 nd -line treatment, ~70% of patients (6006) continued 3 rd -line treatment, and 30% of patients (2522) received best supportive care. Comparing these 2 patient groups, younger age (&lt;65 years, OR: 1.50, 95%CI: 1.35-1.67; p&lt;0.001) and longer treatment durations of 1 st (≥180 days, OR: 1.26, 95%CI: 1.14-1.39; p&lt;0.001) and 2 nd (≥120 days, OR: 1.67, 95%CI: 1.52-1.84; p&lt;0.001) lines were significant factors for 3 rd -line treatment continuation. Prior therapy with oxaliplatin or irinotecan plus molecular targeted drugs was also associated with a higher likelihood of proceeding to 3 rd -line treatment (OR: 1.42, 95%CI: 1.28-1.58; p&lt;0.001). Conclusions: In this study, ~70% of patients were able to transition to subsequent lines at the time of each line transition. However, 30% of patients were unable to continue treatment in real-world practice. To increase treatment continuation rates and maintain patient quality of life, new treatment options and further research are necessary to meet patients’ treatment needs, especially in the later-line treatment setting where unfavorable effects from previous treatments are accumulated.

Real-world biomarker testing and first-line treatment patterns among locally advanced, unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma patients in the US.

348 Background: Advanced-stage gastric cancer and gastroesophageal junction adenocarcinoma (advG/GEJC) are leading causes of cancer-related morbidity and mortality. Chemotherapy is the traditional first-line (1L) therapy for patients in the advanced setting, with targeted and immunotherapy considered based on biomarker expression. This study aimed to describe real-world HER2 and PD-L1 testing practices and 1L treatment patterns among advG/GEJC patients. Methods: A retrospective cohort study was conducted among adult patients diagnosed with advG/GEJC between 01 Jan 2017 and 30 Jun 2023 usingthe US-based Flatiron Health electronic health record-derived de-identified database. HER2 and PD-L1 testing practices were evaluated prior to and up to 1-month post-1L treatment initiation or 6 months post-advG/GEJC diagnosis date in untreated patients. 1L treatment regimens were described overall and stratified by HER2 and PD-L1 expression. Results: Among 4,256 advG/GEJC patients, the average age was 67 years with the majority male (68%), non-Hispanic white (44%), and with metastatic disease (64%). Nearly three quarters (72%) of patients included received a HER2 test and 55% had a HER2 test with a valid result within the timeframe mentioned above. More than a quarter of patients (27%) received a PD-L1 test and 25% had a PD-L1 test with a valid result. PD-L1 testing before the approval of nivolumab in 1L (i.e. before 2021) showed testing at 19% (490/2,629; 17% with a valid result) and from 2021 onward at 40% (643/1,627; 37% with a valid result). Across the full cohort, half of the patients received chemotherapy alone (52%) and one quarter received no treatment (25%). Similar treatment patterns were observed in the subset of 1,117 patients who did not receive a HER2 or PD-L1 test; 54% received chemotherapy alone and 36% no treatment. Of the 340 patients who were tested for HER2 and were HER2 positive, half (52%) received trastuzumab combination therapy, 23% received chemotherapy alone, and 18% had no treatment. Of the 301 patients who received a PD-L1 test with a combined positive score (CPS) ≥5 from 2021 onward, 41% received immunotherapy, 34% received chemotherapy alone and 18% had no treatment. Prior to 2021, most patients with a PD-L1 test and CPS &gt;5 used chemotherapy alone (57%; 132/233), 13% (31/233) received PD-L1 targeted therapies and 19% (43/233) received no treatment. Conclusions: This study describes a potential subset of US advG/GEJC patients who do not receive a HER2 or PD-L1 test and/or do not receive eligible targeted or immunotherapy as part of routine clinical practice. As precision medicine options continue to evolve, these data suggest an opportunity to further understand the drivers for biomarker testing as well as the factors impacting the use of biomarker-informed treatment options.

Trends in surgery and overall survival in non-metastatic anal cancer: A population-based analysis.

