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1.
J Arrhythm ; 40(2): 203-213, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38586849

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disorder with a varying range of organs involved leading to adverse outcomes. However, very little is known, with conflicting results about the association between RA and atrial fibrillation (AF). We aim to evaluate the association between RA and AF, and other clinical outcomes. We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until September 10, 2023. Primary clinical outcomes were AF. Secondary outcomes were acute coronary syndrome (ACS), stroke, and all-cause mortality (ACM). A total of 4 679 930 patients were included in the analysis, with 81 677 patients in the RA group and 4 493 993 patients in the nonrheumatoid arthritis (NRA) group. The mean age of the patients was 57.2 years. Pooled analysis of primary outcomes shows that RA groups of patients had a significantly higher risk of AF (odds ratios [OR], 1.53; 95% confidence interval [CI]: [1.16-2.03], p < .001) compared with NRA groups. Secondary Outcomes show that the RA group of patients had significantly higher odds of ACS (OR, 1.39; 95% CI: [1.26-1.52], p < .001), and ACM (OR, 1.19; 95% CI: [1.03-1.37], p = .02) compared with the NRA groups. However, the likelihood of stroke (OR, 1.02; 95% CI: [0.94-1.11], p = .61) was comparable between both groups of patients. Our study shows that RA groups of patients are at increased risk of having AF, ACS, and ACM.

2.
Cureus ; 16(2): e54983, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38550405

RESUMO

Lymphangioma are benign, slow-growing and rare lymphatic tumors, which may emerge at any location in the body with ovary being a very rare location. Axillary region and neck are the most common sites, while retroperitoneum and mesentery account for <1%. We present a case of a young female of 33 years who had symptomatic pelvic mass and was presented with a complaint of lower abdominal pain of six-month duration and weight loss. Investigation revealed an oval-shaped complex cystic density lesion in the right adnexal region, which was likely neoplastic. Elective laparotomy with right ovarian cystectomy was performed. Histopathological examination revealed ovarian lymphangioma.

3.
J Med Chem ; 67(6): 4259-4297, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38498010

RESUMO

RNA targeting, specifically with small molecules, is a relatively new and rapidly emerging avenue with the promise to expand the target space in the drug discovery field. From being "disregarded" as an "undruggable" messenger molecule to FDA approval of an RNA-targeting small-molecule drug Risdiplam, a radical change in perspective toward RNA has been observed in the past decade. RNAs serve important regulatory functions beyond canonical protein synthesis, and their dysregulation has been reported in many diseases. A deeper understanding of RNA biology reveals that RNA molecules can adopt a variety of structures, carrying defined binding pockets that can accommodate small-molecule drugs. Due to its functional diversity and structural complexity, RNA can be perceived as a prospective target for therapeutic intervention. This perspective highlights the proof of concept of RNA-small-molecule interactions, exemplified by targeting of various transcripts with functional modulators. The advent of RNA-oriented knowledge would help expedite drug discovery.


Assuntos
Descoberta de Drogas , RNA , RNA/metabolismo , Proteínas/metabolismo
4.
Naturwissenschaften ; 111(1): 9, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342817

RESUMO

This article presents an attempt to discriminate between human male and female hair samples using a single strand of scalp hair. The methodology involves the non-destructive application of ATR-FTIR spectroscopy coupled with chemometric analysis. A total of 96 hair samples, evenly distributed between 48 male and 48 female volunteers from India, were collected. Spectral analysis revealed subtle differences between the two groups, and reliance on visual interpretation might introduce biasness. To avoid subjective biases, chemometric techniques such as principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) were employed for enhanced data visualization and separation. PCA results revealed that the first 10 principal components accounted for 93% of the total variance, with three significant PCs. The PLS-DA model demonstrated a remarkable sensitivity and specificity in sex discrimination from hair samples, establishing its efficacy as a robust classification tool. Furthermore, the proposed model exhibited 100% accuracy in predicting unknown samples, underscoring its potential applicability in real-world scenarios. These outcomes affirm the viability of our approach for non-invasive classification of human male and female hair based on single-strand scalp hair analysis.


