Assessing patient risk, benefit, and outcomes in drug development: A decade of ramucirumab clinical trials.

OBJECTIVE: This study aims to evaluate published clinical trials of ramucirumab to assess the risk/benefit profile and burden over time for patients. BACKGROUND: The burden of oncologic drug development on patients paired with increasing clinical trial failure rates emphasizes the need for reform of drug development. Identifying and addressing patterns of excess burden can guide policy, ensure evidence-based protections for trial participants, and improve medical decision-making. METHODS: On May 25, 2023 a literature search was performed on Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov for clinical trials using ramucirumab as monotherapy or in combination with other interventions for cancer treatment. Authors screened titles and abstracts for potential inclusion in a masked, duplicate fashion. Following data screening, data was extracted in a masked, duplicate fashion. Trials were classified as positive when meeting their primary endpoint and safety, negative or indeterminate. RESULTS: Ramucirumab was initially approved for gastric cancer but has since been tested in 20 cancers outside of its FDA approved indications. In our analysis of ramucirumab trials, there were a total of 10,936 participants and 10,303 adverse events reported. Gains in overall survival and progression-free survival for patients were 1.5 and 1.2 months, respectively. FDA-approved indications have reported more positive outcomes in comparison to off-label indications. CONCLUSION: We found that FDA-approved indications for ramucirumab had better efficacy outcomes than non-approved indications. However, a concerning number of adverse events were observed across all trials assessed. Participants in ramucirumab randomized controlled trials saw meager gains in overall survival when evaluated against a comparison group. Clinicians should carefully weigh the risks associated with ramucirumab therapy given its toxicity burden and poor survival gains.

Addressing Unmet Social Needs and Social Risks - A Qualitative Interview-Based Assessment of Parent Reported Outcomes and Impact from a Medical Legal Partnership.

Medical legal partnerships address individual legal needs that can create impediments to health. Little is known about outcomes from medical legal partnerships and their relationship to access to justice. This paper reports outcomes from one medical legal partnership from the perspective of the client, with specific emphasis on impact on health and concepts related to access to justice. We suggest a conceptual model for incorporating medical legal partnerships into a broader framework about access to justice.

The fractional analysis of thermo-elasticity coupled systems with non-linear and singular nature.

It is mentioned that understanding linear and non-linear thermo-elasticity systems is important for understanding temperature, elasticity, stresses, and thermal conductivity. One of the most crucial aspects of the current research is the solution to these systems. The fractional form of several thermo-elastic systems is explored, and elegant solutions are provided. The solutions of fractional and integer thermo-elastic systems are further discussed using tables and diagrams. The closed contact between the LRPSM and exact solutions is displayed in the graphs. Plotting fractional problem solutions demonstrates their convergence towards integer-order problem solutions for suitable modeling. The tables confirm that greater precision is rapidly attained as the terms of the derived series solution increase. The faster convergence and stability of the suggested method support its modification for other fractional non-linear complex systems in nature.

Fractional analysis of non-linear fuzzy partial differential equations by using a direct procedure.

In this study, an accurate analytical solution is presented for fuzzy FPDEs. It is done by using a novel method called the Laplace-residual power series (LRPSM) to build a series solution to the given problems. The fundamental instruments of the employed method are the Laplace transform, fractional Laurent, and fractional power series. Using the idea of a limit at infinity, we provide a series solution to a fuzzy FPDE with quick convergence and simple coefficient finding. We analyze three cases to obtain approximate and exact solutions to show the effectiveness and reliability of the Laplace- residual power series approach. To demonstrate the accuracy of the suggested procedure, we compare the findings to the real data.

Peri-Alkylated Terrylenes and Ternaphthalenes Building-Blocks Towards Multi-Edge Nanographenes.

Since its first synthesis by Clar in 1948, terrylene - a fully connected ternaphthalene oligomer via naphthalene's peri-positions - has gained special focus within the rylene family, drawing interest for its unique chemical, structural, optoelectronic and single photon emission properties. In this study, we introduce a novel synthetic pathway that enhances the solubility of terrylene derivatives through complete peri-alkylation, while also facilitating extensions at the bay-positions. This approach not only broadens the scope of terrylene's chemical versatility but also opens new avenues for developing solution processable novel multi-edge nanographenes and tailoring electronic energy levels through topological edge structures. Our findings include a comprehensive structural and spectroscopic characterization along with transient absorption spectroscopy and photophysics of both the synthesized peri-alkylated terrylene and its phenylene-fused derivative.

