Real-world Data Research Articles

Ocular adverse events associated with GLP-1 receptor agonists: a real-world study based on the FAERS database and network pharmacology

ABSTRACT Objective This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) using data from the FDA Adverse Event Reporting System (FAERS) and network pharmacology methods. Methods FAERS data from 2004 to 2024 were analyzed for ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis (Reporting Odds Ratio, ROR) was used to identify signals, and a drug-gene interaction network explored potential mechanisms. Results Among 17,785,793 FAERS reports, semaglutide and lixisenatide were significantly associated with ocular AEs, with RORs of 1.25 (95% CI, 1.20-1.31) and 1.96 (95% CI, 1.70-2.27), respectively. Commonly reported AEs included blurred vision, visual impairment, and diabetic retinopathy, with some AEs occurring as early as 10 days after treatment initiation. Gene enrichment analysis highlighted potential links between GLP-1-related genes and ocular AEs. Conclusion The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.

Evolution of Real-World Clinical Practice in Time to Surgery Following Thoracolumbar Spinal Cord Injury: An Observational Study of North American Trauma Centers from 2010 to 2020.

This study aims to estimate real-world clinical practice trends in time to surgery following thoracolumbar spinal cord injury (SCI) in trauma centers across North America over the last decade (2010-2020). A multi-center retrospective observational study was conducted using Trauma Quality Improvement Program data from 2010 to 2020. All surgically treated patients with thoracic and lumbar SCI were included. Descriptive plots and a multivariable Poisson regression model with time to spine surgery as the primary outcome were constructed. This study included 4350 adult patients with complete SCI surgically treated across 449 trauma centers. Within this group, 3978 (91.4%) patients were diagnosed with thoracic SCI and 372 (8.6%) patients were diagnosed with lumbar SCI. The overall mean time to surgery was 31.6 h (±34.1). Early surgery (≤24 h) was performed in 2599 patients (59.7%). An estimated annual reduction of 1.6 h in time to surgery was demonstrated over the study period, starting initially at a mean of 47.6 h (±40.6) in 2010, and reaching a mean of 25.3 h (±30) in 2020. Multivariable Poisson regression adjusting for patient, injury, and institution confounders, demonstrated a significant decrease in time to surgery by 5% per year over the study period (incidence rate ratios [IRR] = 0.95, 95% confidence interval [CI]: 0.93-0.96). Moreover, in a secondary analysis including 3270 patients with incomplete thoracolumbar SCI, a comparable significant annual reduction in time to surgery was demonstrated (IRR = 0.93, 95% CI: 0.91-0.94). This study provides real-world data on practice pattern trends with respect to time to spine surgery following traumatic thoracolumbar SCI. Over the years from 2010 to 2020, we found a significant reduction in time to surgery across trauma centers in North America.

Real-world data of perioperative complications in prepectoral implant-based breast reconstruction: a prospective cohort study.

To analyze complications and potential risk factors associated with immediate prepectoral direct-to-implant breast reconstruction (DTIBR). 295 patients (326 operated breasts) with DTIBR between March 2021 and December 2023 were included in this prospective study. Postoperative complications (postoperative bleeding, seroma, infection, necrosis, wound dehiscence, implant exchange/loss) were analyzed for potential risk factors by descriptive and logistic regression analyses. The implant was covered by TiLOOP® Bra Pocket in 227 breasts (69.6%), by "dual-plane" technique in 20 breasts (6.1%), by acellular dermal matrix (ADM) in 1 breast (0.3%). No additional support was used for 78 breasts (23.9%). The use of mesh did not increase the risk for complications. Major complications requiring surgical revision occurred due to postoperative bleeding in 22 (6.7%), seroma in 2 (0.6%), infection in 13 (4.0%), necrosis in 10 (3.1%), and wound dehiscence in 10 (3.1%) breasts. Thirteen (4.0%) implants were exchanged, and 5 (1.5%) were explanted without substitution. One patient had to switch to autologous reconstruction due to skin necrosis. The main reasons for the removal/exchange of implants were infections (11 breasts, 3.4%) and necrosis (4 breasts, 1.2%). The risk for necrosis, infection, and wound dehiscence was mainly associated with the type of incision, especially skin-reducing incisions, and body mass index (BMI) ≥ 30kg/m2. Severe complications occurred primarily in patients with a BMI ≥ 30kg/m2 and when skin-reducing surgical techniques were performed. This study was retrospectively registered at the German Clinical Trials Register (DRKS) on 20.06.2024. DRKS00034493. https://drks.de/search/de/trial/DRKS00034493 .