Assuntos
Quimiometria , Cabelo , Humanos , Masculino , Feminino , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Discriminante , Cabelo/química , Análise de Componente Principal , Proteínas Mutadas de Ataxia Telangiectasia/análise
5.
Artigo em Inglês | MEDLINE | ID: mdl-38321360

RESUMO

OBJECTIVES: There is an unmet need to develop patient-reported outcomes (PRO) measures for Idiopathic Inflammatory Myopathies (IIM). To investigate the feasibility, compliance, and psychometric properties of NIH's Patient-Reported Outcomes Measurement Information System (PROMIS) physical function-20 (PF-20) in a large U.S. IIM population. METHODS: "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of IIM patients, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using smartphone and web-based technology (Tele-Research Cohort [TRC]). The CBC was further randomly divided (1:1 ratio) into a traditional local sub-cohort, and a remote sub-cohort. Data collected included PRO and other patient self-assessments monthly for 6 months. Clinician-reported outcomes were obtained at baseline and 6 months. RESULTS: 120 IIM patients were enrolled (82 TRC/38 CBC, mean age 55 ± 13.4, 75% females, 81% Caucasians), with similar demographics and mean PROMIS PF-20 score between cohorts. The PROMIS PF-20 score was not associated with age, sex or race. The compliance and completion rates were similar between TRC and CBC as well as sub-cohorts. PROMIS PF-20 showed strong test-retest reliability at 1 month. PROMIS PF-20 was significantly associated with all core set measures except extra-muscular global and CK, as well as with most of symptoms, function and physical activity measures. PROMIS PF-20 illustrated concordant change with myositis response criteria and patient assessment, with a large effect size. CONCLUSIONS: PROMIS PF-20 demonstrates favorable psychometric properties including reliability, validity and responsiveness in a large cohort of myositis patients, with similar adherence in local or remotely enrolled patients.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38305340

RESUMO

Pharmaceutical development of cancer therapeutics is a dynamic area of research. Even after decades of intensive work, cancer continues to be a dreadful disease with an ever-increasing global incidence. The progress of nanotechnology in cancer research has overcome inherent limitations in conventional cancer chemotherapy and fulfilled the need for target-specific drug carriers. Nanotechnology uses the altered patho-physiological microenvironment of malignant cells and offers various advantages like improved solubility, reduced toxicity, prolonged drug circulation with controlled release, circumventing multidrug resistance, and enhanced biodistribution. Early cancer detection has a crucial role in selecting the best drug regime, thus, diagnosis and therapeutics go hand in hand. Furthermore, nanobots are an amazing possibility and promising innovation with numerous significant applications, particularly in fighting cancer and cleaning out blood vessels. Nanobots are tiny robots, ranging in size from 1 to 100 nm. Moreover, the nanobots would work similarly to white blood cells, watching the bloodstream and searching for indications of distress. This review articulates the evolution of various organic and inorganic nanoparticles and nanobots used as therapeutics, along with their pros and cons. It also highlights the shift in diagnostics from conventional methods to more advanced techniques. This rapidly growing domain is providing more space for engineering desired nanoparticles that can show miraculous results in therapeutic and diagnostic trials.


Assuntos
Nanopartículas , Neoplasias , Humanos , Distribuição Tecidual , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/uso terapêutico , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/uso terapêutico , Microambiente Tumoral
8.
HLA ; 103(2): e15382, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38358088

RESUMO

HLA-A*11:01:01:68 differs from HLA-A*11:01:01:01 by one nucleotide change in intron 3 at position 1474 (G > A).


Assuntos
Antígenos HLA-A , Nucleotídeos , Humanos , Alelos , Íntrons/genética , Antígenos HLA-A/genética , Sequenciamento de Nucleotídeos em Larga Escala
9.
HLA ; 103(2): e15363, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38305067

RESUMO

HLA-B*15:05:01:02 differs from HLA-B*15:05:01:01 by one nucleotide change in intron 2 at position 517 (C > A).


Assuntos
Genes MHC Classe I , Antígenos HLA-B , Humanos , Sequência de Bases , Alelos , Antígenos HLA-B/genética , Análise de Sequência de DNA , Sequenciamento de Nucleotídeos em Larga Escala
10.
Immunol Invest ; 53(3): 295-347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38206610

RESUMO

Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.