3 Background: The incidence of anal cancer has recently exceeded &gt; 10,000 patients/year in the United States. For non-metastatic squamous cell carcinoma of the anal canal (SCCA), concurrent chemoradiotherapy (CRT) followed by abdominoperineal resection (APR) as salvage surgery for non-responders is a key treatment approach. Over the past two decades, findings from phase III trials (RTOG 98-11 and ACT II) have increased our knowledge about appropriate treatment approaches. ACT II indicated that delayed assessment of tumor response and consideration of APR up until 26 weeks is appropriate, as many patients demonstrate delayed response to treatment. Our analysis examines whether current evidence has influenced real-world clinical practice by analyzing trends in rates of primary APR and overall survival (OS) outcomes. Methods: We conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) registry, including patients diagnosed with non-metastatic SCCA between 2004 and 2020. Patients with T0 or T1N0 stage disease were excluded. Descriptive statistics were generated, and chi-square tests were used to compare characteristics between patients who underwent surgery and those who did not. Temporal trends in surgery and radiation therapy were analyzed using the Cochrane-Armitage trend test. Multivariable logistic regression was employed to identify factors associated with surgery uptake, while OS trends were analyzed using Kaplan-Meier and Cox proportional hazard models. Results: A total of 16,718 patients were included, with 33.1% requiring salvage APR following CRT. The proportion of patients requiring surgery significantly declined from 46.6% in 2004 to 31.1% in 2020 (p &lt; 0.001). Factors associated with surgery included younger age, male gender, and non-Hispanic Black race (p &lt; 0.001). Kaplan-Meier analysis revealed significant improvements in OS over the study period (log-rank p = 0.0002), with more recent years (2016-2020) associated with significantly better OS compared to earlier periods (2004-2007, HR = 0.77, p &lt; 0.001). Conclusions: The significant decrease in rates of salvage APR for non-metastatic SCCA likely reflects the global impact of recent phase III trials. Meanwhile, OS rates have been steadily improving. These findings suggest improved overall knowledge regarding treatment strategies and highlight the real-world impact of clinical investigation in non-metastatic squamous cell carcinoma of the anal canal.

Implementing Mental Practice in Postgraduate Surgical Training for Minimally Invasive Surgery: A Systematic Review and Thematic Analysis.

Unprecedented pressure on the National Health Service (NHS) has meant that there are increasing obstacles to surgical training. Simulation training is an option to improve surgical performance but is limited due to availability, accessibility and financial constraints. Mental practice (MP) has been proposed as a potential solution to supplement the traditional method of apprenticeship-style learning. Despite increasing evidence that MP may be a useful tool to improve surgical performance and reduce surgeon anxiety, it is not widely adopted. This systematic review and thematic analysis aims to identify key themes that would allow for the successful implementation of MP in postgraduate surgical training. Medline, Embase and PsycINFO databases were systematically searched to identify articles that investigate the role of MP in improving surgical performance amongst surgical trainees. Retrieved papers were studied to inform thematic analysis of their content and studies were assessed for bias. A total of 321 studies were retrieved, of which 11 met the inclusion criteria. Overall risk of bias was assessed to be between critical and moderate for seven nonrandomized studies and between fair and good for four randomized studies. Key themes were identified and discussed using a thematic analysis approach. This study has identified that attaining high quality mental imagery is fundamental to success in mental practice and this can be augmented by the use of relaxation therapy and/or motivational imagery. Future research should focus on the application of MP in real-world surgical practice and breaking down complex procedures into fewer operative steps.

Shattering the Shield: Embracing Complexity in Undergraduate Medical Education.

Multimorbidity and patient complexity are increasing, yet undergraduate medical education curricula remain dominated by single disease frameworks, where students are often shielded from exposure to this complexity. Why this shielding continues to occur is understandable; however, this may leave graduates feeling underprepared for real-world practice. This study aimed to explore medical students' experiences of encountering, managing and dealing with complexity and to provide informed recommendations for integrating complexity into clinical teaching. Situated within a constructivist paradigm, this qualitative study involved focus groups (n = 4) with fourth- and fifth-year medical students (n = 17) from two Scottish Universities. Data were analysed using reflexive thematic analysis. Learners in this study recognised multimorbidity, complex communication and emotionally charged interactions in their definitions of complexity. They described varying levels of exposure to complexity and opportunities to engage meaningfully with complex patients. Students felt that supervisors who shield students from learning opportunities with complex patients, together with a failing healthcare system, were critical limiting factors in their development. Learners emphasised the powerful role of supervisors in their learning experiences, which limited their ability to experiment and learn from productive failure but felt that with guided scaffolding and supervision, teaching and learning in this space could be meaningfully enhanced. Exposure to and engagement with complex patients offer critical learning opportunities that may allow students to explore and better develop skills in managing complexity. With appropriate scaffolding, students can be empowered to embrace complexity in the clinical learning environment, potentially equipping them to care for complex patients.

