Typical Clinical Setting Research Articles

HPB O03 - Snapshot Audit of RELEVANCE: REal worLd outcomEs of adjuVant therapy in pANcreatic CancEr

Abstract Background Evidence-based medicine plays a critical role in shaping clinical practices and setting patient expectations. While randomized controlled trials (RCTs) of adjuvant chemotherapy in pancreatic cancer have demonstrated improved survival rates with newer regimens, their selective inclusion criteria often favor patients with better prognoses. This study aims to compare real-world outcomes with those from RCTs to evaluate the effectiveness of adjuvant therapies in typical clinical settings. Method In this retrospective study, we examined overall survival (OS) among patients who received adjuvant chemotherapy (gemcitabine, gemcitabine-capecitabine, or FOLFIRINOX) following the resection of pancreatic ductal adenocarcinoma. We compared survival curves from RCTs (ESPAC 4, PRODIGE-24) with those from real-world cohorts selected based on RCT criteria. Data were collected retrospectively from medical records and institutional databases, covering OS, disease-free survival (DFS), and adverse events. Results From July 2014 to December 2019, 303 pancreatic ductal adenocarcinoma patients underwent resections, with 209 (69%) receiving adjuvant chemotherapy: 91 (44%) received gemcitabine, 69 (34%) gemcitabine-capecitabine, and 37 (18%) FOLFIRINOX. The median OS for gemcitabine was 21.6 months, close to ESPAC 4’s 25.5 months. Gemcitabine-capecitabine had a median OS of 25.2 months versus ESPAC 4’s 28 months. FOLFIRINOX had a lower median OS in our cohort (19.9 months) compared to PRODIGE 24’s 54.4 months. Additionally, gemcitabine OS in PRODIGE 24 was higher (35 months) than in our data. FOLFIRINOX had a 17% completion rate. Conclusion The real-world outcomes for gemcitabine-based adjuvant therapy align closely with RCT results, while FOLFIRINOX appears less effective in typical clinical settings, possibly due to tolerance issues. These findings highlight the importance of incorporating real-world data in clinical decision-making to better predict patient outcomes and improve treatment strategies for pancreatic cancer. Further research is needed to bridge the gap between RCTs and real-world practices, especially concerning patient selection and treatment tolerability.

Optimizing Anemia Detection Using Effective Computational Techniques

Worldwide, anemia is the most common blood disease. The World Health Organization (WHO) defines anemia as the lack of red blood cells, which prevents the body from carrying enough oxygen to satisfy its requirements. Anemia is characterized by decreased erythrocyte mass, blood hemoglobin, and hemocrit levels. Early detection and accurate diagnosis are essential for effective management and therapy. The study's goal is to develop an algorithm for optimizing anemia detection utilizing an effective computational technique. The study proposed a brand-new Dynamic Gannet-tuned Light Gradient Boosting Machine (DG-LGBM) model for the detection of anemia in typical clinical practice settings. In this study, anemia data is collected from a publicly available dataset from Kaggle. The data was preprocessed using data cleaning and normalization for the obtained data. The study aims to improve the predicted accuracy and efficiency of anemia diagnosis by utilizing clinical and biochemical markers. The results demonstrate that, in comparison to traditional methods, the DG-LGBM model performed better in terms of anemia detection rates, highlighting the potential of computational tools to completely transform anemia screening practices. In a comparative analysis, the proposed model is validated using precision (92%), recall (91.71%) f1-score (93.07%), and accuracy (91.06%) values. In addition to advancing the area of medical diagnostics, this study highlights the significance of technology in enhancing healthcare outcomes for impacted communities.

First-in-human microelectrode recordings from the vagus nerve during clinical vagus nerve stimulation.