Using virtual reality to improve verbal episodic memory in schizophrenia: A proof-of-concept trial.

Background: Schizophrenia is associated with impairments in verbal episodic memory. Strategy for Semantic Association Memory (SESAME) training represents a promising cognitive remediation program to improve verbal episodic memory. Virtual reality (VR) may be a novel tool to increase the ecological validity and transfer of learned skills of traditional cognitive remediation programs. The present proof-of-concept study aimed to assess the feasibility, acceptability, and preliminary efficacy of a VR-based cognitive remediation module inspired by SESAME principles to improve the use of verbal episodic memory strategies in schizophrenia. Methods: Thirty individuals with schizophrenia/schizoaffective disorder completed this study. Participants were randomized to either a VR-based verbal episodic memory training condition inspired by SESAME principles (intervention group) or an active control condition (control group). In the training condition, a coach taught semantic encoding strategies (active rehearsal and semantic clustering) to help participants remember restaurant orders in VR. In the active control condition, participants completed visuospatial puzzles in VR. Attrition rate, participant experience ratings, and cybersickness questionnaires were used to assess feasibility and acceptability. Trial 1 of the Hopkins Verbal Learning Test - Revised was administered pre- and post-intervention to assess preliminary efficacy. Results: Feasibility was demonstrated by a low attrition rate (5.88 %), and acceptability was demonstrated by limited cybersickness and high levels of enjoyment. Although the increase in the number of semantic clusters used following the module did not reach conventional levels of statistical significance in the intervention group, it demonstrated a notable trend with a medium effect size (t = 1.48, p = 0.15, d = 0.54), in contrast to the control group where it remained stable (t = 0.36, p = 0.72, d = 0.13). These findings were similar for the semantic clustering ratio in the intervention (t = 1.61, p = 0.12, d = 0.59) and control (t = 0.36, p = 0.72, d = 0.13) groups. There was no significant change in the number of recalled words in either group following VR immersion. Discussion: This VR intervention was feasible, acceptable, and may be useful for improving the use of semantic encoding strategies. These findings support the use of more ecological approaches for the treatment of cognitive impairments in schizophrenia, such as VR-based cognitive remediation.

Designing an ECG curriculum for residents: Evidence-based approaches to improving resident ECG interpretation skills.

Residents enter their training with variable comfort and competency in electrocardiogram (ECG) interpretation. Accurately interpreting an ECG is a fundamental skill in medicine and resident physicians would benefit from a longitudinal, dedicated ECG curriculum as part of their training to enhance interpretation skills and improve patient outcomes. Educators currently employ a wide array of methodologies to teach their trainees proper ECG interpretation skills, with no single modality established as the gold-standard for teaching this crucial skill. We present evidence-based guidance on how educators may develop and implement an effective ECG interpretation curriculum as part of residency training.

Numerical analysis of radiative hybrid nanomaterials flow across a permeable curved surface with inertial and Joule heating characteristics.

The water-based Cu and CoFe2O4 hybrid nano liquid flow across a permeable curved sheet under the consequences of inertial and Lorentz forces has been reported in this analysis. The Joule heating and Darcy Forchheimer effects on fluid flow have been also examined. In the presence of copper (Cu) and cobalt iron oxide (CoFe2O4) nanoparticles, the hybrid nano liquid is synthesized. Radiation and heat source features are additionally incorporated to perform thermodynamics analysis in detail. The second law of thermodynamics is employed in order to estimate the overall generation of entropy. The nonlinear system of PDEs (partial differential equations) is transformed into a dimensionally-free set of ODEs (ordinary differential equations) by employing a similarity framework. The Mathematica built in package ND Solve method is applied to compute the resulting set of nonlinear differential equations numerically. Along with the velocity, and temperature profiles, skin friction and Nusselt number are also computed. Figures and tables illustrate the effects of flow factors on important profiles. Evidently, the outcomes reveal that hybrid nanofluid (Cu + CoFe2O4+H2O) is more progressive than nanofluid (Cu + H2O) and base fluid (H2O) in thermal phenomena. Furthermore, the velocity profile is improved with the greater values of curvature parameter, while the inverse trend is observed against the magnetic parameters. Also, the velocity and energy distribution of hybrid nano-liquid flow boosts with the inclusion of Cu and CoFe2O4 nanoparticles into the base fluid. Velocity distribution diminishes with the increment of volume friction. For high values of inertial factor, skin friction improve while velocity and Nusselt number declines.

