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Progress in Molecular Biology and... 2024Repurposing drugs for rare diseases is a creative and cost-efficient method for creating new treatment options for certain conditions. This technique entails repurposing... (Review)
Review
Repurposing drugs for rare diseases is a creative and cost-efficient method for creating new treatment options for certain conditions. This technique entails repurposing existing pharmaceuticals for new uses by utilizing established information regarding pharmacological characteristics, modes of operation, safety profiles, and interactions with biological systems. Creating new treatments for uncommon diseases is frequently difficult because of factors including small patient groups, disease intricacy, and insufficient knowledge of disease pathobiology. Drug repurposing is a more efficient and cost-effective approach compared to developing new drugs from scratch. It typically requires collaboration among academia, pharmaceutical firms, and patient advocacy groups.
Topics: Rare Diseases; Humans; Drug Repositioning
PubMed: 38942540
DOI: 10.1016/bs.pmbts.2024.03.034 -
Progress in Molecular Biology and... 2024Respiratory infections such as Coronavirus disease 2019 are a substantial worldwide health challenge, frequently resulting in severe sickness and death, especially in... (Review)
Review
Respiratory infections such as Coronavirus disease 2019 are a substantial worldwide health challenge, frequently resulting in severe sickness and death, especially in susceptible groups. Conventional drug development for respiratory infections faces obstacles such as extended timescales, substantial expenses, and the rise of resistance to current treatments. Drug repurposing is a potential method that has evolved to quickly find and reuse existing medications for treating respiratory infections. Drug repurposing utilizes medications previously approved for different purposes, providing a cost-effective and time-efficient method to tackle pressing medical needs. This chapter summarizes current progress and obstacles in repurposing medications for respiratory infections, focusing on notable examples of repurposed pharmaceuticals and their probable modes of action. The text also explores the significance of computational approaches, high-throughput screening, and preclinical investigations in identifying potential candidates for repurposing. The text delves into the significance of regulatory factors, clinical trial structure, and actual data in confirming the effectiveness and safety of repurposed medications for respiratory infections. Drug repurposing is a valuable technique for quickly increasing the range of treatments for respiratory infections, leading to better patient outcomes and decreasing the worldwide disease burden.
Topics: Drug Repositioning; Humans; Respiratory Tract Infections; COVID-19 Drug Treatment; SARS-CoV-2; COVID-19; Antiviral Agents; Animals
PubMed: 38942538
DOI: 10.1016/bs.pmbts.2024.03.033 -
Progress in Molecular Biology and... 2024Personalized medicine has emerged as a revolutionary approach to healthcare in the 21st century. By understanding a patient's unique genetic and biological... (Review)
Review
Personalized medicine has emerged as a revolutionary approach to healthcare in the 21st century. By understanding a patient's unique genetic and biological characteristics, it aims to tailor treatments specifically to the individual. This approach takes into account factors such as an individual's lifestyle, genetic makeup, and environmental factors to provide targeted therapies that have the potential to be more effective and lower the risk of side reactions or ineffective treatments. It is a paradigm shift from the traditional "one size fits all" approach in medicine, where patients with similar symptoms or diagnoses receive the same standard treatments regardless of their differences. It leads to improved clinical outcomes and more efficient use of healthcare resources. Drug repurposing is a strategy that uses existing drugs for new indications and aims to take advantage of the known safety profiles, pharmacokinetics, and mechanisms of action of these drugs to accelerate the development process. Precision medicine may undergo a revolutionary change as a result, enabling the rapid development of novel treatment plans utilizing drugs that traditional methods would not otherwise link to. In this chapter, we have focused on a few strategies wherein drug repurposing has shown great success for precision medicine. The approach is particularly useful in oncology as there are many variations induced in the genetic material of cancer patients, so tailored treatment approaches go a long way. We have discussed the cases of breast cancer, glioblastoma and hepatocellular carcinoma. Other than that, we have also looked at drug repurposing approaches in anxiety disorders and COVID-19.