American Foregut Classification is Superior to Hill Classification in Evaluation of the Gastroesophageal Junction

Background: The American Foregut Society (AFS) classification is intended to be more comprehensive and accurate than the Hill grade in assessing the gastroesophageal junction. However, real-world data regarding predictive ability and interobserver variability are limited. Methods: We performed a multi-reader validation study on images collected from patients who underwent endoscopic evaluation of reflux with hernia provocation using both AFS and Hill classification. The primary outcome was inter-reader agreement, assessed using Fleiss K. Secondary outcomes were percentage of patients with pathologic reflux at each Hill grade or AFS grade, correlation between acid exposure time (AET) and individual components of the AFS grade, and difference in predictive ability based on expert versus non-expert graders. Results: Sixty-four eligible patients were identified. Inter-rater reliability was substantial for AFS classification ( K = 0.65) and fair for Hill classification ( K= 0.28). The AFS grade demonstrated moderate overall correlation with AET (ρ = .36) and the Hill grade demonstrated overall weak correlation (ρ = .28). No single component of the AFS score performed significantly better in predicting pathologic reflux than the AFS grade (AFS F = 9.93, P = .0025) and there was no significant difference in overall grading between expert- and non-expert readers (ρ = .38 vs ρ = .29). Conclusion: The AFS score can classify the GEJ with moderate interobserver agreement and is superior to the Hill grade in predicting acid exposure time. AFS grade has better predictive power than the individual components used in scoring and is robust to differences in reader experience.

Neuroendocrine tumours and pregnancy: Real-world data from an European Neuroendocrine Tumour Centre of Excellence.

Neuroendocrine neoplasms (NENs) arise from the diffuse endocrine system and have been considered to be rare. However, the incidence and prevalence of these tumours have increased in recent years, and they are being seen in younger patients including women in the reproductive age group. Due to the paucity of data, diagnostic and therapeutic strategies in managing such tumours during pregnancy can be challenging to both treating physicians and patients. This article describes the experience and outcomes of managing pregnant women with NEN at a European Neuroendocrine Tumour Society (ENETS) Centre of Excellence. In this retrospective analysis, we evaluated a total of 22 pregnancies in 18 pregnant women with concurrent diagnoses of NENs who were managed at Royal Free Hospital ENETS Centre of Excellence throughout their pregnancy. These were identified from our tumour registry of 3500 NEN patients between 2015 and 2023. Cross-sectional imaging (computed tomography (CT)/magnetic resonance imaging (MRI)), pre- and post-pregnancy, for each patient was reviewed by an experienced radiologist. Tumour growth rate (TGR) was calculated using the formula: TGR = 100 × [exp (TG) - 1]; TG. [3 × log (D2/D1)]/time (months), where D1 is the tumour size at date 1; D2 is the tumour size at date 2; and time (months) = (Date 2 - Date 1 + 1)/30.44. Tumour growth rate pre-conception (TGRpc) and tumour growth rate post-partum (TGRpp) were calculated for each patient. In a sub-group of patients, positivity for oestrogen and progesterone receptors were analysed on the tumour tissue to evaluate whether the presence of these receptors affected tumour progression during the pregnancy. We also reviewed the pregnancy outcome in patients treated with somatostatin analogues during pregnancy. We analysed the data of a total 22 pregnancy encounters in 18 women: 15 pregnancies (68%) preceded the diagnosis of the NEN, whereas the diagnosis of NEN was made during pregnancy or in the post-partum period in 5 (23%) and 2 (9%) pregnancies respectively. Eight patients (44%) had a diagnosis of a pancreatic NEN, whereas 5 (28%) were diagnosed with mid-gut NENs, and a further 5 at other sites. The majority of the patients (n = 12, 67%) had evidence of metastatic disease at the time of diagnosis. Most pregnancies had a successful outcome (n = 19, 86%), whereas 3 patients (14%) had miscarriages in the 1st trimester. Five patients in total of 6 pregnancies were treated with somatostatin analogues as monotherapy during the pregnancy, and all of them had stable disease after pregnancy. All of them delivered healthy babies without any side effects or complications due to therapy. The average TGRpc was -0.8% (n = 5) and the average TGRpp was +0.96% (n = 6); 2 patients who did not have suitable targets for calculation of TGRpc developed new lesions suggesting disease progression. Moreover, 2 of the 4 patients who have had both pre-conception and post-pregnancy scans showed an increase in TGRpp compared to TGRpc. The management of NENs during pregnancy should be multidisciplinary with an individualised approach to each patient. Somatostatin analogues appear to be safe during pregnancy, though further robust studies are needed. Pregnancy per se may accelerate tumour progression, and patients should be counselled regarding this possibility.

Portable Gait Analysis of Patients With Rotating Hinge Knee Megaprosthesis Compared With Total Knee Arthroplasty.