Evaluation of in-service smartphone battery drainage profile for video calling feature in major apps.

Video calling is one of the most energy-intensive features in apps requiring the simultaneous operation of the mobile camera, display screen, audio speaker, and internet services. This feature impacts a smartphone battery's runtime and lifetime. This paper is the first of its kind experimental study, which quantifies the operating profile (discharge current, temperature, and terminal voltage) of video call feature in multiple widely used social media apps, which include WhatsApp, Facebook Messenger, Zoom, Skype, WeChat, Google Hangouts, Imo and Viber. One smartphone each of Vivo and Motorola has been evaluated as the manufacturer-provided application programming interface (API) allowed real-time measurement of the operating profile. Results indicate that the video calling feature for Facebook Messenger and Imo is the most energy efficient. In contrast, Google Hangouts is up to 35% more energy-intensive for video calling than other apps. Measurements also show that Vivo's in-service battery temperature is lower than Motorola due to its efficient chipset. For instance, during active Google Hangouts operation for 1 h, Vivo temperature is limited to 46 °C, whereas Motorola temperature rises to 52 °C. Finally, the influence of app algorithms and codecs on energy efficiency is also discussed with regard to operating performance.

Knowledge and motivations of training in peer review: An international cross-sectional survey.

BACKGROUND: Despite having a crucial role in scholarly publishing, peer reviewers do not typically require any training. The purpose of this study was to conduct an international survey on the current perceptions and motivations of researchers regarding peer review training. METHODS: A cross-sectional online survey was conducted of biomedical researchers. A total of 2000 corresponding authors from 100 randomly selected medical journals were invited via email. Quantitative items were reported using frequencies and percentages or means and SE, as appropriate. A thematic content analysis was conducted for qualitative items in which two researchers independently assigned codes to the responses for each written-text question, and subsequently grouped the codes into themes. A descriptive definition of each category was then created and unique themes-as well as the number and frequency of codes within each theme-were reported. RESULTS: A total of 186 participants completed the survey of which 14 were excluded. The majority of participants indicated they were men (n = 97 of 170, 57.1%), independent researchers (n = 108 of 172, 62.8%), and primarily affiliated with an academic organization (n = 103 of 170, 62.8%). A total of 144 of 171 participants (84.2%) indicated they had never received formal training in peer review. Most participants (n = 128, 75.7%) agreed-of which 41 (32.0%) agreed strongly-that peer reviewers should receive formal training in peer review prior to acting as a peer reviewer. The most preferred training formats were online courses, online lectures, and online modules. Most respondents (n = 111 of 147, 75.5%) stated that difficulty finding and/or accessing training was a barrier to completing training in peer review. CONCLUSION: Despite being desired, most biomedical researchers have not received formal training in peer review and indicated that training was difficult to access or not available.

Implementation of a longitudinal, near-peer ECG didactic curriculum in an internal medicine residency program and impact on ECG interpretation skills.

BACKGROUND: To determine the impact of a longitudinal, near-peer, dedicated ECG didactic curriculum on internal medicine resident ability to accurately interpret ECGs. METHODS: This study employs a prospective cohort design. Internal medicine residents at University at Buffalo participated in monthly ECG didactic sessions over a 7-month period. Residents were invited to complete pre- and post-curriculum questionnaires. Responses were anonymous and participation voluntary. Data collected included basic demographics, career interest, exposure to clinical cardiology, and number of sessions attended. Residents were asked to interpret sixteen unique ECGs, divided evenly among eight common rhythms into both questionnaires. Pre- and post-curriculum cohorts were compared using t-tests and chi-square analyses. Associations between attendance, comfort level in interpretation, and number of correct interpretations were analyzed using Pearson correlations. Multivariate linear regression determined the strongest predictor of the number of correct ECG interpretations. RESULTS: The post-curriculum cohort correctly interpreted a significantly greater percentage of ECGs compared to pre-curriculum cohort (74.5% vs. 60.9%, p < .001). Didactic attendance was significantly associated with comfort level in interpreting ECGs (r = .328, p = .018) and trended towards an increased number of correct interpretations (r = .248, p = .077). Residents who attended three or more sessions demonstrated increased ECG interpretation skills compared to those who attended two or fewer sessions (80.0% vs. 71.1%, p = .048). Number of clinical cardiology rotations attended was significantly associated with correct interpretations (r = .310, p < .001) and was the strongest predictor of accurately interpreting ECGs (ß = 0.29, p = .037). CONCLUSIONS: Participation in a longitudinal, near-peer ECG didactic curriculum improved resident ability to interpret ECGs. A curriculum which contains both didactic sessions and clinical exposure may offer the greatest benefit in improving ECG interpretation skills.

