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Introduction: CDK4/6 inhibitors are the first-line treatment for HR+/HER2- advanced breast cancer. Despite their clinical benefit, they can increase healthcare expenditure. To date, there is no thorough comparison among the three approved CDK4/6 inhibitors in terms of their cost-effectiveness. Objective: To investigate and compare the cost-effectiveness of CDK4/6 inhibitors in combination with letrozole as a first-line treatment for advanced breast cancer with hormonal-receptor-positivity and HER-2-negativity versus one another and versus letrozole monotherapy. Methods: A 10-year within-cycle-corrected Markov's model was employed from the healthcare payer perspective. Costs were obtained from the National Center for Cancer Care and Research (NCCCR) in Qatar. Utilities and transition probabilities were calculated from published landmark trials of PALOMA-2, MONALEESA-2, MONARCH-3, PO25, and other relevant literature. Costs, measured in Qatari Riyal (QAR), and effectiveness, measured in quality-adjusted-life-years (QALYs), were incremented and the incremental cost-effectiveness ratio (ICER) was compared to a willingness-to-pay threshold (WTP) of 1.5 Qatari GDP (448,758 QAR). A deterministic sensitivity analysis was implemented to account for uncertainties. Results: Ribociclib was the most effective option, generating 4.420 QALYs, followed by palbociclib (4.406 QALYs), abemaciclib (4.220 QALYs), then letrozole monotherapy (2.093 QALYs). As for cost-effectiveness, ribociclib dominated palbociclib. However, it was not cost-effective compared to abemaciclib (ICER=1,588,545 QAR/QALY). Ribociclib remained dominant over palbociclib with all uncertainties. The base-case conclusion of ribociclib versus abemaciclib remained robust over all uncertainties. Conclusion: From the healthcare payer perspective in Qatar, ribociclib is the most effective CDK4/6 inhibitor. It was dominant over palbociclib in terms of cost-effectiveness; however, it was not cost-effective compared to abemaciclib at current prices.
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Moringa oleifera (M. oleifera) is globally recognized for its medicinal properties and offers high-quality, protein-rich seeds. This study aimed to explore the potential of M. oleifera seeds as a significant source of protein-based nanoparticles (PBNPs) using the ultrasonication technique after desolvation and to evaluate their cytotoxicity in the human leukemia cell line (THP-1) for the first time. The properties of the PBNPs were confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). The extracted protein from moringa seed cake flour had a significant protein content of 54.20%, and the resulting PBNPs had an average size of 134.3 ± 0.47 nm with a robust zeta potential of -43.15 mV. Notably, our study revealed that PBNPs exhibited cytotoxic potential at high concentrations, especially against the THP-1 human leukemia cell line, which is widely used to study immunomodulatory properties. The inhibitory effect of PBNPs was quantitatively evidenced by a cytotoxicity assay, which showed that a concentration of 206.5 µg mL-1 (log conc. 2.315) was required to inhibit 50% of biological activity. In conclusion, our findings highlight the potential of M. oleifera seeds as a valuable resource in the innovative field of eco-friendly PBNPs by combining traditional medicinal applications with contemporary advancements in protein nanotechnology. However, further studies are required to ensure their biocompatibility.