Assuntos
Nanopartículas , Doenças Respiratórias , Idoso , Humanos , Nanomedicina/métodos , Sistemas de Liberação de Medicamentos/métodos , Imunomodulação , Pulmão
11.
Eur J Breast Health ; 20(1): 15-18, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38187109

RESUMO

Objective: Mastalgia is the most common breast-related complaint. A multitude of hormonal changes and lifestyle associated factors have been implicated in its causation. A long list of treatment modalities have been tried with varying success rates. To identify the most common risk factors and the most effective management strategies for mastalgia in our clinic population. Materials and Methods: A total of 100 women between 18-65 years of age presenting to the breast clinic with mastalgia were followed throughout their course of diagnosis and management. Stepwise treatment was provided, starting with reassurance and breast support and progressing to include pharmacological measures, when necessary. The risk factors and outcomes of treatment were analysed. Results: The majority (66%) were aged 25-47 years and the left breast was found to be most frequently involved. Involvement of the upper outer quadrant was significantly more common. Lump/nodularity was the most prevalent risk factor. Most patients showed a positive response to non-steroid anti-inflammatories (NSAIDs) in addition to reassurance, breast support and dietary changes. Conclusion: A detailed history and clinical examination helps to identify the risk factors and the best approach for the management of mastalgia. Educating women regarding breast self-examination at regular intervals helps in early presentation and diagnosis of the underlying condition. Reassurance, breast support and lifestyle changes are the first line treatment and have good results in a significant number of patients. In our practice topical and oral NSAIDs, evening primrose oil and vitamin E were frequently used as additional treatments to non-pharmacological methods.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 309: 123821, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38183735

RESUMO

Criminal instances involving collision accidents, hit-and-run incidents, abduction, hostage-taking, and the unauthorised transit of forbidden items generally include evidence involving rubber traces from automobile tyres. These traces can be located on the road surface, in clothing, on the victim(s) themselves, or on items as skid marks following sudden stopping and spinning around. These traces serve as crucial evidence by reducing the range of suspects by revealing linkages between the getaway vehicle, the site of the crime, and the perpetrator through the tyre's brand, producer, or origin. This study offered a way for classifying 220 tyre rubber samples from different brands using various machine learning algorithms in PyCaret in conjunction with rapid and non-destructive ATR-FTIR spectroscopy equipped with diamond crystal. On spectral information from ATR-FTIR, pre-processing tools such as baseline correction, smoothing, derivatization, and normalisation were also implemented prior to machine learning. This approach has the potential to be advantageous for efficiently and non-destructively identifying rubber traces as forensic evidence and for facilitating brand recognition of automobile tyres.


Assuntos
Automóveis , Borracha , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Clin Cancer Res ; 30(2): 323-333, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38047868

RESUMO

PURPOSE: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. PATIENTS AND METHODS: Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. RESULTS: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4-31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months-undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.


Assuntos
Cordoma , Neoplasias Pulmonares , Adulto , Humanos , Pemetrexede/efeitos adversos , Cordoma/patologia , Projetos Piloto , Glutamatos/efeitos adversos , Guanina/uso terapêutico , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Neoplasias Pulmonares/tratamento farmacológico
14.
Continuum (Minneap Minn) ; 29(6): 1872-1895, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38085902

RESUMO

ABSTRACT: The journey for a patient with a brain tumor and their loved ones can be extremely challenging due to the high burden of physical symptoms and the emotional distress caused by the diagnosis. Optimizing quality of life by addressing symptoms and reducing this emotional distress can improve treatment tolerance and outcomes and alleviate care partner distress and burden. Symptoms in patients with central nervous system (CNS) tumors can vary in onset and intensity, ranging from headaches, seizures, and focal weakness to emotional distress and cognitive dysfunction. Additionally, care partners may demonstrate distress due to the high burden of care and need appropriate support structures and access to resources to alleviate this stress. Evidence-based recommendations are unfortunately limited given the lack of high-quality research in this area, but patients living with CNS tumors and their loved ones can benefit from early and routine symptom identification and management, compassionate and transparent communication, and practical guidance for the future. These principles are part of palliative care, a field of medicine focused on alleviating suffering in patients with serious, chronic illness. Clinicians involved in the care of patients with CNS tumors must be educated in these important primary palliative care principles. This article focuses on key symptom management, strategies for high-quality communication, a discussion of advance care planning, and an overview of end-of-life care.