Effectiveness of emotion-focused therapy: Main results of a practice–research network study

Background Emotion-Focused Therapy is one of the evidence-based psychotherapies for a range of psychological problems. While most evidence was gained from randomized controlled studies or process research at university settings, there is a need for more outcome research conducted within practitioner–researcher networks assessing the effectiveness of Emotion-Focused Therapy in private practice. Methods A total of N = 70 clients with a variety of psychiatric disorders have been included in the bi-national practitioner researcher network for Emotion-focused Therapy Switzerland–Germany. Symptom change was assessed using CORE-OM, BDI-II, IIP and WSAS. Therapist adherence was assessed by the self-reported version of the PCEPS. Pre–post-follow-up analyses were conducted using paired sample t-tests and hierarchical linear modeling. Results Pre–post-assessment shows small to medium effect sizes for all outcome measures (except for interpersonal problems which did not change). Symptom reduction is maintained for CORE, BDI and WSAS, and increased for IIP at 3 and 6 months follow-up. Therapist adherence is good to excellent in this sample. Conclusions Emotion-Focused Therapy is effective in the real-world practice, as suggested by the small to moderate effect sizes. The smaller effects found in the current study as compared to randomized controlled trials are consistent with the literature and suggest that EFT remains moderately effective when applied in a naturalistic context.

Factors associated with early and late losses of primary patency following drug-coated balloon for dysfunctional arteriovenous fistula.

This study aimed to evaluate the effectiveness of a drug-coated balloon (DCB) for the treatment of dysfunctional arteriovenous fistulas (AVFs) and to identify the risk factors associated with early and late losses of primary patency following DCB in real-world practice. This multicenter, retrospective study included 407 patients (72 ± 11 years, 64.1% males) with dysfunctional AVFs (juxta-anastomotic lesion location in 58.7% of cases, mean size 1.2 mm, mean length 54 mm) who underwent DCB for the first time for the treatment of dysfunctional AVF. The primary outcome measure was the loss of primary patency after DCB. The secondary outcome measures were the factors associated with early (<90 days) and late (⩾90 days) losses of primary patency after DCB. The primary patency rates 6 and 12 months after DCB were 72.5% ± 2.3% and 40.1% ± 2.7%, respectively. The factors associated with the early loss of primary patency were de novo lesions (adjusted hazard ratio [HR], 7.91; [95% confidence interval (CI), 1.90-32.97]; p = 0.005), endovascular treatment (EVT) history within the previous 90 days (adjusted HR, 9.29; [95% CI, 3.09-27.92]; p < 0.001) and juxta-anastomotic stenosis (adjusted HR, 0.30; [95% CI, 0.13-0.70]; p = 0.005). The factors associated with a late loss of primary patency included EVT history within the previous 90 days (adjusted HR, 2.52; [95% CI, 1.89-3.38]; p < 0.001) and pre-dilation balloon size (adjusted HR, 1.99; [95% CI, 1.50-2.64]; p < 0.001). DCB is an effective device to prolong the patency of dysfunctional AVFs in most cases. De novo lesions and their locations were associated with an early loss of primary patency, whereas the vessel preparation balloon size was associated with a late loss of primary patency. EVT history within the previous 90 days was associated with early and late losses of primary patency.