Vagus nerve stimulation (VNS) is an effective treatment for people with drug-resistant epilepsy. However, its mechanisms of action are poorly understood, including which nerve fibers are activated in humans during VNS in typical clinical settings and which are required for clinical efficacy. In particular, there have been no intraneural recordings of vagus nerve fiber activation in awake humans undergoing chronic VNS. In this study, for the first time, we report recordings from the vagus nerve in this setting. The recordings were performed using a sterile tungsten microelectrode inserted percutaneously into the cervical vagus nerve under ultrasound guidance. The clinical VNS systems were used to deliver stimulation while activity in the vagus nerve was recorded. In addition to activating myelinated axons at low currents, we provide evidence that VNS can also activate unmyelinated C fibers in the vagus nerve at currents <1 mA. These results add to our understanding of how VNS exerts its beneficial effects in drug-resistant epilepsy. Here we describe for the first time, electrical recordings from the vagus nerve in awake drug-resistant epilepsy patients with an implanted vagus nerve stimulation (VNS) device. We found that the VNS device was able to activate both myelinated and unmyelinated fibers within the vagus nerve, whichcontributes to our understanding of how VNS works in the context of drug-resistant epilepsy.

Application of motion prediction based on a long short-term memory network for imaging dose reduction in real-time tumor-tracking radiation therapy

PurposeTo demonstrate the possibility of using a lower imaging rate while maintaining acceptable accuracy by applying motion prediction to minimize the imaging dose in real-time image-guided radiation therapy. MethodsTime-series of three-dimensional internal marker positions obtained from 98 patients in liver stereotactic body radiation therapy were used to train and test the long-short-term memory (LSTM) network. For real-time imaging, the root mean squared error (RMSE) of the prediction on three-dimensional marker position made by LSTM, the residual motion of the target under respiratory-gated irradiation, and irradiation efficiency were evaluated. In the evaluation of the residual motion, the system-specific latency was assumed to be 100 ms. ResultsExcept for outliers in the superior–inferior (SI) direction, the median/maximum values of the RMSE for imaging rates of 7.5, 5.0, and 2.5 frames per second (fps) were 0.8/1.3, 0.9/1.6, and 1.2/2.4 mm, respectively. The median/maximum residual motion in the SI direction at an imaging rate of 15.0 fps without prediction of the marker position, which is a typical clinical setting, was 2.3/3.6 mm. For rates of 7.5, 5.0, and 2.5 fps with prediction, the corresponding values were 2.0/2.6, 2.2/3.3, and 2.4/3.9 mm, respectively. There was no significant difference between the irradiation efficiency with and that without prediction of the marker position. The geometrical accuracy at lower frame rates with prediction applied was superior or comparable to that at 15 fps without prediction. In comparison with the current clinical setting for real-time image-guided radiation therapy, which uses an imaging rate of 15.0 fps without prediction, it may be possible to reduce the imaging dose by half or more. ConclusionsMotion prediction can effectively lower the frame rate and minimize the imaging dose in real-time image-guided radiation therapy.

In-silico study of the impact of system design parameters on microcalcification detection in wide-angle digital breast tomosynthesis.

Accurate detection of microcalcifications ( ) is crucial for the early detection of breast cancer. Some clinical studies have indicated that digital breast tomosynthesis (DBT) systems with a wide angular range have inferior detectability compared with those with a narrow angular range. This study aims to (1)provide guidance for optimizing wide-angle (WA) DBT for improving detectability and (2)prioritize key optimization factors. An in-silico DBT pipeline was constructed to evaluate detectability of a WA DBT system under various imaging conditions: focal spot motion (FSM), angular dose distribution (ADS), detector pixel pitch, and detector electronic noise (EN). Images were simulated using a digital anthropomorphic breast phantom inserted with clusters. Evaluation metrics included the signal-to-noise ratio (SNR) of the filtered channel observer and the area under the receiver operator curve (AUC) of multiple-reader multiple-case analysis. Results showed that FSM degraded sharpness and decreased the SNR and AUC by 5.2% and 1.8%, respectively. Non-uniform ADS increased the SNR by 62.8% and the AUC by 10.2% for filtered backprojection reconstruction with a typical clinical filter setting. When EN decreased from 2000 to 200 electrons, the SNR and AUC increased by 21.6% and 5.0%, respectively. Decreasing the detector pixel pitch from 85 to improved the SNR and AUC by 55.6% and 7.5%, respectively. The combined improvement of a pixel pitch and EN200 was 89.2% in the SNR and 12.8% in the AUC. Based on the magnitude of impact, the priority for enhancing detectability in WA DBT is as follows: (1)utilizing detectors with a small pixel pitch and low EN level, (2)allocating a higher dose to central projections, and (3)reducing FSM. The results from this study can potentially provide guidance for DBT system optimization in the future.