Assuntos
Neoplasias Encefálicas , Assistência Terminal , Humanos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Cuidados Paliativos , Qualidade de Vida , Apoio Social
15.
Int Tinnitus J ; 27(1): 40-46, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38050883

RESUMO

BACKGROUND: Tinnitus is the perception of sound in the absence of external acoustic stimulation. Being one of the most common diseases of the ear, it has a global prevalence ranging from 4.1 to 37.2%. To date, it has been difficult to treat tinnitus as its pathophysiology is poorly understood and there are limited treatment options. OBJECTIVE: To investigate the effect of OKN-007 (also known as HPN-07), a nitrone-based investigational drug, in combination with oral N-acetylcycsteine (NAC), for the treatment of hearing loss and chronic tinnitus under an individual expanded access protocol. PATIENT CASE: We report the case of a patient who presented with left-sided ear fullness, mild tinnitus, and mild high frequency sensorineural hearing loss with 100% word recognition. A large enhancing mass seen on MRI revealed a vestibular schwannoma. He underwent subtotal resection of the tumor resulting in a moderate-to-profound sensorineural hearing loss and catastrophic tinnitus. The patient was treated with intravenous OKN-007 at 60 mg/kg dosed three times per week and oral NAC 2500 mg twice daily. RESULTS: Post-treatment audiometric testing revealed an average of 16.66 dB in hearing threshold improvement in three frequencies (125, 250 and 500 Hz) with residual hearing in the affected left ear. His tinnitus loudness matching improved from 90 dB to 19 dB post-treatment. His Tinnitus Handicap Inventory improved from 86/100 (Catastrophic) to 40/100 (Moderate). He also experienced improvements in sleep, concentration, hearing, and emotional well-being, and reported significantly decreased levels of tinnitusrelated distress. CONCLUSIONS: This case report highlights the feasibility and therapeutic potential of the combination of OKN-007 and NAC in treating hearing loss and tinnitus that warrants further investigation.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Perda Auditiva Unilateral , Perda Auditiva , Neuroma Acústico , Zumbido , Masculino , Humanos , Zumbido/diagnóstico , Zumbido/tratamento farmacológico , Zumbido/etiologia , Perda Auditiva Unilateral/diagnóstico , Perda Auditiva Unilateral/etiologia , Perda Auditiva Unilateral/terapia , Neuroma Acústico/complicações , Neuroma Acústico/diagnóstico , Neuroma Acústico/cirurgia , Perda Auditiva/complicações
16.
Cureus ; 15(9): e45293, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37846231

RESUMO

INTRODUCTION: Unutilized cross-matched blood due to excess cross-match requisitions results in unnecessary wastage of inventory, time, labor, and financial resources. This retrospective cross-sectional study aims to assess the blood utilization practices in obstetrics/gynecology (OB/GYN) over a period of seven years with respect to "blood utilization indices" and standard recommendations. MATERIAL AND METHODS: Cross-match requisitions from the OB/GYN Department over a period of seven years (2012-2018) were selected and included in the study using a suitable sampling technique. Patient details were retrieved from the Hospital Information System (HIS) database. The preoperative crossmatch requisitions and blood utilization data were recorded. "Blood utilization indices" and whole blood/component utilization patterns were analyzed. RESULTS: A total of 894 units of blood were cross-matched for 523 patients included in the study. A total of 305 of these patients were transfused with 445 units. During the initial phase of the study (2012-2014), the average cross-match-to-transfusion ratio (CTR, 6.6), transfusion probability (12.3), transfusion index (0.23), and component utilization (4%) were in marked deviation from recommended "blood utilization indices." This was in contrast with the later phase of the study (2015-2018) wherein the average CTR (1.5), transfusion probability (69.3), transfusion index (1.3), and component utilization (91.8%) were compliant with recommended "blood utilization indices." CONCLUSION: A progressive improvement in blood utilization practices was observed in the OB/GYN Department during the study period. Awareness campaigns have contributed to the implementation of rational and judicious blood transfusion practices in our center.