Suhexiang pill for acute ischemic stroke in real-world practice setting (SUNRISE): protocol of a multicenter registry

BackgroundSuhexiang (SHX) pill is widely used for treating acute ischemic stroke (AIS). Experimental and randomized controlled trials suggested that SHX pill was beneficial for patients with AIS. However, the effectiveness of SHX pill in real-world practice setting remains unclear. It is of great importance to investigate the effectiveness and safety of SHX pill in patients with acute ischemic stroke in real-world clinical practice with long-term follow-up.MethodsThe Suhexiang pill for acute ischemic stroke in Real-world Practice Setting (SUNRISE) is a multicenter, prospective, product-specific, observational study designed to provide insight into the administration of SHX pill for patients with AIS in the real-world clinical practice setting, with an initial sample size of 1000. Eligible patients treated with SHX pill within seven days of AIS onset will be consecutively included in this registry. The primary outcome is the proportion of patients independent at 3 months after stroke onset defined by an mRS score of 0, 1, or 2.ConclusionThe findings of the SUNRISE registry will not only provide insights into the characteristics of patients who may benefit from SHX treatment, but also may enable the individualized treatment decision-making of SHX pill in real-world practice setting.Study registrationThis study was registered with the ClinicalTrials.gov (URL: https://clinicaltrials.gov/, Unique identifier: NCT05833932).

Lipid-Lowering Efficiency and Safety of Alirocumab 300 mg Using a 2-mL Autoinjector Device in Real-World Practice: The MARS Study.

Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 used for the reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk patients not reaching their LDL-C target. Recently, a 2-mL prefilled autoinjector has been developed to support the monthly 300-mg dosing regimen with a single-injection administration. Monthly application of 300 mg AlirRocumab (Praluent®) using the 2-mL SYDNEY Device (MARS) is a non-interventional, open, prospective, multi-center cohort study conducted in Germany between 2021 and 2023 with an observational period of 12 weeks. Patients included had primary hypercholesterolemia (heterozygous familial or non-familial) or mixed dyslipidemia and confirmed vascular disease and other risk factors or confirmed familial heterozygous hypercholesterolemia. Primary objectives were to assess the effectiveness of the 2-mL SYDNEY autoinjector measured by the lipid-lowering effect of alirocumab and to document therapy satisfaction, patient adherence, and persistence. Secondary objectives were to assess safety (adverse events) and tolerability. A total of 146 patients were analyzed: 110 (75.3%) patients were proprotein convertase subtilisin kexin type 9 inhibitor naïve and 36 (24.7%) were pre-treated with a proprotein convertase subtilisin kexin type 9 inhibitor. Patient mean age was 65.6 years with a preponderance of male gender (59.6%). At 12 weeks, the LDL-C value had decreased by a median of 59.5 mg/dL (1.5 mmol/L) in naïve patients (median relative decrease: -52.0%). In the pre-treated group, the LDL-C value remained mainly unchanged (median slight numerical relative increase: 1.6%). Treatment satisfaction was rated similarly in both groups with most patients being satisfied/very satisfied and rating the injection as effective, safe, and easy to handle. Twenty-three adverse events in 13 patients (8.0%) were documented. Three patients experienced one serious adverse event each; for five patients, an adverse drug reaction was observed, although none was serious. The occurrence of adverse events was similar in both groups. Alirocumab 300 mg administered with the 2-mL SYDNEY autoinjector was safe and effective in lowering LDL-C after 12 weeks in a routine clinical setting in Germany. The treatment schedule was perceived to be beneficial with excellent device acceptance and satisfaction, potentially increasing patient adherence. Clinicaltrials.gov: NCT05129241.

Thyroid Nodules with Indeterminate Cytology and Negative Molecular Profile: Prevalence of Malignancy and Practice Paradigms for Surveillance.

Background: In the era of molecular testing, thyroid nodules with indeterminate cytology are increasingly being managed nonoperatively. The false-negative rates of these molecular tests, and therefore missed malignancies, are not well defined in real-world clinical practice. Methods: This retrospective study of patients undergoing fine needle aspiration (FNA) biopsy at our health system between November 2017 and March 2022 included nodules with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) III and IV cytology and negative, currently negative, or negative but limited ThyroSeq version 3 (TSv3) results. Surgical pathology of resected nodules, as well as details of ultrasound (US) surveillance practices, was recorded. A range of prevalence of malignancy (PoM) estimates were calculated based on all nodules (PoM low) and surgically resected nodules (PoM high). Results: The study cohort consisted of 556 nodules. TSv3 results were distributed as 443 (80%) negative, 85 (15%) currently negative, and 28 (5%) negative but limited. Overall, 75 nodules were resected: 54 nodules (9.7%) had immediate surgery, and 21 nodules (3.8%) had delayed surgery after surveillance imaging. Currently negative and negative but limited nodules were more likely to undergo immediate surgical resection compared with negative nodules (20%, 18%, and 7%, respectively, p < 0.001). The PoM in molecularly benign TBSRTC III and IV thyroid nodules ranged between 3% and 23% depending on the inclusion of all versus resected nodules. TBSRTC IV molecularly benign nodules had a higher PoM than TBSRTC III (PoM low 7.3% vs. 1.6%, p < 0.001; PoM high 48% vs. 13%, p = 0.0013). In the 90% of nodules that were managed nonoperatively, 63% had at least one surveillance US. Timing of initial surveillance US ranged from 3 to 60 months (median 13 months, interquartile [IQR] 11-19 months). Median follow-up duration was 25 months (IQR 17-34 months). Nodule growth occurred in 24% of nodules; only a minority (7%) underwent repeat FNA. Conclusions: Negative subtype of TSv3 should be considered in clinical management recommendations. For negative but limited samples, repeat FNA should be performed. Optimal surveillance strategy for nonresected negative and currently negative nodules remains unknown. Until further real-world data are available, surveillance ultrasonography is recommended for TSN and TSCN nodules, similar to the ATA guidelines for TBSRTC II nodules.

