Clinical Investigators Research Articles

Integration of Clinical Trial Development in Hematology-Oncology Fellowship Training.

Several barriers to physicians becoming clinical investigators exist, including inexperience, lack of available mentors, and inconsistent instructive approaches with varying degrees of participation during training. These barriers cause fewer hematology-oncology fellows to pursue academic careers. A consensus is needed on structuring education in clinical investigation paired with active participation in development of a clinical trial guided by a mentor with the goal of increasing fellow interest in clinical research and pursuit of careers in academic medicine. The clinical trial development (CTD) program was initiated at Washington University School of Medicine in St. Louis in 2002 as a hands-on learning experience for hematology and oncology fellows in the design, implementation, and publication of clinical trials. Each fellow was required to identify a mentor and propose at least 1 prospective investigator-initiated clinical trial. At the time of data abstraction in July 2023, 118 fellows had participated in the CTD program and initiated protocols in a variety of areas according to their interests. Fellows were included in data abstraction if their fellowship began in 2002 through 2021; the program is ongoing, and the most recent class will graduate in 2024. Disease types were evenly distributed between solid tumor oncology (60 [51%]) or classic and malignant hematology (58 [49%]). Ninety-three fellows (79%) obtained institutional review board approval, and 60 (65%) published their results. Among graduating fellows, 67 (66%) secured an academic faculty appointment. Fellows with institutional review board-approved projects had significantly higher odds of obtaining an academic faculty appointment (odds ratio, 4.96; 95% confidence interval, 1.54, 15.98; P = .007).Next StepsNext steps will be to further evaluate the effect of the mentorship network on early career productivity of trainees that graduate and the feasibility of extending the program to another institution.

Management and treatment of perioperative hypersensitivity.

Perioperative hypersensitivity reactions are rare but potentially catastrophic events. This review acts to summarize recent recommendations for both immediate and poststabilization management of suspected reactions, alongside practical advice for anaesthetists who may be faced with these events. Prompt treatment is essential but may be hampered by delay in recognition. This can occur because there are multiple differential diagnoses for the observed clinical signs as well as variations in clinical presentation. Resuscitation is dependent on the use of adrenaline and fluids. Adrenaline should be administered in small, titrated intravenous boluses. Low-dose infusions should be commenced early if the response to boluses is poor. Large volume fluid resuscitation may be required to maintain adequate circulating volume. Chest compressions are recommended when there is evidence of inadequate perfusion, rather than waiting until cardiac arrest is confirmed. Antihistamines and corticosteroids are no longer recommended in the immediate management phase. Once the patient has been stabilized, it is important to obtain serial tryptase concentrations to aid the subsequent clinic investigation. The decision to proceed or abandon surgery will be based on an individual risk-benefit analysis. All cases of suspected perioperative hypersensitivity, including fatal cases, must be referred for formal investigation. There have been recent updates to management guidelines in perioperative hypersensitivity. Treatment algorithms, treatment packs and referral packs can all help the anaesthetist manage these complex cases, aid the subsequent investigation and ensure patient safety in the future.

A reactogenic "placebo" and the ethics of informed consent in Gardasil HPV vaccine clinical trials: A case study from Denmark.

Medical ethics guidelines require of clinical trial investigators and sponsors to inform prospective trial participants of all known and potential risks associated with investigational medical products, and to obtain their free informed consent. These guidelines also require that clinical research be so designed as to minimize harms and maximize benefits. To examine Merck's scientific rationale for using a reactogenic aluminum-containing "placebo" in Gardasil HPV vaccine pre-licensure clinical trials. We examined the informed consent form and the recruitment brochure for the FUTURE II Gardasil vaccine trial conducted in Denmark; and we interviewed several FUTURE II trial participants and their treating physicians. We also reviewed regulatory documentation related to Gardasil vaccine approval process and the guidelines on evaluation of adjuvants used in human vaccines. It was found that the vaccine manufacturer Merck made several inaccurate statements to trial participants that compromised their right to informed consent. First, even though the study protocol listed safety testing as one of the study's primary objectives, the recruitment brochure emphasized that FUTURE II was not a safety study, and that the vaccine had already been proven safe. Second, the advertising material for the trial and the informed consent forms stated that the placebo was saline or an inactive substance, when, in fact, it contained Merck's proprietary highly reactogenic aluminum adjuvant which does not appear to have been properly evaluated for safety. Several trial participants experienced chronic disabling symptoms, including some randomized to the adjuvant "placebo" group. In our view, the administration of a reactive placebo in Gardasil clinical trials was without any possible benefit, needlessly exposed study subjects to risks, and was therefore a violation of medical ethics. The routine use of aluminum adjuvants as "placebos" in vaccine clinical trials is inappropriate as it hinders the discovery of vaccine-related safety signals.