Topics: Drug Repositioning; Humans; Precision Medicine; COVID-19; Neoplasms
PubMed: 38942534
DOI: 10.1016/bs.pmbts.2024.02.007 -
Korean Journal of Radiology Jul 2024This study aimed to evaluate the diagnostic efficacy and safety of low-contrast-dose, dual-source dual-energy CT before transcatheter aortic valve replacement (TAVR) in...
OBJECTIVE
This study aimed to evaluate the diagnostic efficacy and safety of low-contrast-dose, dual-source dual-energy CT before transcatheter aortic valve replacement (TAVR) in patients with compromised renal function.
MATERIALS AND METHODS
A total of 54 consecutive patients (female:male, 26:38; 81.9 ± 7.3 years) with reduced renal function underwent pre-TAVR dual-energy CT with a 30-mL contrast agent between June 2022 and March 2023. Monochromatic (40- and 50-keV) and conventional (120-kVp) images were reconstructed and analyzed. The subjective quality score, vascular attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared among the imaging techniques using the Friedman test and post-hoc analysis. Interobserver reliability for aortic annular measurement was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The procedural outcomes and incidence of post-contrast acute kidney injury (AKI) were assessed.
RESULTS
Monochromatic images achieved diagnostic quality in all patients. The 50-keV images achieved superior vascular attenuation and CNR ( < 0.001 in all) while maintaining a similar SNR compared to conventional CT. For aortic annular measurement, the 50-keV images showed higher interobserver reliability compared to conventional CT: ICC, 0.98 vs. 0.90 for area and 0.97 vs. 0.95 for perimeter; 95% limits of agreement width, 0.63 cm² vs. 0.92 cm² for area and 5.78 mm vs. 8.50 mm for perimeter. The size of the implanted device matched CT-measured values in all patients, achieving a procedural success rate of 92.6%. No patient experienced a serum creatinine increase of ≥ 1.5 times baseline in the 48-72 hours following CT. However, one patient had a procedural delay due to gradual renal function deterioration.
CONCLUSION
Low-contrast-dose imaging with 50-keV reconstruction enables precise pre-TAVR evaluation with improved image quality and minimal risk of post-contrast AKI. This approach may be an effective and safe option for pre-TAVR evaluation in patients with compromised renal function.
Topics: Humans; Male; Female; Contrast Media; Aged, 80 and over; Transcatheter Aortic Valve Replacement; Tomography, X-Ray Computed; Aged; Acute Kidney Injury; Aortic Valve Stenosis; Radiography, Dual-Energy Scanned Projection; Radiation Dosage; Reproducibility of Results; Renal Insufficiency; Retrospective Studies; Signal-To-Noise Ratio
PubMed: 38942457
DOI: 10.3348/kjr.2023.1207 -
Journal of the American Board of Family... Jun 2024The 2022 Centers for Disease Control's "Clinical Practice Guidelines for Prescribing Opioids for Pain in United States" called for attention and action toward reducing...
BACKGROUND
The 2022 Centers for Disease Control's "Clinical Practice Guidelines for Prescribing Opioids for Pain in United States" called for attention and action toward reducing disparities in untreated and undertreated pain among Black and Latino patients. There is growing evidence for controlled substance safety committees (CSSC) to change prescribing culture, but few have been examined through the lens of health equity. We examined the impact of a primary care CSSC on opioid prescribing, including by patients' race and sex.
METHODS
We conducted a retrospective cohort study. Our primary outcome was a change in prescribed morphine milligram equivalents (MME) at baseline (2017) and follow-up (2021). We compared the differences in MME by race and sex. We also examined potential intersectional disparities. We used paired test to compare changes in mean MME's and logistic regression to determine associations between patient characteristics and MME changes.
RESULTS
Our cohort included 93 patients. The mean opioid dose decreased from nearly 200 MME to 136.1 MME, . Thirty percent of patients had their dose reduced to under 90 MME by follow-up. The reduction rates by race or sex alone were not statistically significant. There was evidence of intersectional disparities at baseline. Black women were prescribed 88.5 fewer MME's at baseline compared with their White men counterparts, .