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BACKGROUND: The utility of preoperative abdominal ultrasonography (US) in evaluating patients with obesity before metabolic bariatric surgery (MBS) remains ambiguously defined. METHOD: Retrospective analysis whereby patients were classified into four groups based on ultrasound results. Group 1 had normal findings. Group 2 had non-significant findings that did not affect the planned procedure. Group 3 required additional or follow-up surgeries without changing the surgical plan. Group 4, impacting the procedure, needed further investigations and was subdivided into 4A, delaying surgery for more assessments, and 4B, altering or canceling the procedure due to critical findings. Machine learning techniques were utilized to identify variables. RESULTS: Four thousand four hundred eighteen patients' records were analyzed. Group 1 was 45.7%. Group 2, 35.7%; Group 3, 17.0%; Group 4, 1.5%, Group 4A, 0.8%; and Group 4B, 0.7%, where surgeries were either canceled (0.3%) or postponed (0.4%). The hyperparameter tuning process identified a Decision Tree classifier with a maximum tree depth of 7 as the most effective model. The model demonstrated high effectiveness in identifying patients who would benefit from preoperative ultrasound before MBS, with training and testing accuracies of 0.983 and 0.985. It also showed high precision (0.954), recall (0.962), F1 score (0.958), and an AUC of 0.976. CONCLUSION: Our study found that preoperative ultrasound demonstrated clinical utility for a subset of patients undergoing metabolic bariatric surgery. Specifically, 15.9% of the cohort benefited from the identification of chronic calculous cholecystitis, leading to concomitant cholecystectomy. Additionally, surgery was postponed in 1.4% of the cases due to other findings. While these findings indicate a potential benefit in certain cases, further research, including a cost-benefit analysis, is necessary to fully evaluate routine preoperative ultrasound's overall utility and economic impact in this patient population.
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INTRODUCTION: Obesity, a major global health concern, is a known risk factor for cardiovascular disease (CVD), often due to dyslipidemia and insulin resistance. Laparoscopic sleeve gastrectomy (LSG) is an effective weight reduction surgery that not only alters body metabolism and gastrointestinal physiology but also significantly lowers cardiovascular disease risk. METHODS: This study explores the impact of weight loss on serum high-sensitivity C-reactive protein (hs-CRP), an established inflammatory marker, and changes in cardiovascular risk factors, particularly high-density lipoprotein-cholesterol (HDL-C) ratios, serum apo A-1, lipid profile, and HOMA-IR in severe obesity undergoing LSG. Anthropometric measurements and blood samples were collected preoperatively and 6 months postoperatively to hs-CRP, HOMA-IR, lipid profile, apo A-1, and low- and high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratios, total cholesterol to HDL-C (TC/HDL-C) ratio, and monocyte to high-density lipoprotein-cholesterol ratio (MHR). RESULTS: In total, 70 patients were analyzed after 6 months and reached %TWL 27.4 ± 9.5 and %EWL 62.0 ± 15.4. Significant improvements were noted in all measured biomarkers. Analysis showed that each unit reduction in BMI significantly affected hs-CRP and HDL-C. Furthermore, moderate associations between hs-CRP and various cardiovascular disease risk biomarkers, including a negative correlation with apo A-1 and positive correlations with total cholesterol (TC), TC/HDL-C, and LDL-C/HDL-C, along with a mild positive correlation with HOMA-IR. CONCLUSION: Weight loss following LSG significantly reduced inflammation and improved atheroprotection. Improved inflammation markers were associated with favorable changes in cardiovascular risk factors, including HDL-C ratios particularly TC/HDL-C, LDL-C/HDL-C, and apo A-1.
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Novel phthalazine derivatives were designed, synthesized and evaluated against Hep G2 and MCF-7 as VEGFR-2 inhibitors. In particular, compounds 2g and 4a were found to be the most potent derivatives among all the tested compounds against MCF-7 and Hep G2 cancer cell lines with IC50 values of 0.15 and 0.12 and 0.18 and 0.09 µM respectively. Moreover, compounds 3a, 3c, 5a and 5b displayed excellent anticancer activities against MCF-7 and Hep G2 cancer cell lines. The highly active derivatives 2g, 3a, 3c, 4a, 5a and 5b were evaluated for their inhibitory activities against VEGFR-2. The tested compounds displayed high to low inhibitory activities with IC50 values ranging from 0.148 to 0.892 µM. Among them, compounds 2g and 4a were found to be the most potent derivatives that inhibited VEGFR-2 with IC50 values of 0.148 and 0.196 µM respectively. Compounds 3a, 3c, 5a and 5b exhibited good activity with IC50 values of 0.375, 0.892, 0.548 and 0.331 µM respectively. Sorafenib was used as a reference drug in this study. Molecular modeling studies were carried out for all compounds against the VEGFR-2 active site. The data obtained from biological testing highly correlated with those obtained from molecular modeling studies. Moreover, MD simulation results indicated the stability of ligand-target interaction. Furthermore, our derivatives 2g and 4a showed a good in silico calculated ADMET profile.