Survival Benefit Associated With Participation in Clinical Trials of Anticancer Drugs

Many cancer clinical investigators view clinical trials as offering better care for patients than routine clinical care. However, definitive evidence of clinical benefit from trial participation (hereafter referred to as the participation effect) has yet to emerge. To conduct a systematic review and meta-analysis of the evidence examining whether patient participation in cancer trials was associated with greater survival benefit compared with routine care. Studies were found through PubMed and Embase (January 1, 2000, until August 31, 2022), as well as backward and forward citation searching. Studies were included that compared overall survival of trial participants and routine care patients. Data extraction and methodological quality assessment were completed by 2 independent coders using Covidence software. Data were pooled using a random-effects model and analyzed based on the quality of the comparison between trial participants and routine care patients (ie, extent to which studies controlled for bias and confounders). The hazard ratio (HR) for overall survival of trial participants vs routine care patients. Thirty-nine publications were included, comprising 85 comparisons of trial participants and routine care patients. The meta-analysis revealed a statistically significant overall survival benefit for trial participants (HR, 0.76 [95% CI, 0.69-0.82]) when all studies were pooled, regardless of design or quality. However, survival benefits diminished in study subsets that matched trial participants and routine care patients for eligibility criteria (HR, 0.85 [95% CI, 0.75-0.97]) and disappeared when only high-quality studies were pooled (HR, 0.91 [95% CI, 0.80-1.05]). They also disappeared when estimates were adjusted for potential publication bias (HR, 0.94 [95% CI, 0.86-1.03]). Many studies suggest a survival benefit for cancer trial participants. However, these benefits were not detected in studies using designs addressing important sources of bias and confounding. Pooled results of high-quality studies are not consistent with a beneficial effect of trial participation on its own.

Synergistic neuromodulation therapy for persistent spinal pain: a proof-of-concept trial on the use of spinal cord and dorsal root ganglion stimulation.

Persistent Spinal Pain Syndrome type 2 (PSPS-T2) poses a significant clinical challenge, demanding innovative therapeutic interventions. The integration of Spinal Cord Stimulation (SCS) and Dorsal Root Ganglion Stimulation (DRG-S) is emerging as a potent synergistic strategy for comprehensive pain management. This single patient-blind proof of concept (POC) trial explores the efficacy and synergistic potential of combined SCS and DRG-S in a patient with refractory PSPS-T2. A 45-year-old male with intractable PSPS-T2 underwent a unique, methodically structured study, involving three treatment phases: Phase A with SCS alone, Phase B with DRG-S alone, and Phase C The patient, blinded to the treatment modalities, provided pain assessments using the Visual Analogue Scale (VAS) and Douleur Neuropathique 4 Questions (DN4) conducted by clinical investigators at each phase. Baseline pain scores were ten and nine, respectively. Distinct responses were noted across the phases. Phase A demonstrated moderate pain relief, while Phase B offered further pain intensity reduction. However, Phase C, combining both strategies, yielded the most significant improvement, remarkably enhancing the patient's quality of life and functional capacity. This POC trial underscores the synergistic potential of SCS and DRG-S in managing complex cases of PSPS-T2, suggesting a paradigm shift towards integrated neuromodulation strategies for enhanced pain control. The development of dual intent implantable pulse generators (IPGs) capable of offering combination therapy simultaneously might be effective for pain management in select cases. The significant pain reduction and functional improvement observed advocate for further research in dual neuromodulation therapies. IRB 20190536.

Imaging of Pain using Positron Emission Tomography.

Positron emission tomography (PET) is a noninvasive molecular imaging technique that utilizes biologically active radiolabeled compounds to image biochemical processes. As such, PET can provide important pathophysiological information associated with pain of different etiologies. As such, the information obtained using PET often combined with MRI or CT can provide useful information for diagnosing and monitoring changes associated with pain. This review covers the most important PET tracers that have been used to image pain including tracers for fundamental biological processes such as glucose metabolism and cerebral blood flow to receptor-specific tracers such as ion channels and neurotransmitters. For tracer type, we describe the structure and radiochemical synthesis of the tracer followed by a brief summary of the available preclinical and clinical studies. By providing a summary of the PET tracers that have been employed for PET imaging of pain, this review aims to serve as a reference for preclinical, translational and clinical investigators interested in molecular imaging of pain. Finally, the review ends with an outlook of the needs and opportunities in this area.