DISCUSSION
Our findings add to the previously documented success of CSSCs in reducing opioid doses for chronic nonmalignant pain to safer levels. We highlight an opportunity for primary care based CSSCs to lead the efforts to identify and address chronic pain management inequities.
PubMed: 38942449
DOI: 10.3122/jabfm.2023.230220R2 -
BMJ Open Quality Jun 2024Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous...
OBJECTIVES
Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous administration process.
DESIGN
A qualitative focus group interview study.
SETTING
Focused interviews were conducted using process mapping with frontline nurses responsible for medication administration in September 2020.
PARTICIPANTS
Front line experiened nurses from a Japanese tertiary teaching hospital.
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary outcome measure was to identify the mental models frontline nurses used during intravenous medication administration, which influence their interactions with patients, and secondarily, to examine the medication process gaps between the mental models nurses perceive and the actual defined medication administration process.
RESULTS
We found gaps between the perceived clinical administration process and the real process challenges with an emphasis on the importance of verifying to see if the drug was ordered for the patient immediately before its administration.
CONCLUSIONS
This novel and applied improvement approach can help nurses and managers better understand the process vulnerability of the infusion process and develop a deeper understanding of the administration steps useful for reliably improving the safety of intravenous medications.
Topics: Humans; Qualitative Research; Medication Errors; Focus Groups; Patient Safety; Infusions, Intravenous; Perception; Female; Administration, Intravenous; Adult; Nursing Staff, Hospital; Male; Japan; Interviews as Topic; Attitude of Health Personnel
PubMed: 38942437
DOI: 10.1136/bmjoq-2024-002809 -
Environmental Research Jun 2024Microplastics (MPs) can enter the reproductive system and can be potentially harmful to human reproductive health. In this study, 13 types of microplastics (MPs) were...
Microplastics (MPs) can enter the reproductive system and can be potentially harmful to human reproductive health. In this study, 13 types of microplastics (MPs) were identified in patient blood, cancer samples, and paracarcinoma samples using Raman spectroscopy, with polyethylene, polypropylene and polyethylene-co-polypropylene being the most abundant polymer types. Futher, cotton was also found in our study. The diversity and abundance of MPs were higher in blood samples than in cancerous tissues, and there was a significant positive correlation between diversity (p < 0.05). Furthermore, the diversity and abundance of MPs in cancerous tissues were higher than in paracancerous tissues. The dimensional sizes of MPs in these samples were also very similar, with the majority of detected MPs being smaller in size. Correlation analysis showed that patient's age correlated with the abundance of MPs in blood samples, body mass index (BMI) correlated with the abundance of MPs in cancerous tissues. Notably, the frequency with which patients consume bottled water and beverages may also increase the abundance of MPs. This study identifies for the first time the presence of MPs and cotton in cancerous and paracancerous tissues of human cervical cancer patients. This provides new ideas and basic data to study the risk relationship between MP exposure and human health.
PubMed: 38942254
DOI: 10.1016/j.envres.2024.119498 -
Journal of Shoulder and Elbow Surgery Jun 2024Previous studies have demonstrated the safety and cost-effectiveness of outpatient total shoulder arthroplasty (TSA), with the majority of studies focusing on 90-day...
BACKGROUND
Previous studies have demonstrated the safety and cost-effectiveness of outpatient total shoulder arthroplasty (TSA), with the majority of studies focusing on 90-day outcomes and complications. Patient selection algorithms have helped appropriately choose patients for an outpatient TSA setting. This study aimed to determine the outcomes of TSA between outpatient and inpatient cohorts with at least a 2-year follow-up.
METHODS
A retrospective review identified patients older than 18 years who underwent a TSA with a minimum of 2-year follow-up in either an inpatient or outpatient setting. Using a previously published outpatient TSA patient-selection algorithm, patients were allocated into three groups: outpatient, inpatient due to insurance requirements, and inpatient due to not meeting algorithm criteria. Outcomes evaluated included visual analog scale (VAS) pain, American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score, range of motion (ROM), strength, complications, re-admissions, and re-operations. Analysis was performed between the outpatient and inpatient groups to demonstrate the safety and efficacy of outpatient TSA with midterm follow-up.