The gait analysis of patients after surgery for tumors around the knee joint relies on the use of a three-dimensional motion capture system. However, obtaining long-term, free-standing, real-world gait data with three-dimensional gait analysis is challenging. In this study, we utilized a portable gait analyzer to collect gait data from patients who underwent rotating hinge knee megaprosthesis (RHK) and total knee arthroplasty (TKA), this study aims to compare via gait analysis patients who underwent megaprosthesis with patients with TKA. A retrospective study was conducted on eight patients with knee bone tumors (RHK group) and ten patients with knee osteoarthritis who underwent standard TKA (TKA group) from January 2018 to January 2022. Gait analysis, was conducted using the Intelligent Device for Energy Expenditure and Activity (IDEEA), and the results were compared with those of a healthy control group. The lower limb alignment of the RHK and TKA groups was evaluated, and the KSS scores of the two groups were collected and compared. Energy consumption during a 20-m walk was measured and compared among the RHK, TKA, and healthy control groups using one-way ANOVA. Paired t-tests were used to compare the operated and nonoperated limbs within groups. All patients exhibited slower walking speeds and cadence than the healthy control participants (p < 0.01), While no significant differences were found between the RHK and TKA groups. The single support time (521.15 ± 94.56 ms) of the RHK-operated limb was significantly shorter than that of the nonoperated limb (576.53 ± 77.40 ms, p = 0.004). The pulling acceleration of the RHK group (0.71 ± 0.27 G) was lower than that of the TKA group (1.04 ± 0.31 G, p = 0.029). The push-off angle in the RHK group (24.91° ± 10.91°) was significantly greater than that in the TKA group (10.64° ± 5.41°, p = 0.007). The RHK group showed significant differences between the operated and nonoperated limbs in terms of swing power, ground impact, footfall, and push-off. The RHK (0.03 ± 0.01 kcal/min/kg) and TKA (0.029 ± 0.01 kcal/min/kg) groups had significantly greater energy expenditures than did the healthy control group (0.02 ± 0.00 kcal/min/kg, p < 0.05). The comparison of HKA angles and KSS scores between the TKA and RHK groups showed statistically significant differences. A portable gait analyzer appears to be suitable for evaluating the effects of RHK. RHK patients demonstrate more pronounced gait abnormalities than TKA patients, reflected in greater energy expenditure, implying reduced walking efficiency. This suggests the need for increased energy expenditure in RHK patients to compensate for abnormal knee joint conditions during walking and maintain body balance.

Real-World Evidence: Integrating Machine Learning with Real-World Big Data for Predictive Analytics in Healthcare.

Real-World Evidence: Integrating Machine Learning with Real-World Big Data for Predictive Analytics in Healthcare.

Multi-label text classification via secondary use of large clinical real-world data sets.

Procedural coding presents a taxing challenge for clinicians. However, recent advances in natural language processing offer a promising avenue for developing applications that assist clinicians, thereby alleviating their administrative burdens. This study seeks to create an application capable of predicting procedure codes by analysing clinicians' operative notes, aiming to streamline their workflow and enhance efficiency. We downstreamed an existing and a native German medical BERT model in a secondary use scenario, utilizing already coded surgery notes to model the coding procedure as a multi-label classification task. In comparison to the transformer-based architecture, we were levering the non-contextual model fastText, a convolutional neural network, a support vector machine and logistic regression for a comparative analysis of possible coding performance. About 350,000 notes were used for model adaption. By considering the top five suggested procedure codes from medBERT.de, surgeryBERT.at, fastText, a convolutional neural network, a support vector machine and a logistic regression, the mean average precision achieved was 0.880, 0.867, 0.870, 0.851, 0.870and0.805 respectively. Support vector machines performed better for surgery reports with a sequence length greater than 512, achieving a mean average precision of 0.872 in comparison to 0.840 for fastText, 0.837 for medBERT.de and 0.820 for surgeryBERT.at. A prototypical front-end application for coding support was additionally implemented. The problem of predicting procedure codes from a given operative report can be successfully modelled as a multi-label classification task, with a promising performance. Support vector machines as a classical machine learning method outperformed the non-contextual fastText approach. FastText with less demanding hardware resources has reached a similar performance to BERT-based models and has shown to be more suitable for explaining the predictions efficiently.

Efficacy and safety of prostatic urethral lift according to preoperative urinary retention and prostate volume: A Japanese real-world multicenter data.