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If absolutely nothing is taken to reduce carbon dioxide (CO2) emissions, atmospheric concentrations of carbon dioxide will rise to 550 parts per million by 2050, which will have disastrous effects on the world's climate and food production. An apparatus has been designed and setup to convert CO2 into a useful and vital product which was silica. The effect of different experimental factors on the compositions by weight percent of SiO2 and Na2CO3 were studied including the CO2 gas flow rate (1.037, 1.648 and 2.26 L/min), initial concentration of sodium silicate (Na2SiO3) solution (5, 7.5 and 10 %wt) and the packing size (15.95, 20.175, and 24.4 mm). An optimization process was performed using the Design Expert software program to achieve the optimum experimental conditions at which the maximum weight percent of SiO2 (main product), the minimum weight percent of (Na2CO3) (side product) and the minimum reaction time were determined. From the optimization process, the maximum weight percent of SiO2 (25.63 %), the minimum weight percent of (Na2CO3) (9.62 %) and the minimum reaction time (7.59 min) were achieved at the following optimum experimental conditions of CO2 gas flow rate = 1.648 L/min, packing size = 24.4 mm and initial concentration of sodium silicate solution = 10 %wt.
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Background: Acute appendicitis is currently considered one of the most common acute surgical diseases of the abdomen and requires emergency surgery. It is also one of the most common abdominal emergencies in both developed and developing countries. The current study is aimed at assessing the specificity and sensitivity of Ultrasound and Computed Tomography in the diagnosis of appendicitis as well as the prevalence of its complications. The association of appendicitis with several laboratory findings will also be evaluated. Methodology: A retrospective study was conducted at Dallah-Namar Hospital, Riyadh City, Saudi Arabia. Results: 720 patients were differentially diagnosed with appendicitis in the study area. Of these, 618 patients had US abdomen/pelvis, with 15 (2.4%) showing positive findings. Amongst the 203 patients noted to have undergone abdominal CT,8 (4.0%) was found to have positive findings. Conclusion: The sensitivity of the US was determined to be relatively low. Also, serum creatinine was found to be elevated among all patients diagnosed with appendicitis. Further research with a larger sample size is needed to be conducted to further support the current findings.
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Skin melanoma is considered the most dangerous form of skin cancer due to its association with high risk of metastasis, high mortality rate and high resistance to different treatment options. Genistein is a natural isoflavonoid with known chemotherapeutic activity. Unfortunately, it has low bioavailability due to its poor aqueous solubility and excessive metabolism. In the current study, genistein was incorporated into transferosomal hydrogel to improve its bioavailability. The prepared transferosomal formulations were characterized regarding: particle size; polydispersity index; zeta potential; encapsulation efficiency; TEM; FTIR; DSC; XRD; in vitro drug release; viscosity; pH; ex vivo anti-tumor activity on 3D skin melanoma spheroids and 1-year stability study at different storage temperatures. The optimized formulation has high encapsulation efficiency with an excellent particle size that will facilitate its penetration through the skin. The transfersomes have a spherical shape with sustained drug release profile. The anti-tumor activity evaluation of genistein transfersome revealed that genistein is a potent chemotherapeutic agent with enhanced penetration ability through the melanoma spheroids when incorporated into transfersomes. Stability study results demonstrate the high physical and chemical stability of our formulations. All these outcomes provide evidence that our genistein transferosomal hydrogel is a promising treatment option for skin melanoma.