RESULTS
A total of 779 TSA were included in this study, allocated into the outpatient (N = 108), inpatient due to insurance (N = 349), and inpatient due to algorithm (N = 322). The average age between these groups was significantly different (59.4 ± 7.4, 66.5 ± 7.5, and 72.5 ± 8.7, respectively; P < 0.0001). All patient groups demonstrated significant improvements in preoperative to final patient-outcomes scores, ROM, and strength. Analysis between cohorts showed similar final follow-up outcome scores, ROM, and strength, with few significant differences that are likely not clinically different, regardless of surgical location, insurance status, or meeting patient-selection algorithm. Complications, reoperations, and readmissions between all three groups were not significantly different.
CONCLUSION
This study reaffirms prior short-term follow-up literature. Transitioning appropriate patients to outpatient TSA results in similar outcomes and complications compared to inpatient cohorts with mid-term follow-up.
PubMed: 38942227
DOI: 10.1016/j.jse.2024.05.012 -
Biochimica Et Biophysica Acta. Reviews... Jun 2024Thymic epithelial tumors (TETs) are rare neoplasms of the anterior mediastinum that arise from thymic epithelial cells. Although surgery is the preferred treatment for... (Review)
Review
Thymic epithelial tumors (TETs) are rare neoplasms of the anterior mediastinum that arise from thymic epithelial cells. Although surgery is the preferred treatment for resectable TETs, the options for unresectable or recurrent advanced-stage TETs are limited beyond platinum-based chemotherapy. The evolving landscape of TET treatments is marked by significant advancements in targeted therapies and immunotherapies, particularly with anti-angiogenic agents and immune checkpoint inhibitors (ICIs). While monotherapies demonstrated certain efficacy, the development of combination strategies is vital for improving patient outcomes. This review consolidates progress in anti-angiogenic therapies and ICIs, emphasizing the evolution of combination therapies of TETs. Furtherly, we particularly discuss new first-line strategies based on these advancements and emphasizes exploring novel treatments like antibody-drug conjugates, immunomodulatory drugs and cytokine-based agents for TETs. Mechanistically, the molecular features of TETs integrated with clinical diagnosis and targeted therapy, and immunophenotyping of TETs along with its impact on the efficacy and safety of immunotherapy are discussed. Thus, this review systemizes the development in the treatment landscape of TETs, integrating the corresponding molecular and immune mechanisms, aiming to provide new references for the treatment of TETs.
PubMed: 38942215
DOI: 10.1016/j.bbcan.2024.189145 -
Journal of Gastrointestinal Surgery :... Jun 2024Perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, and gall bladder cancer are difficult malignancies to treat, and are characterized by a tendency for local...
INTRODUCTION
Perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, and gall bladder cancer are difficult malignancies to treat, and are characterized by a tendency for local recurrence and a generally unfavorable prognosis. Surgical resection offers the only potential cure, conventionally performed via the open approach. While minimally invasive approaches show promise, data remains limited.
METHODS
With IRB approval, we prospectively followed 100 patients between 2013-2023 who underwent robotic surgical resection for perihilar, intrahepatic (IHCC) and gallbladder cholangiocarcinoma. Data are presented as median (mean ± standard deviation). Significance was accepted at p≤0.05.
RESULTS
The median patient age was 70 years, and the median operative duration was 333minutes, with an estimated blood loss of 200mL. Importantly, there were no unplanned conversions, and only 1 intraoperative complication occurred within the IHCC cohort. The median length of stay was 4 days. There was a total of 19 postoperative complications and 19 readmissions within 30 days. Additionally, there were three in-hospital mortalities and five 90-day mortalities. R0 resection was achieved in 87% of patients, and R1 resection in 13%. At a median follow-up of 36 months, 62% of patients demonstrated disease-free survival, while 6% continued to live with the disease and 32% did not survive.
CONCLUSIONS
Our experience demonstrates the feasibility and safety of robotic resection for these complex malignancies, yielding promising short-term outcomes. Further investigation is required to ascertain the long-term oncological outcomes.
PubMed: 38942191
DOI: 10.1016/j.gassur.2024.06.021