17.
J Biomol Struct Dyn ; : 1-16, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37776002

RESUMO

Monkeypox virus (MPXV) is an orthopoxvirus which causes zoonotic infection in humans. Even though sporadic cases of this infection are limited to the African continent, but if the infection continues to increase unabated, it can be a cause of serious concern for the human populace. Smallpox vaccination has been in use against monkeypox infection but it only provides mild protection. In the current study, we have screened novel small molecules (estrone fused heterocycles (EH1-EH7)) exhibiting good binding with monkeypox virus protein and related proteins from Poxviridae family of viruses via computational approaches. EH1-7 series of small molecules selected for the work have been synthesized via cycloaddition methodology. Docking and Molecular Dynamics (MD) results highlight EH4 compound to have strong binding affinity towards monkeypox and other related viral proteins selected for the study. Thus, computational outcomes suggest EH4 as a good candidate against monkeypox. Currently, no antiviral medication has been approved against monkeypox and the treatment is only via therapeutics available for smallpox and related conditions that may be helpful against monkeypox. Our study is thus an attempt to screen novel compounds against monkeypox infection, which would, in turn, facilitate development of novel therapeutics against Poxviridae family. HIGHLIGHTSMonkeypox infection is a public health emergency and necessitates immediate drug discovery.Molecular docking study to screen estrone-fused heterocycles compounds against Monkeypox and other orthopoxviruses.Molecular dynamics simulations revealed interaction/high binding affinities among EH4 heterocyclic compound and profilin-like protein from the monkeypox virus.Estrone-fused heterocycles compounds are promising anti-viral agents as per our in silico analysis.Our study provides evidence for investigating estrone-fused heterocycles compounds for further pharmacological interventions.Communicated by Ramaswamy H. Sarma.


Monkeypox: This orthopoxvirus leads to mpox (monkeypox) disease which shows symptoms similar to that smallpox, however to less severe extent.Poxviridae family: This is commonly a family of double-stranded DNA viruses. The natural hosts for these viruses are arthropods and Vertebrates.Molecular Dynamic simulation: MD simulation is crucial for determining the ligand's stability and revealing the duration of its interaction with the respective macromolecular structure.Molecular Docking: Molecular docking aids in determining specific sites where the ligand binds with the macromolecule as well as its binding affinity. Bioinformatics tools such as docking have been widely employed for aiding drug discovery efforts.Protein binding energy: On docking protein with the ligand, the binding energy shows the free energy change during binding process between protein-ligand.

18.
Sci Rep ; 13(1): 15289, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37714933

RESUMO

The current work involves the use of dehydroacetic acid based chalcone derivatives for the synthesis of spirooxindole grafted pyrrolidine moieties. All the synthesized compounds have been characterized using spectroscopic techniques such as NMR (1H-NMR and 13C-NMR), IR, mass and elemental analysis. Molecular mechanics studies were performed to comprehend the regioselectivity in the product formation. Molecular docking of the synthesized compounds was performed with few bacterial proteins of Bacillus subtilis and Pseudomonas aeruginosa responsible for biofilm formation followed by molecular dynamics simulations with the potential lead compound. Further, to corroborate the results obtained via in silico study, anti-biofilm activity etc. of the synthesized compounds (4a-e) was checked for effectiveness against biofilm formation. Taken together, this study opens up to explore these compounds' multiple roles in diverse fields in the arena of medical sciences.


Assuntos
Bacillus subtilis , Biofilmes , Reação de Cicloadição , Simulação de Acoplamento Molecular
19.
Curr Med Res Opin ; 39(10): 1395-1405, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37583267