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Liberação Controlada de Fármacos , Genisteína , Hidrogéis , Melanoma , Tamanho da Partícula , Neoplasias Cutâneas , Genisteína/administração & dosagem , Genisteína/farmacologia , Genisteína/farmacocinética , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Humanos , Hidrogéis/química , Sistemas de Liberação de Medicamentos/métodos , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Solubilidade , Portadores de Fármacos/química , Química Farmacêutica , Viscosidade , Disponibilidade Biológica , Administração Cutânea , Esferoides Celulares/efeitos dos fármacosRESUMO
Folic acid receptor-targeted drug delivery system is a promising candidate for tumor-targeted delivery because its elevated expression specifically on tumor cells enables the selective delivery of cytotoxic cargo to cancerous tissue, thereby minimizing toxic side effects and increasing the therapeutic index. Pyridine bisfolate-chitosan (PyBFA@CS NPs) and folate-chitosan nanocomposite (FA@CS NPs) were synthesized with suitable particle size (256.0 ± 15.0 and 161.0 ± 5.0 nm), high stability (ζ = -27.0 ± 0.1 and -30.0 ± 0.2 mV), respectively, and satisfactory biocompatibility to target cells expressing folate receptors and try to answer the question: Is the metal center always important for activity? Since almost all pharmaceuticals work by binding to specific proteins or DNA, the in vitro binding of human serum albumin (HSA) to PyBFA@CS NPs and FA@CS NPs has been investigated and compared with PyBFA. Strong affinity to HSA is shown by quenching and binding constants in the range of 105 and 104 M-1, respectively with PyBFA@CS NPs showing the strongest. The compounds-HSA kinetic stability, affinity, and association constants were investigated using a stopped-flow method. The findings showed that all formulations bind by a static quenching mechanism that consists of two reversible steps: rapid second-order binding and a more slowly first-order isomerization reaction. The overall coordination affinity of HSA to PyBFA@CS NPs (6.6 × 106 M-1), PyBFA (4.4 × 106 M-1), and FA@CS NPs (1.3 × 106 M-1) was measured and The relative reactivity is roughly (PyBFA@CS NPs)/(PyBFA)/(FA@CS NPs) = 5/3/1. Additionally, in vitro cytotoxicity revealed that, consistent with the binding constants and coordination affinity, active-targeting formulations greatly inhibited FR-positive MCF-7 cells in compared to FRs-negative A549 cells in the following trend: PyBFA@CS NPs > PyBFA > FA@CS NPs. Furthermore, in vitro drug release of PyBFA@CS NPs was found to be stable in PBS at pH 7.4, however, the in pH 5.4 and in pH 5.4 containing 10 mM glutathione (GSH) (mimicking the tumor microenvironment) reached 43 % and 73 %, respectively indicating that the PyBFA@CS NPs system is sensitive to GSH. Folate-modified nanoparticles, PyBFA@CS NPs, are a promising therapeutic for MCF-7 therapy because they not only showed a greater affinity for HSA, but also showed higher cleavage efficiency toward the minor groove of pBR322 DNA via the hydrolytic way, as well as effective antibacterial activity that avoids the usage of extra antibiotics.â¬â¬â¬â¬â¬â¬â¬â¬â¬â¬â¬â¬ â¬â¬â¬â¬â¬â¬â¬â¬â¬â¬â¬â¬â¬â¬.
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The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area.
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Procedimentos Endovasculares , Aneurisma Intracraniano , Pontuação de Propensão , Humanos , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Procedimentos Endovasculares/métodos , Resultado do Tratamento , Adulto , Embolização Terapêutica/métodosRESUMO
BACKGROUND AND PURPOSE: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment. MATERIALS AND METHODS: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up. RESULTS: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate (P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion. CONCLUSIONS: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment.
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Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Estudos Retrospectivos , Resultado do Tratamento , Idoso , Fatores de RiscoRESUMO
Cephalomedullary nailing for unstable proximal femoral fractures is widely utilized, especially for geriatric osteoporotic fractures. There are two starting points for entry, namely trochanteric tip entry and pyriformis fossa entry, both have advantages and disadvantages, the tip of the greater trochanter seems that it is not the ideal starting point for trochanteric entry nails, the study presents the foothill entry point as a reproducible, technically feasible entry point to overcome the shortcoming of both standard starting points, and it could be easy executed with clear intraoperative fluoroscopic landmarks and lead to appropriate nail position without intraoperative complications.