A low-cost phantom design for evaluating spine SABR calculations in the presence of prosthetic vertebral stabilization.

Dose-perturbation characteristics are important to consider during the calculation of radiation therapy protocols for patients who are going to receive high doses that would reach the tolerance limits of the spinal cord [1]. Several studies have investigated dose perturbations introduced by metal implants in close proximity to spine SABR treatments [2-7]. However, there is a lack of work assessing this effect using the RayStation TPS [8]. We present an initial design for a low-cost phantom to evaluate spine stereotactic ablative radiotherapy (SABR) in the presence of prosthetic vertebral stabilization. The phantom is modular, allowing the prosthetic at the centre of the phantom to be removed by exchanging the central block. It also includes space to insert ion chamber and film. The agreement of the RayStation TPS (v8.0B) collapsed cone convolution (CCC) calculation and measurement was determined for phantom versions with and without prosthetic. There was little to no change in the agreement between the measured and calculated dose when introducing metallic hardware. This suggests that our Raystation-based SABR planning approach for patients with spinal hardware meets clinical expectations. Departments without access to anthropomorphic phantoms may find this design useful but should test their phantom design in typical clinical settings to ensure it is robust to real world situations.

Explainable deep-neural-network supported scheme for tuberculosis detection from chest radiographs.

Chest radiographs are examined in typical clinical settings by competent physicians for tuberculosis diagnosis. However, this procedure is time consuming and subjective. Due to the growing usage of machine learning techniques in applied sciences, researchers have begun applying comparable concepts to medical diagnostics, such as tuberculosis screening. In the period of extremely deep neural nets which comprised of hundreds of convolution layers for feature extraction, we create a shallow-CNN for screening of TB condition from Chest X-rays so that the model is able to offer appropriate interpretation for right diagnosis. The suggested model consists of four convolution-maxpooling layers with various hyperparameters that were optimized for optimal performance using a Bayesian optimization technique. The model was reported with a peak classification accuracy, F1-score, sensitivity and specificity of 0.95. In addition, the receiver operating characteristic (ROC) curve for the proposed shallow-CNN showed a peak area under the curve value of 0.976. Moreover, we have employed class activation maps (CAM) and Local Interpretable Model-agnostic Explanations (LIME), explainer systems for assessing the transparency and explainability of the model in comparison to a state-of-the-art pre-trained neural net such as the DenseNet.

Application of the Hammersmith Infant Neurological Examination in the developmental follow-up of high-risk infants.

To investigate the independent influences affecting the global score of the Hammersmith Infant Neurological Examination (HINE) in the early life of high-risk infants and to provide evidence for early effective screening and for evaluating interventions. We conducted a prospective cohort study of 258 high-risk infants assessed by the HINE and Gesell Developmental Diagnosis Schedule at 3, 6, 9, and 12 months corrected age. A multiple linear regression model was developed to investigate independent influences on HINE global score at 3 months corrected age. The accuracy of the HINE global score was analysed by calculating the discriminant, concurrent, and predictive validities according to ages. There were nine independent influences affecting the HINE global score at 3 months corrected age in high-risk infants. The discriminant, concurrent, and predictive validities of the HINE for gross motor developmental delays at 12 months corrected age were all statistically significant (p < 0.05). Different neonatal clinical settings are related to the HINE global score of high-risk infants early in life. The HINE can be used for longitudinal monitoring of neurological development in the first year of life in a typical Chinese clinical setting and the findings at all four ages tested relate to neuromotor outcomes at 12 months corrected age.