The patterns in urine excretion and transvascular fluid exchange in human subjects during intravenous fluid infusion: A quantitative analysis.

Investigations of responses of animals and humans to changes of plasma volume are usually reported as average responses of groups of individuals. This ignores considerable quantitative variation between individuals. We examined the hypothesis that individual responses follow a common temporal pattern with variations reflecting different parameters describing that pattern. We illustrate this approach using data of Hahn, Lindahl and Drobin (Acta Anaesthesiol Scand.2011, 55:987-94) who measured urine volume and haemoglobin dilution of 10 female subjects during intravenous Ringer infusions for 30 min and subsequent 3.5 h. The published time courses were digitised and analysed to determine if a family of mathematical functions accounted for the variation in individual responses. Urine excretion was characterised by a time delay (Td) before urine flow increased and a time course of cumulative urine excretion described by a logarithmic function. This logarithmic relation forms the theoretical basis of a family of linear relations describing urine excretion as a function of Td. Measurement of Td enables estimation of subsequent values of urine excretion and thereby the fraction of infused fluid retained in the body. The approach might be useful for physiologists and clinical investigators to compare the response to infusion protocols when both test and control responses can be described by linear relations between cumulative urine volume at specific times and Td. The approach may also be useful for clinicians by complementing strategies to guide fluid therapy by enabling the later responses of an individual to be predicted from their earlier response.

Efficacy and safety study of targeted small-molecule drugs in the treatment of systemic lupus erythematosus

BackgroundTargeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is still a lack of evidence on the difference in the efficacy and safety of different targeted small-molecule drugs. Therefore, this study was conducted to assess the efficacy and safety of different targeted small-molecule drugs for SLE.MethodsRandomized controlled trials (RCTs) on targeted small-molecule drugs in the treatment of SLE in PubMed, Web of Science, Embase, and Cochrane Library were systematically searched as of April 25, 2023. Risk of bias assessment was performed for included studies using the Cochrane’s tool for evaluating the risk of bias. The primary outcome indicators were SRI-4 response, BICLA response, and adverse reaction. Because different doses and courses of treatment were used in the included studies, Bayesian network meta-regression was used to investigate the effect of different doses and courses of treatment on efficacy and safety.ResultsA total of 13 studies were included, involving 3,622 patients and 9 targeted small-molecule drugs. The results of network meta-analysis showed that, in terms of improving SRI-4, Deucravacitinib was significantly superior to that of Baricitinib (RR = 1.32, 95% CI (1.04, 1.68), P < 0.05). Deucravacitinib significantly outperformed the placebo in improving BICLA response (RR = 1.55, 95% CI (1.20, 2.02), P < 0.05). In terms of adverse reactions, targeted small-molecule drugs did not significantly increase the risk of adverse events as compared to placebo (P > 0.05).ConclusionBased on the evidence obtained in this study, the differences in the efficacy of targeted small-molecule drugs were statistically significant as compared to placebo, but the difference in the safety was not statistically significant. The dose and the course of treatment had little impact on the effect of targeted small-molecule drugs. Deucravacitinib could significantly improve BICLA response and SRI-4 response without significantly increasing the risk of AEs. Therefore, Deucravacitinib is very likely to be the best intervention measure. Due to the small number of included studies, more high-quality clinical evidence is needed to further verify the efficacy and safety of targeted small-molecule drugs for SLE.

Critical re-evaluation of the identification of iron deficiency states and effective iron repletion strategies in patients with chronic heart failure.