Prostatic urethral lift (PUL) for benign prostatic hyperplasia has recently been initiated in Asia; therefore, few studies with real-world data have been reported. This study evaluated the efficacy and safety of PUL using Japanese real-world multicenter data. Indications for PUL were based on relevant guidelines in Japan. The preoperative patient status, postoperative progress at 1 and 3 months, and perioperative complications were evaluated. Also, we compared preoperative urinary retention and nonurinary retention patients, and prostate volumes <30, 30 to <50, and ≥50 mL. A total of 160 patients were included in the study. The mean age was 75 years and the mean prostate volume was 44 mL. The International Prostate Symptom Score, quality of life score, maximum flow rate, and postvoid residual volume significantly improved 1 and 3 months postoperatively compared to preoperatively. The catheter-free rates in the preoperative urinary retention group were 58.1%, 72.1%, 83.7%, and 88.4% on postoperative days 1, 7, 30, and 90, respectively. The catheter-free rates in the nonurinary retention group were 94.9%, 98.3%, and 100% on postoperative days 1, 7, and 14, respectively. The group with a prostate volume ≥50 mL had a longer operation time and used significantly more implants; however, no difference was observed in the postoperative urinary status among the three groups. PUL can be considered a safe and effective procedure for both preoperative urinary retention and nonurinary retention patients with prostate volumes <100 mL in older patients with comorbidities.

Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Results of Polish multicenter observational study.

Patients with head and neck squamous cell carcinoma (HNSCC) who have progressed following primary treatment (PT) have a poor prognosis. In this group, nivolumab has been demonstrated to significantly improve outcomes. This study presents the efficacy of nivolumab in Polish patients with recurrent and/or metastatic (R/M) HNSCC using real-world data. The analyzed group consisted of 324 adult patients with R/M HNSCC following platinum-based therapy. Patients were divided into 3 groups based on the time from completion of PT to nivolumab initiation (tPT-N): within 6 months (refractory), between 6 and 24 months (sensitive, tPT-N ≤24), and beyond 24 months (sensitive, tPT-N >24). Survival analysis and the Cox proportional hazards model were performed to evaluate how various risk factors affect patient outcomes. The 1-year and 2-year overall survival (OS) was 19.1%, 6.1%, 30.7%, 9.4%, and 45.7%, 29.1% in refractory, sensitive tPT-N ≤24, sensitive tPT-N >24 patients, respectively and was higher for both sensitivity groups vs. refractory (p = .004) and for sensitive tPT-N >24 versus refractory and sensitive tPT-N ≤24 (p <.001). Patients with nasopharyngeal cancer had OS significantly higher than patients with other primary tumor localization. The multivariate Cox analysis showed a significant favorable effect of tPT-N >24 (HR = 0.53, p = .001) and nasopharyngeal cancer on OS (HR = 0.20, p = .008). Conversely, female sex was identified as an unfavorable factor for OS (HR = 1.48, p = .020). In our study, we established that the benefit of nivolumab increases with the increasing tPT-N. The probability of death is significantly lower in male patients and patients with nasopharyngeal cancer regardless of tPT-N.

Cost-Effectiveness of Pembrolizumab as First-Line Treatment in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer in the United States.

First-line treatment of persistent, recurrent, or metastatic (advanced) cervical cancer in patients who have a combined positive score (CPS) ≥ 1 with pembrolizumab + chemotherapy versus standard-of-care chemotherapy provides meaningful improvements in overall survival. We conducted a cost-effectiveness analysis from a US payer perspective. A societal perspective scenario was also considered, including productivity gains. The cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy was assessed using a state-transition model comprising the health states "pre-progression," "post-progression," and "death," with a 1-week cycle length and 50-year time horizon. Patient-level KEYNOTE-826 data informed the efficacy, safety, and health-related quality of life of pembrolizumab + chemotherapy versus chemotherapy at first-line and subsequent treatments. Real-world data were sought to cost subsequent treatments according to US clinical practice. Transition probabilities were derived from parametric survival models fit to time-to-progression, progression-free survival, and post-progression survival patient-level KEYNOTE-826 data. Sensitivity analyses explored the impact on outcomes from variables such as bevacizumab use. According to the state-transition model, pembrolizumab + chemotherapy extended mean life expectancy versus chemotherapy from 1.8 to 6.7 life-years. The mean gain of 4.9 life-years/patient was mostly caused by pembrolizumab delaying progression. Total discounted quality-adjusted life-years (QALY) were 5.0 and 1.3 per patient for pembrolizumab + chemotherapy and chemotherapy, respectively (mean gain: 3.7 QALY/patient). Pembrolizumab + chemotherapy had comparable safety outcomes to chemotherapy alone. Total costs incurred were US $320,247 (pembrolizumab + chemotherapy) versus US $105,446 (chemotherapy; mean incremental costs: US $214,801/patient). The incremental cost-effectiveness ratio of pembrolizumab + chemotherapy versus chemotherapy was US $58,446/QALY. Sensitivity analyses showed results were insensitive to bevacizumab use. Including productivity gains led to an incremental cost-effectiveness ratio of US $58,385 per QALY. Our model-based analysis suggests that first-line treatment of pembrolizumab + chemotherapy in advanced cervical cancer with a CPS ≥ 1 offers a substantial clinical benefit over standard-of-care chemotherapy alone and is cost-effective at a willingness-to-pay threshold of US $150,000. The approximate doubling of life-years and QALYs associated with pembrolizumab + chemotherapy represents a step improvement in the treatment of advanced cervical cancer. ClinicalTrials.gov Identification Number: NCT03635567.