Intracranial Phosphaturic Mesenchymal Tumor Detected by 68 Ga-DOTATATE PET/CT.

A 68 Ga-DOTATATE PET/CT scan was conducted to locate the causative tumor responsible for suspected tumor-induced osteomalacia in a 56-year-old woman. The PET/CT images showed a focus in the right occipital region. Subsequent MRI showed an extra-axial nodule in the right occipital region, mimicking a meningioma. Although rare, an intracranial phosphaturic mesenchymal tumor was still suspected because of the typical clinical settings. Finally, phosphaturic mesenchymal tumor was confirmed by the postoperative pathology.

The development of an electrochemical immunosensor utilizing chicken IgY anti-spike antibody for the detection of SARS-CoV-2

This paper introduces a novel approach for detecting the SARS-CoV-2 recombinant spike protein combining a label free electrochemical impedimetric immunosensor with the use of purified chicken IgY antibodies. The sensor employs three electrodes and is functionalized with an anti-S IgY antibody, ELISA and immunoblot assays confirmed the positive response of chicken immunized with SARS-CoV2 S antigen. The developed immunosensor is effective in detecting SARS-CoV-2 in nasopharyngeal clinical samples from suspected cases. The key advantage of this biosensor is its remarkable sensitivity, and its capability of detecting very low concentrations of the target analyte, with a detection limit of 5.65 pg/mL. This attribute makes it highly suitable for practical point-of-care (POC) applications, particularly in low analyte count clinical scenarios, without requiring amplification. Furthermore, the biosensor has a wide dynamic range of detection, spanning from 11.56 to 740 ng/mL, which makes it applicable for sample analysis in a typical clinical setting.

Globally shared TCR repertoires within the tumor-infiltrating lymphocytes of patients with metastatic gynecologic cancer

Gynecologic cancer, including ovarian cancer and endometrial cancer, is characterized by morphological and molecular heterogeneity. Germline and somatic testing are available for patients to screen for pathogenic variants in genes such as BRCA1/2. Tissue expression levels of immunogenomic markers such as PD-L1 are also being used in clinical research. The basic therapeutic approach to gynecologic cancer combines surgery with chemotherapy. Immunotherapy, while not yet a mainstream treatment for gynecologic cancers, is advancing, with Dostarlimab recently receiving approval as a treatment for endometrial cancer. The goal remains to harness stimulated immune cells in the bloodstream to eradicate multiple metastases, a feat currently deemed challenging in a typical clinical setting. For the discovery of novel immunotherapy-based tumor targets, tumor-infiltrating lymphocytes (TILs) give a key insight on tumor-related immune activities by providing T cell receptor (TCR) sequences. Understanding the TCR repertoires of TILs in metastatic tissues and the circulation is important from an immunotherapy standpoint, as a subset of T cells in the blood have the potential to help kill tumor cells. To explore the relationship between distant tissue biopsy regions and blood circulation, we investigated the TCR beta chain (TCRβ) in bulk tumor and matched blood samples from 39 patients with gynecologic cancer. We found that the TCR clones of TILs at different tumor sites were globally shared within patients and had high overlap with the TCR clones in peripheral blood.

Clinical Management of COPD in the Real World: Can Studies Reveal Errors in Management and Pathways to Improve Patient Care?

Real world data comprise information on health care that is derived from multiple sources outside typical clinical research settings. This review focuses on what real world evidence tells us about problems with the diagnosis of chronic obstructive pulmonary disease (COPD), problems with the initial and follow-up pharmacological and non-pharmacological management, problems with the management of exacerbations and problems with palliative care. Data from real world studies show errors in the management of COPD with delays to diagnosis, lack of confirmation of the diagnosis with spirometry, lack of holistic assessment, lack of attention to smoking cessation, variable adherence to management guidelines, delayed implementation of appropriate interventions, under-recognition of patients at higher risk of adverse outcomes, high hospitalisation rates for exacerbations and poor implementation of palliative care. Understanding that these problems exist and considering how and why they occur is fundamental to developing solutions to improve the diagnosis and management of patients with COPD.