According to current guidelines, iron deficiency is defined by a serum ferritin level <100 ng/ml or a transferrin saturation (TSAT) <20% if the serum ferritin level is 100-299 μg/L. These criteria were developed to encourage the use of intravenous iron as an adjunct to erythropoiesis-stimulating agents in the treatment of renal anaemia. However, in patients with heart failure, these criteria are not supported by any pathophysiological or clinical evidence that they identify an absolute or functional iron deficiency state. A low baseline TSAT-but not serum ferritin level-appears to be a reliable indicator of the effect of intravenous iron to reduce major heart failure events. In randomized controlled trials, intravenous iron decreased the risk of cardiovascular death or total heart failure hospitalization in patients with a TSAT <20% (risk ratio 0.67 [0.49-0.92]) but not in patients with a TSAT ≥20% (risk ratio 0.99 [0.74-1.30]), with the magnitude of the risk reduction being proportional to the severity of hypoferraemia. Patients who were enrolled in clinical trials solely because they had a serum ferritin level <100 μg/L showed no significant benefit on heart failure outcomes, and it is noteworthy that serum ferritin levels of 20-300 μg/L lie entirely within the range of normal values for healthy adults. Current guidelines reflect the eligibility criteria of clinical trials, which inadvertently adopted unvalidated criteria to define iron deficiency. Reliance on these guidelines would lead to the treatment of many patients who are not iron deficient (serum ferritin level <100 μg/L but normal TSAT) and ignores the possibility of iron deficiency in patients with a low TSAT but with serum ferritin level of >300 μg/L. Importantly, analyses of benefit based on trial eligibility-driven guidelines substantially underestimate the magnitude of heart-failure-event risk reduction with intravenous iron in patients who are truly iron deficient. Based on all available data, we recommend a new mechanism-based and trial-tested approach that reflects the totality of evidence more faithfully than the historical process adopted by clinical investigators and by the guidelines. Until additional evidence is forthcoming, an iron deficiency state in patients with heart failure should be defined by a TSAT <20% (as long as the serum ferritin level is <400 μg/L), and furthermore, the use of a serum ferritin level <100 μg/L alone as a diagnostic criterion should be discarded.

Investigator Participation in Clinical Research: An Examination of Barriers and Facilitators in the Indian Clinical Trials Settings

Background: This study aims to improve clinical research by identifying the barriers and facilitators for investigators conducting trials. We explore investigator demographics, challenges faced, and factors promoting engagement. Additionally, we examine how investigators’ background influences their experiences with both barriers and facilitators, ultimately aiming to foster a patient-centric clinical trial ecosystem. Methods: A quantitative, exploratory study investigated barriers and facilitators in clinical trials among 132 investigators in India. A self-designed questionnaire captured experiences with challenges, strategies, and facilitators. Pilot testing ensured tool validity and reliability. Ethical considerations were addressed, and data analysis will identify key factors impacting investigator engagement. This study aims to improve the clinical research ecosystem in India. Results: The study aims to identify the facilitators and barriers experienced by the research investigators. An online questionnaire survey was used in this cross-sectional investigation. The study's population consists of 132 respondents, with 68 (51.5%) males and 64 (48.5%) females. Clinical Research Coordinators (CRCs) (41.7%), Research Associates (RA’s) (27.3%), Supporting staff (19.7%), Co-Investigators (Co-I) (6.8%), and Principal Investigators (PIs) (4.5%) which were the majority of respondents. The most common barriers found among the principal investigators regarding the limited resources (p=0.014) towards the clinical trials. Inadequate training (p=0.461), Complex regulations (p=0.625), and Communication barriers (p=0.853) did not seem like barriers to the clinical research staff. Whereas some of the staff faced barriers (p=0.118) with the complex regulations and Inadequate training on the other hand most of the respondents considered the same statements as facilitators (p=0.963) with their daily working activities. Conclusion: The Barriers and Facilitators experienced by the clinical investigators, It was found that there is no difference in viewpoint. As per the results, Research associates agreed more with the facilitators and the principal investigators faced barriers.

Abstract PO3-02-01: Educational Opportunities to Improve Community Healthcare Professionals’ Management of High-Risk HR-Positive/HER2-Negative Early Breast Cancer