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The most common form of acetabular fracture is believed to be the posterior wall; its incidence ranges from 25% to 47%. Managing such fractures has been difficult in the past and until recently. To obtain a favorable functional outcome, an accurate diagnosis and a well-executed treatment strategy are essential. Objective: To evaluate the clinical and functional outcomes of employing a spring plate augmented by a traditional 3.5 mm reconstruction plate for the treatment of comminuted posterior wall acetabular fractures. Patients and Methods: A prospective case series was performed on 24 patients with comminuted fractures of the posterior wall. After an average of 6 days, the patients underwent surgery. Eighteen patients were fixed with one spring plate, six patients were fixed with two spring plates, and all were reinforced with a 3.5-mm reconstruction plate. Each case was followed once every three months until the fracture healed and then regularly every six months thereafter. Results: There were 21 men and 3 women. The average follow-up period was 14 months, and the median age was 34.5 years. The main reason for injuries was motor vehicle collisions. The mean operation time was 107.5 min. The clinical results were evaluated by the MAP and m HHS, and the means were 10.2 (5-12) and 86 (64-96), respectively. Only two patients developed avascular necrosis and were treated by total hip replacement, another three (12.5%) had mild arthritis. Conclusion: Comminuted acetabulum posterior wall fractures can be stabilized with spring plates. It could be used in conjunction with the primary reconstruction plate as a viable alternative for stable and anatomical reduction. High patient satisfaction and good functional results make this approach effective.
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Introduction: The aim was to assess the hemostatic impact of B-Lynch sutures following an open myomectomy for efficacy. Material and methods: In this prospective clinical research, performed in Alazhar university hospitals (Al-Hussain, Damietta, Assiut) and Minia University Maternity Hospital, 250 women scheduled for open myomectomy between January 2021 and January 2023 had multiple fibroid uteri with uterine sizes corresponding to 12-22 weeks. There were two groups of women. Group I (125) underwent standard open myomectomy surgery, whereas Group II (125) underwent normal open laparotomy surgery followed by B-Lynch sutures. Certain inclusion and exclusion criteria were applied to every patient. We recorded vital data, length of the procedure, complications (bleeding during the procedure, bleeding from multiple bites, bladder injury, fever, wound infection), complete blood count before and after surgery, need for blood transfusion, postoperative vital data, time until ambulation, passing flatus, and ability to eat and drink, as well as the amount of blood lost during and after the procedure. Results: There was no statistically significant difference between the two groups in age, parity, weight, number of fibroids, or uterine size as measured by ultrasonography. Between groups I and II, there was a significant difference in the average intraoperative blood loss (Group I lost 562.6 ml, whereas Group II lost 411.3 ml) as well as the mean blood loss following surgery (205 ±82 ml in Group I and 117 ±41 ml in Group II). No significant difference was observed in the mean length of hospital stay between groups I and II (2 ±0.3 days and 2 ±0.6 days, respectively). Conclusions: Using a B-Lynch suture can help minimize blood loss during and after an open myomectomy. Therefore, if the uterus is large and has a lot of fibroids, it is recommended to be done frequently.
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Computer vision syndrome (CVS) refers to a set of eye-related symptoms that arise from prolonged computer usage. A survey was conducted to investigate the demographic characteristics, factors contributing to, and preventive measures against CVS. Out of 159 participants, 31.0% experienced seven or more symptoms, indicating a notable prevalence. The study found no significant correlation between age or academic years and CVS occurrence (P values of 0.481 and 0.392, respectively). However, gender exhibited a statistically significant relationship, with females students showing a higher prevalence than males (P=0.018; τ=0.105*). Notably, the distance from the screen had a highly significant inverse correlation with CVS occurrence (P=0.000; τ=-0.207**), indicating that greater distance reduced the risk. Additionally, using a screen filter (P=0.000; τ=0.184**) and adjusting screen brightness (P=0.017; τ=0.101*) were associated with CVS occurrence. Among preventive measures, only the use of an anti-glare screen showed a significant association with reducing CVS risk (P=0.018; τ=-0.099*). Given these findings, raising awareness about CVS among medical students is recommended, especially as curricula in medical colleges evolve.