Pareto-Optimized AVQI Assessment of Dysphonia: A Clinical Trial Using Various Smartphones

Multiparametric indices offer a more comprehensive approach to voice quality assessment by taking into account multiple acoustic parameters. Artificial intelligence technology can be utilized in healthcare to evaluate data and optimize decision-making processes. Mobile devices provide new opportunities for remote speech monitoring, allowing the use of basic mobile devices as screening tools for the early identification and treatment of voice disorders. However, it is necessary to demonstrate equivalence between mobile device signals and gold standard microphone preamplifiers. Despite the increased use and availability of technology, there is still a lack of understanding of the impact of physiological, speech/language, and cultural factors on voice assessment. Challenges to research include accounting for organic speech-related covariables, such as differences in conversing voice sound pressure level (SPL) and fundamental frequency (f0), recognizing the link between sensory and experimental acoustic outcomes, and obtaining a large dataset to understand regular variation between and within voice-disordered individuals. Our study investigated the use of cellphones to estimate the Acoustic Voice Quality Index (AVQI) in a typical clinical setting using a Pareto-optimized approach in the signal processing path. We found that there was a strong correlation between AVQI results obtained from different smartphones and a studio microphone, with no significant differences in mean AVQI scores between different smartphones. The diagnostic accuracy of different smartphones was comparable to that of a professional microphone, with optimal AVQI cut-off values that can effectively distinguish between normal and pathological voice for each smartphone used in the study. All devices met the proposed 0.8 AUC threshold and demonstrated an acceptable Youden index value.

Estimating the restraint of SARS-CoV-2 spread using a conventional medical air-cleaning device: Based on an experiment in a typical dental clinical setting

Droplets or aerosols loaded with SARS-CoV-2 can be released during breathing, coughing, or sneezing from COVID-19-infected persons. To investigate whether the most commonly applied air-cleaning device in dental clinics, the oral spray suction machine (OSSM), can provide protection to healthcare providers working in clinics against exposure to bioaerosols during dental treatment. In this study, we measured and characterized the temporal and spatial variations in bioaerosol concentration and deposition with and without the use of the OSSM using an experimental design in a dental clinic setting. Serratia marcescens (a bacterium) and ΦX174 phage (a virus) were used as tracers. The air sampling points were sampled using an Anderson six-stage sampler, and the surface-deposition sampling points were sampled using the natural sedimentation method. The Computational Fluid Dynamics method was adopted to simulate and visualize the effect of the OSSM on the concentration spatial distribution. During dental treatment, the peak exposure concentration increased by up to 2-3 orders of magnitude (PFU/m3) for healthcare workers. Meanwhile, OSSM could lower the mean bioaerosol exposure concentration from 58.84PFU/m3 to 4.10PFU/m3 for a healthcare worker, thereby inhibiting droplet and airborne transmission. In terms of deposition, OSSM significantly reduced the bioaerosol surface concentration from 28.1PFU/m3 to 2.5PFU/m3 for a surface, effectively preventing fomite transmission. The use of OSSM showed the potential to restraint the spread of bioaerosols in clinical settings. Our study demonstrates that OSSM use in dental clinics can reduce the exposure concentrations of bioaerosols for healthcare workers during dental treatment and is beneficial for minimizing the risk of infectious diseases such as COVID-19.