Comparing PSA Screening Patterns and Their Role as Predictor of Prostate Cancer Diagnosis: Analysis of a Contemporary North American Cohort.

PSA screening remains a pivotal tool for early prostate cancer (PCa) detection. International guidelines rely on evidence from three major randomized clinical trials: ERSPC, PLCO, and CAP. We aim to examine the percentage of patients in real-world practice who get PSA screening as defined by each of the aforementioned trials. Moreover, we seek to evaluate if the different PSA screening patterns have a different impact on PCa incidence and its features at diagnosis. Our institutional database was queried to identify men aged 55-69 who received at least one PSA test, did not develop PCa or die within 6 years of the initial test, had follow-up within our system at least 6 years after the initial test, and did not have a previous PCa diagnosis. A total of 28,612 patients met our selection criteria. We categorized patients into three distinct PSA screening patterns based on testing frequency (PLCO: 1 PSA test per year for 6 years; ERSPC: 2 or 3 PSA tests over 6 years; CAP: 1 PSA test over 6 years). Our primary outcomes were any PCa incidence and clinically significant PCa (csPCa, defined as ISUP ≥ 3) incidence. Secondary outcome was the rate of cM1 disease. Competing risks cumulative incidence curves were used to depict any PCa and csPCa diagnosis with death before a diagnosis considered a competing risk. Multivariable competing risks regression (CRR) was used to assess the impact of the different screening patterns on any PCa and csPCa incidence, after adjusting for confounding factors. The most prevalent PSA screening pattern was ERSPC, including 15,530 patients (54.3%), followed by the CAP with 9003 patients (31.5%), and the PLCO with only 4079 patients (14.2%). The median (IQR) follow-up time was 4.8 (1.7-10.8) years. At 10 years, any PCa incidence was 7.4% versus 5.6% versus 2.5% for PLCO versus ERSPC versus CAP, respectively, while for csPCa, the rates were 2.5% versus 2.5% versus 1.2% (both p < 0.001). On multivariable analyses, PLCO and ERSPC patterns were associated with 2.92-fold and 2.31-fold higher risks from 1 year to the next of any PCa diagnosis, respectively, compared to CAP pattern (both p < 0.001). Similarly, patients with PLCO and ERSPC patterns had 2.07-fold and 2.31-fold higher risks, respectively, of csPCa diagnosis compared to CAP pattern (both p < 0.001). In men with PCa diagnosis, the rates of cM1 disease were respectively 1.7% vs 5.6% vs 10.8% for PLCO versus ERSPC versus CAP, respectively (p = 0.0009). We observed that the most common screening pattern in "real-world" clinical practice is close to what ERSPC recommend, and this pattern seems to achieve a reasonable reduction in the risk of advanced PCa, while limiting overdiagnosis.

Retrospective Cohort Study of Elderly Users of Single- or Multiple-Inhaler Triple Therapy for the Treatment of Asthma in the USA.