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Anthracycline antibiotic is one of the most effective anti-tumor drugs used to manage certain types of breast cancers, lymphomas, and leukemias. However, anthracyclines induce a dose-dependent cardiotoxicity that may progress to heart failure. Thus, using a sensitive predictor of early cardiac dysfunction in patients treated with anthracyclines can help detect subclinical cardiac dysfunction early and help initiate interventions to protect these patients. Among parameters of myocardial measure, cardiac magnetic resonance (CMR)-measured native myocardial T1 mapping is considered a sensitive and accurate quantitative measure of early subclinical cardiac changes, particularly cardiac inflammation and fibrosis. However, to understand the quality and the validity of the current evidence supporting the use of these measures in patients treated with anthracyclines, we aimed to conduct a systematic review of clinical studies of this measure to detect early myocardial changes in cancer patients treated with anthracyclines. The primary outcome was the level of native T1 mapping. We performed fixed-effects meta-analyses and assessed certainty in effect estimates. Of the 1780 publications reviewed (till 2022), 23 were retrieved, and 9 articles met the inclusion criteria. Our study showed that exposure to anthracycline was associated with a significant elevation of native myocardial T1 mapping from baseline (95% CI 0.1121 to 0.5802; p = 0.0037) as well as compared to healthy control patients (95% CI 0.2925 to 0.7448; p < 0.0001). No significant publication bias was noted on the assessment of the funnel plot and Egger's test. According to the Q test, there was no significant heterogeneity in the included studies (I2 = 0.0000% versus healthy controls and I2 = 14.0666% versus baseline). Overall, our study suggests that native myocardial T1 mapping is useful for detecting anthracycline-induced cardiotoxicity in patients with cancer.
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Antraciclinas , Antibióticos Antineoplásicos , Cardiotoxicidade , Cardiopatias , Neoplasias , Valor Preditivo dos Testes , Humanos , Antraciclinas/efeitos adversos , Neoplasias/tratamento farmacológico , Antibióticos Antineoplásicos/efeitos adversos , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Cardiopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Diagnóstico Precoce , Fatores de Risco , Adulto , Idoso , Medição de Risco , Imageamento por Ressonância Magnética , Função Ventricular Esquerda/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Myeloproliferative neoplasms (MPNs) are hematological disorders characterized by abnormal production of myeloid cells due to genetic mutations. Since 2013, researchers have identified somatic mutations in the Calreticulin (CALR) gene, primarily insertions or deletions, in two Philadelphia chromosome-negative MPNs; essential thrombocytosis (ET) and primary myelofibrosis (PMF), and occasionally in chronic myelomonocytic leukemia (CMML). This study aims to identify the various types of CALR mutations and their impact on CALR-positive MPN patients' clinical manifestations and outcomes. METHODS: A single-center retrospective study was conducted. The data was collected from pre-existing records. The study was carried out on Philadelphia-negative MPN patients who were being followed up on at the NCCCR (National Center for Cancer Care and Research) to assess the clinical manifestation and outcome of disease treatment. All patients included, were followed in our center between January 1, 2008, and November 20, 2021. RESULTS: A total of 50 patients with CALR-positive MPN were reviewed with a median follow-up of three years (1-11). This cohort included 31 (62%) patients with ET, 10 (20%) patients with PMF, and 9 (18%) patients with prefibrotic myelofibrosis (pre-MF). The study involved 38 (76%) male and 12 (24%) female patients. There were 16 (32%) patients diagnosed before the age of 40, 24 (48%) patients diagnosed between the ages of 40 and 60; and 10 (20%) patients diagnosed after the age of 60. Molecular analysis showed 24 (48%) patients with CALR type 1, 21 (42%) patients with CALR type 2, and 5 (10%) patients with none Type 1, none Type 2 CALR mutations. Two patients have double mutations; 1(2%) with none Type 1, none Type 2 CALR and JAK2 mutations, and 1(2%) with CALR type 1 and MPL mutations. The thrombotic events were 3 (6%) venous thromboembolisms, 3 (6%) abdominal veins thromboses, 2 (4%) strokes, and 4 (8%) ischemic cardiac events. Only 4 (8%) patients progressed to Myelofibrosis and were carrying CALR 1 mutations, and 1 (2%) patient progressed to AML with CALR 2 mutation. CONCLUSION: The data shows a significant rise in CALR-positive MPN diagnoses in younger people, emphasizing the need for a better assessment tool to improve disease management and reduce complications.