Abstract P2-01-01: Interim analysis (n=200) from ELEANOR: a multi-national, prospective, non-interventional study among patients with HER2+ and HR+ early breast cancer treated with extended adjuvant neratinib in the clinical routine

Abstract Background Recent advances in the treatment of human epidermal growth factor receptor positive (HER2+) early breast cancer (eBC) have led to a reduction in recurrence risk; still a relevant percentage of patients relapses over time, predominantly presenting with distant recurrence. Neratinib is registered in Europe as extended adjuvant treatment for adult patients with HER2+, hormone receptor positive (HR+) eBC, who completed adjuvant trastuzumab-based therapy within one year prior to start of neratinib. In the ExteNET study, neratinib improved the absolute 5-year invasive disease-free survival (iDFS) rate by 5.1% versus placebo in this population (90.8% vs. 85.7%; HR 0.58 [95% CI 0.41-0.82]), mainly by reducing the rate of distant metastases. According to explorative analyses from ExteNET, the effect may be even more pronounced in patients with non-pCR after neoadjuvant trastuzumab treatment and/or in patients completing the full duration of neratinib therapy (i.e. ≥11 months of neratinib treatment). Diarrhea, the most common grade 3 adverse event (neratinib: 39% without primary diarrhea prophylaxis, median cumulative duration 5 days; placebo: 1%; no grade 4 events) can generally be managed through adequate prophylaxis and treatment management. ELEANOR is the first non-interventional study (NIS) of real-world use of neratinib and its management in eBC patients in Germany, Austria and Switzerland. Methods Enrollment of 300 adult female patients with HER2+/HR+ eBC is planned in accordance with the SmPC specifications. Primary endpoint is the rate of patients adherent to neratinib treatment (i.e. neratinib use for ≥75% of treatment days). Secondary objectives include characterization of patients scheduled to receive neratinib, details on neratinib treatment, recurrences, safety/tolerability, and health-related quality of life (HRQoL). CANKADO, an eHealth application developed to support patient/physician communication, is an integral part of the NIS. Here, we report results of the preplanned interim analysis based on 200 enrolled patients. Results At data cut-off (May 2022), 202 patients had been observed for 3 months; patient enrollment is ongoing. Median age was 53.0 years and 66.3% of patients were at increased risk of disease recurrence (defined as non-pCR or AJCC stage &amp;gt; I). Most patients had received prior neoadjuvant treatment (79.7%). Post-neoadjuvant treatment included dual HER2 blockade with trastuzumab and pertuzumab (38.8%/23.9% of pCR/non-pCR patients) and trastuzumab-emtansine (T-DM1, 53.5% of non-pCR patients). Neratinib treatment had been documented for 187 patients, treatment was ongoing for 46.0% of patients. Diarrhea was the most common adverse event (78.6% any grade, 19.3% grade 3, 2 patients grade 4), but was markedly lower when indirectly compared to ExteNET (39% grade 3). The neratinib dose escalation schedule was chosen for 36.4% of patients and led to a decreased incidence of severe diarrhea (16.2% grade 3, no grade 4 events). 93.9% (95% CI: 87.9-97.5%) of 115 evaluable patients adhered to neratinib treatment. Conclusion The results of this preplanned interim analysis reflect the current treatment landscape in Germany, Austria and Switzerland. These results confirm, in line with the observed adherence data, that extended adjuvant neratinib use is feasible in typical clinical practice settings. Furthermore, treatment management strategies such as diarrhea prophylaxis or neratinib dose escalation are routinely used and can increase treatment tolerability markedly. The study is funded by Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland). Citation Format: Rupert Bartsch, Nadia Harbeck, Denise Wrobel, Matthias Zaiss, Jürgen Terhaag, Dagmar Guth, Andrea Distelrath, Rachel Wuerstlein, Mark-Oliver Zahn, Diana Lüftner, Michael Schwitter, Marija Balic, Christian Jackisch, Volkmar Müller, Gabriel Rinnerthaler, Marcus Schmidt, Khalil Zaman, Timo Schinköthe, Anna Resch, Urs Breitenstein. Interim analysis (n=200) from ELEANOR: a multi-national, prospective, non-interventional study among patients with HER2+ and HR+ early breast cancer treated with extended adjuvant neratinib in the clinical routine [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-01.