Comparison of combined substrate-based mapping techniques to identify critical sites for ventricular tachycardia ablation.

BACKGROUND: Established electroanatomic mapping techniques for substrate mapping for ventricular tachycardia (VT) ablation includes voltage mapping, isochronal late activation mapping (ILAM), and fractionation mapping. Omnipolar mapping (Abbott Medical, Inc.) is a novel optimized bipolar electrogram creation technique with integrated local conduction velocity annotation. The relative utilities of these mapping techniques are unknown. OBJECTIVE: The purpose of this study was to evaluate the relative utility of various substrate mapping techniques for the identification of critical sites for VT ablation. METHODS: Electroanatomic substrate maps were created and retrospectively analyzed in 27 patients in whom 33 VT critical sites were identified. RESULTS: Both abnormal bipolar voltage and omnipolar voltage encompassed all critical sites and were observed over a median of 66 cm2 (interquartile range [IQR] 41.3-86 cm2) and 52 cm2 (IQR 37.7-65.5 cm2), respectively. ILAM deceleration zones were observed over a median of 9 cm2 (IQR 5.0-11.1 cm2) and encompassed 22 critical sites (67%), while abnormal omnipolar conduction velocity (CV <1 mm/ms) was observed over 10 cm2 (IQR 5.3-16.6 cm2) and identified 22 critical sites (67%), and fractionation mapping was observed over a median of 4 cm2 (IQR 1.5-7.6 cm2) and encompassed 20 critical sites (61%). The mapping yield was the highest for fractionation + CV (2.1 critical sites/cm2) and least for bipolar voltage mapping (0.5 critical sites/cm2). CV identified 100% of critical sites in areas with a local point density of >50 points/cm2. CONCLUSION: ILAM, fractionation, and CV mapping each identified distinct critical sites and provided a smaller area of interest than did voltage mapping alone. The sensitivity of novel mapping modalities improved with greater local point density.

Factors affecting repurchase intention of organic food among generation Z (Evidence from developing economy).

Organic food has gained much importance due to consumers' rising environmental and health concerns. Purchase intention of organic food has been explored widely, but the repurchase intention of organic food has gained little attention among researchers. So, it has become important to explore repurchase intention among generation Z; a generation considered more educated and aware of rising environmental concerns. Generation Z is more tech-savvy and brand conscious, so its impact on repurchase intention through consumer satisfaction has been explored. The data in this paper was collected from 400 respondents through a structured questionnaire in Islamabad, Pakistan. We used the PLS-SEM approach for data analysis and results; we found that social media influence and brand purchase impact brand awareness and positively impact brand awareness on consumer satisfaction. Moreover, it is also found that consumer satisfaction positively impacts the repurchase intention of organic food. Our study found that Generation Z has a strong social media influence, so marketers' managers must consider and address the issues when consumers consider social media for their concerns and suggestion.

Impact of Cardiac Implantable Electronic Devices on Cost and Length of Stay in Patients With Surgical Aortic Valve Replacement and Transcutaneous Aortic Valve Implantation.

Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) in aortic stenosis are associated with arrhythmic complications that can require cardiac implantable electronic device (CIED) implantation, but impact on healthcare-associated cost (HAC) and length of stay (LOS) are unknown. This study aimed to assess differences among SAVR/TAVI patients with CIED implantation on HAC and LOS. Patients hospitalized for SAVR or TAVI between 2011 and 2017 on the National Inpatient Sample database were identified and stratified according to presence/type of CIED implantation. During this period, 95,262 patients were identified; 6,435 (6.8%) patients received CIED (median [interquartile range] age: 74.0 [66.0 to 82.0] years). The median adjusted HAC was $44,271 and LOS was 6 days. CIED implantation was associated with longer LOS and higher adjusted HAC in patients with SAVR and TAVI (p <0.0001). Patients with in-hospital death and complications because of SAVR or TAVI had longer preceding in-hospital days of admission. Male patients admitted to small hospitals and the West region had the highest HAC. In conclusion, CIED implantation for arrhythmias results in higher HAC and longer LOS in patients with aortic stenosis for both SAVR and TAVI.