Abstract Background: The treatment landscape for patients with hormone receptor–positive/HER2-negative early breast cancer (HR+/HER2- EBC) has evolved with the emergence of adjuvant CDK4/6 inhibitor therapy as a new option for patients with a high risk of disease recurrence. Adjuvant abemaciclib plus aromatase inhibitors (AIs) is guideline recommended for high clinical risk HR+ disease and reduces risk of recurrence regardless of Ki-67 expression level. Here, we examine healthcare professionals’ (HCPs’) awareness and practice regarding the use of adjuvant abemaciclib. Methods: Between November 2022 and June 2023, we conducted a series of regional educational activities for HCPs focused on management of high-risk HR+/HER2- EBC. Each activity included an interactive lecture led by a clinical investigator with expertise in managing patients with high-risk HR+/HER2- EBC and polling questions designed to assess key aspects of HCP knowledge and practice in the optimal management of high-risk HR+/HER2- EBC. A wider HCP audience was able to view an interactive on-demand webcast with the same content and embedded polling questions. Results: In total, 701 HCPs participated in one of 20 live (n = 373) activities or the one associated on-demand (n = 328) webcast. The distribution of HCP participation differed between the live and online activities with more physicians participating in the online activity vs the live activity (59% vs 34%, respectively); the converse was true for nurse participation (9% online vs 34% live). Polling result trends were similar between the live and online activities. At baseline, 38% (n/N = 182/405) of HCPs chose adjuvant therapy with an AI plus abemaciclib for a patient with high-risk, node-positive HR+/HER2- EBC consistent with expert and guideline recommendations. Following the education, 92% (n/N = 405/439) of HCPs selected AI plus abemaciclib for appropriate patients. Before education, 32% of HCPs (n/N = 147/454) were aware that adjuvant abemaciclib plus endocrine therapy improved invasive disease-free survival compared with endocrine therapy alone in patients with high-risk, node-positive HR+/HER2- EBC regardless of Ki-67 expression level, which increased to 87% (n/N = 370/425) following the education. Regarding the management of grade 2 neutropenia associated with adjuvant abemaciclib therapy, HCP knowledge was low at baseline (32%, n/N = 141/446) and improved to 80% (n/N = 332/415) after education. Conclusions: HCPs’ knowledge of and practice concerning adjuvant abemaciclib as a newer approved therapy for patients with high-risk HR+/HER2- EBC remain suboptimal. These results suggest an ongoing need for expert guidance and educational activities on the use of adjuvant abemaciclib therapy for appropriate patients with high-risk HR+/HER2- EBC. As the treatment landscape for HR+/HER2- EBC continues to evolve with the potential approval of additional new therapies, this need will only increase with a clear impact on optimizing and individualizing adjuvant therapy strategies for patients with HR+/HER2- EBC. Citation Format: Marie Becker, Timothy Quill, Erika Hamilton, Joyce O'Shaughnessy. Educational Opportunities to Improve Community Healthcare Professionals’ Management of High-Risk HR-Positive/HER2-Negative Early Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-01.

Efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease: A protocol for meta-analysis and systematic review.

The incidence of gastroesophageal reflux disease (GERD) is increasing year by year, the clinical manifestations are complex and diverse, and the adverse effects of long-term use of proton pump inhibitors and gastrointestinal motility drugs have been of great concern in recent years. The effectiveness of tegoprazan in the treatment of GERD is still controversial. This protocol describes a systematic review and meta-analysis to evaluate the efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease. PubMed, Embase, Cochrane Library and Web of Science will be searched from the database inception to 1 March 2023. All randomized controlled trials related to tegoprazan for GERD will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be complete resolution of major symptoms, complete resolution of heartburn, proportion of heartburn-free days, chronic cough, hoarseness, and adverse events. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The results of this study will provide reliable evidence to evaluate the efficacy and safety of tegoprazan in the treatment of GERD and help patients, physicians and clinical investigators choose the most appropriate treatment.

Trends in clinical management of lactational mastitis among women attending Australian general practice: a national longitudinal study using MedicineInsight, 2011–2022

ObjectiveTo examine longitudinal trends in clinical management of lactational mastitis in women attending general practice.DesignOpen cohort study.SettingAustralian general practice using data from MedicineInsight.ParticipantsWomen aged 18 to 44 years with one...

Biomedical Researchers Should be Taught Statistics Differently than Biostatisticians in Training: Illustration of a Module within a Clinical Research Seminar Course

The predominant model for biomedical research is team science. Two critical members of the team are the clinical investigator and the biostatistician. Typically, the biostatistician performs statistical analyses and the clinical investigator interprets the results. Clinical investigators have different background and interests than biostatisticians, and should be taught statistics differently. Concepts should be phrased in plain language, illustrations should replace mathematical derivations, and underlying statistical concepts should be explicitly named. Consistent with basic principles of constructivism, clinical investigators and biostatisticians will (and should) have different but overlapping mental maps of statistics. Our approach is illustrated through the description of a module within a research seminar course for clinical investigators.