RESUMO

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. While two approved fixed-dose inhaled corticosteroid/long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) triple therapies reduce all-cause mortality (ACM) versus dual LAMA/LABA therapy in patients with COPD, head-to-head studies have not compared the effects of these therapies on ACM. We compared ACM in adults with moderate-to-very severe COPD receiving budesonide/glycopyrrolate/formoterol fumarate (BGF) in ETHOS versus fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in IMPACT using a matching-adjusted indirect comparison (MAIC). METHODS: A systematic literature review identified two studies (ETHOS [NCT02465567]; IMPACT [NCT02164513]) of ≥52 weeks reporting ACM as an efficacy endpoint in patients receiving triple therapy. As ETHOS and IMPACT lack a common comparator, an unanchored MAIC compared ACM between licensed doses of BGF (320/18/9.6 µg) from ETHOS and FF/UMEC/VI (100/62.5/25 µg) from IMPACT in patients with moderate-to-very severe COPD. Using on- and off-treatment data from the final retrieved datasets of the intention-to-treat populations, BGF data were adjusted according to aggregate FF/UMEC/VI data using 11 baseline covariates; a supplementary unadjusted indirect treatment comparison was also conducted. P-values for these post-hoc analyses are not adjusted for Type I error. RESULTS: ACM over 52 weeks was statistically significantly reduced by 39% for BGF versus FF/UMEC/VI in the MAIC (hazard ratio [HR] [95% CI]: 0.61 [0.38, 0.95], p = 0.030) and unadjusted analysis (HR [95% CI]: 0.61 [0.41, 0.92], p = 0.019). CONCLUSION: In this MAIC, which adjusted for population heterogeneity between ETHOS and IMPACT, ACM was significantly reduced with BGF versus FF/UMEC/VI in patients with moderate-to-very severe COPD.


Chronic obstructive pulmonary disease (known as COPD) is a leading cause of death worldwide, being responsible for over 3 million deaths in 2019. People living with COPD are more likely to die. Importantly, a sudden worsening of COPD symptoms (known as an exacerbation) is associated with a higher chance of death from heart-related and breathing-related problems. Therefore, reducing risk of death is an important treatment goal for COPD. Of the three medications approved for treating COPD that combine three drugs in a single-inhaler device, there are two­referred to generically as budesonide/glycopyrrolate/formoterol fumarate (BGF) and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)­that can reduce the risk of death in people living with COPD compared with treatments that combine two drugs. However, no studies have directly compared the risk of death in people living with COPD treated with these medicines. We compared the risk of death in people living with moderate-to-very severe COPD who received either BGF during a clinical trial called ETHOS or FF/UMEC/VI during a clinical trial called IMPACT. To make this comparison, we used a method called "matching-adjusted indirect comparison", which used specific features (such as sex, breathing difficulty, and whether they were current smokers) to match patients from the two studies to ensure similar groups were examined. Our analysis showed a 39% decrease in the chance of death in patients who received BGF compared with patients who received FF/UMEC/VI. This finding may be important for doctors to improve patient health and reduce the risk of death in people living with COPD.

20.
Chem Biodivers ; 20(9): e202300495, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37539766

RESUMO

The present study was designed to appraise the photoprotective, antioxidant, and antibacterial bioactivities of Ruellia tuberosa leaves extracts (RtPE, RtChl, RtEA, RtAc, RtMe, and RtHMe). The results showed that, RtHMe extracts of R. tuberosa was rich in total phenolic content, i. e., 1.60 mgGAE/g dry extract, while highest total flavonoid content was found in RtAc extract, i. e., 0.40 mgQE/g. RtMe showed effective antioxidant activity (%RSA: 58.16) at the concentration of 120 µL. RtMe, RtEA and RtHMe exhibited effective in vitro antibacterial activity against Gram-negative bacteria (E. coli). In silico docking studies revealed that paucifloside (-11.743 kcal/mol), indole-3-carboxaldehyde (-7.519 kcal/mol), nuomioside (-7.275 kcal/mol), isocassifolioside (-6.992 kcal/mol) showed best docking score against PDB ID 2EX8 [penicillin binding protein 4 (dacB) from Escherichia coli, complexed with penicillin-G], PDB ID 6CQA (E. coli dihydrofolate reductase protein complexed with inhibitor AMPQD), PDB ID 2Y2I [Penicillin-binding protein 1B in complex with an alkyl boronate (ZA3)] and PDB ID 2OLV (from S. aureus), respectively. Docked phytochemicals also showed good drug likeness properties.


Assuntos
Acanthaceae , Extratos Vegetais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Compostos Fitoquímicos/farmacologia , Acanthaceae/química
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