Novel Light Convolutional Neural Network for COVID Detection with Watershed Based Region Growing Segmentation.

A rapidly spreading epidemic, COVID-19 had a serious effect on millions and took many lives. Therefore, for individuals with COVID-19, early discovery is essential for halting the infection's progress. To quickly and accurately diagnose COVID-19, imaging modalities, including computed tomography (CT) scans and chest X-ray radiographs, are frequently employed. The potential of artificial intelligence (AI) approaches further explored the creation of automated and precise COVID-19 detection systems. Scientists widely use deep learning techniques to identify coronavirus infection in lung imaging. In our paper, we developed a novel light CNN model architecture with watershed-based region-growing segmentation on Chest X-rays. Both CT scans and X-ray radiographs were employed along with 5-fold cross-validation. Compared to earlier state-of-the-art models, our model is lighter and outperformed the previous methods by achieving a mean accuracy of 98.8% on X-ray images and 98.6% on CT scans, predicting the rate of 0.99% and 0.97% for PPV (Positive predicted Value) and NPV (Negative predicted Value) rate of 0.98% and 0.99%, respectively.

Percentage of Age-Predicted Cardiorespiratory Fitness May Be a Stronger Risk Indicator for Incident Type 2 Diabetes Than Absolute Levels of Cardiorespiratory Fitness.

PURPOSE: There are inverse and independent associations between cardiorespiratory fitness (CRF) and several adverse cardiometabolic outcomes. The percentage of age-predicted CRF (%age-predicted CRF) is comparable to absolute CRF as a risk indicator for some of these outcomes, but the association between %age-predicted CRF and risk of type 2 diabetes (T2D) has not been previously investigated. We aimed to assess the association between %age-predicted CRF and T2D in a prospective cohort study. METHODS: Cardiorespiratory fitness, as measured directly by peak oxygen uptake, was assessed in 1901 men aged 42-60 yr who underwent cardiopulmonary exercise testing. The age-predicted CRF estimated from a regression equation for age was converted to %age-predicted CRF using (achieved CRF/age-predicted CRF) × 100. Hazard ratios (95% CI) were estimated for T2D. RESULTS: During a median follow-up of 26.8 yr, 227 T2D cases were recorded. The risk of T2D decreased continuously with increasing %age-predicted CRF ( P value for nonlinearity = .30). A 1-SD increase in %age-predicted CRF was associated with a decreased risk of T2D in analysis adjusted for established risk factors (HR = 0.68: 95% CI, 0.59-0.79). The corresponding adjusted risk was (HR = 0.51: 95% CI, 0.35-0.75) comparing extreme tertiles of %age-predicted CRF. The respective estimates for the association between absolute CRF and T2D were-HR (95% CI)-0.71 (0.60-0.83) and 0.64 (0.44-0.95). CONCLUSIONS: Percentage of age-predicted CRF is linearly, inversely, and independently associated with the risk of incident T2D and may be a stronger risk indicator for T2D compared to absolute CRF in a general population of middle-aged and older men.

Characterizing cutaneous leishmaniasis in a conflict-affected region: a study from North Waziristan, Pakistan.

Background/aim: Cutaneous leishmaniasis is an emerging tropical disease that remains a serious public health issue in Pakistan, particularly in North Waziristan. The current research was carried out to investigate the presence of cutaneous leishmaniasis in this region. Materials and methods: This prospective observational study was conducted from October 2018 to December 2020 at District Head Quarter Hospital Miranshah in North Waziristan with the collaboration of the Pathology Department of Gomal Medical College Dera Ismail Khan, Khyber Pakhtunkhwa. Needle aspirates were used for the microscopic Giemsa-stained slides. SPSS was used for data analysis. Results: Of the 5406 clinically-suspected cases, 2603(48.2%) were positive by microscopic examination. Of these 2603 patients, 1474 (57%) were male and 1129 (43%) were female. Most of the lesions were on the face, followed by upper and lower limbs. The 5-10-year age group had the highest percentage of 1167 (45%). A single lesion affected 96.6% of the patients, while 2.7% had double lesions and 0.7% had triple lesions. A high number of cutaneous leishmaniasis were seen from April to August, while the lowest number was seen November to December. Conclusion: This study provides extensive information in relation to the existence of cutaneous leishmaniasis in the North Waziristan district of Pakistan, as well as the detailed demographic features of those affected by the disease.