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Calreticulina , Mutação , Transtornos Mieloproliferativos , Centros de Atenção Terciária , Humanos , Calreticulina/genética , Masculino , Feminino , Transtornos Mieloproliferativos/genética , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Catar/epidemiologia , IdosoRESUMO
BACKGROUND: Medication review with follow-up is essential for optimising medication utilisation among the older adult population in primary healthcare. AIM: This study aimed to evaluate the feasibility of implementing medication reviews with follow-up for older adults in community pharmacies and examined potential outcomes on medication use. METHOD: A pilot randomised controlled trial was conducted with 4 cluster-randomised community pharmacies to assess the feasibility of the intervention. Two community pharmacies served as intervention and control groups. Both groups recruited older adults over 60 who were followed over 6 months. The translated Medication use Questionnaire (MedUseQ) was administered at baseline and 6 months for both groups. The outcomes were to assess the feasibility of conducting medication review with follow-up and the probable medication use outcomes from the intervention. RESULTS: The intervention and control groups comprised 14 and 13 older adults. A total of 35 recommendations were made by pharmacists in the intervention group and 8 in the control group. MedUseQ was easily administered, providing some evidence the feasibility of the intervention. However, there were feasibility challenges such as a lack of pharmacists, collaborative practice, difficulties with the tool language, time constraints, and limited funds. Questionnaire results provided a signal of improvement in medication administration, adherence, and polypharmacy among intervention participants. The incidence of drug related problems was significantly higher in the control group (median = 1) after 6 months, U = 15, z = - 2.98, p = 0.01. CONCLUSION: Medication review with follow-up is potentialy practical in community pharmacies, but there are feasibility issues. While these challenges can be addressed, it is essential to study larger sample sizes to establish more robust evidence regarding outcomes. CLINICAL TRIAL REGISTRY: ClinicalTrials.Gov NCT05297461.
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Serviços Comunitários de Farmácia , Estudos de Viabilidade , Farmacêuticos , Humanos , Projetos Piloto , Idoso , Feminino , Masculino , Seguimentos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Adesão à Medicação/estatística & dados numéricos , Polimedicação , Inquéritos e Questionários , Reconciliação de Medicamentos/métodosRESUMO
Herein, we demonstrate the prospects of tackling several environmental problems by transforming a local rice husk residue into an effective adsorbent, which was then applied for the treatment of real landfill leachate (LL). The study focused on establishing (i) the effect of simple washing on morphological aspects, (ii) evaluating target adsorption capacity for total iron (Fe) and nickel (Ni), (iii) determining regeneration and reuse potential of the adsorbent and (iv) complying to the requirements of worldwide legislations for reuse of treated LL wastewater. The adsorbent was prepared by employing a simple yet effective purification process that can be performed in situ. The LL was collected post-membrane treatment, and the characterizations revealed high concentrations of Fe, Ni, and organic matter content. The simple washing affected the crystallinity, resulting in structural alterations of the adsorbents, also increasing the porosity and specific surface. The adsorption process for Ni occurred naturally at pH 6, but adjusting the pH to 3 significantly improved removal efficiency and adsorption capacity for total Fe. The kinetics were accurately described by the pseudo-second-order model, while the Langmuir model provided a better fit for the isotherms. The adsorbent was stable for 5 reuses, and the metals adsorbed were recovered through basic leaching. The removal capacities achieved underscore the remarkable effectiveness of the process, ensuring the treated LL wastewater meets rigorous global environmental legislations for safe use in irrigation. Thus, by employing the compelling methods herein optimized it is possible to refer to the of solving three environmental problems at once.