Clinical investigator perspectives on patient outcomes in children with neuronopathic mucopolysaccharidosis II during intrathecal idursulfase-IT treatment

BackgroundMucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by iduronate-2-sulfatase gene (IDS) deficiency and downstream glycosaminoglycan accumulation. Two-thirds of patients present with neuronopathic disease and evaluating cognitive function in these patients is challenging owing to limitations of currently available tests. During the clinical development of intrathecal idursulfase (idursulfase-IT), regulatory authorities requested qualitative data to further understand the neurocognitive changes observed by the investigators through the clinical trials.ResultsThis qualitative study consisted of semi-structured interviews with all nine of the principal investigators who participated in the idursulfase-IT phase 2/3 (NCT02055118) and extension (NCT02412787) trials. These investigators enrolled the 56 patients with neuronopathic MPS II who qualified for the extension phase of the trial. The investigators were asked to rate the disease status of their patients. Of the 56 patients, 49 (88%) were rated as having disease that was improved/improving, stabilized or slowing progression compared with the expected outcomes with no treatment. Three patients were rated as worsening, while the remaining four patients were considered to have slowing progression or worsening disease. Similar results were demonstrated for patients aged from 3 to under 6 years at baseline, with 33 of 39 patients (85%) rated as having disease that was improved/improving, stabilized or slowing progression. Of the seven patients rated with slowing progression/worsening or worsening disease, five of them had an IDS variant other than missense, while two had a missense class variant. All the assigned improved/improving ratings were in patients receiving idursulfase-IT from the start of the phase 2/3 trial. Moreover, patients under 3 years of age at baseline were all rated as either improved/improving or stabilized disease. In a blinded review of patient profiles, investigators were requested to assign a disease status rating to 18 patients with large IDS deletions; 67% of these patients were rated as improved/improving or stabilized disease.ConclusionsThis qualitative analysis provides a snapshot of clinicians’ considerations when evaluating treatment in patients with neuronopathic MPS II, compared with the expected decline in cognitive function in the absence of treatment. The results highlight the importance of robust assessment tools in treatment evaluation.

Impact assessment of integrated-pathy on cancer-related fatigue in cancer patients: an observational study.

Integrated-pathy aims to integrate modern medicine with traditional systems via applying the holistic approach of Ayurveda, Yoga, and natural medicine. This is important for addressing the challenges surrounding the delivery of long-term palliative care for chronic ailments including cancer. The prime intent of this study was to substantiate the underlying hypothesis behind the differential and integrative approach having a positive impact on Quality of Life of cancer patients. Cross-sectional Observational study. A standardized questionnaire was developed and used, after obtaining written informed consent from patients to assess the impact of Integrated-pathy on patients (n = 103) diagnosed with cancer receiving care at Patanjali Yoggram. The research was carried out over 8 months. All participants received a uniform treatment protocol as prescribed by Patanjali. For the sample size determination and validation, α and 1-β was calculated and for the significance of the pre- and post-treatment QoL ratings, Shapiro wilk test and other descriptive statistics techniques were explored. A total of 103 patients seeking cancer special-healthcare were interviewed, out of which 39 (37.86%) remained finally based on the inclusion/exclusion criteria with age (25-65years), types of cancers (Carcinoma and Sarcoma), chemotherapy/radiotherapy received or not, before opting Integrated-pathy. Follow-ups revealed a significant increase in the QoL (17.91%) after receiving the integrated therapy over a course of at least 1 month. Further, a significant reduction in cancer-related pain followed by an increase in QoL index was reported in the patients. Shapiro-wilk test revealed significant pairing (p < 0.001) with validation of the model using test. To bolster evidence-based backing for Integrated-pathy, there is a need for clearly delineated clinical indicators that are measurable and trackable over time. Clinical investigators are encouraged to incorporate Integrated-pathy into their proposed interventions and conduct analogous studies to yield sustained advantages in the long run.

Clinical photodynamic therapy: The evolution of photodynamic therapy treatment of head and neck cancer