Learning Dynamic Selection and Pricing of Out-of-Home Deliveries

Home delivery failures, traffic congestion, and relatively large handling times have a negative impact on the profitability of last-mile logistics. A potential solution is the delivery to parcel lockers or parcel shops, denoted by out-of-home (OOH) delivery. In the academic literature, models for OOH delivery are so far limited to static settings, contrasting with the sequential nature of the problem. We model the sequential decision-making problem of which OOH location to offer against what incentive for each incoming customer, taking into account future customer arrivals and choices. We propose dynamic selection and pricing of OOH (DSPO), an algorithmic pipeline that uses a novel spatial-temporal state encoding as input to a convolutional neural network. We demonstrate the performance of our method by benchmarking it against two state-of-the-art approaches. Our extensive numerical study, guided by real-world data, reveals that DSPO can save 19.9 percentage points (%pt) in costs compared with a situation without OOH locations, 7%pt compared with a static selection and pricing policy, and 3.8%pt compared with a state-of-the-art demand management benchmark. We provide comprehensive insights into the complex interplay between OOH delivery dynamics and customer behavior influenced by pricing strategies. The implications of our findings suggest that practitioners adopt dynamic selection and pricing policies. History: This paper has been accepted for the Transportation Science special issue on TSL Conference 2023. Funding: This work was supported by TKI DINALOG.

Serum triglyceride to high density lipoprotein cholesterol ratio in late pregnancy as a potential predictor of adverse birth outcomes: an analysis of real-world data

BackgroundThe association between serum triglyceride to high density lipoprotein cholesterol ratio (THR) in late pregnancy and adverse birth outcomes (ABO) remains controversial because of inconsistent results. The present study assessed the association between maternal serum THR and incidence of ABO [preterm birth (PTB), small and large for gestational age (SGA/LGA), low birth weight (LBW) and macrosomia] in a Chinese population.MethodsA total of 11,553 consecutive participants from a real-world database with data on lipid profiles and birth outcomes were included. Logistic regression models were applied to assess the association between THR and incident ABO. Mediation analysis was performed to investigate the contribution of pregnancy complications [gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP) and pre-eclampsia (PE)] to this association.ResultsApproximately 6.6% (762/11,553), 8.9% (1023/11,553), 15.5% (1792/11,553), 4.3% (494/11,553), and 7.4% (851/11,553) of individuals developed PTB, SGA, LGA, LBW and macrosomia, respectively. Significant trends across the quintiles of THR toward decreasing incidence of SGA and LBW and increasing incidence of LGA and macrosomia were observed. The multivariate-adjusted odds ratios (OR) in the top quintile of serum THR (> 3.16) versus the bottom quintile (< 1.44) were 0.52 for PTB, 0.48 for SGA, 0.64 for LBW, 2.80 for LGA and 3.80 for macrosomia, respectively. A 1-standard deviation (SD) increase in serum THR was associated with decreased risk of PTB [OR = 0.84, 95% confidence interval (CI): 0.76–0.93), SGA (OR = 0.71, 95% CI:0.65–0.78) and LBW (OR = 0.76, 95% CI:0.65–0.90) and increased risk of LGA (OR = 1.40, 95% CI:1.32–1.49) and macrosomia (OR = 1.49, 95% CI:1.38–1.62). In mediation analyses, PE mediated − 19.8%, -10.6% and − 24.6% of THR-associated PTB, SGA and LBW, respectively, GDM accounted for − 3.7%, 6.8% and 4.3% of THR-associated PTB, LGA and macrosomia, respectively, and ICP explained − 1.9% and − 2.1% of THR-associated PTB and LBW, respectively. In addition, incorporating THR to ABO predictive models significantly improved the area under the curve for SGA (0.743 vs. 0.753, P < 0.001), LGA (0.734 vs. 0.745, P < 0.001) and macrosomia (0.786 vs. 0.800, P < 0.001).ConclusionReal-world data showed an association between serum THR in late pregnancy and ABO risk, and this association may be partially mediated by prevalent pregnancy complications (PE/GDM/ICP), suggesting a potential role of THR in predicting ABO (SGA/LGA/macrosomia).