Data quality - The foundation of real-world studies.

Real-world data, routinely collected from multiple sources outside typical clinical research settings, are useful in conducting real-world studies. Sub-optimal and inconsistent data quality is a challenging issue which should be addressed whilst planning and conducting real-world studies. This brief review discusses the quality aspects of data needed for RWS.

Evaluation of Radical Thoracic Re-Irradiation: A Single Institution Retrospective Study

<h3>Purpose/Objective(s)</h3> The ability to deliver radical thoracic re-irradiation is limited by the balance between efficacy and potential toxicity. The aim of our study was to evaluate the safety and efficacy of radical thoracic re-irradiation. <h3>Materials/Methods</h3> A single institution retrospective analysis was performed on all patients who received two or more courses of radical thoracic radiotherapy, for sequential malignancies, between January 2011 and October 2019. All radical dose-fractionation schemes were included. The dose was converted to a Biologically Equivalent Dose, to ensure the cumulative dose delivered to the organs at risk (OAR) with re-irradiation did not exceed standard limits. The primary endpoint was the rate of acute (within 6 weeks) and late (within 1 year) toxicity as assessed by CTCAE V4.0. Secondary endpoints included progression free survival and overall survival which were calculated from the date of last radiotherapy using the Kaplan-Meier method. The study was approved by the institutional ethics board and patients provided informed consent. <h3>Results</h3> 43 patients had received at least one prior course of radical thoracic radiotherapy. 7/43(16%) and 2/43(5%) had received two and three prior courses respectively. The median follow-up from last completed radiotherapy was 19.8 months (0 - 64 months). The median age was 73 and 23/43(53%) of the cohort were female. Stereotactic Ablative Body Radiotherapy and External Beam Radiotherapy techniques were used in 48/97(49%) and 49/97(51%) of the treatment courses respectively. The primary tumor was non-small cell lung cancer in 78/97(80%), small cell lung cancer in 8/97(8%), head and neck cancer in 6/97(6%) and breast cancer in 5/97(5%). The median time from 1^st to 2^nd radiotherapy was 19 months. Following last re-irradiation, acute grade 1 and 2 toxicities were observed in 30/43(70%). The acute toxicities were cough 14/43(33%), dyspnea 9/43(21%), esophagitis 11/43(26%), fatigue 24/43(56%), erythema 6/43 (14%) and chest wall pain 2/43(5%). One patient had a fatal event during re-irradiation after an acute upper gastrointestinal hemorrhage but causality could not be established. Another patient had a grade 3 respiratory infection. Cumulative late grade 1 and 2 toxicities were observed in 7/31(23%) of the evaluable cohort including hemoptysis 1/31 (3%), cough 2/31(6%), dyspnea 3/31(10%), chest wall pain 3/31(10%) and fatigue 3/31(10%). There was no other grade 3 or higher acute or late toxicities. At time of analysis 33/43(77%) of patients had died. One-year overall survival and progression free survival were 64% (95%CI: 50-79%) and 49% (95%CI: 33-64%) respectively. Limitations of the study include its retrospective nature and patient heterogeneity. <h3>Conclusion</h3> Radical thoracic re-irradiation was generally well tolerated in a typical clinical setting when the cumulative dose delivered to OAR did not exceed standard constraints.

Feasibility of a 4-Week Manual Therapy and Exercise Intervention on Posture and Function in Community-Dwelling Older Adults: A Pilot Study.