Escalation to single- or multiple-inhaler triple therapy (SITT; MITT) is a recommended option for patients with asthma who remain uncontrolled by medium-dose inhaled corticosteroid/long-acting β2-agonist; however, characterization of elderly users of triple therapy is limited. This real-world cohort study describes demographics and clinical characteristics of elderly patients with asthma with and without comorbid chronic obstructive pulmonary disease (COPD) who are new users of triple therapy, and asthma treatment patterns preceding triple therapy initiation. This retrospective cohort study used administrative claims data from the Optum Clinformatics Data Mart database. Eligible patients were ≥ 65years of age with asthma or with asthma and comorbid COPD who initiated either triple therapy with single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; 100/62.5/25μg) or MITT between September 18, 2017 and September 30, 2020. Demographics, clinical characteristics, healthcare resource utilization, healthcare costs, and asthma treatment patterns were described in the 12-month period before triple therapy initiation (baseline period). In total, 15,557 patients were included. Among FF/UMEC/VI initiators with asthma (N = 635) mean age was 73.3years and 66.6% were female. During the baseline period, > 75% of patients used controller therapy, > 92% used rescue medications, 27.9% experienced ≥ 1 asthma-related exacerbation, with mean annual exacerbation rate of 0.42, and mean all-cause healthcare costs were $23,407. Patients with asthma initiating MITT and patients with asthma and comorbid COPD initiating FF/UMEC/VI or MITT had similar characteristics, healthcare resource utilization, healthcare costs, and asthma treatment patterns to FF/UMEC/VI initiators with asthma. Triple therapy is often initiated following use of other asthma controller medications in real-world practice. Substantial rescue medication use and high disease and economic burden among this elderly patient population suggest that their asthma was not adequately controlled prior to triple therapy initiation. This retrospective study provides an early profile of elderly patients with asthma in the USA.

AdvantAGE: Implementation and Evaluation of an Interprofessional Transitional Care Model for Frail Older Adults-Protocol of an Effectiveness-Implementation Hybrid Study.

To implement and evaluate an Advanced Practice Nurse-led transitional care model (AdvantAGE) to reduce rehospitalisation rates in frail older adults discharged from a Swiss geriatric hospital. The study adopts an effectiveness-implementation hybrid design (Type 1) to simultaneously evaluate the effectiveness of the care model and explore the implementation process. The primary outcome, the 90-day rehospitalisation rate, will be evaluated using a matched-cohort design with a prospective intervention group and a retrospective control group. Secondary outcomes include the number of emergency department visits, health-related quality of life and intervention costs. The care model was developed through comprehensive contextual analysis and pilot testing in an iterative approach. It comprises five core elements: continuous support, care coordination, comprehensive health management at home, medication and self-management and advance care planning. Data collection includes both quantitative and qualitative methods, utilising routine hospital data, structured and semi-structured interviews and observations. Qualitative data will provide insights into implementation outcomes, potential barriers and facilitators. Additionally, a process evaluation will offer an in-depth understanding of individual intervention effects and reasons for rehospitalisation. The AdvantAGE project, grounded in implementation science methodology, aims to significantly improve transitional care outcomes for frail older adults. The results are expected to provide essential recommendations for scaling up the model to other settings. The study addresses the issue of frequent rehospitalisations in older adults, which carry risks of functional and cognitive decline. By implementing a comprehensive transitional care model, the study aims to improve continuity of care, reduce readmissions and enable frail older adults to remain in the community longer. The project highlights the importance of contextually adapted intervention and implementation strategies to bridge the gap between research and real-world healthcare practice. The project employs a participatory approach, engaging representatives from the hospital and primary care settings, the cantonal health department and older people and their caregivers. This study has been registered at clinicaltrials.gov on 5 January 2024 (Identifier: NCT06190288).

Previous treatment decreases efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer

BackgroundPralsetinib is a selective RET inhibitor. The ARROW trial revealed that RET fusion-positive non-small-cell lung cancer (NSCLC) can benefit from pralsetinib with tolerable adverse events (AEs). However, the efficacy and safety of pralsetinib in real world has rarely been reported.Materials and methodsThis study reviewed the efficacy and safety of pralsetinib in RET fusion-positive NSCLC patients between March 2021 and December 2021. Progression-free survival (PFS) and overall survival (OS) were evaluated by a Kaplan-Meier analysis and log-rank test. A Cox regression model was performed to identify independent prognostic factors.ResultsA total of 28 patients were enrolled, and the median follow-up time was 18.1 months. The objective response rate and disease control rate of the whole cohort were 57.2% and 71.4%, respectively, and the median PFS and OS were 8.1 months [95% confidence interval (CI), 3.1–13.2] and 13.8 months (95% CI, 2.8–24.8), respectively. Baseline characteristics of the treatment naive group and pre-treated group were listed. The median PFS tended to be better in treatment naive group (18.3 vs. 8.0 months, P = 0.067), while the median OS were similar between the two groups (28.4 vs. 11.6 months, P = 0.308). Patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 2 had worse median PFS comparing with those with ECOG PS score of 0–1 (3.8 vs. 12.6 months, P = 0.004). Besides, patients previously treated with platinum-based chemotherapy (PBC) also revealed worse median PFS comparing with those without previous PBC (8.0 vs. 18.6 months, P = 0.023). Furthermore, patients previously treated with anti-programmed death-1 (PD-1) antibody or multikinase inhibitors (MKIs) showed worse median OS compared with those without previous anti-PD-1 antibody (5.0 vs. 22.0 months, P = 0.002) or MKIs (6.2 vs. 28.4 months, P = 0.015). The most common AEs was increased aspartate aminotransferase (39.3%).ConclusionPralsetinib was effective in RET fusion-positive NSCLC with tolerable AEs in real-world practice. Efficacy of pralsetinib was decreased in patients previously treated with PBC, immunotherapy, or MKIs.

The Scope of Nurses' Assessment of Deteriorating Patients in Coronary Care Units: A Mixed Methods Study.

Despite the high acuity of coronary care unit (CCU) patients and their risk of deterioration, little is known about how nurses assess them. Increase understanding of the scope of nurses' assessments of deteriorating CCU patients. Online mixed methods survey. The mRAPIDS (modified Rescuing a Patient in Deteriorating Situations) tool was used to measure assessment scope in responses to a patient vignette with a higher mRAPID score signalling broader scope (maximum score 24). Reflections on day-to-day practice were collected concurrently and thematically analysed. Themes were integrated with scores using a joint display table and organised into domains. Comparing 'fit' between data showed expansion (overlap with broader nonoverlapping findings) and disconcordance (contradictory findings). Thirty-four nurses responded, and scope of assessment was found to be narrow (median mRAPIDS 5). Two domains were identified that helped explain this finding 'the act of assessment' and 'education and experience'. Participants emphasised the importance of education and experience, neither increased assessment scope. This study showed that participant assessments were generally narrower than widely accepted best practice (ABCDE assessment). Participant assessments did not reflect gold standard A-E assessment, which may partly reflect a need for assessment frameworks that are more compatible with real-world practice. Further research is required to understand the role of healthcare assistants in the care of deteriorating CCU patients. Clinical judgement is important, but not yet well understood in rapid response systems. This study offers preliminary understanding of nurses' assessments of deteriorating patients in CCUs. American Psychological Association, Mixed Methods Standards. Reviewed protocol, aided result interpretation and shared ideas for future research.

Patient reported outcome measures in cardiovascular research and care: PRO(M)s and CONS.

Patient-reported outcome measures (PROMs) are vital tools in cardiovascular disease (CVD) research and care, providing insights that complement traditional clinical outcomes like mortality and morbidity. PROMs capture patient experiences with CVD, such as quality of life, functional capacity, and emotional well-being, allowing clinicians to assess how interventions impact daily life. PROMs are integral to cardiovascular investigations as well as management, especially in chronic conditions and rehabilitation, where they inform on the impact of personalized care plans by tracking symptom progression and patient adherence. Selecting and applying to cardiovascular research and practice effective PROMs involves evaluating their validity, reliability, and sensitivity to change, with instruments like the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Seattle Angina Questionnaire (SAQ) widely used for heart failure and coronary artery disease, respectively. Implementing PROMs in real-world practice requires addressing challenges related to workflow integration and patient adherence, emphasizing their value in patient-centered care. As digital health advances, remote PROM data collection through mobile applications and wearable devices will enhance access to and extent of PROMs, and AI-driven analytical tools will provide real-time, automated and plausible more poignant insights for personalized treatment. Future efforts should focus on culturally adapting PROMs for diverse populations to ensure global applicability. PROMs should also be established as essential components of innovative research and responsive, patient-centered cardiovascular care.