Retrospective Analysis of RSV Infection in Pediatric Patients: Epidemiology, Comorbidities, Treatment, and Costs in Dubai (2014-2023)

Background: Infections attributable to respiratory syncytial virus (RSV) are a major cause of hospitalization among young children worldwide. Despite substantial clinical and economic burden, real-world data associated with RSV infections in the United Arab Emirates (UAE) are limited. Objectives: This study aimed to assess among children (&lt;18 years) diagnosed with RSV the epidemiology, seasonality, comorbidities, treatment patterns, length of hospital stay, healthcare resource utilization (HCRU), and costs associated with pediatric infection in Dubai, UAE. Methods: This 10-year retrospective cohort study (Jan. 1, 2014–Sept. 30, 2023) utilized Dubai Real-World Database, a private insurance claims database. Patients aged &lt;18 years with a first-episode diagnosis claim (primary or secondary, or a hospital admission) for RSV any time during the index period (Jan. 1, 2014–June 30, 2023) were included. Outcomes were analyzed during a 3-month follow-up. Patients were stratified into 3 cohorts: Cohort 1 (&lt;2 years), Cohort 2 (2 to &lt;6 years), and Cohort 3 (6 to &lt;18 years). Results: Of 28 011 patients identified, 25 729 were aged &lt;18 years with RSV infection. An increasing trend in reported cases was observed from 2014 to 2022, with an average annual increase of 55%. Half of study patients (49.3%) belonged to Cohort 1, with a mean age of 0.6 years, while less than 2% had known risk factors and 22% of the patients in cohort 1 were hospitalized. In Cohort 1, 32.0% had upper respiratory tract infections, 39.4% had lower respiratory tract infections, and 44.4% of patients had an “other respiratory disease.” The average length of hospitalization was about 4 days across all cohorts. The total hospitalization cost was highest in patients &lt;2 years, amounting to US $9 798 174 (median, US $2241.30). Conclusion: Among the RSV patients, 49.3% were &lt;2 years of age and few had recognized risk factors. Among patients &lt;2 years, 22% were hospitalized, with an average hospital stay of 4 days; the cost of hospitalization totaled US $9 798 174. These findings can inform healthcare stakeholders about future policy measures and the need for effective preventive strategies.

Utilization of Syndromic Vaginitis Diagnostic Testing Reduces 6-Month Follow-Up Outpatient Service Healthcare Costs—A Real-World Data Analysis

Background/Objectives: Vaginitis is a common infection among women of reproductive age. Although various diagnostic methodologies exist, diagnosis without the utilization of available diagnostic tests remains prevalent. This study aimed to assess downstream healthcare utilization and the cost of patients with and without diagnostic testing. Methods: This retrospective, observational study utilized the IQVIA PharMetrics® Plus database from July 2020 to October 2023. Patients with an index claim (ICD-10 code indicating vaginitis) were categorized into two cohorts: those who received a syndromic polymerase chain reaction (PCR) test and those who had no documented test on the index date or within two days. Total and service-specific healthcare resource utilization and costs were assessed for 6 months following the index event. This study was designed to inform how Syndromic Vaginitis PCR testing is used to make treatment decisions and to track outpatient and inpatient healthcare utilization for 6 months post index date represented by cost. Results: Patients who received a Syndromic Vaginitis PCR test had significantly fewer outpatient medical services in the 6 months following initial diagnosis compared to those who received no diagnostic test. This was largely attributed to a substantial decrease in other medical service visits, resulting in mean cost savings of USD 2067 (Syndromic PCR = USD 6675, SD = USD 17,187; No Test = USD 8742, SD = USD 29,894) (p-value 0.0009). Conclusions: Many vaginitis patients do not receive testing, but Syndromic Vaginitis PCR testing may be an effective diagnostic tool for reducing costs associated with vaginitis infections.

Adversarial Attacks and Defenses in Multivariate Time-Series Forecasting for Smart and Connected Infrastructures

The emergence of deep learning models has revolutionized various industries over the last decade, leading to a surge in connected devices and infrastructures. However, these models can be tricked into making incorrect predictions with high confidence, leading to disastrous failures and security concerns. To this end, we explore the impact of adversarial attacks on multivariate time-series forecasting and investigate methods to counter them. Specifically, we employ untargeted white-box attacks, namely the Fast Gradient Sign Method (FGSM) and the Basic Iterative Method (BIM), to poison the inputs to the training process, effectively misleading the model. We also illustrate the subtle modifications to the inputs after the attack, which makes detecting the attack using the naked eye quite difficult. Having demonstrated the feasibility of these attacks, we develop robust models through adversarial training and model hardening. We are among the first to showcase the transferability of these attacks and defenses by extrapolating our work from the benchmark electricity data to a larger, 10-year real-world data used for predicting the time-to-failure of hard disks. Our experimental results confirm that the attacks and defenses achieve the desired security thresholds, leading to a 72.41% and 94.81% decrease in RMSE for the electricity and hard disk datasets respectively after implementing the adversarial defenses.