The modern era of photodynamic therapy (PDT) treatment of human cancer began in earnest in 1978, with the publication by Dougherty et al. of the first large series of humans with refractory or recurrent skin cancers successfully treated with PDT using HpD (Photofrin). The first human series of head and neck cancer patients successfully treated with PDT (Photofrin) was published in 1985, by Keller et al. Since that time, numerous clinical investigators around the world have treated thousands of head and neck cancer patients with PDT in clinical trials. These head and neck cancer PDT clinical trials enrolled patients with various stages of disease, and locations of the tumor and were treated using a variety of photosensitizers. Head and neck cancer PDT treatments were performed as the primary treatment with the intent to cure, as a late-stage treatment for palliation of the tumor, or as an adjuvant or neoadjuvant treatment in combination with surgery, radiation, chemotherapy and most recently immunotherapy. Over the past five decades, head and neck cancer PDT has evolved as newer and more targeted photosensitizers became available for clinical use, as well as advances in laser and fiberoptic technologies allowing for the activating light to be successfully and more easily delivered deep into large invasive tumors. In addition, PDT can be accurately delivered using endoscopic, robotic, CT, ultrasound and MRI guidance thereby specifically targeting the tumor and reducing treatment morbidity. Significant progress has been achieved in the ease of use and treatment efficacy of head and neck cancer PDT in various stages of the disease.

Attitudes on data reuse among internal medicine residents.

NYU Langone Health offers a collaborative research block for PGY3 Primary Care residents that employs a secondary data analysis methodology. As discussions of data reuse and secondary data analysis have grown in the data library literature, we sought to understand what attitudes internal medicine residents at a large urban academic medical center had around secondary data analysis. This case report describes a novel survey on resident attitudes around data sharing. We surveyed internal medicine residents in three tracks: Primary Care (PC), Categorical, and Clinician-Investigator (CI) tracks as part of a larger pilot study on implementation of a research block. All three tracks are in our institution's internal medicine program. In discussions with residency directors and the chief resident, the term "secondary data analysis" was chosen over "data reuse" due to this being more familiar to clinicians, but examples were given to define the concept. We surveyed a population of 162 residents, and 67 residents responded, representing a 41.36% response rate. Strong majorities of residents exhibited positive views of secondary data analysis. Moreover, in our sample, those with exposure to secondary data analysis research opined that secondary data analysis takes less time and is less difficult to conduct compared to the other residents without curricular exposure to secondary analysis. The survey reflects that residents believe secondary data analysis is worthwhile and this highlights opportunities for data librarians. As current residents matriculate into professional roles as clinicians, educators, and researchers, libraries have an opportunity to bolster support for data curation and education.

Abstract 7229: In situ trans-differentiation therapy effectively terminates the growth and recurrence of glioblastoma

Abstract Background: Glioblastoma (GBM) is the most common and malignant brain tumor in adults, and remains almost invariably lethal due to its aggressive and invasive nature. The standard first-line treatment for GBM is surgical resection, postoperative radiotherapy and chemotherapy with temozolomide (TMZ), but it exhibits short-term effects due to a high recurrence rate of GBM is its (up to almost one hundred percent). This long-existing clinical challenge has demanded development of novel and effective therapeutic strategies. In situ cell trans-differentiation therapy which direct reprograms tumor cells into terminally differentiated benign cells represents a novel therapeutic strategy for tumors. We further explored the application of in situ trans-differentiation therapy for glioblastoma. Results: In the present study, we have conducted a large-scale screen for transcription factors which can reprogram glioblastoma cells into terminally differentiated postmitotic cells. Over-expression of a combo of selected trans-differentiation factors that possess the highest trans-differentiation rate effectively reprogramed human glioma cells into neuronal-like cells with characteristic neuronal morphology and expression of neuronal genes in culture, as a result substantially reducing glioblastoma cell proliferation and tumor development after orthotopic transplantation. With replicable recombinant oncolytic virus vectors, product candidate can specifically replicate in glioma cells, therefore transcription factors can be specifically delivered to all tumor cells rather than normal cells. In either cell line-derived or patient-derived tumor tissue xenograft models, intra-tumoral injection product candidate inhibited glioblastoma cells growth at an exceptionally high efficiency. Remarkably product candidate combination with TMZ resulted in a complete regression of tumor and no recurrence was observed in animal model cases. Conclusion: In summary, our findings have established a novel therapeutic approach for treating glioblastoma by terminating sustained proliferation of glioma cells via transcription factors-induced in situ cell trans-differentiation and supported further clinic investigations in patients. Citation Format: Huihui Zhao, Zhaozhong Li, Xiaohui Zhang, Congjian Zhao, Zhao Zhu, Yueguang Liu. In situ trans-differentiation therapy effectively terminates the growth and recurrence of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7229.

Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial

BackgroundTelomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years.MethodsThe CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20–75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements.Findings1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group.ConclusionPatients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease.Trial RegistrationClinicaltrials.gov number NCT00924937.