Thoracic hyperkyphosis is a common condition that progresses with aging and has been associated with impaired functional performance, increased risk of falls, and even mortality. Previous studies to improve posture primarily used exercise for durations of 3 months or longer. The purpose of this pilot study was to examine the feasibility of a manual therapy intervention in community-dwelling older adults over a 4-week time frame that is comparable to the typical clinical setting, to test the appropriateness and procedures for the measurement of posture and function in the older population with hyperkyphosis, and to collect preliminary data to describe change in posture and function measures. Twenty-four participants with hyperkyphosis or forward head posture were recruited, and 22 participants completed this pilot study. Feasibility was measured based on attendance, tolerance, safety, and retention. Issues with measurement procedures were recorded. The intervention included manual therapy and exercise 3 times a week for 4 weeks to target spinal and peripheral joint stiffness, muscle lengthening, and muscle activation. Outcomes included height, kyphotic index (KI), Block Test, Acromion to Table (ATT), Timed Up and Go (TUG), 5 times sit-to-stand (5XSTS), Functional Reach (FR), 2-minute walk test (2MWT), and Patient-Specific Functional Scale (PSFS). Data collected at visits 1, 6, and 12 were analyzed using 1-way repeated-measures multivariate analysis of variance. Measurement and intervention protocols were found to be feasible. A significant effect for the aggregate dependent variables change over time was found. Univariate analysis of each dependent variable showed significance except for FR. All postural measures (height, KI, Block Test, and ATT) significantly improved statistically. The KI and ATT exceed the minimal detectable change for clinical significance. Function showed statistical improvements in the TUG, 5XSTS, 2MWT, and PSFS. Clinical significance was reached with the PSFS. Seven of 9 measures showed a statistically significant change in just 2 weeks. This pilot study suggests that manual therapy and exercise applied to older adults shows promise for improvement in measures of posture and functional performance in a clinically feasible 4-week time frame.

Endovascular treatment for wake-up stroke and daytime unwitnessed stroke: A meta-analysis

BackgroundEvidence from sources outside the typical clinical research setting, such as a real-world setting, may complement evidence from randomised controlled trials (RCTs). The aim of the present study was to carry out a meta-analysis of available real-world evidence that focused on the efficacy and safety of endovascular treatment in patients with wake-up stroke (WUS) or daytime unwitnessed stroke (DUS) compared to that in patients treated ≤ 6 h after the onset of an ischemic stroke. MethodsData mining was conducted on 1 May 2021 from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials Cochrane Library. The study reviewed all published that assessed the effect of endovascular treatment in WUS and DUS compared to that received by patients with ischemic stroke. Relevant data were extracted and the narrative was reviewed and analysed. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). FindingsThe meta-analysis showed no significant differences between the two groups in the rates of functional independence (OR, 0.81; 95% CI, 0.65–1.02; P = 0.07), symptomatic intracerebral haemorrhage (OR, 0.86; 95% CI, 0.57–1.30; P = 0.470), and all-cause mortality (OR, 0.92; 95% CI, 0.73–1.16; P = 0.50). There was also no heterogeneity between the trials. ConclusionThe pooled analysis provided evidence to support the use of endovascular treatment in WUS and DUS with favourable perfusion imaging. The meta-analysis confirmed the main findings of RCTs of endovascular treatment in WUS and DUS in a real-world setting and therefore strengthens the validity of this treatment strategy.

Analyzing longitudinal binary data in clinical studies

In clinical studies, it is common to have binary outcomes collected over time as repeated measures. This manuscript reviews and evaluates two popular classes of statistical methods for analyzing binary response data with repeated measures: likelihood-based Generalized Linear Mixed Model (GLMM), and semiparametric Generalized Estimating Equation (GEE). Recommendations for choice of analysis model and points to consider for implementation in clinical studies in the presence of missing data are provided based on a comprehensive literature review, as well as, a simulation study evaluating the performance of both GLMM and GEE under scenarios representative of typical clinical trial settings. Under Missing at Random (MAR) assumption, GLMM is preferred over GEE, and the SAS PROC GLIMMIX marginal model is recommended for implementing GLMM in analyzing clinical trial data. When there is an underlying continuous variable used to define the binary response, and the missing proportion is high and/or unbalanced between treatment groups, a two-step approach combining Multiple Imputation (MI) and GEE (MI-GEE) is recommended.