Real-World Comparison of Oral Versus Injectable Semaglutide for the Reduction of Hemoglobin A1C and Weight in Patients with Type 2 Diabetes

Background: No head-to-head comparisons of semaglutide formulations currently exist in the literature. In practice, many may think that oral and injectable semaglutide formulations are interchangeable, although there is currently limited real-world data to determine whether this is accurate. Objective: The purpose of this study was to determine the effect of oral versus injectable semaglutide on hemoglobin A1C (HbA1C) and weight in patients with type 2 diabetes (T2D). Methods: This was a retrospective single-center review of adult patients who had a diagnosis of T2D and were treated with oral or injectable semaglutide between November 1, 2019, and July 31, 2022. Primary outcome was a comparison of changes in HbA1C (%) and weight (kg) from baseline to 6 months between patients receiving oral versus injectable semaglutide, stratified according to highest dose received. Secondary outcomes included frequency of dose reductions and discontinuations, achievement of clinical goals, and presence of an embedded clinical pharmacist at patients’ primary care office. Results: A total of 105 patients were included. Patients experienced mean decreases in HbA1C and weight from baseline to 6 months of −1.75% ( P &lt; 0.001) and −3.64 kg ( P = 0.015), respectively, in the oral semaglutide group and −1.35% ( P &lt; 0.001) and −5.26 kg ( P &lt; 0.001), respectively, in the injectable semaglutide group. When directly comparing semaglutide formulations, oral semaglutide demonstrated a 0.4% greater numerical reduction in HbA1C ( P = 0.523) and injectable semaglutide demonstrated a 1.62-kg greater numerical reduction in weight ( P = 0.312). Adverse events (AEs) occurred more frequently with oral semaglutide than with injectable semaglutide (16.7% vs 4.9%). Discontinuation due to AEs was more common with oral semaglutide. Conclusion: In this study, patients with T2D who received oral semaglutide demonstrated greater reductions in HbA1C, whereas those treated with injectable semaglutide had greater reductions in weight, although there were no statistically significant reductions in HbA1C or weight between the 2 formulations. Rates of AEs and discontinuation were more common in the oral semaglutide group.

Treatment satisfaction in patients with hidradenitis suppurativa: A real-world survey from the EU5 and US.

Introduction Hidradenitis suppurativa (HS) is a debilitating, inflammatory skin disorder. Treatment strategies in patients with HS are challenging; real-world evidence in a HS population is warranted for greater disease understanding. The objective of this analysis was to describe real-world treatment patterns and treatment satisfaction in patients with HS. Methods This was a cross-sectional market research survey with retrospective data collection in patients with HS from the United States and five European countries (France, Germany, Italy, Spain, United Kingdom) between November 2020 and April 2021, using physician- and patient-reported surveys. Eligible physicians were general dermatologists actively managing patients with HS; dermatologists were required to have consulted with ≥2 patients with HS in the previous 12 months. Adult (≥18 years) and adolescent (10‒17 years) HS patients visiting a participating dermatologist were included. Outcomes included treatment patterns, flare status, treatments prescribed in response to flares, previous surgeries, barriers to biologics, and patient- and physician-reported satisfaction with the disease control provided by treatment. Results Survey data from 1787 patients were collected from 312 dermatologists. The most frequently prescribed treatments were topicals, oral antibiotics, and antiseptic washes/creams at diagnosis and sampling. At sampling, biologics were more frequently prescribed in patients with more severe disease (prescribed in 26.6%, 31.0% and 52.4% of patients with mild, moderate, and severe disease, respectively); oral antibiotics (48.8%), topicals (37.4%), and biologics (34.3%) were the most frequently prescribed treatment classes in response to a flare. Of patients currently not receiving a biologic, dermatologists reported that 18.9% of patients' condition warranted their use. Approximately one quarter of dermatologists (24.5%) and patients (27.4%) were not satisfied with current treatment; of patients who were dissatisfied, 12.8% reported they would never raise their dissatisfaction with their doctor. Conclusion These real-world data suggest a high disease burden and potential undertreatment in patients with HS. Patients received multiple treatments, and a notable proportion underwent surgery. Robustly integrating the patient voice in HS treatment decisions may lead to better outcomes and improved treatment satisfaction.

Retrospective Analysis of RSV Infection in Pediatric Patients: Epidemiology, Comorbidities, Treatment, and Costs in Dubai (2014-2023)

Background: Infections attributable to respiratory syncytial virus (RSV) are a major cause of hospitalization among young children worldwide. Despite substantial clinical and economic burden, real-world data associated with RSV infections in the United Arab Emirates (UAE) are limited. Objectives: This study aimed to assess among children (&lt;18 years) diagnosed with RSV the epidemiology, seasonality, comorbidities, treatment patterns, length of hospital stay, healthcare resource utilization (HCRU), and costs associated with pediatric infection in Dubai, UAE. Methods: This 10-year retrospective cohort study (Jan. 1, 2014–Sept. 30, 2023) utilized Dubai Real-World Database, a private insurance claims database. Patients aged &lt;18 years with a first-episode diagnosis claim (primary or secondary, or a hospital admission) for RSV any time during the index period (Jan. 1, 2014–June 30, 2023) were included. Outcomes were analyzed during a 3-month follow-up. Patients were stratified into 3 cohorts: Cohort 1 (&lt;2 years), Cohort 2 (2 to &lt;6 years), and Cohort 3 (6 to &lt;18 years). Results: Of 28 011 patients identified, 25 729 were aged &lt;18 years with RSV infection. An increasing trend in reported cases was observed from 2014 to 2022, with an average annual increase of 55%. Half of study patients (49.3%) belonged to Cohort 1, with a mean age of 0.6 years, while less than 2% had known risk factors and 22% of the patients in cohort 1 were hospitalized. In Cohort 1, 32.0% had upper respiratory tract infections, 39.4% had lower respiratory tract infections, and 44.4% of patients had an “other respiratory disease.” The average length of hospitalization was about 4 days across all cohorts. The total hospitalization cost was highest in patients &lt;2 years, amounting to US $9 798 174 (median, US $2241.30). Conclusion: Among the RSV patients, 49.3% were &lt;2 years of age and few had recognized risk factors. Among patients &lt;2 years, 22% were hospitalized, with an average hospital stay of 4 days; the cost of hospitalization totaled US $9 798 174. These findings can inform healthcare stakeholders about future policy measures and the need for effective preventive strategies.

Management of Adult Patients with Newly Diagnosed or Relapsed Primary Immune Thrombocytopenia in Eastern Austria.

Treatment sequence in primary immune thrombocytopenia (ITP) is based on national and international recommendations, treatment availability, and physician expertise. This article aimed to provide real-world data on treatment sequence and responses to first- and second-line treatments in newly diagnosed and relapsed adult ITP patients. We analyzed a cohort of 46 adult ITP patients from the Vienna ITP Biobank, who started first-line therapy within 1 week before their first study visit between February 2016 and March 2023. We investigated clinical patient characteristics and patient management in our specialized center and examined the impact of the international ASH guidelines on ITP treatment. Forty-six primary ITP patients, 27 (58.7%) with newly diagnosed ITP and 19 (41.3%) with relapsed ITP, were investigated. Most patients were female (65.2%) with a median platelet count of 9 × 109/L, and 31 patients (67.4%) had bleeding symptoms. All patients received first-line treatment with oral prednisolone; 15 patients received oral prednisolone combined with intravenous immunoglobulins (IVIGs), which were more commonly administered in newly diagnosed than in relapsed ITP patients. First-line therapy resulted an overall response in 82.6% of patients after a median (interquartile range [IQR]) time of 10 (5-25) days. There was no difference in treatment responses between newly diagnosed and relapsed ITP patients, but newly diagnosed patients had a shorter time to response (median [IQR]: 8 [5-14] and 14 [8-27], p = 0.02). Twenty-three (50%) of the patients (11/27 newly diagnosed [40.7%], 12/19 relapsed [63.2%]) required second-line ITP therapy. Thrombopoietin-receptor agonists (TPO-RAs) were the most commonly used second-line therapy with a response rate of 73.7%, and a median (IQR) time to treatment response of 15 (12-20) days. Overall response rates to TPO-RA treatment did not differ between newly diagnosed and relapsed ITP. Following the publication of novel guidelines in 2019, the median (IQR) duration of corticosteroid treatment shortened (100-52 days, p = 0.01), as did the time to second-line treatment (160-47 days, p = 0.01), and the median number of first-line therapies decreased from 2 (1-3) to 1 (1-2). Initial treatment with corticosteroids was effective in the majority of newly diagnosed and relapsed ITP. Response rates to initial corticosteroid treatment in ITP patients are consistent with previous data, but only 50% achieve sustained remission. TPO-RAs, which are well tolerated and effective, are the most commonly used second-line therapy in our study population. International guidelines have led to faster treatment transitions and reduced splenectomy rates. Integration of real-life experience, expert consensus, and guidelines optimizes ITP patient management.